Insertable device including flexible circuit

Abstract

The described embodiments relate to medical devices that include an invasive probe that, when inserted into a vessel (e.g., vasculature) of an animal (e.g., a human or non-human animal, including a human or non-human mammal), can be used to aid in the diagnosis and / or treatment of a lesion in the vessel (e.g., a growth or deposit within the vasculature that completely or partially occludes the vasculature). The invasive probe can have one or more sensors for sensing characteristics of the lesion, including by detecting one or more characteristics of the tissue and / or biomaterial of the lesion.

Description

[Background technology]

[0001] Obstruction of blood vessels (including veins or arteries) can occur in various parts of animals (e.g., humans or non-human animals) and can have serious consequences. In ischemic stroke, for example, a blood clot completely or partially blocks blood flow in a cerebral artery. If the blood clot is not treated promptly, insufficient blood flow can cause irreparable damage to the brain.

[0002] Obstruction can be caused by blood clots resulting from the aggregation of red blood cells and / or white blood cells and / or platelets within a blood vessel. Coagulation can be triggered by a variety of factors, including injury, abnormal blood flow at the site of obstruction, diseases / conditions that make the animal prone to clotting, and / or other factors.

[0003] The common treatment for blood clots is chemical dissolution of the clot, which is feasible within the first 4.5 hours after vascular occlusion. Another common option is mechanical thrombectomy, which involves removing the clot from the blood vessel using a suction catheter or stent retriever.

[0004] A stent retriever includes a stent attached to the end of a wire. The stent is deployed within the vascular structure and within the blood clot, expands within the clot, and after a typical waiting time of 0.5 to 10 minutes, is withdrawn to pull the clot out of the vessel. Because the stent retriever does not optimally grasp the blood clot, some parts of the clot may be left behind by the retriever or lost from the retriever, resulting in the need for multiple consecutive treatments (an average of 3) to treat the occlusion and restore circulation within the vessel. Each iteration increases damage to the vessel wall, increasing both the duration of intervention and the duration of impaired blood flow due to the occlusion, potentially leading to irreversible damage. The physical and mechanical processes of blood clot grasping are currently not well understood, but the two most common explanations for suboptimal grasping of blood clots are: (1) the stent retriever never deploys into the blood clot, and only the friction induced by the stent retriever pressing the blood clot against the wall is involved in the retrieval of the blood clot; and (2) the stent deploys into the blood clot, but there is insufficient time for the stent to fuse with the blood clot.

[0005] When an aspiration catheter is used to remove a blood clot, the clinician inserts the catheter into the vascular structure and manipulates the catheter to aspirate the clot into the catheter. Depending on the diameter of the catheter, the catheter can be positioned in direct contact with the clot or in a proximal region of the blood vessel. Depending on the composition and viscosity of the clot, the aspiration method may vary. Some problems can arise with aspiration catheters. For example, once a blood clot is aspirated into the catheter, it can obstruct the flow within the catheter. In such a situation, the clinician may not realize whether the clot is obstructing the tip of the catheter or inside the catheter, obstructing the tube, until the catheter is removed. If the clot is obstructing the tip of the catheter, there is a risk that the clot may be inadvertently released during catheter removal, resulting in the clot traveling through the bloodstream and potentially becoming an embolism that obstructs a blood vessel in another part of the animal. [Overview of the Initiative]

[0006] The present invention relates to a circuit board for use with an invasive probe inserted into an animal tube, wherein the circuit board is - The first area, • Interconnection layer, • A first polymer layer disposed on the first side of the interconnection layer, A first region comprising: a first region comprising: a second polymer layer disposed on the second side of the interconnection layer opposite the first side; - The second area, • One or more integrated circuits, • An interconnection layer connected to one or more integrated circuits, • An interconnection layer and a first polymer layer disposed on the first side of one or more integrated circuits, • An interconnection layer on the opposite side of the first side and a second polymer layer disposed on the second side of one or more integrated circuits, A second area comprising, In the first region, the first thickness of the first polymer layer coincides with the second thickness of the second polymer layer. The first flexibility of the first region is greater than the second flexibility of the second region.

[0007] According to another advantageous aspect of the present invention, the circuit board is A first integrated circuit arranged to operate one or more sensors to detect a value of -1 or more, - A second integrated circuit comprising one or more circuits electrically connected to the first integrated circuit and operated by the first integrated circuit.

[0008] The present invention also relates to a circuit board for use with an invasive probe inserted into an animal tube, wherein the circuit board is - The first area, • Interconnection layer, • A first polymer layer disposed on the first side of the interconnection layer, A first region comprising: a first region comprising: a second polymer layer disposed on the second side of the interconnection layer opposite the first side; - The second area, ·A first integrated circuit arranged to operate one or more sensors to detect one or more values; ·A second integrated circuit electrically connected to the first integrated circuit and comprising one or more circuits operated by the first integrated circuit; ·An interconnect layer electrically connecting the first and second integrated circuits; ·A first polymer layer disposed on the first side portions of the interconnect layer and the first and second integrated circuits; ·A second polymer layer disposed on the second side of the interconnect layer, and the first and second integrated circuits on the opposite side of the first side, a second region.

[0009] According to another advantageous aspect of the present invention, the circuit board has the following features, namely - In the first region, the first thickness of the first polymer layer matches the second thickness of the second polymer layer; - The first flexibility of the first region is greater than the second flexibility of the second region; including one or more of the above, alone or in combination.

[0010] The present invention also relates to an invasive probe, preferably a guide wire, - A housing; - One or more electrical components; - The circuit board described above, the circuit board is at least partially disposed within the housing, one or more electrical components are mounted on the circuit board, and the circuit board is ·A region of the circuit board extending from the housing and having two or more conductive contacts disposed outside the non-flexible housing, the two or more conductive contacts comprising a first contact and a second contact; ·At least one interconnect layer electrically connecting the two or more conductive contacts to one or more electrical components; A first wire is electrically connected to the first contact disposed outside the non-flexible housing; A second wire is electrically connected to a second contact located outside the non-flexible housing.

[0011] According to another advantageous aspect of the present invention, the invasive probe has the following features, namely - The invasive probe further comprises at least one additional wire, Two or more conductive contacts are three or more conductive contacts, including one or more additional conductive contacts disposed on the outside of the non-flexible housing. The first wire, the second wire, and at least one additional wire are joined together in a ribbon shape, each of the first wire, the second wire, and at least one additional wire is electrically insulated from the other wires of the ribbon, and each wire of the ribbon is electrically connected to one of three or more conductive contacts. - Each wire in the ribbon is equipped with an insulating jacket that electrically insulates the wires within the ribbon. For each wire of a ribbon electrically connected to one of three or more conductive contacts on a circuit board, the insulating jacket of the wire shall be in contact with the other conductive contacts on the circuit board. - Three or more conductive contacts on the circuit board are distributed outside the non-flexible housing across the region of the circuit board extending from the non-flexible housing. Each wire in the ribbon includes an opening within the insulating jacket associated with the wire at a position corresponding to the location of one of three or more conductive contacts to which the wire is electrically connected. The invasive probe further comprises three or more regions of conductive material that bond the ribbon to the circuit board, and the three or more regions of conductive material are positioned on the circuit board at positions corresponding to each of the three or more conductive contacts. - The circuit board is flexible, The ribbon is flexible, Three or more regions of the conductive material form three or more non-flexible regions, each of which is positioned on the circuit board. - The invasive probe further comprises an insulating adhesive disposed in close proximity to the region where the first wire, the second wire, and / or additional wires are electrically connected to the first contact, the second contact, and / or additional conductive contact. - The invasive probe is a guide wire comprising a core wire made of a conductive material, each of which a first wire, a second wire, and / or additional wires are arranged on the outer surface of the core wire, and the core wire is preferably connected to a potential reference via a capacitor. - The first wire, the second wire, and / or additional wires include at least one of a ground wire and a positive potential wire for supplying power to the circuit board, and a signal carrier wire for providing a time-dependent signal to the circuit board, wherein the signal carrier wire is positioned between the ground wire and the positive potential wire. - At least one integrated circuit is configured to implement a digital communication protocol by supplying a digital time-dependent signal through at least one of a first wire, a second wire, and / or an additional wire. - The first region radially encloses at least a portion of the second region with respect to the longitudinal direction of the housing. - The invasive probe further comprises an elongated core. - At least a portion of the second region is positioned adjacent to the elongated core. - The invasive probe may further be equipped with a jacket. - The first region is a flexible region. - The second region is the inflexible region. - The first region is configured to have a bending radius in the range of 1 micron to 50 microns. - The first region is configured to enclose at least a portion of the second region. - The thickness of the first polymer layer and the thickness of the second polymer layer shall coincide within the first region. - One or more integrated circuits in the second region are positioned closer to the top surface of the first polymer layer than to the bottom surface of the second polymer layer. - One or more sensors shall include an electrode array. - The first integrated circuit is configured to control or receive data from one or more sensors. - The second integrated circuit includes a filtering capacitor. This includes one or more of these, either individually or in any technically possible combination.

[0012] The present invention also relates to a method for manufacturing the aforementioned invasive probe, wherein the housing includes a slot, - A step of positioning the above-mentioned flexible circuit board with respect to the housing, wherein the positioning includes positioning a second region of the flexible circuit board within a slot of the housing. The present invention relates to a method comprising the steps of: winding a first region of a flexible circuit board around a housing while the second region is positioned within the slot.

[0013] According to another advantageous aspect of the present invention, the method has the following features, namely - Wrapping the first region around the housing includes applying consistent pressure to the first region before and / or during wrapping. - The method further includes joining each of the multiple wires of the invasive probe to each of the multiple conductive contacts of the invasive probe, Multiple conductive contacts are formed on a flexible circuit board of an invasive probe, the flexible circuit board is partially disposed within a non-flexible housing, and the multiple conductive contacts are disposed outside the non-flexible housing. - The method further includes using a non-conductive material to bond at least a portion of the flexible circuit board to the housing. This includes one or more of these, either individually or in any technically possible combination.

[0014] The embodiments described relate to a medical device comprising an invasive probe that, when inserted into a duct (e.g., a vascular structure) of an animal (e.g., a human or non-human animal, including humans or non-human mammals), can assist in the diagnosis and / or treatment of a lesion in the duct (e.g., proliferation or deposits within a vascular structure that completely or partially occlude the vascular structure). The invasive probe may have one or more sensors for detecting the characteristics of the lesion, including by detecting one or more characteristics of the tissue and / or biomaterial of the lesion. The medical device may be configured to analyze the characteristics of the lesion and, based on the analysis, provide treatment recommendations to a clinician. Such treatment recommendations may include methods for treating the lesion, e.g., which treatments to use to treat the lesion and / or how to use the treatment device.

[0015] A particular embodiment relates to a guidewire comprising: a solid elongated core having a proximal region and a distal region; a jacket surrounding at least a portion of the proximal region of the elongated core; one or more conductive wire leads extending along the elongated core and positioned to be at least partially disposed between the elongated core and the jacket; a flexible structure positioned around at least a portion of the distal region of the elongated core; and an electronic circuit electrically connected to one or more conductive wire leads and coupled to the distal region of the elongated core.

[0016] A particular embodiment relates to a guidewire comprising a solid elongated core, a multifilar coil positioned around a portion of the solid elongated core, a housing coupled to the solid elongated core and disposed between the multifilar coil and the distal end of the elongated core, and a circuit disposed on a flexible substrate wound within and / or around at least a portion of the housing, wherein the flexible substrate comprises a circuit including one or more impedance sensors.

[0017] A particular embodiment relates to an apparatus for detecting the impedance of tissue in the vascular system, the apparatus comprising a housing having a recess formed thereon, and a flexible substrate having a plurality of electrodes and at least one first integrated circuit electrically coupled to the plurality of electrodes, the at least one first integrated circuit having a first circuit for generating a probe signal and using the probe signal to drive the plurality of electrodes, and a second circuit for processing a detection signal received by the plurality of electrodes in response to transmitting the probe signal to the outside of the flexible substrate, the flexible substrate being wrapped around the housing and having a portion passing through the recess of the housing, and the plurality of electrodes being disposed on the outside of the housing and oriented outward relative to the housing.

[0018] A particular embodiment relates to a method for assembling a guidewire for use in vascular surgery, the method comprising the steps of forming a jacket having a recess formed through it; passing a solid elongated core through the recess of the jacket; passing one or more conductive wire leads through the recess of the jacket and positioning the one or more conductive wire leads between the jacket and the elongated core; passing a portion of a multifilament coil through the recess of the jacket; and necking the jacket to reduce the size of the lumen.

[0019] A particular embodiment relates to a method for assembling a device to be inserted into an anatomical tube of an animal. The method includes the steps of forming a tubular jacket that defines a lumen, passing an elongated core through the lumen of the tubular jacket, passing a portion of a flexible structure through the lumen of the tubular jacket, and necking the tubular jacket to reduce the size of the lumen.

[0020] In one embodiment, a medical device for diagnosing and / or treating lesions in the tubules of an animal is described. In some embodiments, the medical device comprises an invasive probe for insertion into the tubules of an animal and removal from the tubules after diagnosis and / or treatment, the invasive probe comprising at least one sensor for measuring one or more characteristics of a lesion, at least one processor, and at least one storage medium on which executable instructions are encoded, causing the at least one processor to perform a method including the steps of determining one or more treatment recommendations for a method of treating the lesion, at least in part based on an analysis of one or more characteristics, and outputting one or more treatment recommendations to a user via a user interface.

[0021] In certain embodiments, the medical device comprises an invasive probe positioned to be inserted into an animal's tube during diagnosis and / or treatment of a lesion in the tube and removed from the tube after diagnosis and / or treatment, wherein the invasive probe is configured to take one or more measurements of the lesion in the tube, and the invasive probe comprises at least one impedance sensor and at least one circuit for driving at least one impedance sensor to take multiple measurements of the impedance of the lesion, each measurement of the multiple impedance measurements corresponding to one of a plurality of frequencies, and is a measurement of the impedance of the lesion when an electrical signal of the corresponding frequency is applied to the lesion.

[0022] Certain embodiments of the present invention relate to a method for operating a medical device for diagnosing and / or treating lesions in animal tubules, the medical device comprising an invasive probe that is inserted into the animal tubule and removed from the tubule after diagnosing and / or treating the lesion. In some embodiments, the method includes the steps of: generating data representing one or more characteristics of a lesion in the animal tubule using the invasive probe of the medical device while the invasive probe is positioned inside the animal tubule, wherein generating the data includes operating at least one sensor of the invasive probe to measure one or more characteristics of the lesion; determining one or more therapeutic recommendations regarding how to treat the lesion using at least one processor of the medical device, at least in part on the analysis of the one or more characteristics; and outputting one or more therapeutic recommendations for presentation to a user via a user interface.

[0023] According to a particular embodiment, a method for operating a medical device for diagnosing and / or treating a lesion of an animal's vascular structure, the medical device comprising an invasive probe inserted into the animal's vascular structure and removed from the vascular structure after diagnosing and / or treating the lesion, the method comprising the steps of: generating data indicating one or more electrical properties of a lesion of an animal's vascular structure using the invasive probe of the medical device while the invasive probe is positioned within the animal's vascular structure, the generation of data comprising operating at least one sensor of the invasive probe to measure one or more electrical properties of the lesion; and outputting information indicating one or more electrical properties for presentation to a user via a user interface.

[0024] In some embodiments, the apparatus is described. According to a particular embodiment, the apparatus comprises at least one processor and, when executed by the at least one processor, a process of receiving a plurality of reports from a plurality of medical devices over time regarding medical treatments performed on a plurality of lesions of an animal's tubule, wherein each of the plurality of reports includes one or more characteristics of the lesion treated in the corresponding medical treatment, one or more parameters of the corresponding medical treatment performed to treat the lesion, and an indication of the outcome of the corresponding medical treatment, and over time, based on the plurality of reports regarding the medical treatment, one or more between the characteristics of the lesion and the parameters of successful and / or unsuccessful treatment of the lesion. The method comprises: a step of learning numerical relationships, wherein learning one or more relationships includes determining one or more conditions for associating each of a plurality of treatment options with respect to the characteristics of a lesion, such that when the characteristics of a lesion satisfy one or more conditions relating to the corresponding treatment option, the corresponding treatment option is recommended for the treatment of the lesion; and at least one storage medium on which executable instructions are encoded causing a method to be performed, the method comprising: a step of configuring a plurality of medical devices to make recommendations to a clinician from among the plurality of treatment options based on an evaluation of the characteristics of a lesion with respect to one or more conditions relating to each of the plurality of treatment options.

[0025] When executed by at least one processor, at least one storage medium on which executable instructions causing at least one processor to execute the method are encoded is described according to a particular embodiment. In some embodiments, the method includes: receiving multiple reports from multiple medical devices over time regarding medical treatments performed on multiple lesions of an animal's tubule, each of which reports includes one or more characteristics of the lesion treated in the corresponding medical treatment, one or more parameters of the corresponding medical treatment performed to treat the lesion, and an indication of the outcome of the corresponding medical treatment; learning one or more relationships over time, based on the multiple reports on medical treatments, between the characteristics of the lesion and the parameters of successful and / or unsuccessful treatment of the lesion, wherein learning one or more relationships includes determining one or more conditions to associate with each of the multiple treatment options, such that the one or more conditions are associated with the characteristics of the lesion so that the corresponding treatment option is recommended for the treatment of the lesion when the characteristics of the lesion satisfy one or more conditions relating to the corresponding treatment option; and configuring multiple medical devices to make recommendations to a clinician from among the multiple treatment options based on an evaluation of the characteristics of the lesion with respect to one or more conditions relating to each of the multiple treatment options.

[0026] A particular embodiment describes a method that includes operating at least one processor to receive multiple reports over time from multiple medical devices regarding medical treatments performed on multiple lesions of an animal's tubule, wherein each of the multiple reports includes one or more characteristics of the lesion treated in the corresponding medical treatment, one or more parameters of the corresponding medical treatment performed to treat the lesion, and instructions for the outcome of the corresponding medical treatment; and, over time, learning one or more relationships between the characteristics of the lesion and the parameters of successful and / or unsuccessful treatment of the lesion, based on the application of a machine learning process to the multiple reports on medical treatments, wherein learning one or more relationships includes determining one or more conditions to associate with each of the multiple treatment options, wherein one or more conditions are associated with the characteristics of the lesion so that the corresponding treatment option is recommended for treatment of the lesion when the characteristics of the lesion satisfy one or more conditions relating to the corresponding treatment option; and configuring multiple medical devices to make recommendations to a clinician from among the multiple treatment options based on an evaluation of the characteristics of the lesion with respect to one or more conditions relating to each of the multiple treatment options.

[0027] According to some embodiments, a method for diagnosing and / or treating lesions in animal tubules is described. In certain embodiments, the method includes the steps of: inserting an invasive probe of a medical device into an animal tubule, wherein the invasive probe comprises at least one sensor for measuring one or more properties of tissue and / or biomaterial of a lesion; operating the medical device to generate one or more recommendations for treating the lesion, at least in part, based on one or more properties measured by the at least one sensor of the invasive probe; treating the lesion in accordance with one or more recommendations of the medical device for treating the lesion; and removing the invasive probe from the animal tubule.

[0028] According to some embodiments, a medical device configured to diagnose and / or treat lesions in the tubules of an animal is described. In certain embodiments, the medical device comprises inserting an invasive probe of the medical device into the tubules of an animal, the invasive probe comprising at least one sensor configured to measure one or more properties of the tissue and / or biomaterial of a lesion, and further configured to generate one or more recommendations regarding the treatment of the lesion, at least in part, based on the measurement of one or more properties by the at least one sensor of the invasive probe, and further configured to deliver treatment to the lesion in accordance with the one or more recommendations regarding the treatment of the lesion. In certain embodiments, the medical device is also configured to remove a lesion from the tubules of an animal.

[0029] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention, when considered in conjunction with the accompanying drawings. In the event that this specification and the documents incorporated by reference contain conflicting and / or inconsistent disclosures, this specification shall prevail. Accordingly, the above is a non-limiting summary of the invention as defined by the accompanying claims.

[0030] The attached drawings are not intended to be drawn to a fixed scale. In the drawings, each identical or nearly identical component shown in various figures is represented by similar numbers. For clarity, not all components are labeled in all drawings. [Brief explanation of the drawing]

[0031] [Figure 1] This is a flowchart illustrating how a clinician may operate a medical device to diagnose and / or treat a lesion, according to embodiments described herein. [Figure 2] This is a diagram of an example of a medical device according to some embodiments. [Figure 3] This is a diagram of an example of an invasive probe according to some embodiments. [Figure 4]This is a flowchart of a process that may be implemented in some embodiments to determine the composition of a lesion. [Figure 5] This is a flowchart of a process that may be implemented in some embodiments to determine the composition of a lesion. [Figure 6] This is a diagram illustrating an example frequency spectrum of the absolute value of the impedance of a lesion. [Figure 7] An exemplary model of lesion impedance, which can be implemented using the method shown in Figure 4, including a constant-phase element, is presented. [Figure 8] An exemplary model of lesion impedance, which can be implemented using the method shown in Figure 4, including a constant-phase element, is presented. [Figure 9] An exemplary model of lesion impedance, which can be implemented using the method shown in Figure 4, including a constant-phase element, is presented. [Figure 10] An exemplary model of lesion impedance, which can be implemented using the method shown in Figure 4, including a constant-phase element, is presented. [Figure 11] An exemplary system for implementing the method shown in Figure 4 is provided. [Figure 12] This is a flowchart illustrating an exemplary method for the operation of a medical device, according to some embodiments described herein, for generating treatment recommendations. [Figure 13] This is a flowchart of another exemplary method for some embodiments of the operation of a medical device, according to embodiments described herein, for generating treatment recommendations based partially on the composition of a lesion. [Figure 14] This is a flowchart of an exemplary method for generating treatment recommendations using conditions, which may be implemented in some embodiments. [Figure 15A] This is a flowchart illustrating an exemplary process, which may be implemented in some embodiments, for causing a server to analyze treatment reports and determine the conditions for configuring a medical device. [Figure 15B]This is a flowchart illustrating an exemplary process, which may be implemented in some embodiments, for causing a server to analyze treatment reports and determine the conditions for configuring a medical device. [Figure 16] This is an example of a process that may be implemented in some embodiments for generating a treatment history. [Figure 17] This is a block diagram of a computing device in which some embodiments may operate. [Figure 18] This figure shows an example of the effective capacitance of a cell structure determined by the method shown in Figure 4. [Figure 19] Examples of systems created in accordance with aspects of this disclosure are shown. [Figure 20] Examples of systems created in accordance with aspects of this disclosure are shown. [Figure 21A] This is a histogram showing the determined effective capacitance of multiple cell types under controlled conditions. [Figure 21B] This is a histogram showing the determined effective capacitance of multiple cell types under uncontrolled conditions. [Figure 22] This is a flowchart illustrating an exemplary method for some embodiments of the operation of a medical device, according to embodiments described herein, for generating treatment recommendations based in part on the characteristics of cancerous and / or non-cancerous tissue. [Figure 23] This is a flowchart illustrating an exemplary method for some embodiments of the operation of a medical device, according to embodiments described herein, for generating treatment recommendations based in part on the characteristics of cancerous and / or non-cancerous tissue. [Figure 24] This is a flowchart illustrating an exemplary method for some embodiments of the operation of a medical device, according to embodiments described herein, for generating treatment recommendations based in part on the characteristics of cancerous and / or non-cancerous tissue. [Figure 25] This graph shows the amplitude and phase spectra of the experimental data. [Figure 26A] This is a histogram showing the distribution of various parameters. [Figure 26B] This is a histogram showing the distribution of various parameters. [Figure 27A] This is a histogram showing the distribution of various parameters. [Figure 27B] This is a histogram showing the distribution of various parameters. [Figure 27C] This is a histogram showing the distribution of various parameters. [Figure 27D] This is a histogram showing the distribution of various parameters. [Figure 27E] This is a histogram showing the distribution of various parameters. [Figure 27F] This is a histogram showing the distribution of various parameters. [Figure 28] This is a histogram showing the distribution of effective capacitance values ​​for different cell types. [Figure 29] This is a histogram showing the distribution of effective capacitance values ​​for different cell types. [Figure 30] This is a histogram showing the distribution of effective capacitance values ​​for different cell types. [Figure 31] This is a schematic diagram showing an example of a guide wire that may be implemented in some embodiments. [Figure 31A] A portion of the guidewire in Figure 31 is shown in more detail. [Figure 31B] Figure 31 shows possible implementation configurations for the guidewire having multiple rows of multifilar coils. [Figure 32] Figure 31 shows an example of a connector assembly that may be used in some embodiments along with the guide wire. [Figure 33] Figure 31 shows an example of a sensor assembly that may be used in some embodiments, along with the guide wire. [Figure 34] This is a schematic diagram showing a guide wire having multiple segments according to one embodiment. [Figure 35] An example of a housing that may be used in some embodiments, along with the guide wire shown in Figure 31, is presented. [Figure 36A] An example of a flexible circuit that may be used in some embodiments is shown in Figure 31, along with the guide wires. [Figure 36B] An example of an assembly using the housing of Figure 35 and the flexible circuit of Figure 36A, according to some embodiments, is shown. [Figure 37] This is a schematic diagram showing another example of a guide wire that may be implemented in some embodiments. [Figure 38] This is a schematic diagram showing yet another example of a guide wire that may be implemented in some embodiments. [Figure 39] Additional details and some of the guide wires in Figure 38 in multiple cross-sections are shown according to some embodiments. [Figure 40] This is a schematic diagram showing yet another example of a guide wire that can be implemented in some embodiments. [Figure 41A] This is a schematic cross-sectional side view of a flexible circuit board according to one embodiment. [Figure 41B] This is a schematic cross-sectional side view of a flexible circuit board according to one embodiment. [Figure 41C] A schematic cross-sectional view of the distal portion of a guidewire, which has a flexible circuit board wound around the housing according to one embodiment, is shown. [Figure 42] This is a flowchart of a method for positioning and winding a flexible circuit board within a non-flexible housing of a guide wire, according to some embodiments. [Figure 43A] A schematic diagram shows a region of a circuit board disposed outside a non-flexible housing, having conductive contacts of the circuit board attached to wires disposed outside the non-flexible housing, according to some embodiments. [Figure 43B] A schematic diagram shows a region of a circuit board disposed outside a non-flexible housing, having conductive contacts of the circuit board attached to wires disposed outside the non-flexible housing, according to some embodiments. [Figure 44] A schematic representation of the material's flexure along the bending radius of the neutral axis in some embodiments is shown. [Modes for carrying out the invention]

[0032] Embodiments described herein relate to medical devices comprising an invasive probe that can assist in the diagnosis and / or treatment of lesions of a tubule, which, when inserted into a tubule of an animal (e.g., a human or non-human animal, including humans or non-human mammals), may be an occlusion (e.g., a blood clot) that completely or partially occludes the tubule. The tubule may be, for example, a blood vessel or other tubule of an animal, and the lesion may be formed, whole or in part, by proliferation within the tubule, accumulation of material within the tubule, and / or any other cause of the lesion. The invasive probe may have one or more sensors for detecting the characteristics of the lesion, including by detecting one or more characteristics of the tissue and / or biomaterial of the lesion. The medical device may be configured to analyze the characteristics of the lesion and, based on the analysis, provide treatment recommendations to a clinician. Such treatment recommendations may include methods for treating the lesion, such as which treatment to use to treat the lesion (e.g., whether to use a suction catheter or a stent retriever if the lesion should be removed), and / or methods for using the treatment device (e.g., the rate at which to extract the stent retriever).

[0033] Tubes within animals can be narrow in diameter. As a result of the narrow tube diameter, the diameter of the invasive probe inserted into the tube is also limited, which limits the size of the probe and therefore the available space for the components of the invasive probe. Furthermore, when navigating an animal to reach a tube and / or navigating the tube, the invasive probe may need to move through curved and tortuous pathways in the animal's anatomical structure, which can themselves be narrow. To navigate these pathways, the invasive probe may need to be flexible. However, electrical components can be fragile when bent. Therefore, to ensure the reliability of the components of the invasive probe, at least some of the components of the invasive probe can be positioned to prevent them from being subjected to bending forces, such as by being housed on and / or within a non-flexible housing. While such a non-flexible housing can enhance the reliability of the components, its non-flexibility puts it under tension for the purpose of ensuring the flexibility of the invasive probe for navigating the animal's anatomical structure. To satisfy both objectives, the non-flexible housing may need to be even smaller to limit the portion of the invasive probe that is non-flexible, ensuring that the invasive probe can navigate animal anatomical structures and tubes.

[0034] The limited space of the non-flexible housing means that there is limited space in which components of the invasive probe, such as electrical components, can be arranged, which may limit the number of components included in the invasive probe. Limiting the number of components may, in turn, limit the functionality of the invasive probe. However, the inventors have recognized and understood that there may be advantageous ways of arranging components within the non-flexible housing that may allow for an increase in the number of components in order to improve functionality while maintaining the small size of the non-flexible housing.

[0035] Some embodiments include a flexible circuit that can be manufactured to include sensors and electronic circuits (e.g., integrated circuits, conductive pads, interconnect layers, wires) for examining lesions or blockages in a tube. The flexible circuit may be a flexible circuit board on which one or more integrated circuits are arranged. In some embodiments, the circuit board may be flexible so that it can be wrapped around at least a portion of an invasive probe and / or around it. By wrapping the flexible circuit board, it may be possible to increase the surface area of ​​the circuit board while reducing the volume occupied by the flexible circuit, the diameter required for the circuit board, or other internal dimensions of the invasive probe on which the flexible circuit board is arranged. Increasing the surface area can provide more surface area for arranging electrical components such as integrated circuits, thereby providing a technique for arranging multiple (e.g., two or more) integrated circuits on or within a non-flexible housing of an invasive probe (e.g., a guidewire).

[0036] Those skilled in the art will understand that a wound flexible circuit board applies flexural forces to the components within the flexible circuit board and / or components attached to the flexible circuit board. Such flexural forces can degrade and / or damage the components of the circuit board, potentially affecting the reliability of the invasive probe. The inventors have recognized and understood that certain designs of flexible circuits can mitigate these risks and enable the reliability of the components while allowing for flexibility and winding.

[0037] In some embodiments, the flexible circuit comprises a first region (e.g., a flexible region) and a second region (e.g., a rigid region or a non-flexible region), wherein the first region is more flexible than the second region. This is advantageous because the circuit can provide one or more relatively flexible portions to the flexible circuit that can be wound around part of an invasive probe or part of the flexible circuit board itself, while when the entire flexible circuit is wound, one or more other portions are relatively less flexible and are not wound or bent, or are bent less than the first portion.

[0038] The first region(s) of the flexible circuit may include some electrical components (e.g., passive components), such as passive interconnecting materials (e.g., conductive traces or other circuit board interconnecting structures), which carry electrical signals within the flexible circuit and between components of the invasive probe, and the first region(s) may be arranged to be flexible to reduce the bending force applied to these electrical components and / or to allow bending forces to be applied to the electrical components to reduce the risk of degrading or destroying the components. For example, the first region may include a first layer of flexible material, such as polyimide or another material, located above the first region, and a second layer of flexible material located below the first region, with one or more layers of interconnecting material (e.g., conductive material) disposed between the two layers of flexible material. The two layers of flexible material may be located in the first region having coincided flexibility, for example, by having coincided (e.g., identical) thicknesses. By matching the flexibility of the upper and lower flexible layers, it becomes possible to apply bending force to the interconnecting material, thereby reducing the risk of deterioration or breakage of the interconnecting material due to damage.

[0039] The second region(s) of the flexible circuit is less flexible than the first region and may include a chip or integrated circuit of the invasive probe (e.g., one or more integrated circuits for operating one or more sensors of the invasive probe to detect, for example, the electrical properties of the tissue(s) of a tube contacted by the invasive probe). In some embodiments, the second region(s) which is less flexible than the first region(s) may be inflexible. Making the second region inflexible or less flexible may protect the integrated circuit(s) of the second region from being subjected to bending forces that could degrade or destroy the integrated circuit. In some embodiments, the flexible circuit may be located within the invasive probe relative to the inflexible housing of the invasive probe, and the integrated circuit of the second region(s) is located within the inflexible housing in a position where the inflexible housing can provide some protection from or prevent bending forces from being applied to the second region(s).

[0040] In some embodiments, a first region of the flexible circuit comprises an organic or polymer material that provides or maintains flexibility to the flexible circuit board, and a second region of the flexible circuit may further comprise one or more inorganic components (e.g., a chip comprising silicon and / or one or more other inorganic semiconductor materials) that are less flexible than the organic components.

[0041] In certain embodiments, the flexible circuit board comprises two or more integrated circuits (e.g., a first integrated circuit, a second integrated circuit) configured to detect parameters or values ​​(e.g., impedance) of a lesion in the tube. The functions of these two integrated circuits may be divided to promote increased reliability of data detection. For example, the first integrated circuit may include an active circuit that can be operably coupled and driven to one or more sensors for measuring the impedance of the lesion and may be directly connected to the sensors (which may be implemented as one or more electrode pairs) within the flexible circuit. The first integrated circuit may be located on the flexible circuit board closer to the sensor(s) than the second integrated circuit. In some such embodiments, the second integrated circuit may include a passive circuit driven by the active circuit of the first integrated circuit and may be configured to process information received from the first integrated circuit, such as filtering electrical signals prior to or as part of transmission along a communication wire of an invasive probe. In some embodiments, the two or more integrated circuits may be housed within a non-flexible region of the flexible circuit. In some such cases, the inflexible region may be two inflexible regions connected by a flexible region within a flexible circuit.

[0042] Certain embodiments of this specification also include techniques for connecting the circuit board of an invasive probe (e.g., a flexible circuit board) to other parts of the invasive probe, such as one or more wires that provide power and / or communication to the electronics of the invasive probe. Those skilled in the art will understand that the connection points between the wires and the circuit board are potential weak points that can degrade or break if forces, including bending forces, are applied. Due to the bending forces that are expected to be applied to the invasive probe as it navigates the anatomical structures of an animal, those skilled in the art will understand that it is desirable to include the connection points for the wires of the invasive probe within a non-flexible housing where the connection points can be protected from bending forces. However, as mentioned above, the dimensions of the tube, and therefore the dimensions of the invasive probe, may be relatively small, and there may be limited space within the non-flexible housing. Including the connection points within the non-flexible housing may limit the space available for the components, which may include limiting the space available for the wires and thus limiting the number of wires. Limiting the number of wires may, undesirably, limit the functionality of the invasive probe. Therefore, in order to take advantage of the reliability benefits of a non-flexible housing, there is a conflict between reliability and functionality that arises from including connection points within the non-flexible housing.

[0043] The inventors have recognized and understood the advantages of specific arrangements for the connection points of wires in an invasive probe, which enable improved reliability even when the connection points are located outside the non-flexible housing of the invasive probe. In some embodiments described herein, at least a portion or region of a flexible circuit board may extend outside the non-flexible housing. This region of the flexible circuit board may be flexible and may include two or more conductive contacts, including a first contact and a second contact. Two or more wires (e.g., a first wire, a second wire) located outside the housing may each be electrically connected to one of the two or more conductive contacts in the region outside the non-flexible housing. The electrical connection may be made in a manner that can advantageously provide electrical communication between the circuit and other parts of the guide wire without short-circuiting the two or more wires and while providing more space for components within the housing. For example, the wires of the invasive probe may be arranged as ribbon wires with the insulating jackets of the wires physically joined. In this example, each insulating jacket for each wire of the ribbon can contact each conductive contact of the flexible circuit, but each wire is electrically connected to only one of the conductive contacts. In this example, a conductive material can be used to bond the ribbon wires to each of the conductive contacts, forming an electrical connection between each wire and its respective conductive contact. Advantageously, the conductive material can also be inflexible when placed on the flexible circuit, conductive contacts, and / or ribbon wires. In this case, the conductive material can form an inflexible region outside the inflexible housing in this example, and the inflexible region is separated by a region that does not contain the more flexible conductive material. Through this arrangement of regions of conductive material, an inflexible region with interspersed flexible regions can be provided, which may allow the invasive probe to be flexible enough overall to navigate the anatomical structures of an animal, while also providing inflexibility in the target region of the invasive probe to enhance the reliability of the electrical connection between the wires and the flexible circuit.

[0044] The various examples described herein illustrate medical devices in relation to vascular structural lesions and methods for treating vascular structural lesions. However, it should be understood that embodiments are not limited thereto. The techniques described herein for detecting the characteristics of lesions and generating treatment recommendations can be used in conjunction with any suitable anatomical conduits of an animal. Such conduits may include, for example, vascular structural ducts and gastrointestinal tracts. Those skilled in the art will understand that conduits within anatomical structures are different from anatomical cavities. For example, a conduit may have one dimension (e.g., width) that is significantly smaller than another dimension (e.g., length).

[0045] Therefore, in some embodiments, the invasive probe may be a component of a medical device for the diagnosis and / or treatment of lesions of vascular structures. For example, the medical device may be a thrombectomy device, and the invasive probe may be a component of the thrombectomy device. Thus, the invasive probe may be a component of a guidewire, aspiration catheter, microcatheter, stent retriever, and / or another thrombectomy device. In some embodiments, the medical device may include two or more of the guidewire, aspiration catheter, and stent retriever, and the invasive device may be a component of one or more of these, including all of them.

[0046] As described above, some embodiments described herein relate to medical devices comprising invasive probes that, when inserted into an animal (e.g., a human or non-human animal, including humans or non-human mammals), can assist in the diagnosis and / or treatment of the animal's biological structures. In some embodiments, the biological structures may be lesions of the animal, and in some cases may be lesions of the animal's tubules or lesions occurring elsewhere in the animal's anatomical structure (i.e., elsewhere than tubules). The lesions may be abnormalities in the animal's anatomical structure, e.g., deviations from the normal structure and / or function of a part of the animal, e.g., abnormalities associated with injury, medical condition, or disease. The lesions may appear in different parts of the animal, e.g., contained within the animal's tubules. Lesions of tubules may, for example, act as occlusions that completely or partially block the tubule. The tubules may be, for example, blood vessels or other tubules of the animal, and the lesions may be formed, whole or in part, by proliferation within the tubule, accumulation of material within the tubule, and / or any other cause of the lesion. Some embodiments of the invasive probe may have one or more sensors for detecting characteristics of a biological structure (e.g., a lesion), which may include determining the composition of the biological structure.

[0047] In some embodiments, detecting the composition of a biological structure may involve identifying one or more biomaterials within the structure, including one or more cells and / or one or more tissues and / or one or more plaque materials present within the structure. The identified biomaterials of the structure may be all the biomaterials present in the biological structure, or only a portion of the biomaterials present in the structure. If only a portion of the biomaterials is identified, the identified material(s) may be a specific type of material (compared to other materials such as plaque material) or a specific type of tissue / cell (e.g., red blood cells present in the lesion, and not other types of cells). If the composition is determined and only one or more types(s) of biomaterials are identified, determining the composition may involve determining the amount(s) of the identified material(s) in the biological structure, for example, by calculating one or more ratios of the identified material(s) to the total material of the lesion.

[0048] The inventors recognized that a tool that reduces the time required to diagnose and / or successfully treat lesions (such as blood clots) formed in neurovascular structures, including cerebral vascular structures, would be desirable and advantageous. Blood clots can develop at the site of an occluded blood vessel (e.g., as a thrombus) or in other areas of the vascular system, such as within the limbs, and subsequently break off and travel to the brain (e.g., as an embolism), remaining within the blood vessels of the brain. If the occlusion caused by the blood clot restricts or blocks the flow of blood and oxygen, the patient may suffer a stroke. Patients suffering a stroke are often treated with catheterization. Treatment typically involves percutaneously placing a catheter into the carotid artery by advancing the catheter along a very flexible, small guidewire. The clinician then attempts to remove the blood clot by various means. The first attempt to remove the blood clot is often to apply aspiration using an aspiration catheter. If this is unsuccessful, another option is a mechanical removal tool, such as a stent retriever. Different types of blood clots are more or less susceptible to the effects of aspiration removal, and aspiration often fails due to the nature of the clot. The more arteries in the brain are blocked, the greater the potential for brain damage. Therefore, time can be critical when treating these patients. The inventors recognized that the need to experiment with and continuously use various tools—namely, guidewires, aspiration catheters, and sometimes stent retrievers—until the clot is removed can complicate efforts to minimize treatment time and lead to adverse outcomes for the patient.

[0049] The inventors have further recognized that the insertion of tools, including catheters and guidewires, through cerebral vascular structures is often problematic. The cerebral blood vessels are connected to the rest of the vascular system via the carotid arteries. These arteries have a particularly tortuous shape, complicating tool insertion. Specifically, the carotid arteries contain S-shaped bends in the region adjacent to the sphenoid segment (often referred to as M1) and the insular segment (often referred to as M2). To insert a tool into the cerebral vascular structure from an origin elsewhere in the body (for example, starting from the periphery such as the limbs), clinicians pass the tool through these S-shaped bends. However, these S-shaped bends complicate insertion and make tool design more complex.

[0050] Tools typically bend and flex as they are navigated through vascular structures, but the meandering shape of an S-shaped bend often causes the tool to twist or yield, maintaining the bend even when no external mechanical force is applied to the tool as it passes. Twisting can be a bend or fold of the tool that is maintained even when no external mechanical force is applied to the tool, resulting from the deformation of one or more materials of the tool. Tool twisting, even slight or slight bending, can cause many problems. Firstly, twisting or bending can make it difficult to transmit torque along the length of the tool. Torque transmission allows the distal end of the tool, located within the vascular structure, to be manipulated from the proximal end of the tool, which is potentially located outside the animal and operated by the clinician. If twisting or bending prevents or limits torque transmission, this can significantly limit the clinician's ability to properly maneuver the tool through the patient's vascular structure on the other side of the S-shaped bend. Secondly, while tools typically bend and flex easily back and forth in response to torque applied by a clinician, once twisting or bending occurs, the tool may no longer bend and flex in the same way. As a result of twisting or bending, the tool may instead resist the application of torque. When the tool resists in this way, potential energy can accumulate until the applied force overcomes the resistance imposed by the twisting / bending. At the point when the resistance is overcome, the tool may react suddenly and forcefully, snapping to a new position. This phenomenon is called "whipping." Such whipping can occur as a result of twisting / bending that occurs while passing through an S-shaped bend. In the region passing through an S-shaped bend, the vascular structure is delicate and small in size, and whipping can cause significant damage to the vascular structure. Any damage to the cerebral vascular structure can be serious, as complete and proper loss of blood flow to the brain can cause permanent damage within minutes.

[0051] Due to the risk of whipping, a key aspect of tool design for insertion into cerebral vascular structures is to reduce the likelihood of torsion occurring.

[0052] The inventors have recognized that a device inserted into a body tube (including insertion into a neurovascular structure via an S-shaped bend), comprising multiple sensors for measuring one or more properties of a biological structure, can be advantageously designed and adapted to mitigate or eliminate some or all of the aforementioned problems of typical conventional tools. For example, sensors that measure the impedance of a biological structure at one or more points on the biological structure or at one or more points in the environment of the biological structure may be configured to process the measurements to yield information about the nature of the biological structure they encounter, such as information that can identify and / or characterize the biological structure, or information about how to treat the biological structure.

[0053] However, adding sensors in this way is strictly contrary to the goal of reducing the effects of torsion. Multiple sensors are typically not included in the types of devices described herein. Including multiple sensors in a typical conventional device of a conventional design would increase the size of the insertable device to an undesirable degree. In addition, conventionally, such insertable devices include a hollow tube in the core of the insertable device, and wires for carrying control signals and / or data to the sensor (conventional devices have at most one sensor) run along the tube along the length of the insertable device. Increasing the number of sensors according to conventional designs results in a corresponding increase in the number of wires, and in such conventional devices, an increase in the diameter of the tube. Such an increase in the diameter of the tube may also increase the range of torsional effects. Such devices are not suitable for use in nerve and vascular structures due to their larger diameter and increased effects of torsion.

[0054] Accordingly, the inventors have developed and described herein an alternative to conventional designs for insertable devices including guidewires for use with an insertable probe containing multiple sensors for detecting one or more properties of a biological structure. Such devices may be suitable for use in some embodiments in neurovascular structures.

[0055] Embodiments of insertable devices are described herein, some of which include a plurality of sensors for detecting one or more properties of a biological structure. In some embodiments, the device includes a plurality of sensors while also being small in size, less susceptible to torsion, and having a good ability to transmit torque for a clinician operating the device to navigate the device through a vascular structure or other tube.

[0056] Some embodiments of the insertable devices described herein have a solid core. The insertable device may include one or more sensors on a probe at the end of an elongated body, and at least a portion of the probe and elongated body may be inserted into the body of an animal. In some such solid-core devices, the innermost portion of the probe and / or body may be solid, such as being made from a solid steel rod. This is in contrast to conventional insertable devices, which typically have a hollow core along an elongated body. Compared to hollow-core devices, of which conventional catheters are one example, certain embodiments of the invasive devices described herein are more likely to maintain their cross-sectional shape even when rigidly bent. As a result, some embodiments of the invasive devices described herein are advantageous for use in tortuous anatomical structures such as cerebral vascular structures.

[0057] As described above, the treatment of a lesion (e.g., treatment of a thrombus) may often involve using different combinations of procedures together, or selecting a specific treatment option (e.g., one tool) from a set of treatment options (e.g., multiple available tools). The difficulty in pre-determining which treatment is most likely to succeed is due to the large variability between the nature and composition of the lesion, which is often unknown for a particular lesion. A particular treatment may be particularly suitable for treating a specific type of lesion (e.g., a thrombus with a particular nature or composition), but those same treatments may not be sufficiently effective or the best choice when used in combination with other types of lesions. The inventors have recognized that the design and use of an insertable device capable of determining the nature and / or composition of a lesion may be advantageous in eliminating or mitigating this uncertainty in selection. In particular, as a result, the inventors have developed a tool for detecting one or more characteristics or attributes of a lesion, which may enable the identification and / or characterization of the lesion and / or the determination of an appropriate treatment for the lesion. Certain embodiments of the disclosed insertable device, for example, an embodiment having multiple sensors for detecting one or more values ​​of a biological structure (e.g., a lesion) at one or more locations on the biological structure, can provide such functionality. Information obtained through the use of the sensors may then be used to determine one or more properties of a blood clot, such as the composition of the blood clot, which can in turn assist the system and / or clinician in selecting or recommending treatment for the biological structure.

[0058] In some embodiments, the invasive probe may include one or more sensors for measuring the impedance of a biostructure. The sensors can measure the impedance of a lesion when an electrical signal having a specific frequency is applied to the lesion. The medical device may be configured to determine the composition and / or one or more properties of the biostructure based on the impedance values. For example, each sensor may operate to detect the impedance spectrum of the biomaterial in contact with the sensor, so that different sensors of the invasive probe may simultaneously produce different impedance spectra for different biomaterials of the biostructure. In some embodiments, the medical device may then generate treatment recommendations, partly based on the determined composition. As described above, determining the composition may involve identifying the amount of one or more biomaterials in the biostructure, which may be less than the total amount of material in the biostructure. For example, in some embodiments, the amount of a biostructure composed of red blood cells is determined.

[0059] In some embodiments, multiple sensors of an insertable device may be located within a probe section of the device, which may be located within a distal "working zone" (e.g., the last 30-50 cm of the device) at the end of the elongated body of the insertable device. In conventional devices, wire leads are typically electrically insulated and located within a hollow core, but in embodiments where multiple sensors are located within a device having a solid core, the inventors have recognized that a different approach to electrical insulation of the electrical wires and connections would be advantageous. Such insulation of electrical components can prevent or reduce the opportunity for contact with environmental factors (e.g., liquids) that could cause short circuits. In some embodiments, the wire leads are wound around the solid core or otherwise arranged along it, and a protective jacket surrounds the wire leads. In some embodiments, the jacket may be thin enough to be robust enough to isolate the wire leads and their connections from fluids, but without substantially changing the thickness of the invasive probe. In some embodiments, the jacket is made of polyimide.

[0060] The inventors have also found that, in certain embodiments, certain operational and performance advantages can be obtained by positioning both the sensor and other electronic circuits of a device in the distal portion of a device that can be inserted into the body of an animal and may need to navigate complex anatomical structures of small size. The inventors have further found that, in certain embodiments, signal noise and / or attenuation can be limited by positioning the circuit that operates the sensor, which includes a circuit that processes the value detected by the sensor, in close proximity to the sensor. In particular, for devices with long, slender bodies, the further the processing components are from the biological structure being detected, the more susceptible the signal typically becomes to noise and attenuation.

[0061] In some embodiments, due to limitations on the dimensions of anatomical structures that the insertable device can navigate, the diameter of the distal end of the device, including at least a portion of the probe and elongated body, may be advantageously not exceed 0.014 inches (double quotes are used herein to indicate measurements in inches), i.e., 0.36 mm (millimeters).

[0062] As briefly described above and in more detail below, in some embodiments, sensors and / or circuits may be disposed on a flexible substrate, including a flexible circuit board, to house the sensors and circuits within the probe area of ​​an insertable device. These substrates can function as supports for the chip hosting the sensors and circuits. Because they are flexible, in some embodiments the substrates may be curved to substantially limit their overall dimensions, including being wound around themselves within (or at least partially within) the insertable device. For example, at least a portion of the flexible substrate may be wound around the solid core of the insertable device. When the sensors are placed on the flexible substrate, they can be positioned so that the sensors are located outside the probe when the flexible substrate is wound around the outside of the probe of the insertable device.

[0063] In some embodiments, such flexible substrates may be rigidly wound, and it may be beneficial for the flexible substrates to be made from extremely thin, durable flexible materials. In some embodiments, chips located on the circuit board (e.g., chips hosting processing circuits) may not be flexible enough to be bent. In some such embodiments, the chips or other components may be located inside the probe, with electrical interconnections to the flexible sensing element and interconnections to the wire leads. To protect the soldering points of small wires attached to the flexible circuit from any environmental factors (e.g., liquids) that could cause a short circuit in the electronic equipment, in some embodiments it may be desirable to embed all soldering points in a polymer such as epoxy or cyanoacrylate (e.g., cyanoacrylate).

[0064] In some embodiments, there may be little to no packaging of the active electronics to accommodate the electronic circuitry within the probe. For example, the chip used in some embodiments may be initially packaged using standard packaging techniques, but then "thinned" to remove part of the packaging before being placed in the insertable device. To avoid or reduce the possibility of electrical interconnection breakage within the flexible substrate, it may be desirable in some cases to avoid extreme bending of the flexible electronics, or to place certain elements that are more sensitive to bending on the mechanically neutral plane of the substrate and limit the stress within those elements while the substrate is bent.

[0065] Some of the disclosed devices are configured to have good torque capabilities to assist clinicians in maneuvering and navigating insertable devices within the body of an animal. In some cases, the insertable device can be torqued sufficiently so that clinicians can apply torque to the device, bend it, and navigate sharp curves in anatomical structures encountered along the path to a target area within the body (e.g., the location of a suspected lesion).

[0066] In some such embodiments, the torque-responsive device has a core that has a tapered shape from the proximal end (closer to the clinician) to the distal end (closer to the tip located furthest away in the animal's body). Closer to the proximal end, which is the area handled by the clinician, the core can be made thicker to provide higher torque transmission. Closer to the distal end, the area may require higher flexibility to be guided through the meandering anatomical structures of a part of the body. In this area, the thickness of the core can be reduced, thereby increasing flexibility. In some embodiments, this core may be constructed from a high-strength flexible material. For example, the core may be or may include high-strength stainless steel such as HiTen 304V stainless steel.

[0067] In one example, the insertable device has a length of approximately 200 cm between the handle and the tip and includes multiple segments, some of which are tapered. The longest of these segments may, in some embodiments, have a length of 130 cm to 170 cm and a diameter of 0.010 inches (0.25 mm) to 0.014 inches (0.36 mm). Distal to this segment, developing into the tool's more flexible "working zone," is a tapered section which may have a length between 5 cm and 10 cm and a diameter tapering to approximately 0.005 inches (0.13 mm). Following the taper is a 10 cm tapered segment, and then there may be another taper having a length of 5 cm to 10 cm and tapering to a diameter of approximately 0.003 inches (0.08 mm). The distal portion may have a length of 5 cm to 10 cm and a diameter of approximately 0.003 inches (0.08 mm). A flexible substrate may be wrapped around this distal portion of the probe. However, it should be understood that these dimensions and taper are merely illustrative, and other embodiments are possible. Also, it should be understood that the term “diameter” is used herein to refer not only to structures having a circular cross-section, but also to structures not having a circular cross-section. In these situations, the term diameter refers to the maximum width of the non-circular cross-section of the structure.

[0068] In some embodiments, to further enhance torque transmission, some probes may be at least partially wound using a filament coil. The filament coil may consist of a single filament or multiple filaments forming a multifilar coil. In some such embodiments, a multifilar coil may be formed by winding one or more wires / filaments around the solid core of the probe. The wire(s) of the coil can, in some embodiments, provide an effective means for torque transmission. That is, when torque is applied to the probe handle by a clinician striking one end of the wire(s) of the coil, the torque applied to the wire(s) is transmitted from winding to winding along the length of the probe. In some embodiments, the filament coil may be located within a region of the guidewire where the inner solid core has a tapered shape and is more flexible than other regions of the solid core. By adding the coil to this region, flexibility can be maintained (e.g., without significantly reducing flexibility) while adding torque.

[0069] The torque capacity of a file coil can be adjusted as desired by adjusting the pressure at which the windings are assembled relative to each other. In some cases, the closer the wires are positioned to each other, the greater the torque transmission.

[0070] The embodiments described herein relate to vascular structures, including cerebral vascular structures, and are described as being advantageous for certain features of human anatomical structures (e.g., the S-shaped bend in the upper part of the carotid artery); however, it should be understood that the embodiments are not limited to operation in human vascular structures. The embodiments can instead operate with any type of anatomical structure and with any type of animal, including non-human mammals or non-mammals.

[0071] In some embodiments, the invasive probe may include a sensor for measuring the impedance of a lesion. The sensor can measure the impedance of a lesion when an electrical signal having a specific frequency is applied to it. The medical device may be configured to determine the composition of the lesion based on the impedance value. The medical device can then generate treatment recommendations, partially based on the determined composition.

[0072] The various examples described herein illustrate medical devices in relation to vascular structural lesions and methods for treating vascular structural lesions. However, it should be understood that embodiments are not limited thereto. The techniques described herein for detecting lesion characteristics and generating treatment recommendations can be used in conjunction with any suitable anatomical conduits of an animal. Such conduits may include, for example, vascular structural ducts and gastrointestinal tracts. Those skilled in the art will understand that conduits within anatomical structures are different from anatomical cavities. For example, a conduit may have one dimension (e.g., width) that is significantly smaller than another dimension (e.g., length). A conduit may have a variablely tubular shape, while a cavity may not be tubular.

[0073] Therefore, in some embodiments, the invasive probe may be a component of a medical device for the diagnosis and / or treatment of lesions of vascular structures. For example, the medical device may be a thrombectomy device, and the invasive probe may be a component of the thrombectomy device. Thus, the invasive probe may be a component of a guidewire, aspiration catheter, microcatheter, stent retriever, and / or another thrombectomy device. In some embodiments, the medical device may include two or more of the guidewire, aspiration catheter, and stent retriever, and the invasive device may be a component of one or more of these, including all of them.

[0074] The inventors recognized and understood that conventional medical devices, including conventional thrombectomy devices, do not provide information regarding the characteristics of lesions in vascular structures, including blood vessels, and that conventional medical devices do not provide information regarding the status of treatment of the lesions. The inventors further recognized and understood that this lack of information contributes to the difficulty of treating lesions. For example, without information regarding the composition of the lesion, clinicians may have difficulty selecting from available treatment options, as each treatment option may work best for lesions with different compositions. Furthermore, without information regarding the status of treatment for the lesion, clinicians cannot know whether treatment is being carried out successfully or unsuccessfully. Due to this lack of information, multiple treatments may be required to accurately treat the lesion. Each of these treatments increases the risk of injury to the patient and, more importantly, increases the duration of the lesion for some lesions. If blood vessels are partially or completely blocked by the lesion, reduced blood flow can cause damage to the animal's tissues.

[0075] Accordingly, according to embodiments described herein, a medical device can determine the characteristics of a lesion, monitor the performance of a treatment, and generate recommendations on how to treat the lesion before and / or during treatment. This additional information can assist clinicians in initially deciding how to treat a lesion, and in performing treatment to ensure, or at least increase the likelihood, that the lesion will be eliminated with a single treatment and that subsequent treatments will not be required for the same lesion. The medical device can provide information to clinicians in real time during a medical intervention, for example, by providing clinicians with real-time information on the interaction between the medical device and the lesion. In some embodiments, real time may include providing information to clinicians within a period of time of corresponding data detected by the medical device, which may be less than 5 seconds, less than 10 seconds, less than 30 seconds, less than 1 minute, or less than 5 minutes, and may depend on the requirements of the analysis performed on the data to generate recommendations.

[0076] While examples relating to lesions of the tubules are described below, it should be understood that not all lesions form within the tubules, and some embodiments may work with lesions located in areas of the body other than the tubules. For example, some cancerous cells may form in other parts of the body of an animal (e.g., a human). Some embodiments described herein relate to the diagnosis and / or treatment of lesions such as cancerous cells not typically found within the tubules. However, some cancerous cells can be found within the tubules, and it should be understood that other embodiments described herein relate to the diagnosis and / or treatment of such cancerous cells.

[0077] Furthermore, while some of the examples described below relate to lesions, it should be understood that the embodiments are not limited to working with lesions, but can work with any target biological structure having any suitable composition of biomaterial.

[0078] General description of the technology To provide context for describing exemplary components of a medical device operating according to some embodiments described herein, Figure 1 is a flowchart of the process a clinician may follow to operate such a medical device. Figures 2 and 3 show examples of medical devices, and the following other figures illustrate in detail other components of the device and how such a device may operate.

[0079] Process 100 may be used to diagnose and / or treat lesions in subjects that are animals. The animals may be human or non-human animals, including, for example, human or non-human mammals. Lesions may be intravascular lesions, such as intravascular lesions, such as intravesical lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions, such as intravascular lesions. Embodiments described herein include: - In vascular structures, blood clots (including red blood cells, white blood cells, fibrin, thrombi, embolus, and / or platelets) formed at the site of the lesion or formed elsewhere in the body and lodged at the site of the lesion. - Proliferation from the tube wall toward the center of the tube, such as proliferation of scar tissue or other proliferation following injury to endothelial cells at the lesion site. -Otherwise, tissues extending from the wall of the tube toward the center of the tube that are anatomically "normal" or "healthy" in relation to that tube at that site (e.g., smooth muscle cells, elastic fibers, external elastic membrane, internal elastic member, loose connective tissue, and / or endothelial cells), - Accumulation of plaque material at the site of the lesion, including the accumulation of cholesterol, calcium, fatty substances, cellular waste products, fibrin, and / or other materials that may be found in the fluid flowing through the tubules of animals (e.g., in the case of vascular structural lesions, substances found in the blood of animals), - Cancer cells found in the tubules, such as metastases and / or lymphomas, and / or - Any other tissue and / or biological material that may cause lesions in the animal's tubules, It can operate on lesions with different characteristics, such as those mentioned above.

[0080] Lesions of different characteristics can form outside the ducts. These lesions include cancerous cells such as carcinomas, myelomas, leukemias, lymphomas, melanomas, neoplasms, mixed types, and / or sarcomas.

[0081] In some embodiments, the histology of a lesion (e.g., which of the biomaterials listed above the lesion contains) can be determined by identifying the composition of the lesion based on multiple impedance spectra of the lesion, the composition of which may indicate the biomaterials present within the lesion. Such identification of biomaterials may include identifying the tissues and / or cells present within the lesion, and / or the plaque material present within the lesion, and / or the relative amounts of such tissues, cells, or plaque material within the lesion. In some embodiments, identifying the biomaterials present in a lesion may include identifying the state of each biomaterial, such as whether the tissue / cell is healthy or unhealthy. An unhealthy state of a cell may include, for example, whether the cell is inflamed, diseased, cancerous, or otherwise abnormal.

[0082] It should be understood that the embodiments are not limited to working with lesions of any particular form or composition, or lesions at any particular location within the anatomical structure of the subject. As stated above, for the sake of clarity, various examples in which the tubes are vascular structures of animals are provided below.

[0083] Prior to the commencement of process 100 in Figure 1, the subject may exhibit symptoms of a vascular structure lesion. An initial determination may be made by the clinician to determine whether a lesion is present and its potential location, for example, by using imaging techniques such as angiography. Based on the initial determination of symptoms and lesion location, the clinician may choose to insert an invasive device into the subject's vascular structure to further diagnose and / or treat the lesion. The clinician may be, for example, a physician (e.g., an internist or surgeon), or another healthcare professional such as a nurse or medical technician operating the medical device (potentially under the supervision of a physician). In some embodiments, the clinician may be located in the same room as the subject, including next to the subject, while in other embodiments, the clinician may be located remotely from the subject (e.g., in a different room in the same building as the patient, or geographically remote from the patient) and operate a user interface to control the medical device via one or more wired and / or wireless networks, including the Internet or other wide area network (WAN).

[0084] Process 100 begins in block 102, in which the clinician inserts an invasive probe into the vascular structure of the subject. The invasive probe inserted by the clinician in block 102 may be located at the distal end of a guidewire for a medical device and may be molded, sized, and positioned for insertion into a vascular structure. In addition, in block 102, the clinician may feed the invasive probe through the vascular structure of the subject until the invasive probe is positioned close to the lesion. To do so, the clinician may monitor the position of the invasive probe within the subject using imaging techniques, such as using angiography techniques. The insertion and feeding of the invasive probe in block 102 may be carried out using preferred techniques for inserting a device into a vascular structure, including the use of known techniques, and embodiments are not limited to this method.

[0085] In block 104, the clinician manipulates an invasive probe to determine one or more characteristics of a lesion. Characteristics may include the phenotype and / or genotype of a biological structure, such as a lesion, including characteristics that distinguish biological structures or the phenotype of a biological structure. Characteristics may also be characteristics that influence the treatment of a lesion (or other biological structure), and lesions having a characteristic may be treated differently from lesions not having the characteristic, or lesions having different values ​​for the characteristic may be treated differently. Such characteristics may be histological, relating to the anatomical structure of the lesion, and / or anatomical, relating to how the lesion is located within the animal's body or how it interacts with the animal's body. Thus, characteristics can describe a lesion. Illustrative characteristics include the location of the lesion, the size of the lesion (e.g., length), the composition of the lesion, or other characteristics, which are described in detail below. To determine characteristics, one or more sensors of the invasive probe may make one or more measurements of the tissue and / or other biological material of the lesion, and / or other tissues / materials at the site of the lesion, such as healthy tissue located near the lesion. Examples of sensors and measurements are described in detail below. To operate the invasive probe in block 104, the clinician can contact the lesion using one or more sensors on the invasive probe and / or operate the user interface of the medical device to trigger the invasive probe to use the sensor(s) to detect characteristics of the lesion.

[0086] In some embodiments, determining one or more characteristics of a lesion may include identifying the composition of the lesion, for example, by identifying the amounts of different types of cells or tissues present within the lesion. For example, an examined lesion may be identified as consisting of 50% red blood cells, 30% fibrin, and 20% platelets.

[0087] In block 106, the clinician operates a medical device to generate and output treatment recommendations for a lesion based on the determined characteristics of the lesion. As described in detail below, the treatment recommendations generated by the medical device based on the characteristics of the lesion may include recommendations on how to treat the lesion, such as which treatment device to use to treat the lesion (e.g., whether to use a suction catheter or a stent retriever if the lesion material is to be removed from the subject) and / or how to use the treatment device (e.g., how quickly to extract the stent retriever). Also, as described in detail below, the medical device may generate treatment recommendations based on various analyses, such as comparing the characteristics of the lesion to the conditions associated with each of several different treatment options and outputting a recommendation for a treatment option if the characteristics of the lesion meet the corresponding conditions for the treatment option. Output from the medical device may be via any preferred form of user interaction, including visual, auditory, and / or tactile feedback to the clinician via a user interface. In some embodiments, the medical device can automatically analyze the lesion(s) determined in block 104 and generate / output treatment recommendations in block 106 without further user intervention. In other embodiments, a clinician can operate the user interface of the medical device to request analysis and generation / output of treatment recommendations.

[0088] In block 108, the clinician reviews the treatment recommendations of the medical device and selects a treatment option, and in block 110, treats the lesion using the selected treatment option.

[0089] In some embodiments, the selected treatment option may include the insertion of additional invasive medical components into the vascular structure of the subject. If the invasive probe inserted in block 102 was a component of a guidewire, for example, a further treatment device may be inserted along the guidewire. In a specific example of such a case, if the medical device recommends the complete or partial removal of the lesion using a stent retriever, a stent retriever may be inserted into the vascular structure. In another example, if the medical device recommends removal using an aspiration catheter instead, the clinician may insert an aspiration catheter into the vascular structure. In yet another example, if the medical device recommends stent implantation, a stent implanter may be inserted into the vascular structure.

[0090] In other embodiments, treatment may not require the insertion of another device. For example, the invasive probe inserted in block 102 may not be a component of a guidewire, but instead may be a component of a therapeutic device such as a stent retriever. In such a case, the treatment in block 110 may be performed using the therapeutic device inserted in block 102. For example, if the invasive probe inserted in block 102 is a component of a stent retriever, the treatment recommendations in block 106 may be specific to the method of operating the stent retriever, such as the amount to expand the stent, the amount of time to wait for the blood clot to fuse with the stent, and / or the force or speed at which to pull out the stent and blood clot. In such an embodiment, in block 110, a clinician can treat a lesion by operating the stent retriever as recommended by the medical device in block 106.

[0091] When the lesion is treated in block 110, process 100 is terminated. Additional actions that may be taken after the treatment of the lesion in some embodiments are described below.

[0092] Examples of medical devices As described above, Figure 1 provided a general description of how medical devices according to some embodiments described herein can be operated to diagnose and / or treat lesions within the vascular structure of an animal. Figures 2 and 3 provide examples of some embodiments of medical devices, including an invasive probe that can be inserted into the vascular structure as part of such diagnosis and / or treatment.

[0093] Figure 2 shows a medical device 200 that may be operated by a clinician 202 to diagnose and / or treat a medical condition in a subject 204. The medical condition in the animal 204 (e.g., human) could be a lesion of the vascular structure 204A, shown in the example of Figure 2 as a lesion within the cranial blood vessels of a human, which may cause ischemic stroke. As described above, lesion 204A may be a blood clot, plaque buildup, excessive proliferation of smooth muscle tissue, and / or other vascular lesions.

[0094] The medical device 200 shown in Figure 2 includes a guidewire 206, a handle 208, and an invasive probe 210. At least a portion of the invasive probe 210 and the guidewire 206 can be inserted into the vascular structure of the subject 204 until the invasive probe 210 is positioned in close proximity to the lesion 204A. Thus, the invasive probe 210 may be shaped and positioned differently for insertion into a vascular structure (or other tube). In some embodiments, the invasive probe 210 is attached to a guidewire that is about 300 micrometers, or a microcatheter with a diameter of about 300 μm to 4 mm, or another device having a diameter suitable for insertion into an animal tube. In some such embodiments, such a device may be about 1 meter or 2 meters long, and the invasive probe 210 is located at one end of the guidewire / device, for example, within the last 5 centimeters of the device.

[0095] The invasive probe 210 inserted into the subject 204 may include one or more sensors 212 and a measuring unit 214. In some embodiments, the sensor(s) 212 may measure one or more electrical properties of the lesion 204A, including measuring one or more electrical properties of the tissue and / or biomaterial of the lesion 204A. The measuring unit 214 may receive data generated by the sensor(s) 212 and, in some embodiments, may generate one or more electrical signals applied to the lesion 204A as part of measuring one or more electrical properties.

[0096] Examples of sensor 212 are described in detail below. In one particular example, sensor(s) 212 may be an impedance sensor, and the measurement unit 214 may drive sensor(s) 212 to perform electrical impedance spectroscopy (EIS) of lesion 204A. For example, the measurement unit 214 may include one or more oscillators for generating electrical signals of one or more frequencies, and these frequencies may be specific frequencies selected (and configured to be generated by the oscillators of the measurement unit 214) to distinguish different tissues and / or different biomaterials in order to help identify the composition of lesion 204A, as described in detail below. In embodiments arranged to test tissues / materials using multiple frequencies, the measurement unit 214 may include multiple oscillators, one oscillator being specific to each frequency being tested and configured to generate a signal of that frequency.

[0097] In some embodiments where the measurement unit 214 generates an electrical signal applied to the lesion 204A, it may be advantageous for the measurement unit 214 to be contained within an invasive probe 210 and inserted into the vascular structure of the subject 204. This allows the measurement unit 214 to be positioned close to the sensor 212 and the lesion 204A, thereby limiting noise in the electrical signal applied to the lesion 204A. If the measurement unit 214 is located within the handle 208, for example, the electrical signal generated by the measurement unit 214 travels the length of the guidewire 206 before being output by the invasive probe 210 to be applied to the lesion 204A. When the signal travels the length of the guidewire 206, electrical noise may affect the signal quality. By positioning the measurement unit 214 within the invasive probe 210, noise in the signal can be limited. When the measuring unit 214 is positioned within the invasive probe 210, it may be positioned within the lumen of the invasive probe 210, on the surface (inside or outside) of the invasive probe 210, or embedded in a film attached to the surface (inside or outside) of the invasive probe 210.

[0098] In some embodiments, the measurement unit 214 may be configured as an application-specific integrated circuit (ASIC). In some such embodiments, the ASIC may be manufactured using a packaging process that reduces the silicon substrate layer. For example, during manufacturing, an integrated circuit may be manufactured having an “active” silicon layer containing functional components on top of a silicon substrate layer that does not contain active components. The substrate layer may be the bottom layer in the layer stack, and in some cases, it may be the thickest layer. Conventionally, the substrate layer is left in place after manufacturing to provide structural stability to the integrated circuit. In some embodiments, the measurement circuit 214 may be manufactured using a process that includes removing the silicon substrate layer after manufacturing the active layer and before packaging. The manufacturing process may include removing the substrate from the bottom of the wafer, which may be on the side opposite to where the active components were manufactured. In some embodiments, all of the silicon substrate may be removed. In other embodiments, substantially all of the silicon substrate may be removed, and “substantially” removed means leaving only enough silicon substrate to ensure the proper electrical function of the active layer components, without leaving any silicon substrate solely for structural support. After the silicon substrate is removed, the integrated circuit can be housed in the packaging material.

[0099] In some embodiments, by positioning the measurement unit 214 close to the sensor 212 and lesion 204A, the distance traveled by the electrical signal is limited, thereby reducing signal attenuation. Reducing signal attenuation can be particularly important at higher frequencies, as electrical wires tend to exhibit a low-pass frequency response. By reducing the distance the signal travels, the cutoff frequency of the electrical path between the signal source and the lesion can be increased, thereby increasing the range of frequencies usable for diagnosis or treatment. As a result, the ability to distinguish between tissue or cell types can be significantly improved. By positioning the measurement unit 214 close to the sensor 212 and lesion 204A, the cutoff frequency can be increased to up to 1 MHz in some embodiments, up to 10 MHz in other embodiments, or up to 25 MHz in yet another embodiment. For comparison, if the measurement unit 214 is located within the handle 208, the cutoff frequency may be limited to less than 500 kHz.

[0100] It should be understood that the embodiments are not limited to the sensor(s) 212 being an EIS sensor or being driven to perform EIS operation. In some embodiments, the sensor(s) 212 may be or include one or more electrical, mechanical, optical, biological, or chemical sensors. Specific examples of such sensors include inductance sensors, capacitance sensors, impedance sensors, EIS sensors, electrical impedance tomography (EIT) sensors, pressure sensors, flow sensors, shear stress sensors, mechanical stress sensors, deformation sensors, temperature sensors, pH sensors, chemical composition sensors (e.g., O2 ions, biomarkers, or other compositions), acceleration sensors, and motion sensors. These sensors may include known commercially available sensors.

[0101] In some embodiments, a measurement unit 214 included in the invasive device 210 may be configured to drive a sensor 212 and / or process results from the sensor to generate data that is sent back to the handle 208 along the guidewire 206. This may be, for example, in an embodiment where treatment recommendations are generated by the medical device 200. Data describing the characteristics(s) of the lesion 204A may be transmitted along the length of the guidewire 206. To limit the effects of noise during such transmission, in some embodiments, the measurement unit 214 may include an analog-to-digital converter (ADC) or other components for generating digital data for transmission over a communication channel (e.g., one or more wires) extending through the guidewire 206.

[0102] According to embodiments described herein, a clinician 202 can treat a lesion 204A in accordance with one or more treatment recommendations generated by a medical device 200. Although not shown in Figure 2, the medical device 200 may include a controller that generates and outputs such treatment recommendations for the treatment of lesion 204A. The controller may be implemented as a lesion analysis facility, which in some embodiments is implemented as executable code executed by at least one processor of the medical device 200. The lesion analysis facility can analyze the characteristics(s) of lesion 204A determined by the medical device 200 (e.g., by an invasive probe 210) in relation to configured information relating to one or more treatment recommendations. As one particular example, as will be described in detail below, the lesion analysis facility can compare the characteristics(s) of lesion 204A with conditions related to various treatment recommendations and output a treatment recommendation when the characteristics(s) satisfy the conditions(s) of that treatment recommendation.

[0103] In some embodiments, a processor for running a lesion analysis facility, and a storage medium (e.g., memory) for storing information configured for the lesion analysis facility and treatment recommendations, may be located within the handle 208. Thus, the lesion analysis facility running on the processor(s) within the handle 208 can receive data from the measurement unit 214 via the communication channel of the guidewire 206, indicating one or more characteristics of the lesion 204A.

[0104] However, in other embodiments, the processor for running the lesion analysis facility, and the storage medium (e.g., memory) for storing the configured information for the lesion analysis facility and treatment recommendations, may be disposed separately from the guidewire 206 and handle 208, for example, by being housed in a separate computing device. The computing device may be located in close proximity to the guidewire 206 and handle 208, for example, by being located in the same room. Alternatively, the computing device may be located away from the guidewire 206 and handle 208, for example, by being located in a different room in the same building, or by being geographically distant from the guidewire 206 and handle 208. In certain embodiments, the processor / medium is separate from the guidewire 206 and the handle 208, and the computing device may receive data indicating one or more characteristics of lesion 204A via one or more wired and / or wireless communication networks, including direct wiring from the handle 208 to the computing device, a wireless personal area network (WPAN) between the handle 208 and the computing device, a wireless local area network (WLAN) between the handle 208 and the computing device, a wireless wide area network (WWAN) between the handle 208 and the computing device, and / or the Internet. Therefore, in some embodiments, the handle 208 may include one or more network adapters for communicating via one or more networks.

[0105] When a treatment recommendation is generated by the medical device 200, the treatment recommendation may be output by the medical device 200 for presentation to the clinician 202 and / or any other user. The output may be to another device and / or one or more displays such as display 216, or other forms of user interface, via one or more networks. In the example of Figure 2, the lesion analysis facility runs on a processor located within the handle 208 and can generate a treatment recommendation, which can be output to display 216 for presentation to the clinician 202 via the wireless network adapter of the handle 208. Embodiments are not limited in this respect, and other forms of user interfaces may be used. Any suitable visual, auditory, or tactile feedback may be used. For example, if the treatment recommendation is to recommend removal of the lesion using either a suction catheter or a stent retriever, the handle 208 may include light-emitting diodes (LEDs) or other visual elements for each option and present the treatment recommendation by illuminating the appropriate LEDs. As another example, if the treatment recommendation relates to how to operate the stent retriever, and in particular is a recommendation on when to begin extraction following a waiting period, the signal to begin extraction may be output using a tactile signal provided via a vibration unit incorporated in the handle 208. Those skilled in the art will understand that, as with the computing devices described above, elements of the user interface may be located within the handle 208 or separately from (or even remotely from) the handle 208.

[0106] Power may be supplied to the invasive probe 210 via a power cable extending along the length of the guide wire 206. The power cable may be connected to a power source in the handle 208, which may be a battery, an energy harvester, a connection to a grid power source, or a connection to another energy source, and the embodiments are not limited thereto.

[0107] In some embodiments, the handle 208 may include one or more sensors not shown in Figure 2. Sensors(s) incorporated into the handle 208 can monitor the operation of the medical device 200 and inform the clinician 202 of the method of treatment performed. For example, an accelerometer or other motion sensor may be placed within the handle 208 to detect the movement of the handle 208 that controls the movement of the guidewire 206 and the invasive probe 210. For example, by monitoring the accelerometer, it may be determined whether the clinician 202 performed multiple treatments (e.g., multiple passes using a suction catheter or stent retriever) to remove the lesion, or whether the lesion could be extracted in only one pass.

[0108] In some embodiments, the handle 208 may be detachable from the guidewire 206 and reusable between operations. Thus, the invasive probe 210 and / or guidewire 206 may be configured to be non-reusable, or instead to be disposable for hygienic reasons, while the handle 208 may be detachably attached to the guidewire 206 and configured to be reused together with other guidewires 206 and invasive probes 210. For example, the guidewire 206 and handle 208 may have complementary interfaces that allow the handle 208 to connect to the guidewire 206 and interface with components of the guidewire 206 (e.g., communication channels, power cables) and the invasive probe 210.

[0109] A clinician 202 may operate the medical device 200 via a user interface of the medical device, the user interface including a display 216, which may be at least partially located within a handle 208. For example, the handle 208 may allow the clinician 202 to move the guidewire 206 and the invasive probe 210 back and forth within a vascular structure and / or trigger the movement of the invasive probe 210.

[0110] The operation of the invasive probe 210 may depend on the components of the invasive probe 210. For example, the invasive probe 210 may include sensors 212 for detecting one or more characteristics of the lesion 204A. The invasive probe 210 may further include a measuring unit 214 that operates the sensors to detect one or more characteristics, such as by applying an electrical signal to the lesion 204A and operating one or more sensors to perform one or more measurements of the lesion 204A during and / or after the application of the electrical signal. In some embodiments, the invasive probe 210 may include one or more components for treating the lesion 204A, including implanting a stent and / or removing the lesion 204A. The lesion removal components may include those related to any preferred technique for removing the lesion, and the embodiments are not limited thereto. In some embodiments, for example, the invasive probe 210 may include a stent retriever component (e.g., a balloon) for retrieving a lesion using a stent, and / or an aspiration catheter component for aspirating the lesion into the catheter. The invasive probe 210 may further include other sensors not shown in Figure 2, for example, an optical coherence tomography (OCT) sensor.

[0111] A user interface for the medical device, which may be incorporated entirely or partially within the handle 208, may thus enable the clinician 202 to perform some different actions using the invasive probe 210. For example, the user interface of the handle 208 may enable the clinician 202 to trigger the sensor 212 and the measuring unit 214, apply electrical signals, and / or measure the lesion 204A, and / or perform one or more therapeutic actions to treat the lesion 204A.

[0112] While examples have been described in which the medical device 200 may include therapeutic components for performing one or more actions to treat the lesion 204A, it should be understood that embodiments are not limited thereto. In some embodiments, the medical device 200 may be a guidewire for an additional therapeutic device, positioned in close proximity to the lesion 204A and inserted along the guidewire to treat the lesion 204A. For example, after insertion of the invasive probe 210 and guidewire 206, the clinician 202 may insert another device along the length of the guidewire 206, or remove the guidewire 206 and invasive probe 210 and then insert a new device. The newly inserted device may be, for example, a stent implanter, a suction catheter, a stent retriever, or other device for treating the lesion 204A. In some embodiments in which an additional device is inserted, the handle 208 may be compatible with the additional device, and therefore the additional device and the handle 208 may have a compatible interface, and the user interface of the handle 208 may be used to operate the additional device.

[0113] In addition, while examples are provided in which a clinician 202 manually operates the medical device 200 in accordance with treatment recommendations, the embodiments are not limited thereto. In alternative embodiments, the medical device 200 may automatically treat a lesion based on input from the sensor 212. For example, as can be understood from the brief description above and the detailed description below, the medical device 200 may generate treatment recommendations regarding how to treat the lesion 204A. In some embodiments, the medical device 200 may, in accordance with the treatment recommendations, insert and / or operate a suction catheter, stent retriever, stent implanter, or other device without user intervention (but, in some embodiments, under the supervision of the clinician 202) to treat the lesion 204A in accordance with the treatment recommendations.

[0114] It should be understood that the embodiments are not limited to being invasive or operating with medical devices that include invasive components inserted into the body of an animal. For example, a non-invasive probe may have a measuring unit and / or sensor (such as an EIS sensor) that operates as described herein, including operating using a frequency or characteristic selected as described herein, or using a model trained as described herein. Such a non-invasive device may be used, for example, for the diagnosis and / or treatment of skin lesions.

[0115] Furthermore, it should be understood that the techniques described herein are not limited to use with insertable devices such as guidewires or other tools that are inserted and then removed, but may also be used with implantable devices. For example, the types of measuring units and sensors described herein may be used in conjunction with a stent, such as when the sensor is positioned directly on the stent. In this way, monitoring of the tissue in the area where the stent is positioned may be performed only once after the stent has been placed in place. The sensor can detect one or more characteristics (e.g., composition) of the tissue in the area where the stent is placed. The detected characteristics may be used to infer the characteristics of one or more biological structures that are in contact with the stent and to make a determination about one or more biological structures. For example, the system may be used to determine whether the tissue in contact with the stent is healthy, whether scar tissue or other unhealthy tissue has formed, or whether an occlusion has formed.

[0116] Figure 3 shows an example of an invasive probe 210 in which some embodiments may function. The invasive probe 210 in the example of Figure 3 includes a mesh 300 arranged similarly to a stent. In some embodiments, the invasive probe 210 may be capable of functioning as a stent retriever. In other embodiments, the invasive probe 210 may not be capable of functioning as a stent retriever, but may include a mesh 300 or other structure that provides multiple contact points between the sensor and the lesion to detect lesion characteristics with higher accuracy than might be possible using only a single sensor.

[0117] However, it should be understood that in some embodiments (not the embodiment shown in Figure 3), the invasive probe 210 may include only one sensor, which may be located at the distal end of the invasive probe 210. Such a sensor may be implemented as two electrodes, one of which may apply an electrical signal to the lesion, and the other which may receive the applied signal. Based on a comparison of the applied signal and the received signal, one or more decisions can be made, as will be described in detail below.

[0118] However, the inventors have recognized and understood that including additional sensors in the invasive probe 210 may allow for the determination of more detailed information. For example, including additional sensors within the invasive probe 210 may allow for the creation of more accurate information regarding the composition of the lesion compared to using only a single sensor. Such additional sensors may, for example, allow impedance spectra to be determined for each of multiple locations along the invasive probe, and as a result, in some cases, different impedance spectra may be determined at different locations for the same lesion. This may include, for example, determining an impedance spectrum using each sensor. In this case, each impedance spectrum is the impedance spectrum of the biomaterial of the lesion in contact with the sensor (which has two electrodes). Some lesions may include multiple different biomaterials (e.g., different tissues or cells, or different plaque materials). If each sensor of the invasive probe is in contact with a different biomaterial, each sensor may determine a different impedance spectrum for each different biomaterial. However, for some lesions, two or more sensors of the invasive probe may be in contact with the same biomaterial, in which case they may produce the same or substantially the same impedance spectrum. Therefore, in some embodiments, the invasive probe can operate each sensor to generate an impedance spectrum of the biomaterial of the lesion. Generating impedance spectra for each of the multiple biomaterials of the lesion (i.e., multiple impedance spectra for each lesion) is in contrast to determining a single impedance spectrum for the entire lesion. Techniques for determining the composition of a lesion using multiple sensors, including performing EIS, are described below.

[0119] Accordingly, Figure 3 shows an example of an invasive probe 210 having a plurality of sensors arranged along the outer and / or inner surface of the probe 210. Sensors 302 (including sensors 302A, 302B, 302C, and 302D, and collectively referred to herein as sensor(plural) 302) may be arranged along the structure 300. In some embodiments, each sensor may be or include one or more electrodes for applying and / or detecting the applied electrical signal.

[0120] In some embodiments, although not shown in Figure 3, the invasive probe 210 may include a balloon to expand the structure 300 outward when inflated, allowing for better contact with the lesion. During use, for example, the structure 300 may be inserted whole or partially into the lesion until sensors located at the distal end of the structure 300 detect that they have passed the other side of the lesion, and thereafter the structure 300 may be expanded using the balloon until sensors 302 detect contact at multiple points. The expansion of the structure 300 may be controlled by a controller of the invasive probe 210 (e.g., measurement unit 304), or by a lesion analysis facility located elsewhere in the medical device and / or by a clinician via the user interface of the medical device.

[0121] In some embodiments, the measurement unit 304 can operate the sensor 302 to perform one or more measurements, including generating one or more electrical signals to be applied to a lesion and analyzing the data generated by the sensor 302. The analysis of the data generated by the sensor 302 may include performing analog-to-digital conversion of the data to be transmitted outside the patient along a guidewire, for example, to a lesion analysis facility or user interface as described above.

[0122] While examples have been provided where sensor 302 is an electrical sensor, it should be understood that the embodiments are not limited thereto. For example, sensor 302 may be one or more electrical, mechanical, optical, biological, or chemical sensors, or may include several of them. Specific examples of such sensors include inductance sensors, capacitance sensors, impedance sensors, EIS sensors, electrical impedance tomography (EIT) sensors, pressure sensors, flow sensors, shear stress sensors, mechanical stress sensors, deformation sensors, temperature sensors, pH sensors, chemical composition sensors (e.g., O2 ions, biomarkers, or other compositions), acceleration sensors, and motion sensors.

[0123] Examples of insertable devices for in vivo detection To substantially reduce the time it takes for clinicians to diagnose and (where applicable) treat biological structures (e.g., lesions) by removing blood clots from a patient's vascular system, the inventors have developed an invasive probe having a sensor that can be used to determine one or more properties of a biological structure. Using information about the properties (may be multiple) of the biological structure, clinicians can distinguish between healthy tissue and different types of lesions, and clinicians can select the most appropriate treatment for a particular type of lesion. Described below are embodiments of insertable devices having a design that can accommodate these sensors while maintaining a size that is largely standardized in the market for its fit to various human anatomical structures. In some embodiments, such a design includes a probe assembly having a flexible circuit. Being flexible, these circuits can be folded or coiled as desired, thus substantially limiting the space they occupy.

[0124] The types of invasive probes described herein may be implemented as guidewires in some embodiments. Examples of these guidewires are described below in relation to Figures 31–44. However, it should be understood that these are merely illustrative examples of guidewire embodiments, and other embodiments are also possible.

[0125] Figure 31 shows an exemplary implementation of an insertable device according to the technology described herein. The example in Figure 31 is a guidewire, which is an insertable device having an elongated body and a probe having multiple sensors. However, it should be understood that the embodiments are not limited to operating with a guidewire or an insertable device that is a guidewire.

[0126] The probe may include the sensor assembly 3, the coil 9, and the tip 10, as well as the distal portion of the core wire 1, and other components extending within the assembly 3, the coil 9, and the tip 10. The elongated body of the guidewire may include a component of the guidewire positioned proximal to the sensor assembly 3 (i.e., to the left of the sensor assembly 3 in Figure 31). Thus, the elongated body can form the majority of the length of the guidewire in the example of Figure 31.

[0127] The types of invasive probes described herein may be designed to be sufficiently flexible to effectively transmit torque throughout the length of the probe and to navigate through steep curves. These invasive probes are therefore particularly suited for use in tortuous blood vessels, such as those found along the path from the human torso to the human brain. Torque capacity can be enhanced, in at least some embodiments, by using a core with high tensile strength and by housing the core within a multifilar coil having one or more wires. The position and number of coils may be adjusted to provide a desired balance between torque capacity and rigidity. In at least some embodiments, flexibility can be enhanced by tapering the shape of the core. In particular, the core may be shaped to be smaller in the distal region, thus increasing the flexibility of the core where flexibility is most desirable.

[0128] Therefore, the backbone of the guidewire in Figure 31 is the core wire 1. The core wire 1 is located at the center of the device, coaxially with the device, along all or at least most of the elongated body and / or probe. The core wire 1 can be made from stainless steel, nickel-titanium, or other material having a high tensile strength that exceeds a threshold (e.g., greater than 200 MPa, greater than 350 MPa, or greater than 500 MPa). The core wire may be a centerless grounding wire (e.g., a solid core) and in some embodiments may have a distal end that gradually tapers. The tapered shape may help increase the flexibility of the guidewire at the distal end, which in some cases may help the guidewire navigate through meandering anatomical structures. As seen in Figure 32, the wire also includes a proximal grounding section to accommodate the contact assembly, as described below.

[0129] Exemplary versions of the core wire are made from very high-strength 304V Hi-ten stainless steel wire. The maximum diameter may be approximately 0.012 inches (0.30 mm), but may range from 0.008 inches (0.20 mm) to 0.014 inches (0.36 mm). Typical wire lengths may be 200 cm, but can be as long as 300 cm (as is typical for "replacement length" intervention guidewires) or as short as 90 cm or less.

[0130] The connector assembly 20 may connect the proximal end of the core wire 1 to a handle, which can be held by a clinician to maneuver the guidewire through the patient's vascular structure. An electrical connector located at the proximal end of the guidewire may connect to the handle, which can function as a torque "transmitter" and be used to apply torque to the guidewire and push it. However, in some cases, the device may be operable without a handle, or may not have a handle at all. This is because some clinicians prefer to operate insertable devices without the extra weight of a handle and instead use a conventional torquer positioned as close as possible to the introducer placed in the patient. In cases where a handle is compatible with the insertable device, clinicians such as these may only connect the handle when making measurements using the device's sensors.

[0131] The distal region of the guidewire may include a sensor assembly 3 which may include one or more sensors. In at least some embodiments, the sensors may be positioned to detect the impedance of the tissue surrounding the guidewire (e.g., the inner wall of a tube or blood clot). In some embodiments, the sensor assembly 3 may include a circuit for generating a probe signal to be transmitted toward the surrounding tissue and / or a circuit for processing the signal reflected by the tissue. As will be further described below, the sensor assembly 3 is sized and positioned to accommodate the sensor(s) and circuit within a limited space. In at least some embodiments, the sensor assembly 3 may be located within the last 7 cm of the distal guidewire, more preferably about 3 cm proximal to the very end of the guidewire.

[0132] The distal region of the sensor assembly 3 may include the coil 9 and the tip 10. The coil 9 may be included to provide the distal end of the guidewire with sufficient flexibility to bend through a sharp curve. In some situations, this portion of the guidewire may be pre-bent (e.g., manually, by a clinician, automatically during manufacturing, or otherwise) to a predetermined curvature depending on the tube into which the guidewire will be inserted, before insertion into the patient. This pre-bent can assist the clinician in maneuvering the guidewire through the patient's vascular structure. In some embodiments, the coil 9 is made from a radiopaque material such as platinum, gold, or a platinum alloy such as platinum-iridium. Due to its radiopaqueness, the position of the end of the guidewire may be monitored as it is inserted into the patient, for example, via X-ray imaging. In some embodiments, the tip 10 may be positioned at the end of the guidewire or soldered to the coil 9. The tip 10 may have a curved shape to assist the guidewire in navigating anatomical canals (e.g., vascular structures) by sliding against the inner wall of the canal without perforating tissue. In addition, or alternatively, the tip 10 may be shaped to ensure that the coil assembly (e.g., multifilar coil and distal coil) is held in place relative to the core wire 2. This shape can reduce the possibility of these coils and / or other distal components separating from the core wire and potentially embolizing. This shape of the tip 10 may, in some embodiments, be or include a solder ball to assist navigation and / or limit the risk of separation / embolization.

[0133] The coil 9 can be short enough to assist the clinician in positioning the sensor assembly in relation to a lesion. In some situations, for example, the clinician can push the guidewire forward until the coil 9 passes the lesion, expecting that the sensor assembly 3 has established contact with the lesion. The position of the coil 9 may be visible due to its radiopaqueness, while the position of the sensor assembly 3 may not be visible (at least in some embodiments). Nevertheless, the clinician can still infer the position of the sensor guidewire based on the position of the coil 9. The inventors have found that in certain disclosed embodiments, the accuracy of inferring the position of the sensor assembly relative to the coil 9 can be improved by having a shorter coil. In some cases, if the area appearing in the X-ray image is short enough, the position of the sensor assembly can be easily inferred. However, at the same time, the coil 9 may be long enough to be pre-bent by the clinician. Therefore, in some embodiments, the coil 9 may have a length between 10mm and 50mm, 15mm and 50mm, 15mm and 40mm, 10mm and 40mm, 15mm and 30mm, 10mm and 30mm, 10mm and 20mm, 30mm and 40mm, 20mm and 30mm (approximately 25mm, etc.), or any other suitable value.

[0134] The guidewire may form part of a system including the guidewire, such as the system illustrated in Figure 2 and described above in relation thereto, and a computing device separate from the guidewire. In such a system, the sensor assembly 3 may be configured to communicate electrically with a medical device (e.g., a computer) disposed outside the guidewire via one or more wire leads 4. Being solid, the core wire does not have a longitudinal cavity through which the wire leads pass, as in conventional catheters. Thus, in the embodiment shown in Figure 31, the wire lead(s) may be wound around the core wire 1 or otherwise extend along it. The wire lead(s) may have a diameter of about 0.001 inches (0.03 mm), but other sizes are also possible.

[0135] The wire leads may be formed from a suitable conductive material such as copper, gold, aluminum, or an alloy of these materials.

[0136] In some embodiments, the lead wires may be individually insulated using an insulating coating, which may be any suitable insulator, but advantageously, in some embodiments, it may be polyimide. In some embodiments, the wires may be joined together to form a multi-strand ribbon. Joining the individual wires in this way can add resilience during the manufacturing / assembly of the device, as the ribbon is much stronger than the individual leads, reducing the possibility of breakage or damage during assembly / manufacturing. Joining the leads to a ribbon can also allow for better control of the wire leads within the device, such as by controlling the order or arrangement of the leads relative to each other. Controlling the order or arrangement can help reduce crosstalk between wires, for example, by placing a ground wire between two other wires (e.g., a clock wire and a communication wire in the device that contain those wires).

[0137] For example, the ribbon includes at least three lead wires suitable for any known parallel or serial communication protocol (such as I2C, UART, SCSI, or SPI). In this case, crosstalk between these lead wires is generally observed.

[0138] For example, in the case of the SPI (Serial Peripheral Interface) protocol, the ribbon is... - Ground wire (GND) and positive potential wire (VDD) for supplying power to the sensor assembly, - Clock wire (CLK) for providing a clock signal to the sensor assembly. - A "master-out-slave-in" (MOSI) wire for transporting uplink signals from the connector assembly to the sensor assembly (for example, for writing to or reading registers within the sensor assembly). - A "master-in-slave-out" (MISO) wire for carrying downlink signals from the sensor assembly to the connector assembly (for example, to confirm commands or transmit register values). It includes five lead wires, each forming a distinct shape.

[0139] As an example, each lead wire has a diameter of 25 μm and is insulated with a 5 μm thick polyimide insulating coating. A thicker insulator would be beneficial, but it would reduce the cross-sectional area of ​​the core wire, which is detrimental to the mechanical properties of the guide wire.

[0140] To minimize crosstalk between wire leads (for example, to prevent noise propagation from the clock wire to the remaining lead wires), the wire leads are arranged in the ribbon in the order of VDD, CLK, GND, MOSI, MISO, such that the clock wire is placed between the ground wire and the positive potential wire. This is advantageous because the ground wire (whose potential is constant over time) acts as a shield to avoid excessive noise in the MOSI and MISO lines caused by the clock signal. A similar effect can be obtained by placing a positive potential wire between the clock wire and either the MOSI wire or the MISO wire.

[0141] Preferably, a capacitor is provided in parallel with the sensor assembly and connected to the ground wire and the positive potential wire to stabilize the power supplied via the ground wire and the positive potential wire.

[0142] Advantageously, the core wire is made of a conductive material and connected directly or via a capacitor to a potential reference (e.g., ground or a grounding wire). This feature is advantageous because it significantly reduces crosstalk between lead wires passing through the core wire. Due to this feature, the core wire also acts as an electromagnetic shield against external electromagnetic interference arising from the environment surrounding the guide wire.

[0143] Preferably, the core wire is connected to a potential reference at the handle 208. This allows for the use of a separate, very bulky component that would not be possible on the invasive probe 210 side. For example, if a capacitor is used for such a connection, the capacitor has a capacitance of about 1 μF. However, a larger capacitance value is also beneficial because it provides filtering over a wider frequency band, especially at lower frequencies.

[0144] Preferably, a delay is provided between uplink signal generation and downlink signal reading to mitigate the effects of establishment time, which is inherent to the guide wire (resulting from the resistivity and capacitive coupling of the lead wire) and causes a phase shift between the uplink and downlink signals. For example, in a connector assembly, the value of the uplink signal is changed on the falling edge of the clock signal, and the value of the downlink signal is read 1 / 4 of a cycle later.

[0145] Preferably, the square wave signal on the lead wire is avoided, and therefore high-frequency harmonics that would cause further interference are eliminated.

[0146] A jacket 12 can be used to surround the wire lead(s) to electrically insulate them from environmental factors (e.g., fluids) present in the patient's body and to mechanically protect them from torque or friction. The jacket 12 can surround the core wire 1 and wire lead(s) 4 for at least a portion of the guidewire. The jacket 12 may extend along most of the length of the guidewire by extending along most of the length of the elongated body. The jacket 12 may extend beyond half the length of the guidewire and beyond half the length of the elongated body. As shown in Figure 31, the jacket 12 may extend along 160 cm of the elongated body, the total guidewire length (in the example in Figure 31) is 201 cm, and the total length of the elongated body is 195 cm. Thus, in this example, the jacket 12 extends over 80% of the length of the guidewire and 82% of the length of the elongated body.

[0147] The jacket 12 may be made from any of a number of materials, including but not limited to polyimide, polyethylene terephthalate (PETE), or polytetrafluoroethylene (PTFE), or a combination thereof and / or other materials.

[0148] In some embodiments, the jacket 12 is formed by a necking process. For example, a jacketed guidewire may be formed by passing a core wire, wire leads, and a multifilar coil (or at least a portion of a multifilar coil) through a lumen of tubular plastic. The tubular plastic may be formed from Teflon heat shrink, polyimide, or PET, or other polymers. Some polymers, such as PTFE or PET heat shrink, can be reduced in diameter to tightly fit onto the core and components simply by applying heat. Some polymers, such as polyimide or PET, may not heat shrink. Some of these other polymers can have their diameter reduced to tightly compress around the core and components by a combination of heat and tension, a process called necking. During the necking process, the material may be heated and stretched so that a force is applied along the length of the elongated body of the guidewire as the material is applied. Necking allows the diameter of the tube of the jacket material (e.g., polyimide) on which the jacket is formed to be reduced to a desired diameter, such as a diameter that tightly holds the wire leads in place. In one example, the jacket diameter is 0.015 inches (0.38 mm) to 0.020 inches (0.51 mm) (e.g., about 0.017 inches, or 0.43 mm) before necking, and is reduced to 0.012 inches (0.30 mm) to 0.015 inches (0.38 mm) (e.g., about 0.014 inches, or 0.36 mm) by necking. In some embodiments, multiple polymers can be combined to form the jacket. For example, layers of polyimide and PTFE may be combined. In some such embodiments, the layers of different polymers may be separate layers rather than layers of mixed polymers. For example, the PTFE layer may be positioned outside the polyimide layer so that the PTFE layer is the outer layer. In such an embodiment, the polyimide layer may provide higher strength and precision than the PTFE layer, but the PTFE layer may be positioned outside the polyimide layer and provide reduced friction compared to the polyimide layer.

[0149] In some embodiments, the guidewire is torqueable, meaning it can transmit torque from a proximal to a distal portion so that it can be manipulated by a clinician. Torque capability allows the clinician to better control the orientation of the distal end of the guidewire and thus facilitate the manipulation of the guidewire along a desired path in the patient's vascular system. To facilitate torque transmission, in some embodiments, a multifilar coil 2 is placed on the core wire 1 and then coupled to other components of the guidewire, such as the core wire 1 and / or a sensor assembly 3. The multifilar coil 2 can be fabricated by winding some wires, such as one to ten wires or one to five wires. For example, Figure 31A shows a portion of a multifilar coil having three wires (21, 22, and 23) arranged around a core wire, these wires wound in a repeating continuous pattern as shown. An exemplary version of coil 2 may be fabricated by simultaneously winding some 304v HiTen wires within the coil such that each wire is placed adjacent to one another and wound tightly with little or no space between each wire. Each wire may have an outer diameter of 0.0015 inches (0.04 mm) to 0.003 inches (0.08 mm). The outer diameter of the core wire and the guide wires including coil 2 may be between 0.010 inches (0.25 mm) and 0.014 inches (0.36 mm) (for example, between 0.012 inches (0.30 mm) and 0.013 inches (0.33 mm)).

[0150] The advantage of a multifilar coil lies in its unique ability to reliably transmit torque while being highly flexible and having thin walls. The number of wires forming the multifilar coil can be selected to provide the desired torque capacity. For example, in some embodiments, torque can be increased by including additional wires in the multifilar coil. In some embodiments, torque may be a linear function of the number of wires included in coil 2. Furthermore, a slight increase in wire diameter and / or coil diameter can also increase torque performance, although at the expense of some flexibility. Thus, the desired torque capacity and flexibility can be selected by adjusting the various parameters available in the multifilar coil.

[0151] The stiffness of a guidewire can be adjusted, among other parameters, by changing the separation between adjacent wires within the coil. For example, wires packed tightly together with virtually no gaps between them can result in a stiffer guidewire that is more resistant to movement (less flexible). Separating the wires further from each other increases the flexibility of the guidewire, which may be more suitable for complex anatomical navigation.

[0152] In some embodiments, torque transmission can be further increased by including additional coils of the type described above. For example, Figure 31B shows two multifilar coils 2 A and 2 BThe figure shows a portion of the guide wire being wound around the coil. As shown in Figure 31B, the two filaments may be wound in different layers, one on top of the other. In some such embodiments, the two layers may be wound in different ways, such as different winding directions and / or different stiffnesses. The winding direction, referred to as "off-center" as left-center or right-center, can affect the nature of the torque capacity in a particular direction. By combining two layers of coil with coils positioned in opposite directions, the coil assembly will have similar torque characteristics in both directions. This may be advantageous for some (but not all) applications. Providing different layers of coil with different characteristics may allow for further fine-tuning of torque capacity characteristics. The multifilar coil 2 may be connected to a housing that accommodates the sensor assembly 3 by any preferred method, such as via laser welding.

[0153] The jacket 12 may extend along only a portion of the coil 2 at the interface between the jacket 12 and the coil 2. At this interface where the jacket 12 extends along the guide wire together with the coil 2, the jacket 12 may be wound around the coil 2 (as shown in Figure 31), or the coil 2 may be wound around the jacket 12. The majority of the length of the coil 2 may extend along a section of the guide wire where the jacket 12 is not present.

[0154] In some embodiments, as shown in Figure 31, the wire lead for the sensor assembly 3 may extend along a guide wire in the coil 2, which is disposed between the core 1 and the coil 2. Thus, the wire lead may extend along the length of the jacket 12 and along the length of the coil 2 to reach the sensor assembly 3, and along the length of the wire lead, the wire lead may be disposed between the jacket 12 and the coil 2.

[0155] In some embodiments, a lubricating coating may be used to reduce friction and thus increase the ability of the insertable device to navigate through the patient's vascular structure. In one example, a hydrophilic coating may be applied to the outer surface of the insertable device, e.g., the outer surface of the multifilar coil (or torque tube) and / or generally to the distal portion of the insertable device. Alternatively or additionally, one or more layers of PTFE may be used as a coating along at least a portion of the insertable device to reduce friction. The PTFE layer(s) may form, for example, the outer surface of the jacket 12 as described above. In some embodiments, friction along the elongated body of the insertable device is reduced using the PTFE outer surface, and friction within the probe is reduced using the hydrophilic coating.

[0156] Figure 31 shows the possible lengths of different sections of the guidewire. In this non-limiting example, the connector assembly 20 is 10 cm long, the non-tapered section of the guidewire is 160 cm long, the section between the non-tapered section and the sensor assembly 3 is 25 cm long, the sensor assembly is 3 mm long, and the distal end (including the coil 9 and tip 10) is 3 cm long. Naturally, other dimensions are possible, some of which are described in relation to Figure 34.

[0157] Figure 32 shows an exemplary implementation of a connector assembly 20 according to some non-limiting embodiments. The connector assembly can first be constructed by mounting an insulating tube 21, for example, made of polyimide, over the proximal portion of the core wire 1. A contact ring 22, made of, for example, stainless steel or other easily formed metal tubing, is mounted on the insulator, and one wire lead 4 is stripped of the insulator and coupled to the contact ring 22 (using a bonding material 23). Each subsequent contact ring may be similarly positioned and spaced apart. The insulating tube 21 may be made of polyimide, and its outer diameter will vary based on the size of the guide wire on which it operates, resulting in an outer diameter smaller than the guide wire. For example, tube 21 may have a diameter of 0.006 inches (0.15 mm) to 0.014 inches (0.36 mm) (e.g., about 0.012 inches, i.e., 0.30 mm) for a guide wire having a diameter of 0.010 inches (0.25 mm) to 0.018 inches (0.46 mm). Tube 21 may also have a wall of 0.001 inches (0.03 mm) and a length of 5 cm to 15 cm (e.g., 10 cm). Contact ring 22 may have an outer diameter of 0.012 inches (0.30 mm) to 0.015 inches (0.38 mm) (e.g., 0.014 inches, i.e., 0.36 mm), a wall of 0.001 inches (0.03 mm), and a length of 0.5 cm to 1.0 cm. The contact rings can be separated in particular using polyimide spacers or other tubular plastic spacers of a similar diameter size to the contact rings.

[0158] As described above, the sensor assembly 3 may, in some embodiments, include sensors and electronic circuits. Sufficient space is required to assemble the sensors and circuits together with guide wires. Furthermore, in some situations, it may be desirable to limit the diameter of the guide wires to less than (or equal to) 0.014 inches (0.36 mm), or to other preferred values, which makes packaging the sensors and circuits difficult. In some embodiments, flexible circuits can be used to assemble the sensors and circuits with guide wires. Being flexible, these circuits can be folded or wound, thus limiting the amount of space they occupy.

[0159] Figure 33 shows in more detail a portion of the guidewire of Figure 31 in some non-limiting embodiments. In this example, the sensor assembly 3 comprises a flexible circuit 5 (also referred to as a flexible substrate). The flexible circuit 5 may include electronic circuits and sensors and may be supported by a sensor housing 6. In some embodiments, as will be further described below in relation to Figures 36A-36B, the flexible circuit may be wound around a portion of the housing 6. As shown, wire leads 4 may be inserted into the housing 6 and connected to the flexible circuit 5. The housing 6 can be attached to the multifilar coil 2 in any preferred way, such as by using a laser weld 7. In addition, or alternatively, solder joints, adhesives, or some similar means may be used. The coil 9 may be coupled to the distal end of the sensor housing 6 by a solder joint 8, adhesive, or similar means.

[0160] In some embodiments, the diameter of the core wire 1 may vary along its length to increase flexibility as needed. In one example, the diameter may be tapered along its length such that the diameter at the distal end is smaller than the diameter at the proximal end. In this way, flexibility at the distal end is increased relative to the proximal end without necessarily sacrificing torque capacity. Figure 34 schematically shows a tapered core wire 1 according to some non-limiting embodiments. In this example, the core wire 1 includes segments A, B, C, D, E, F, and G. Segment A may include the connector assembly 20 and may have a length of 5 cm to 15 cm, such as about 10 cm. In segment A, the core wire may have a diameter between 0.006 inches (0.15 mm) and 0.010 inches (0.25 mm) (e.g., about 0.0080 inches (0.20 mm)). Segment B may have a length of 1 cm to 3 cm, such as about 2 cm. Segment B may have a tapered shape such that the diameter of the core wire increases between 0.009 inches (0.23 mm) and 0.014 inches (0.36 mm) (e.g., approximately 0.011 inches (0.28 mm)). Segment C, which may include the jacket 12, may have a length of 100 cm to 200 cm or 130 cm to 170 cm (e.g., approximately 155 cm). In segment C, the core wire may have a width between 0.010 inches (0.25 mm) and 0.014 inches (0.36 mm) (e.g., approximately 0.011 inches (0.28 mm) or approximately 0.012 inches (0.30 mm)). The multifilar coil 2 may be included in segment E and, if desired, in segments D and / or F or parts thereof. Segment D may have a length of 6 cm to 10 cm, such as approximately 8 cm. Segment D may have a tapered shape such that the diameter of the core wire decreases between 0.004 inches (0.10 mm) and 0.006 inches (0.15 mm) (for example, to about 0.005 inches (0.13 mm)). Segment E may have a length of 7 cm to 13 cm, such as about 10 cm. In segment E, the core wire may have a width between 0.004 inches (0.10 mm) and 0.006 inches (0.15 mm) (for example, to about 0.005 inches (0.13 mm)).Segment F may have a length of 6 cm to 10 cm, for example, about 8 cm. Segment F may have a tapered shape such that the diameter of the core wire decreases to between 0.002 inches (0.05 mm) and 0.004 inches (0.10 mm) (for example, about 0.003 inches (0.08 mm)). Segment G may include the sensor assembly 3, the coil 9, and the tip 10, and may have a length of 4 cm to 10 cm, such as about 7 cm. In segment G, the core wire may have a width between 0.002 inches (0.05 mm) and 0.004 inches (0.10 mm) (for example, about 0.003 inches (0.08 mm)).

[0161] The specific dimensions described above may be designed to provide a desired amount of torque capacity in the proximal and central portions of the guidewire, a desired amount of flexibility in the last 10cm to 30cm of the guidewire, and sufficient space to accommodate sensors and electronic circuits in the last 3cm to 7cm. However, it should be understood that not all embodiments are limited to the dimensions provided in relation to Figure 34.

[0162] Figures 35 to 36B show further details of the components constituting the sensor assembly 3 in some non-limiting embodiments. In particular, Figure 35 shows a perspective view of possible mounting configurations of the sensor housing 6. In some embodiments, the housing 6 is formed from a stainless steel tube, but other materials may be used as an alternative or in addition.

[0163] The housing 6 may be long enough to accommodate the sensor and / or circuit, but may be short enough so that its rigidity does not impair the steering capability of the guidewire at the distal end. For example, the housing 6 may have a length of approximately 2mm to 5mm, 2mm to 4mm, 2mm to 4mm, 3mm to 5mm, 3mm to 4mm (e.g., approximately 3.5mm), and a maximum diameter of 0.012 inches (0.30mm) to 0.015 inches (0.38mm) (e.g., approximately 0.014 inches, i.e., 0.36mm), but other dimensions are also possible.

[0164] Each end of the housing 6 may have an opening 15 through which the core wire 1 can pass. In some embodiments, the area of ​​the housing near the end may include a flared or enlarged boss 17, which may be designed so that the multifilar coil 2 and coil 9 are inserted into and coupled to the housing.

[0165] In the center of the housing, a notched recess 19 may be formed on the side of the housing, as shown in Figure 35. The recess 19 may be formed by removing a portion of the side wall of the housing. The recess 19 may be sized to accommodate a flexible circuit 5 (not shown in Figure 35) therein. For example, the length of the recess 19 may be about 1 mm to 2.5 mm, for example, 1.3 mm to 1.7 mm. Part of the flexible circuit may be inserted into the inside of the housing 6 through the recess 19, and another part may be wrapped around the housing, as will be further described below.

[0166] Figures 36A and 36B show possible layouts of the flexible circuit 5 according to some embodiments. The flexible circuit 5, which may be made from a flexible material 28 such as polyimide, may include a sensor array 25, an integrated circuit 26 (which may include an application-specific integrated circuit or other logic circuits), and solder pads 27 for connecting wire leads 4. The integrated circuit 26 may include a chip that performs the functions of a measurement unit, such as the measurement unit 214 described above in relation to Figure 2.

[0167] The sensor array 25 may include multiple sensors for detecting one or more characteristics of the tissue surrounding the guidewire. In one example, the sensor array may be arranged as an impedance sensor array. However, it should be understood that embodiments of the present disclosure are not limited to any particular type of sensor. Possible alternative types of sensors include pressure sensors and flow sensors, but other types of sensors may be used. In at least some embodiments in which an impedance sensor array is used, the sensor array may include multiple electrodes. In the example in Figure 36A, nine electrodes (25) are arranged in three columns and three rows. 11 ,twenty five12 and 25 13 and 25 21 and 25 22 and 25 23 and 25 31 and 25 32 and 25 33 ) are included. Of course, any other suitable number of electrodes may be used. To increase the probability that at least a portion of the sensor contacts the blood clot being sampled, multiple columns may be included.

[0168] Some of the electrodes can be driven by signals (referred to as probe signals) generated by one or both of integrated circuits 26 and can propagate the signals outside the guide wire in the form of electromagnetic waves. In this regard, the electrodes essentially function as antennas. These electrodes are referred to as transmission (TX) electrodes. The transmitted electromagnetic waves can be reflected by the tissue surrounding the guide wire. The remaining electrodes, referred to as reception (RX) electrodes, can receive the reflected electromagnetic waves. As described in detail below, in some embodiments, the electrodes can be operated in three groups, and one of the electrodes in each group can operate as a TX electrode, while the other electrodes operate as RX electrodes.

[0169] Signals obtained in response to the reception of electromagnetic waves (referred to as detection signals) can be transferred to one or both of integrated circuits 26 for processing (e.g., analog-to-digital conversion). In some embodiments, the circuitry of the integrated circuit can be configured to infer the impedance of the reflecting tissue based on a comparison between the transmitted signal and the received signal (e.g., by taking the ratio of the transmitted voltage to the received current). These measurements of impedance can be repeated at different frequencies, and thus, an impedance spectral response of the tissue is obtained. Data indicating the impedance measurements can be transmitted via solder pads 27 and wire leads 4 to a medical device outside the guide wire for further processing.

[0170] While the embodiments described herein involve separate electrodes used for electromagnetic wave transmission and reception, it should be understood that in other embodiments, the same electrode may be used for both transmission and reception.

[0171] Figure 36B shows possible arrangements of the flexible circuit 5 in relation to the housing 6 according to some non-limiting embodiments. As shown, one end of the flexible circuit (e.g., the end with the solder pad 27) is positioned within a cavity formed by the housing 6. Wire leads 4, which can be inserted through the housing via an opening 15 (shown in Figure 35), are connected to their respective contacts 27 within the housing. The contacts 27 may be, or include, a solder pad, silver-filled epoxy, conductive adhesive, or other conductive material. The flexible circuit may then be folded or wound around the core wire 1 (which may pass through the housing via the opening 15), and the circuit may be positioned such that the integrated circuit 26 is positioned corresponding to a recess 19 (shown in Figure 35) when the flexible circuit is wound. The flexible circuit may be wound around the housing 6, and the integrated circuit 26 may be positioned so that they stack on top of each other in the recess 19 (or inside the cavity). The remaining portion of the flexible circuit can be wrapped around the housing such that the sensor array 25 is positioned outside the housing and oriented outward relative to the housing (i.e., facing outward from the housing). In one example, the electrode array (electrode 25 11 ,twenty five 12 , and 25 13 The distance between the first row (including the first row) is sized so that, once the flexible circuit is wound around the housing, the rows are angle-offset by approximately 120°, thereby distributing them evenly around the outside of the guide wire.

[0172] Within each row, some electrodes may be positioned for transmission and others for reception, but the role of each electrode may change over time. During one time interval, one electrode for each row may function as a TX electrode, and the other two electrodes may function as RX electrodes. The TX electrode may transmit electromagnetic waves, and the RX electrodes may receive waves reflected from adjacent tissue. In some such embodiments, different RX electrodes in each row are positioned to detect impedance at different depths within the tissue. This can be achieved by positioning the RX electrodes at different distances from the TX electrodes, i.e., one RX electrode (e.g., electrode 25) 12 ) is the TX electrode (for example, electrode 25 11 Positioned at a first distance relative to ) and another RX electrode (e.g., electrode 25 13 The RX electrode is positioned at a second distance from the TX electrode, and the first and second distances are different from each other. Due to the different distances from the TX electrode, the RX electrode receives waves at different angles of incidence. Waves with different angles of incidence have different penetration depths into the tissue, and as a result, can provide indicators of impedance at different depths. Detecting impedance at different depths can enhance the ability to characterize blood clots (e.g., infer the type, composition, or other properties of the blood clot).

[0173] Further details of some embodiments of the flexible circuit are provided below.

[0174] Referring here to Figure 41A, a flexible circuit board 4100 is schematically shown. As shown in the figure, the flexible circuit board may comprise a first flexible region 4110 and a second non-flexible region 4120. In some embodiments, the first region has greater flexibility than the second region. This may advantageously allow a portion of the flexible circuit to wrap around a portion of itself and / or another portion of an invasive probe (e.g., a guidewire). For example, as schematically shown in Figure 41B, the flexible region 4110 can bend and flex around the non-flexible region 4120. Further details regarding the degree of flexibility between these two regions will be described in more detail elsewhere in this specification.

[0175] A flexible circuit board may include polymer or organic layers that contribute to the flexibility of the circuit board. For example, referring back to Figure 41A, the flexible circuit board 4100 may comprise a first integrated circuit 4124, a second integrated circuit 4126, and a first polymer layer 4121 and a second polymer layer 4122 disposed on an interconnection layer 4130. As schematically shown in the figure, the first polymer layer 4121 can be disposed on the upper surface of the interconnection layer 4130, and the second polymer layer 4122 can be disposed on the opposite back surface of the interconnection layer 4130. However, it should be understood that other configurations of the first and second polymer layers other than those shown in Figure 41A are possible.

[0176] The polymer layers (e.g., a first polymer layer, a second polymer layer) may contain, or may contain, any suitable polymer or organic material for providing flexibility to the circuit. In exemplary embodiments, the polymer layers contain polyimide. However, other polymer materials are also suitable. Non-limiting examples of other suitable polymer materials include, for example, polyolefins such as polyethylene, polypropylene, polyimide, paraliene, and polysiloxane, as well as benzocyclobutene (BCB). Other polymers or organic materials are also possible.

[0177] In some embodiments, the first polymer layer 4121 and the second polymer layer 4122 may have coincided flexibility, so that during the bending of the two layers, the compressive and expansive forces acting on the interconnect layer 4130 when bent in one direction coincide with the compressive and expansive forces acting on the interconnect layer when bent in the opposite direction. This is referred to as being in the neutral plane of the region. Having coincided flexibility on both sides of the interconnect layer 4130, and therefore being in the neutral plane at least in the flexible region, can help improve the reliability of the interconnect layer 4130 and the flexible circuit by reducing the risk of damage to the interconnect layer 4130 due to bending. In some embodiments, this coincided flexibility can be sustained through the flexible region 4110 and through the transition between the flexible region 4110 and the non-flexible region 4120. Therefore, in some such embodiments, the interconnection layer 4130 can be maintained within the neutral plane between layers 4110 and 4120 at each transition between the flexible region 4110 and the non-flexible region 4120.

[0178] In some embodiments, this matched flexibility can be achieved by arranging the thicknesses of the first and second polymer layers to provide the desired flexibility to the flexible circuit without damaging (e.g., cracking) the circuit (e.g., the interconnection layer 4130 of circuit 4100). For example, within a first region (e.g., a flexible region), the first and second polymer layers may have matched thicknesses. The two thicknesses can match when they are identical or within a threshold tolerance for being identical. In some embodiments, tolerances for matching thicknesses may result in the flexibility of the two layers matching or applying the same force or a force within each other's tolerances to the interconnection layer 4130 during bending. The tolerance for force may be such that the two forces are substantially equal to mitigate the risk of degradation or breakage of the interconnection layer 4130 due to bending. In some embodiments, the flexibility of layers 4121 and 4122 may be substantially identical, or the thicknesses of layers 4121 and 4122 may be substantially identical. As used in this context, the term "substantially" refers to the majority or most, such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least approximately 99.999%.

[0179] In some embodiments, the first polymer layer and / or the second polymer layer (e.g., within the first region, within the second region) may have a specific thickness. In some embodiments, the thickness of the first polymer layer and / or the second polymer layer is 1 micron or more, 5 microns or more, 10 microns or more, 15 microns or more, 20 microns or more, 25 microns or more, 30 microns or more, 40 microns or more, 50 microns or more, 60 microns or more, 70 microns or more, 80 microns or more, 90 microns or more, or 100 microns or more. In some embodiments, the thickness of the first polymer layer and / or the second polymer layer is 100 microns or less, 90 microns or less, 80 microns or less, 70 microns or less, 60 microns or less, 50 microns or less, 40 microns or less, 30 microns or less, 25 microns or less, 20 microns or less, 15 microns or less, 10 microns or less, 5 microns or less, or 1 micron or less. Combinations of the above ranges are also possible (e.g., 1 micron or more and 100 microns or less). Other ranges are also possible.

[0180] As described above, a flexible circuit board may also include an interconnection layer, such as the interconnection layer 4130 in Figure 41A. The interconnection layer 4130 in Figure 41A may be formed by one or more layers of a conductive material (e.g., gold as described above) that form conductive traces, vias, leads, conductive pads, or other known conductive elements of the circuit board within the flexible circuit board. For ease of explanation, the interconnection layer 4130 is referred to herein as a “layer” (singular term), but those skilled in the art will understand that the interconnection layer 4130 may comprise one, two, or another preferred number of layers.

[0181] The interconnection layer can, in non-limiting examples, provide electrical communication to two or more components, such as a first integrated circuit and a second integrated circuit, between a second integrated circuit and one or more conductive contacts to which one or more wires of the invasive probe are connected, or between the circuit of the invasive probe and an electrical circuit in the proximal portion of the invasive probe.

[0182] The interconnection layer can be any suitable material for providing electrical signals transmitted from one component to another. In one embodiment, the interconnection layer is gold or contains gold. However, other suitable materials can be used for the interconnection layer. In some embodiments, the interconnection layer contains a conductive metal. Non-limiting examples of conductive metals for the interconnection layer include gold, platinum, palladium, nickel, silver, copper, aluminum, and combinations / alloys thereof such as AlSiCu. In some embodiments, the interconnection layer contains an organic material such as a conductive organic material like Pedot:PSS (poly(3,4-ethylenedioxythiophene)polystyrene sulfonate). The conductive interconnection layer can be formed using known techniques such as chemical vapor deposition (CVD) or vapor deposition to deposit the entire layer, or using deposition methods such as inkjet printing.

[0183] In some embodiments, the location of the interconnection layer (e.g., within a first region, within a second region) is such that the desired flexibility of the flexible circuit can be achieved without destroying or damaging the interconnection layer. In some embodiments, the interconnection layer within the first region (e.g., the flexible region, region 4110 in Figure 41A) is positioned between the first polymer layer and the second polymer layer (e.g., in between). In some embodiments, in the transition between the first and second regions, and within the second region (e.g., the non-flexible region, region 4120 in Figure 41B), the interconnection layer 4130 is positioned closer to the top surface of the first polymer layer compared to the bottom surface of the second polymer layer. Closer to the top surface may include the upper third of the flexible circuit. (In this example, “upper” refers to the side of the flexible circuit where the interconnect layer forms an electrical connection with leads or other contacts for an integrated circuit. In some embodiments, at the transition between the flexible region 4110 and the non-flexible region 4120, the interconnect layer 4130 may remain within the neutral plane between the two layers of polymer. Remaining within the neutral plane may involve transitioning from being relatively central between two polymer layers of matched thickness, with the second polymer layer 4122 having a thickness below the interconnect layer 4130 greater than the thickness of the first polymer layer 4121 above the interconnect layer 4130, to being in the upper part of the device (e.g., the upper third). Other positioning of the interconnect layer within the polymer layers is also possible, and those skilled in the art may, considering the teachings of this disclosure, select the position of the interconnect layer to maintain the flexibility of the flexible circuit without damaging the circuit when the circuit is bent.

[0184] In some embodiments, the flexible circuit board comprises one or more integrated circuits (e.g., “chips”). For example, in Figure 41A, the flexible circuit board 4100 includes a first integrated circuit 4124 and a second integrated circuit 4126. One or more integrated circuits may be made of an inorganic solid material such as a silicon chip and may be relatively rigid or inflexible compared to an organic polymer layer. In some embodiments, one or more integrated circuits are arranged within a second region (e.g., an inflexible region). As described above, this provides the flexible circuit board with a flexible region and a relatively inflexible region.

[0185] In some embodiments, the non-flexible region is created by positioning the integrated circuit adjacent to (e.g., directly adjacent to) the second polymer layer and depositing or otherwise forming the first polymer layer adjacent to the integrated circuit. The first polymer layer can be formed to have a specific desired thickness, which can be a desired range of thicknesses (e.g., a target thickness with an allowable margin greater than or less than the target thickness). The thickness dimension in these examples may be the height / vertical dimension in the cross-section of Figure 41A.

[0186] In some embodiments, a desired thickness can be achieved by controlling how the material is deposited, applied, multiplied, or otherwise initially formed on the first polymer layer. In other embodiments, a desired thickness can be achieved by processing the material of the first polymer layer to remove a portion of the initially formed material, thereby achieving the desired thickness. For example, in some embodiments, a polymer layer can be deposited or otherwise formed, including forming a polymer layer on an integrated circuit positioned on a second polymer layer. This initial polymer layer may have an uncertain thickness, and may be an initially uncontrolled thickness, or it may be a controlled thickness that is within a desired initial manufacturing range for the desired thickness, but not identical to the desired thickness. In such an embodiment, the initial polymer layer may deviate from the desired thickness, but the amount of deviation may be unknown, so the thickness of the initial polymer layer can be determined. This can be determined by measuring the thickness of the initial polymer layer. For example, low-coherence interference microscopy using a laser and interference pattern may be used to measure the thickness. Alternatively, in one embodiment where at least one region of the flexible circuit does not have a polymer layer (e.g., the layer was not deposited or was removed), the step height can be measured using a surface profile measuring device.

[0187] Following the measurement, a process may be performed to remove a portion of the initial polymer layer, the amount of which is determined based on the measured thickness and is the amount of material resulting in a first polymer layer having the desired thickness. The embodiments are not limited to performing this process to remove material in any particular way, and known techniques can be used. For example, the initial polymer layer may be etched to achieve the desired thickness. In some embodiments, following the removal of a portion of the initial polymer layer, conductive contacts can be positioned on an integrated circuit within the area of ​​the initial polymer layer that has been processed to remove material.

[0188] In some embodiments, the integrated circuit may be encapsulated by a layer or coating that protects the integrated circuit from substances in the tube (e.g., fluids) that could short-circuit or otherwise damage the circuit. For example, the integrated circuit may be encapsulated in a waterproof material to allow immersion of an invasive probe into a bodily fluid without the risk of the bodily fluid interfering with the operation of the integrated circuit. In some embodiments, such encapsulation layer may be silicon dioxide (e.g., SiO2) and / or silicon nitride (e.g., SiN x It may be Si3N4, or may contain it. Such a encapsulation layer can also increase the inflexibility of the second region or protect the integrated circuit.

[0189] Flexibility can be measured by the bending radius that can be achieved (without breaking the material). As an example, Figure 44 schematically shows a neutral material and a bent material. As shown in the figure, the neutral material has a neutral axis 4410, and when the material is bent, the neutral axis 4410 is also bent as indicated by the bent portion 4420. In the bent state, a radius of the neutral axis 4430 is formed relative to the neutral axis 4410. The bending also causes the formation of an inner radius 4440 and an outer radius 4450.

[0190] In some embodiments, the flexible circuit board (or components of the flexible circuit, such as a first region, polymer layer, or interconnect) may have a specific bending radius without causing cracks or other damage to the circuit board or its components. In some embodiments, the flexible circuit board has a bending radius of 1 micron or more, 3 microns or more, 5 microns or more, 7 microns or more, 10 microns or more, 12 microns or more, 15 microns or more, 18 microns or more, 20 microns or more, 25 microns or more, 30 microns or more, 40 microns or more, or 50 microns or more in the flexible region. In some embodiments, the flexible circuit board has a bending radius of 50 microns or less, 40 microns or less, 30 microns or less, 25 microns or less, 20 microns or less, 18 microns or less, 15 microns or less, 12 microns or less, 10 microns or less, 7 microns or less, 5 microns or less, 3 microns or less, or 1 micron or less. Combinations of the above ranges are also possible (e.g., 10 microns or more and 25 microns or less). Other ranges are also possible.

[0191] The flexible region of a flexible circuit board is sufficiently flexible to have a specified bending radius, while maintaining its functionality during or after bending / wrapping / folding at that radius, thereby having flexibility within a specified range. The non-flexible region may similarly have a bending radius below a desired bending radius threshold or within a desired radius range. Therefore, the bending radius of the non-flexible region may be smaller than the bending radius of the flexible region, and the flexibility of the non-flexible region may be smaller than the bending radius of the flexible region.

[0192] Flexibility can be measured using various techniques. For example, a rod having a radius corresponding to a desired winding radius / diameter may be provided, and a substrate (e.g., a flexible circuit board) may be wound around the rod several times and then tested for functionality to evaluate whether the substrate can withstand bending at that radius. If so, the substrate has sufficient flexibility to achieve the desired flexibility at the desired winding radius / diameter. For small winding diameters / radii, such rod techniques may be difficult or impractical. In such cases, the substrate may be folded, and then pressure may be applied to achieve a desired thickness of the folded substrate stack. The folded substrate can then be tested for functionality to determine whether it withstood folding / winding at that thickness. By performing several consecutive tests, the maximum folding / bending / winding radius that the substrate can withstand can be determined. The bending radius can be calculated by dividing the thickness of the folded substrate stack by the thickness, and then dividing that thickness by the number of layers / folds. Testing the functionality of the rod during winding or folding may include monitoring electrical parameters such as resistance during the test to determine whether there are any changes that could indicate damage or breakage to components (e.g., interconnects).

[0193] As described elsewhere in this specification, a first region of a circuit board (e.g., a flexible region) can be wound around at least a portion of a second region (e.g., a non-flexible region), and can also be wound within and / or around one or more components of an invasive probe. For example, as schematically shown in the cross-sectional view of Figure 41C, the invasive probe 4140 shows a first region 4110 wound around a second region 4120. As shown in the figure, a flexible circuit (e.g., a first region of a flexible circuit) begins within a housing 4150 adjacent to a core 4160, and is then wound around a portion of the housing 4150 containing the elongated core 4160, and is disposed within the jacket 4170 of the invasive probe. As shown in the example in Figures 41A and 41B, the flexible circuit board 4100 in Figure 41C includes a first flexible region that begins adjacent to the elongated core 4160 and then wraps around the housing 4150 until a second region 4120 of the second integrated circuit 4126 is positioned within the housing 4150 so that it can be seated flat within a region protected from bending forces (see, for example, the opening in the housing shown in Figure 35). Next, another flexible region 4110 continues to wrap around the housing 4150 until another non-flexible region 4120 positions the first integrated circuit 4124 within the housing 4150, where the first integrated circuit 4124 can be seated flat and protected from bending forces and is aligned with the second integrated circuit 4124. Next, another flexible region 4110 follows the housing and circuits 4124, 4126 and wraps around them, as shown. This last flexible region 4110 may include one or more electrodes of the sensor, as shown in the example in Figure 36A, the electrodes may be positioned on the outside of the invasive probe and in contact with one or more tissues of the animal tube. In some embodiments, at least one of the flexible regions (e.g., this last region) is configured to form one or more complete turns around a portion of the flexible circuit, a portion of the invasive probe (e.g., a guidewire).

[0194] Flexible circuit boards and integrated circuits can be adapted and positioned so that a second region (e.g., two or more integrated circuits in the second region) is aligned within the invasive probe when the flexible circuit board is in a wound configuration. Alignment may mean that two circuits are positioned so that one is placed on top of the other, as shown in the figure. For example, in Figure 41C, the first integrated circuit 4124 and the second integrated circuit 4126 are aligned.

[0195] The first circuit 4124 may, in some embodiments, include one or more active electronic components operably associated with one or more sensors (not shown) and capable of detecting one or more values ​​of tissue(s) of an animal tube contacted by the sensors(s). This may include one or more components for generating and applying one or more electrical signals of one or more frequencies, and one or more components for determining the impedance of the tissue(s) based on an analysis of the electrical signals received from the tissue(s) in response to the application. The first circuit 4124 may include components and functions of a measuring unit (e.g., measuring unit 214 in Figure 2) as described elsewhere in this specification. As described above, noise in the signals received by the first circuit 4124 can be reduced by positioning the first circuit 4124 on the flexible circuit 4100 closer to the sensors(s) / electrodes (e.g., closer than the second circuit 4126 as shown (see, for example, the example in Figure 36A)). The second circuit 4126 may include passive components driven by the active components of the first circuit 4126. For example, the second circuit 4126 may be configured to process (e.g., perform impedance filtering) one or more values ​​received by the first integrated circuit 4124. In such an embodiment, it may be possible to separate sensing and processing while still being part of a single flexible circuit board.

[0196] Figure 41C shows two integrated circuits, but the disclosure is not so limited, so it should be understood that a flexible circuit board may have more than two circuits. Those skilled in the art will be able to select an appropriate number of integrated circuits for a flexible circuit board while maintaining the desired flexibility and functionality based on the teachings of the disclosure.

[0197] Figure 42 shows a flowchart for positioning and aligning a flexible circuit within a housing (e.g., a non-flexible housing) of an invasive probe. In some embodiments, Method 4200 begins by positioning the flexible circuit board within a slot in the housing, as shown in block 4205. The slot in the housing may be sized and shaped to accommodate a portion (which may be a flexible portion) of the flexible circuit board. The flexible portion positioned within the slot may, in some embodiments, be a portion that begins within the non-flexible housing and extends outward from the non-flexible housing, such as a portion containing one or more conductive contacts to which one or more wires are connected. In some embodiments, once the flexible circuit is initially positioned within the slot in the housing in block 4205, a bonding material is applied to the housing and the flexible circuit to fix / bond this initial portion of the flexible circuit to this inner portion of the housing. In some embodiments, the bonding material may be an adhesive (e.g., glue). The adhesive may be an insulating adhesive such as epoxy (which may have favorable adhesive properties to metals and polyimides and may be advantageously able to withstand high temperatures), cyanoacrylate (e.g., cyanoacrylate), or silicone adhesive. Referring back to the cross-section in Figure 41C, the central portion of the flexible circuit 4100, shown adjacent to the elongated core 4160, may be bonded to the elongated core 4160 and / or housing 4150 using a bonding material.

[0198] In some embodiments, the flexible circuit board is configured such that the entire flexible circuit board, and / or one or more flexible regions of the circuit board, completely wrap around a non-flexible housing. In some embodiments, during wrapping, a consistent or uniform tension is applied to at least a portion of the flexible circuit board, as shown in block 4210, so that the non-flexible portion remains in the slot and a uniform or desired wrapping can be achieved. In addition, in some embodiments, the integrated circuits of the flexible circuit board (e.g., circuits 4124, 4126 in Figures 41A-41C) are positioned on the flexible circuit board so that the integrated circuits are aligned once the circuit board is wrapped. Applying a consistent or uniform tension to the flexible circuit board during wrapping can ensure that the wrapping is performed under desired tension so that the desired positioning of the circuits of the flexible circuit board and other components relative to the housing and / or other components of the flexible circuit board is achieved.

[0199] This consistent or uniform tension can be achieved in various ways, including, in some embodiments, fixing weights that are fixed during winding to the flexible circuit board.

[0200] Next, as shown in block 4215, the first flexible region of the flexible circuit board is wound, and the winding process begins. Embodiments are not limited to specific techniques for achieving winding. In some embodiments, winding can be achieved by moving the flexible circuit around the housing while maintaining the housing in place. In other embodiments, winding may be achieved by rotating the housing such that the flexible circuit extends away from the housing as the housing rotates, so that the flexible circuit begins to wind around the housing. The flexible region can be wound around a non-flexible region and / or a portion of the housing. The non-flexible region can then be aligned, as shown in block 4420, and the second flexible region can subsequently be wound around the flexible circuit (or other components), as shown in block 4225.

[0201] In some embodiments, following winding, an insulating material may be applied to the winded flexible circuit and housing assembly. The insulating material may be, for example, an insulating adhesive.

[0202] Process 4200 in Figure 42 has been described without specific reference to the entity performing the process. As can be understood from the above, Process 4200 is a manufacturing process that may be performed by a preferred manufacturing entity. In some cases, some or all of the process may be performed by a human worker assembling an invasive probe or its components. In other cases, some or all of the process may be performed by one or more machines arranged to perform the process. Embodiments are not limited to this.

[0203] In some embodiments, the flexible circuit board may be housed within a housing, but at least a portion of the flexible circuit may extend outside the housing. For example, Figure 43A schematically shows a flexible circuit board 4100 wound around a housing 4150. Region 4305 of the flexible circuit board 4100 is connected to a region initially disposed within a slot (e.g., in block 4205 in Figure 42) and coupled to the housing. Region 4305 extends outside the housing and includes one or more conductive contacts, such as a first contact 4310 and a second contact 4312. One or more wires of an invasive probe are connected to these conductive contacts to provide power and / or communication to the circuits of the flexible circuit board (e.g., circuits 4124, 4126).

[0204] As described above, outside the non-flexible housing, flexural forces are applied to the components of the invasive probe during navigation through the anatomical structure of an animal. To protect the connection between the wire and the conductive contact, the connection may be made within a housing where no flexural force is applied to the connection, or less flexural force is applied to the connection. However, placing the connection within the housing may limit the space available for the components (circuits, wires, etc.) within the housing and thus limit their functionality. By positioning one or more conductors outside the housing, more space is advantageously provided for the circuit board within the housing, including space for the non-flexible portion of the flexible circuit board. The reliability of the connection can be improved while maintaining the flexibility of the invasive probe in the region of region 4305 by using the techniques described below to fix the wire in region 4305 and achieve electrical connection.

[0205] Each contact of one or more conductive contacts can be attached to a wire extending toward the proximal portion of the guidewire. For example, in Figure 43A, the ribbon 4315 includes one or more wires that are physically joined in their insulating jackets to form a ribbon and extend toward the proximal region of the invasive probe. Each wire may be electrically connected to only one of the conductive contacts. For example, the first wire 4320 of the ribbon 4315 is electrically connected to contact 4310, the second wire (not shown) of the ribbon is electrically connected to the second contact 4312, and so on. However, as can be seen from Figure 43A, each of the wires of the ribbon 4315 is in contact with all of the conductive contacts, at least through the insulating jacket of the wires within the ribbon 4315. More specifically, in the example shown in Figure 43A, the ribbon 4315 covers the conductive contacts, but each wire of the ribbon 4315 is electrically connected to only one conductive contact, and each conductive contact is electrically connected to only one wire of the ribbon 4315.

[0206] Figure 43B shows a cross-sectional side perspective view of the connection described above. For example, the first wire 4320 connects to the first contact 4310 through the opening 4330. The wire insulator 4322 of the first wire 4320 insulates the first wire 4320 from the other wires of the ribbon and from the conductive contacts to which the first wire 4320 is not connected. For example, as shown in Figure 43B, since there is no opening in the jacket 4322 within the region of conductive contact 4312, the wire 4320 is electrically insulated from the conductive contact 4312 and is not electrically connected to the contact 4312. The same applies to the other contacts in region 4305 (see Figure 43A showing the five contacts in that example). As a result of the opening 4330, the first wire 4320 connects only to the first contact 4310. Similarly, it should be understood that the opening 4430 is located only within the insulating jacket 4322 of the first wire 4320, and there is no corresponding opening in the insulating jacket of the other wires of the ribbon at the location of the first contact 4310 (the other wires are not shown in the cross-section of Figure 43B). This ensures that the first wire 4320 makes electrical contact only with the first contact 4310 of the conductive contact, and the first contact 4310 makes electrical contact only with the first wire 4320.

[0207] However, the other wires of the ribbon 4315 include openings corresponding to the locations of the conductive contacts to which those wires are connected. For example, in the region of contact 4312 (where the first wire 4320 is not connected and therefore no opening exists in Figure 43B), an opening exists within the insulating jacket of another wire of the ribbon 4315.

[0208] The opening 4430 is an opening within the insulator 4322. The opening of the opening 4430 may be formed, for example, by laser cutting or other process for forming an opening in the insulating jacket 4322.

[0209] In some embodiments, a conductive bonding material (not shown in Figure 43B) is disposed in and around the opening 4330 to provide an electrical contact for the first wire 4320 to the first contact 4310. The conductive bonding material may be, for example, a silver-filled epoxy (where the penetration of conductive microballs within the epoxy provides conductivity), a carbon-filled adhesive (e.g., on epoxy, silicone, cyanoacrylate), or a conductive adhesive such as solder. The conductive bonding material bonds the first wire 4320 and ribbon 4315 to the first contact 4310 and region 4130, ensuring a good electrical connection between the first wire 4320 and the contact 4310.

[0210] In some embodiments, conductive coupling material (see Figure 43A), which is disposed within each region of a conductive contact to electrically connect each wire to one of the individual conductive contacts, is disposed across each of the wires of the ribbon 4315, including wires that are not electrically connected to a particular conductive contact. As can be understood from the above, at each location of a conductive contact, an opening is formed in only one insulating jacket of one wire of the ribbon. Therefore, despite the presence of conductive coupling material in that region, as a result of the insulating jacket, only one wire of the ribbon is connected to each conductive contact. Thus, applying conductive coupling material to all wires may be unnecessary from an electrical point of view. However, the presence of conductive coupling material serves another purpose here. As mentioned above, the region 4305 of the flexible circuit will be subjected to flexural forces during the navigation of the animal's anatomical structure, and these flexural forces may degrade or break the wire connections to the conductive contacts. In the exemplary embodiment of Figure 43B, the conductive coupling material may help protect and secure the connections by bonding the entire width of the ribbon to the entire width of region 4305. When the conductive bonding material hardens, it forms areas of reduced flexibility within the flexible region 4305. This reduction in flexibility protects the electrical connection of the wire to the conductive contacts during bending. However, in this embodiment, the conductive bonding material is applied only to the region of each conductive contact, and the regions of conductive bonding material are separated by regions without conductive bonding material, so that the entire region 4305 maintains the desired flexibility. Those regions without conductive bonding material preserve their flexibility, allowing the entire region 4305 to have the desired flexibility for navigating the anatomical structure of an animal while also protecting the electrical connections.

[0211] In some embodiments, the entire region 4305 (or at least the region of the conductive bonding material and conductive contacts) is coated with an insulating material such as epoxy, or an adhesive such as silicone or cyanoacrylate, or a spray coating of a polymer, or a conformal coating of epoxy, parylene, polyimide, or other insulating material.

[0212] Figures 43A and 43B show two wires in a ribbon, but the ribbon may also include additional wires (e.g., a third, fourth, and fifth wire), and it should be understood that additional conductive contacts (e.g., a third, fourth, and fifth contact) on the flexible circuit board may provide electrical communication to the proximal portion of the guide wire. Each of the one or more wires can be electrically contacted to each of the one or more conductive contacts through each of the one or more openings made in the insulator of the one or more wires.

[0213] Figure 37 shows an alternative mounting configuration of the guidewire assembly according to some embodiments. In this example, the wire body constituting the proximal 150-160 cm of the guidewire between the proximal connector assembly 20 and the multifilar coil comprises a metal torque tube 32. This metal tube is made of stainless steel or nitinol and has an outer coating such as PTFE (TEFLON). The distal core wire 31 and proximal core wire 34 may be soldered or bonded (35) to the torque tube 32, thereby achieving transition to the multifilar coil 2 and distal grinding of the core wire 31, and the connector assembly 20 may then be constructed in substantially the same manner as the wire assembly shown in Figure 31. In some embodiments, the wire lead 4 exits the multifilar coil, then enters the torque tube through the distal solder joint, and then returns out of the torque tube at the proximal end, so in some such embodiments, a plastic jacket 33 may cover the wire lead 4.

[0214] The main advantage of using a metal torque tube is that the wire can be housed inside and therefore better protected. Furthermore, because the outer diameter of the torque tube is larger than the maximum diameter of the core wire 1 used in the guide wire assembly in Figure 31, the torque tube can transmit torque more effectively. For example, a stainless steel torque tube may be 0.013 inches (0.33 mm) compared to 0.011 to 0.012 inches (0.28 mm to 0.30 mm) for a full-length core wire. One disadvantage of using a torque tube is that it twists more easily than a full-length stainless steel core wire.

[0215] Figure 38 shows another example of a guidewire assembly. In this example, the multifilar coil used in the guidewire assembly shown in Figure 31 is replaced with a highly flexible torque tube 42 made of a nitinol tube or other material having a number of continuously cut slots. Guidewires using similar torque tubes are commercially available, such as Synchro® Guidewire, sold by Stryker Corporation. Figure 39 shows an exemplary version of a flexible torque tube. This torque tube is made, for example, from a 0.014-inch (0.36 mm) OD nitinol tube with a wall thickness of approximately 0.002 inches to 0.003 inches (0.05 mm to 0.08 mm). The continuous slots 43 are made using a laser, a grinding cutting wheel, wire EDM machine, etc. This version shows slots 43 fabricated such that each slot is approximately 0.006 inches (0.15 mm) deep and 0.002 inches (0.05 mm) wide, with the centerline of each slot 43 being 0.005 inches (0.13 mm) away from the next slot. The slots may be cut in an advancing angle sequence, with the first slot and the diametrically opposed slots cut at 0 degrees, and then using the first slot angle as a baseline, the next set may be 90 degrees, 10 degrees, 100 degrees, 20 degrees, 110 degrees, and so on. These angles and advances are shown in sections AA through DD.

[0216] The advantage of this type of torque tube is that, like a driveshaft coupler or universal joint, it can transmit torque truly one-to-one around very steep curves. The disadvantage of this type of torque tube is its high manufacturing cost.

[0217] Figure 40 shows another example of a guidewire assembly. This example is similar to the assembly shown in Figure 31. The main difference is that the distal end of the stainless steel core wire 1 is shortened and joined to the nitinol wire 60 using a tube coupler 61 and either laser welding, soldering, or adhesive to complete the joint. The nitinol wire 60 with a diameter of 0.005 inches to 0.007 inches (0.13 mm to 0.18 mm) has the advantage of being very flexible and not twisting even in the steepest bends.

[0218] While these examples illustrate some embodiments of the present invention, it will be understood that many combinations of the mechanical features detailed in these versions can be combined to create more versions that are still encompassed in the spirit of the embodiments of the present invention.

[0219] Examples of sensor and detection technologies As described above, in some embodiments, the measurement unit of an invasive probe can be configured to operate the sensor of the invasive probe to perform electrical impedance spectroscopy (EIS). Figures 4 to 11 illustrate examples of how such a sensor and measurement unit can be arranged and illustrate examples of techniques for the operation of such a sensor and measurement unit. However, it should be understood that embodiments are not limited to operating according to the EIS examples described in this section.

[0220] The techniques described in this section with respect to FIGS. 4-11 enable the discrimination of tissue and / or biological materials of lesions in tubes of animals, including mammals such as humans. "Discrimination" here is understood to mean the possibility of distinguishing lesions of different compositions by determining, for example, one or more types of cells of the lesion (e.g., red blood cells and / or white blood cells, or different types or states of endothelial cells) and / or one or more types of other biological materials of the lesion (e.g., plaque materials such as cholesterol). More generally, the discrimination enabled by the techniques described in this section includes determining at least one item of information regarding the tested lesion. Examples of information that can be determined by these techniques are described below.

[0221] As schematically shown in FIG. 4, the cell discrimination method 10 includes a first step 12 of determining the frequency spectrum of the impedance of the lesion to be tested.

[0222] The spectrum should be understood here to mean a set of pairs of impedance values of the lesion, the latter of which may be complex numbers and may be those of the corresponding frequencies. Thus, this spectrum is discrete and may contain only a finite number of pairs. These pairs can be separated, in particular, by only a few Hz, further by dozens of Hz, and further by hundreds of Hz. However, in other embodiments, the spectrum determined in this step is continuous, quasi - continuous over a frequency band, or discretized. Quasi - continuous should be understood to mean that the spectrum is determined for consecutive frequencies separated by 100 Hz or less, preferably 10 Hz or less, more preferably 1 Hz or less. The frequency band over which the impedance of the tissue is determined extends, for example, from 10 kHz, preferably from 100 kHz. In fact, at low frequencies, the membrane of the tissue / material of the lesion acts as an electrical insulator, and as a result, the impedance is very high and, in particular, hardly changes. Further, the frequency band over which the impedance of the tissue / material is determined extends, for example, up to 100 MHz, preferably up to 1 MHz. In fact, at high frequencies, the walls of the tissue / material constituting the lesion become transparent from an electrical point of view. Thus, the measured impedance no longer represents the biological structure. This spectrum may be the frequency spectrum of the real part and / or imaginary part and / or absolute value and / or phase of the complex impedance of the lesion.

[0223] This first step 12 of determining the frequency spectrum of the impedance of the lesion can be carried out, in particular, as will be described below in connection with FIG. 5.

[0224] First, during step 14, two, preferably three, and more preferably four electrodes are positioned in contact with the lesion to be tested, and the electrodes are connected to an AC current generator. Measurement using four electrodes is preferable because it allows two electrodes to be used to pass current through the lesion to be tested and the potential difference between the other two electrodes to be measured. This can improve the accuracy of the measurement. Next, during step 16, an AC current is applied between the electrodes in contact with the lesion. Then, during step 18, by changing the frequency of the applied current, the corresponding voltage is measured at the electrode terminals for different frequencies. Finally, during step 20, for each frequency at which the measurement is performed, the ratio between the measured voltage and the applied current is calculated. This ratio gives the impedance of the lesion to be tested as a function of the measurement frequency. The calculated ratio makes it possible to define the frequency spectrum of the impedance of the lesion.

[0225] If the spectrum is continuous or pseudocontinuous, in this particular case, as shown in Figure 6, it can be represented in the form of a curve that gives the absolute value of the lesion's impedance as a function of frequency, the latter of which is plotted according to a logarithmic scale. Note that the logarithmic scale is used on the x-axis.

[0226] In step 22 of the discrimination method 10 in Figure 4, different models of lesion impedance, i.e., different electrical circuits capable of modeling the lesion, are selected. Here, a model including a constant phase element, rather than capacitance, is selected. In practice, constant phase elements have been shown to model the behavior of lesions more realistically than capacitance.

[0227] A constant-phase element (or CPE) is,

number

number

number

number

[0228] In the following explanation, a phase-constant element whose impedance is given by the above equation [1a] or [1b] is selected as an example.

[0229] The impedance model of the lesion can be selected from those described below, particularly with respect to Figures 7-10. Clearly, the simpler the model, the simpler the calculation. However, more complex models can correlate better with the impedance spectrum obtained by measurement and therefore give more accurate results.

[0230] According to the first model 24 shown in Figure 7, the impedance of the lesion is modeled by a first resistor 26 connected in series with a parallel connection 28 of a constant-phase element 30 and a second resistor 32.

[0231] In this case, the total resistance of the lesion is Z tot teeth,

number

[0232] Such a model describes particularly well the tissue covering the measurement electrodes, like a set of individual parallel implementations, each individual implementation being composed of a parallel implementation of individual resistances and individual capacitances and a series individual resistance. Such an implementation makes it possible to model the distribution of the time constants across the surface of the measurement electrodes according to different parallel circuits whose parameters can be different, each of these parallel circuits representing different tissue / material of the lesion. Thus, the fact that the tissue / material of the lesion can exhibit different electrical properties, particularly different resistances and / or capacitances, is modeled.

[0233] The second model 34 shown in FIG. 8A complements the model 24 of FIG. 7 by attaching a second phasing element 36 in series. The impedance Z of this second phasing element 36 CPE,2 is also

Number

[0234] Thus, the total impedance Z of the lesion part according to this second model 34 tot is given by the following formula.

Number

[0235] A modification 34' of the second model 34 is shown in FIG. 8B and is different from the model of FIG. 8A by adding a capacitance C in parallel with the circuit of FIG. 8A for a better fit of the impedance curve at high frequencies.

[0236] The third model 38 shown in Figure 9 corresponds to the model in Figure 7 and is connected in parallel with the third resistor 40 of resistor R3. In this case, the total impedance Z of the lesion tot It is given by the following formula.

number

[0237] Finally, a fourth exemplary model 42 is shown in Figure 10. This model 42 includes a first resistor 26 mounted in parallel with a series configuration of the constant-phase element 30 and the second resistor 32, as shown in the figure.

[0238] Total impedance of the lesion Z tot For this model 42, it is given by the following equation.

number

[0239] Next, the discrimination method proceeds to step 44, during which the impedance of the constant-phase element 30 is determined for each model selected in step 22, optimizing the correlation between the lesion impedance model and the spectrum determined in step 12.

[0240] This step of optimizing the correlation between the lesion impedance model and the spectrum determined in step 12 can be implemented by any optimization method known to those skilled in the art. As an example, the least squares method can be implemented, which allows for a practical and relatively simple implementation of this step 44.

[0241] In practice, other parameters of different models, besides the impedance parameters of the constant-phase element, are also determined during this step 44. These parameters may also be useful in obtaining information about the lesion being tested and / or the tissue / materials that comprise it.

[0242] Next, an intermediate step 46 of the discrimination method 10 may be provided. This step 46 is to determine a model that appears to correlate best with the measured spectrum of the lesion's impedance. This best model may, for example, minimize the standard deviation of the measured spectrum. In the following description, it is assumed that model 24 is retained as the one that correlates best with the measured spectrum of the lesion's impedance.

[0243] During step 48, the effective capacitance (or apparent capacitance) of the lesion is estimated from the impedance parameters of the phase-constant element and the corresponding model.

[0244] Theoretically, this effective capacitance represents the set of individual capacitances of elements of the cellular structure. Effective capacitance represents the dispersed local capacitance of elements of the cellular structure. These elements of the cellular structure may be all or part of the nucleus of the cell, or other parts of the cell such as the Golgi apparatus, vesicles, mitochondria, lysosomes, and other elements that may play a role in membrane interactions. Effective capacitance can also be influenced by the cellular geometry and intercellular space. Effective capacitance is a model that allows for the representation of the electrical membrane behavior of some or all of a lesion. This model allows for the proper identification of the tissue / material of the lesion.

[0245] More specifically, this effective capacitance is determined by identifying the impedance of the lesion using a model that includes individual parallel implementations, each of which includes at least one individual resistor and one individual capacitance. Each implementation may include, in particular, a first individual resistor in series with a parallel implementation of individual capacitances having a second individual resistor, and preferably consists of the first individual resistor. These individual implementations are intended to model the behavior of each tissue / material in the lesion. In this case, the effective capacitance is the capacitance that arises from the presence of all individual capacitances in the lesion.

[0246] For Model 24 (or 34 or 34'), the determination of the effective capacitance may be carried out in particular as follows: The impedance of Model 24 with a phase-constant element is compared to the impedance of an equivalent or identical model in which the phase-constant element is replaced by the effective capacitance. More precisely, the calculation of the effective capacitance can be carried out by comparing the real and / or imaginary and / or phase and / or absolute values ​​of the impedance of the model selected for a lesion with a phase-constant element to the identical model in which the phase-constant element is replaced by the effective capacitance.

[0247] For Model 24 (or 34 or 34'), for example, the admittance equation for Model 24, which is directly estimated from equation [3], is given a time constant.

number

number

number

[0248] If a different model of the impedance of a lesion with a constant-phase element is selected, it is possible to determine the corresponding formula for the effective capacitance. To do this, the impedances R1, R2, Z of model 24, 34, or 34' are determined as a function of the parameters of the selected model. CPE and Z CPE,2 It is sufficient to calculate (in the appropriate case) that Model 24, 34, or 34' is electrically equivalent to the model of the lesion's impedance. The effective capacitance can then be calculated by replacing R1, R2, Z0, and α with their corresponding values ​​expressed as functions of the parameters of the selected model.

[0249] Next, the cell identification method 10 proceeds to step 66, which estimates items of information regarding the tissue / material of the lesion from the previously determined effective capacitance.

[0250] This estimation may be performed, in particular, by comparing the effective capacitance value determined in step 48 with a pre-established value. The pre-established value can be obtained, in particular, during a test performed on a tissue of known composition in a known medium and using known test conditions. The pre-established values ​​may be grouped together in a database of effective capacitance values, grouping together the effective capacitance measured for different types of cells and / or different states of different cells and / or different test conditions. The effective capacitance value can be compared to a database of effective capacitance values ​​for cell types and states that are likely to be found in this measurement. For comparison, the effective capacitance Ceff can be used together with other parameters. The comparison does not need to be an exact match and includes determining whether the effective capacitance value falls within a given range.

[0251] Therefore, identifying the tissue / material of the lesion, that is, - Type of tissue and / or other biomaterial within the lesion, - In particular, the composition of lesions when they consist of different types of biomaterials or tissues / cells / other biomaterials in different states. - If the lesion consists of tissue, the types of cells contained in the tissue and / or the number of layers of cells present in the tissue. - If the lesion is composed of other biomaterials such as plaque material, the type of material contained in the lesion, and / or - The state of the cells contained in the lesion, especially if the cells are healthy, inflamed, or degenerated, especially if one or more cancerous cells are present, or if the lesion is infected. It is possible to determine at least one of the information items.

[0252] As an example, Figure 18 shows the effective capacitances 68, 70, 72, and 74 determined in relation to tests conducted according to the method described above, in the form of diagrams.

[0253] In connection with the experiment, cells were cultured until cellular confluence was obtained. In the example experiment performed, two days of culture in an incubator at 37°C and 5% CO2 was required to obtain confluence of the tissues to be tested. The determination of the impedance spectra of the different tissues to be tested was performed using an impedance spectroscopy system. Spectra were determined between 1 kHz and 10 MHz by applying an AC voltage that was estimated to be very low so as not to electrically excite the cells to be studied, but sufficient to obtain accurate measurements. In the example experiment performed, an AC voltage amplitude of 20 mV was maintained.

[0254] The effective capacitance 68 is the capacitance of the static test medium only. This test medium is a cell culture medium. The effective capacitance 70 is the capacitance of bovine aortic endothelial cells (BAECs). The effective capacitance 72 is the capacitance of bovine aortic smooth muscle cells (BAOSMCs). Finally, the effective capacitance 74 is the capacitance of platelets (or thrombi). As this figure shows, the effective capacitances of different cell types show clearly different values ​​from one another, which allows for accurate and effective differentiation of different cell types without the risk of confusion.

[0255] Therefore, one advantage of the above discrimination method is that it enables the discrimination of tissue / material within the lesion in contact with the electrode from a simple measurement of the frequency spectrum of the impedance of the lesion being tested. The results obtained are accurate. There is no need to proceed with normalization of the measured impedance, nor is there a need to perform a reference measurement in the absence of the sample being tested. Thus, this method can be implemented without requiring prior sampling of the cells or cellular structures being tested, and in some embodiments, it can be implemented in vivo.

[0256] It should be noted that when effective capacitance is determined, this single value is often sufficient to distinguish the tissue / material of the lesion. The parameters of the selected model of impedance of the lesion being tested can also be compared to pre-established values ​​to determine the results of the effective capacitance comparison. For example, if the cells of a lesion are inflamed, the junctions between cells will be looser. The resistance at low frequencies, i.e., resistance 32 in model 24, is lower compared to healthy cells. By comparing this resistance value with pre-established values ​​for healthy, non-inflammatory cells, it may then be possible to determine the inflammatory state of these cells.

[0257] It should also be noted that other parameters of the model may be considered to determine the tissue / material of the lesion. However, these other parameters can also allow for the determination of additional items of information about the lesion being examined. For example, the resistances 26 and 32 of model 24, R2 or total R1+R2, may be considered to determine the thickness of the cellular structure when the lesion contains tissue. To do this, the values ​​R2, and possibly R1, are determined simultaneously with the determination of the impedance of the constant-phase elements in particular, so as to optimize the correlation between model 24 and the measured impedance spectrum. The values ​​R2 or total R1+R2 can then be compared to corresponding values ​​predetermined under known conditions, e.g., in vitro. These predetermined values ​​may be stored in a data storage device.

[0258] As mentioned earlier, this method can be easily implemented in the context of devices that can be inserted into animal subjects (for example, into the vascular structures of human subjects).

[0259] As an example, Figure 11 shows an example 100 of a system for implementing the method described above.

[0260] The system 100 essentially comprises means 102 for measuring the impedance of a lesion 104, in this case a monolayer of confluent cells, immersed in a medium 105, for example, blood, and an electronic control unit 106 connected to the measuring means 102 for implementing a method and determining the tissue of the lesion 104 as a function of the measured impedance.

[0261] The measuring means 102 here comprises an alternating current generator 108 connected to two electrodes 110, 112 that are in contact with the lesion 104. The measuring means 102 also comprises a device 114 for determining the intensity passing through the lesion 104, which is linked to the lesion 104 by two electrodes 116, 118 that are in contact with the lesion 104. An electronic control unit 106 is connected to the generator 108 and the intensity measuring device 114 so that, for example, the impedance of the lesion 104 can be determined from the measurement of voltage and intensity at the terminals of electrodes 110, 112, 116, 118.

[0262] The electrodes 110, 112, 116, and 118 are made of a conductive material such as gold.

[0263] Herein, advantageously, the measuring means 102 further comprises a medical device 120, in this case an invasive probe, which can be inserted into an animal subject. In this case, electrodes 110, 112, 116, 118, an AC voltage generator, and an intensity measuring device can be fixed onto this medical device. The medical device is, for example, as described in application FR3026631 A1 MEDICAL DEVICE PROVIDED WITH SENSORS HAVING VARIABLE IMPEDANCE, filed on 3 October 2014, and its entire contents, in particular the description of the implantable medical device including the measuring device, are incorporated herein by reference.

[0264] In this case, the AC power generator 108 may include an armature such as an antenna electrically isolated from the body of the medical device or the body of the medical device, adapted to emit current under the influence of an electromagnetic field emitted by an interrogation unit outside the stent 120. The electrodes can form a sensor having variable impedance, the impedance of which changes as a function of the cellular structure covering the electrodes. Finally, the electronic control unit can receive items of information regarding the impedance between the electrodes, particularly by the emission of a magnetic field by an antenna fixed on the body of the implantable medical device 120.

[0265] Therefore, the stent 120 may allow for checking the precise progress of endothelial healing after the stent 120 has been implanted. In fact, such a stent 120, in cooperation with an electronic control unit, can enable the determination of whether the cellular structures formed on the surface of the endothelium essentially consist of healthy endothelial cells, inflamed endothelial cells, smooth muscle cells, and / or platelets by implementing the method shown in Figure 4.

[0266] The present invention is not limited to the examples described above, and numerous modifications are possible within the scope of the definitions given by the appended claims.

[0267] Therefore, for example, in step 22, it is possible to select a single model of the lesion's impedance. In this case, it is not necessary to perform optimization for multiple models. Thus, this method is simpler and faster to implement in this case. In particular, it is possible to proceed in this way when the model is considered more appropriate.

[0268] Furthermore, in some of the examples described, tissue / material discrimination is essentially based on a comparison of the calculated effective capacitance with a pre-established value. However, as a variation, it is possible to proceed with tissue / material discrimination from the parameters of a selected model of the lesion's impedance. However, simply comparing the effective capacitance values ​​is simple and appears to allow for reliable cell discrimination.

[0269] Figure 19 shows an example of a system 300 fabricated according to an aspect of this disclosure. This system includes a measurement module 301 which may be part of an implanted device, such as a stent, or a device for in vitro culture of cells.

[0270] The measurement module may have at least two electrodes and may be as described above with reference to Figure 11.

[0271] The system 300 also includes an internal processing unit 302 configured, for example, to generate an impedance spectrum from data from a measurement module.

[0272] The system 300 may include an emitter 303 for wirelessly transmitting data (data from the measurement module 301 and / or impedance spectrum determined by the internal processing unit 302) to a receiver 304, the receiver of which may be external if the measurement is performed in vivo. Transmission may be performed under any wireless protocol, such as RFID, NFC, Bluetooth, WiFi, radio, or infrared, among others. In some embodiments, transmission may include transmission over one or more wired and / or wireless local and / or wide-area communication networks, including the Internet.

[0273] System 300, based on the received data, calculates the impedance spectrum (when receiving data from the emitter 303 to the measurement module 301) and / or various parameters and effective capacitance C. eff An external processing unit 305 for calculating Ceff The system may include a display means 306, such as an LCD screen, for displaying information about the cell type and / or state determined based on a comparison of a value representing the cell type and / or state with reference data. To determine various parameters and effective capacitance, the external processing unit 305 is configured with information about one or more equivalent circuit models for impedance and can determine at least one parameter of the model(s) in the manner described above. The external processing unit 305 can also be configured, as described above, to select one of the models(s) as the model for determining the effective capacitance following the determination of the model(s) parameters. The external processing unit can make the selection based on the degree of fit between the equivalent circuit model and the impedance spectrum. Based on at least one type and / or state of the cells thus identified, the system can provide information representing the progress of the healing process, for example, information about the current state of the treated area (e.g., tissue) (including the positioning of implants such as stents), and / or information about changes in the status of the area over time that may reflect the response to the treatment within the area, such as a healing or scarring response.

[0274] The external processing unit may be a dedicated device including dedicated hardware such as an ASIC, EEPROM, or other components specifically configured to perform the operations of the external processing unit described above. In other embodiments, the external processing unit may be a general-purpose device such as a laptop or desktop personal computer, a server, a smart / mobile phone, a personal digital assistant, a tablet computer, or other computing device. When the external processing unit is implemented using a general-purpose device, the general-purpose device may include one or more processors and a non-temporary computer-readable storage medium (e.g., instruction registers, on-chip cache, memory, a hard drive, a removable medium such as an optical medium) on which instructions for execution by the processor(s) are encoded, causing the processor(s) to perform the operations described above as being performed by the external processing unit. In some embodiments, the internal processing unit may be any suitable IC chip or other hardware component with processing capabilities. External and internal processing units may be located in close proximity to each other (e.g., in the same room or within 5 feet), such as when the external processing unit is implemented in a server and data is transmitted over one or more networks or the Internet, or they may be located far apart from each other (e.g., in different parts of a building or building complex) or geographically far apart (e.g., several miles apart).

[0275] In a modified example, as shown in Figure 20, part of the processing is performed on a remote server 310 to which data is transmitted, for example, via the Internet.

[0276] Examples Figure 25 shows a collection of amplitude and phase impedance spectra measured for three cell types, namely platelets, smooth muscle cells, and endothelial cells.

[0277] Comparative Example Firstly, an equivalent circuit model without CPE is used, consisting of a solution resistance in series with R0Cmix and a double-layer capacitance Cdl in series (with the R0 resistor in parallel with the Cmix capacitance).

[0278] Next, the Cmix parameter, which describes the effect of the cell layer on complex impedance, is calculated.

[0279] Figure 26A shows the distribution of Cmix for two cell types. It is possible to distinguish between the two cell types. However, when a third cell type is added, as shown in Figure 26B, the three cell types are no longer distinguishable.

[0280] Using a more advanced approach, if we implement the CPE elements into an equivalent circuit model, for example, using Model 34 shown in Figure 8A, there are six parameters that describe the system: R0, Rinf, Q0, β, Qdl, and α.

[0281] These parameters can be calculated so that the impedance of the equivalent circuit model best fits the experimental impedance spectrum curve in Figure 25.

[0282] Next, as shown in Figures 27A to 27F, the distribution of each parameter for the three cell types can be displayed.

[0283] For each parameter, it is not possible to clearly distinguish between the three cell types, and therefore, a linear combination of these parameters cannot provide the desired cell classification.

[0284] Examples Figure 28 shows the distribution of values ​​representing the effective capacitance Ceff for the three cell types, determined based on the above equation [8].

[0285] It is possible to clearly distinguish all three cell types. The accuracy is over 90%. Cell differentiation is significantly improved compared to Figures 27A-27F.

[0286] If the equivalent circuit is circuit 34' in Figure 8B, the Ceff distribution shown in Figure 29 is obtained.

[0287] If we assume that R0-Rinf is large with respect to Rinf, then equation [8] can be simplified to Ceff=(1-α) / α.

[0288] The distribution of the obtained Ceff is shown in Figure 30. It can be seen that the three cell types can still be distinguished with an accuracy of approximately 85%.

[0289] The distributions shown in Figures 28-30 can serve as reference data for cell type determination.

[0290] For example, the impedance spectrum may be measured under similar conditions to the impedance spectrum in Figure 25, and the values ​​of the parameters R0, Rinf, Q0, β, Qdl, and α are determined based on this spectrum. This determination can be based on least-squares fitting of the amplitude and phase impedance curves using the equivalent circuit model 34 in Figure 8.

[0291] Next, given the parameter values ​​R0, Rinf, Q0, and α, the effective capacitance Ceff can be calculated, and by comparing this value with the distribution in Figure 28, it can be determined which cell type it corresponds to. For example, a low value of Ceff in nF / cm2 indicates that the cell is type 1, a value of approximately 50 to 100 indicates that the cell is type 3, and a value greater than approximately 100 indicates that the cell is type 2.

[0292] How to operate medical devices Examples of medical devices, sensors, and methods for detecting lesion tissue / material are described in detail above with respect to Figures 2 to 11. Examples of technologies that may be implemented by and / or operated by such medical devices are described below with respect to Figures 12 to 16.

[0293] Figure 12 illustrates a process 1200 that may be carried out by a medical device operating according to some of the techniques described herein. The medical device in the example of Figure 12 may be a medical device in which the invasive probe may include only a single sensor that may include one or two electrodes. As can be understood from the foregoing description, a limited amount of information about a lesion may be determined from a single sensor compared to multiple sensors arranged along an invasive probe (for example, in the example of Figure 3). In the example of Figure 12, the sensor of the invasive probe may be located within a treatment device such as within a suction catheter and a stent retriever, and / or within a guidewire inserted before insertion of the suction catheter or stent retriever. The medical device may generate treatment recommendations based on the characteristics of the lesion(s) determined using the sensor.

[0294] Process 1200 begins in block 1202, in which a sensor attached to a guidewire is operated to detect one or more characteristics of a lesion adjacent to the sensor. Prior to the start of process 1200, an invasive probe of the guidewire, of which the sensor is part, may be inserted into the animal's vascular structure and moved in close proximity to the predicted location of the lesion. The sensor is then operated to detect when the sensor makes contact with the lesion. Contact with the lesion may be determined by evaluating the change in value over time of the value output by the sensor. For example, the sensor may output one value when it comes into contact with blood, which may be when the sensor is positioned in the middle of a blood vessel in an area not occluded by a lesion. As the invasive probe is moved forward until it makes contact with the lesion, the value output by the sensor may change as contact is made. In this way, the location of the lesion can be determined using a single sensor. The sensor may also be operated to determine the length of the lesion, for example, by continuing to advance the invasive probe until the sensor is no longer in contact with the lesion and the output value returns to the value associated with contact with blood.

[0295] In the example in Figure 12, using only a single sensor, the medical device may not understand the composition of the lesion and may not be able to provide treatment recommendations regarding which treatment option may be best for treating a particular lesion. However, the medical device may be able to generate information about the progress or success of the treatment, which can be used to determine whether the selected treatment option is being carried out correctly. Based on this information, the medical device can generate treatment recommendations regarding whether to change the treatment being performed to another treatment.

[0296] In one treatment protocol, which may be implemented in embodiments such as those shown in Figure 12, a suction catheter may be used as a first option for treating a lesion. Thus, in block 1204, the suction catheter is positioned close to the invasive probe of the guidewire and is inserted into the vascular structure until it is positioned close to the lesion. In some embodiments, the guidewire may not be inserted initially; rather, the suction catheter may be inserted in block 1202 until it is positioned close to the lesion. In such cases, a sensor may be a component of the suction catheter. Embodiments are not limited to this.

[0297] In block 1204, after positioning the aspiration catheter close to the lesion, the aspiration catheter is manipulated to attempt to aspirate the lesion into the catheter. After a certain period of time, sensors on the guidewire and / or aspiration catheter may be operated to determine whether the aspiration catheter is affecting the lesion. Some lesions, such as hard lesions, may not be aspirable using the aspiration catheter. Other interventions (such as a stent retriever) may be used for these lesions. Therefore, in block 1204, in addition to manipulating the aspiration catheter to attempt aspiration, sensors may be operated to determine whether a change has been observed in the lesion. This may be done, for example, by positioning a sensor within the lesion, such as the portion of the lesion closest to the aspiration catheter, prior to the initiation of aspiration, and after a certain period of time, determining whether the value output by the sensor indicates that the sensor is no longer in contact with the lesion (or rather, in contact with blood, for example).

[0298] If, during the operation of the aspiration catheter, (and potentially as a result thereof), the sensor is no longer in contact with the lesion, a determination may be made in block 1206 that the lesion is being aspirated. In this case, a treatment recommendation may be generated, and an output may be produced indicating that the aspiration catheter appears to be successfully treating the lesion and that continued operation of the aspiration catheter is recommended. In the example in Figure 12, process 1200 then terminates. However, it should be understood that in some embodiments, continuous determination over time may be made as to whether the aspiration catheter is continuing to successfully treat the lesion, so that a change may be recommended where appropriate, or so that a determination may be made when the lesion is completely aspirated.

[0299] However, if the value output by the sensor has not changed during aspiration, indicating that aspiration is not affecting the lesion, a treatment recommendation may be generated indicating that the aspiration catheter is no longer recommended, and instead, another treatment option is recommended. In the example in Figure 12, the second option for treating the lesion may be a stent retriever. Therefore, in block 1208, a recommendation to use a stent retriever may be output. In block 1210, the lesion can be treated by operating the stent retriever to remove the lesion with the stent retriever. For example, the stent retriever may be inserted until it is positioned in close proximity to the lesion. In some embodiments, as described above, the sensor on which detection is performed may be a component of a guidewire separate from the treatment device. In such cases, the stent retriever may be inserted along the guidewire following the removal of the aspiration catheter until the stent retriever is positioned in close proximity to the lesion (or, following the removal of the guidewire, along a microcatheter inserted along the guidewire). In another example, the sensor may be integrated with the stent retriever and may detect when the stent retriever is positioned in close proximity to the lesion. Medical devices can generate therapeutic recommendations regarding the positioning of a stent retriever for lesion removal through values ​​generated using sensors. For example, a sensor may be used to detect when an invasive probe traverses a lesion and the distal end of the invasive probe is positioned beyond the lesion, as described above. To help ensure that the lesion is completely captured by the stent, it may be best to position the stent retriever across the lesion so that one end of the stent protrudes beyond the lesion. Thus, therapeutic recommendations regarding proper stent positioning can be made by operating the sensor to detect beyond the lesion and recommending that the stent retriever be inserted until the stent or sensor extends through the lesion.

[0300] Process 1200 ends when the stent retriever is operated to remove the lesion in block 1210.

[0301] Figure 13 shows an example of a method for operating a medical device to generate treatment recommendations for a lesion, according to another embodiment. In the embodiment of Figure 13, the invasive probe may include a plurality of sensors arranged along the outside of the probe, as in the example of Figure 3 described above. As can be understood from the foregoing, using such an array of sensors, several different characteristics of the lesion, including the composition of the lesion, may be determined. For example, the composition of the lesion may be determined, as described above, by performing an EIS process on the lesion. The composition of the lesion may indicate different biomaterials present within the lesion, such as different tissues or cells, or other biomaterials such as plaque material. In some such embodiments, for example, each sensor (e.g., two electrodes of each sensor) may be in contact with the biomaterial of the lesion, and some sensors may be in contact with different biomaterials of the lesion than the others. Next, each sensor can be operated according to the techniques described herein to determine the impedance spectrum of the biomaterial that the sensor has contacted. Then, using this set of impedance spectra, the composition of the lesion can be determined, for example, by identifying different biomaterials present within the lesion. This compositional information may be similar to information that can be determined by performing histology on the lesion. The characteristics of a lesion may be determined as a whole by identifying (e.g., diagnosing) the type of lesion from the different impedance spectra of the lesion and / or the different biomaterials present within the lesion (e.g., different tissues or plaque materials).

[0302] For example, by performing the EIS process on different biomaterials of a lesion, it is possible to determine whether any of the following cells or tissues are present in the lesion: platelets, fibrin, thrombi, red blood cells, white blood cells, smooth muscle cells, elastic fibers, external elastic membranes, internal elastic members, loose connective tissue, endothelial cells, or any other tissue of the intima, media, or adventitia. Furthermore, by performing the EIS process on the lesion, the relative amounts of each of the present cells or tissues can be determined. In a simple example, it may be determined that a lesion consists of 50% red blood cells, 30% fibrin, and 20% platelets. From this information, the lesion can be classified as a specific type of lesion from a set of lesions, for example, by diagnosing the lesion as one type of lesion rather than another type of lesion.

[0303] Process 1300 in Figure 13 begins in block 1302, in which an invasive probe of a medical device is inserted into the vascular structure of an animal subject and operated to detect one or more characteristics of the lesion, including the composition of the lesion. Based on the characteristics, including the composition, the medical device can select a treatment option to recommend in block 1304. The medical device can select a treatment option in any preferred manner, including by the techniques described below in relation to Figures 14-15B.

[0304] The treatment option may be selected based on the composition of the lesion. For example, if the composition of the lesion indicates that it consists of smooth muscle tissue rather than a thrombus, the medical device may determine that stent implantation is the recommended treatment. This may be because the lesion does not consist of extractable cells / material, but rather intravascular proliferation. As another example, if the composition of the lesion indicates that it is a soft lesion, such as a soft lesion consisting of a newly formed thrombus, the medical device may recommend an aspiration catheter. This may be because the soft lesion can be aspirated. As yet another example, if the composition of the lesion indicates that it is a hard lesion, such as a hard blood clot, the medical device may recommend a stent retriever because the hard lesion is less likely to be successfully aspirated.

[0305] Once a treatment is recommended in Block 1304, the medical device may monitor the performance of the selected treatment option in Block 1306. The medical device may monitor the treatment using one or more sensors, such as one or more sensors characterized in Block 1302, or one or more sensors of a treatment device operated to perform the treatment. For example, in some embodiments, following the recommendation in Block 1304, the clinician may insert another device (e.g., a suction catheter, stent retriever, etc., as needed) into the vascular structure of the subject, and the other device may include an invasive probe having a sensor arrangement as described herein. In such an embodiment, the medical device may monitor the performance of the treatment using the sensors of the invasive probe of the other device.

[0306] Monitoring of treatment in block 1306 can generate information regarding the status and / or progress of treatment. For example, if treatment is performed using an aspiration catheter, monitoring may generate information regarding the extent to which the lesion has been aspirated and / or the remaining amount of lesion to be aspirated. Progress may be monitored, for example, by the medical device periodically or occasionally inflating a structure (e.g., a stent-like mesh in Figure 3) to bring the remaining portion of the lesion into contact with sensors and determining the extent of the remaining lesion. After the determination has been made, the structure may be removed to continue aspirating the lesion. On the other hand, if treatment is performed using a stent retriever, monitoring can generate information regarding the extent to which the stent has fused with the lesion during stent inflation. For example, by monitoring sensors along the outside of the stent (e.g., using the arrangement of sensors on the stent as in the example in Figure 3), it may be determined whether each portion of the stent corresponding to each sensor has fully expanded into the lesion. This determination may be made in any preferred manner, including monitoring the change over time of the values ​​generated by each sensor and determining when the value of each sensor has stopped changing. When each sensor stops changing its value, this can indicate that there were no further changes in the interaction between the lesion and the stent, and therefore the stent has fully expanded into the lesion, and the lesion has healed around the stent.

[0307] Making such decisions can assist in the performance of treating the lesion. Therefore, in block 1308, information regarding the status of treatment is output by the medical device via the user interface for presentation to the clinician. In addition, in block 1310, the medical device can generate one or more treatment recommendations regarding how to carry out the treatment. For example, as described above, if the medical device determines that the lesion has completely fused with the stent during the operation of the stent retriever, the medical device may output a treatment recommendation to begin stent removal.

[0308] If the treatment is successfully performed, process 1300 will end.

[0309] While an example of monitoring treatment is given in the context of generating treatment recommendations, it should be understood that similar techniques may be used to present clinicians with error messages or other messages regarding the status of treatment. For example, if a sensor on a treatment device indicates the presence of a lesion over a period of time, and then the sensor no longer detects the lesion, the medical device may determine that the treatment device is improperly positioned or that the lesion has been lost. This may indicate that the device needs to be repositioned, or potentially more problematically, that the lesion has become embolized. Messages to clinicians via the user interface may indicate such potential problems.

[0310] In addition, while the example in Figure 13 illustrates how a medical device can be operated to provide treatment recommendations related to the initial selection of treatment and subsequent methods of performing that treatment, it should be understood from the foregoing that embodiments are not limited thereto. For example, in some embodiments, a medical device may include one or more sensors as described herein and may be operated to generate treatment recommendations regarding how the device operates without generating initial recommendations for using the device. For example, as described above, a stent retriever or aspiration catheter may include one or more sensors for generating data regarding the status or performance of treatment and may generate treatment recommendations. As another example, a guidewire for the treatment of chronic total occlusion (CTO) may generate information about the tissue / material in contact with the sensor and generate treatment recommendations. In CTO procedures, the guidewire may be inserted through smooth muscle tissue or vascular plaque when it is not possible to penetrate the coagulated thrombus. Based on the detected characteristics of the tissue / material in contact with the sensor, treatment recommendations can be made when the guidewire can be positioned and advanced against the smooth muscle tissue, and when the guidewire has advanced through the endothelial tissue and is again in the blood vessel on the other side of the lesion. In addition, in some embodiments, one or more measurements of smooth muscle tissue thickness or other characteristics of the vessel wall may be taken to provide information about the risk of the guidewire puncturing the tissue rather than navigating through it. For example, if the measurement indicates thinning of the smooth muscle tissue on one side of the invasive probe of the guidewire, this may indicate that there is a risk of the invasive probe puncturing the vessel wall. Treatment recommendations may be made to proceed more slowly and / or to withdraw the guidewire, or alternative recommendations may be generated.

[0311] Those skilled in the art will understand from the description herein that there are various methods by which a medical device may be configured to generate treatment recommendations based on the characteristics of a lesion and / or the status of treatment. Figures 14–15B show examples of techniques that may be used to generate treatment recommendations.

[0312] Figure 14 shows process 1400, which may be implemented by a medical device in some embodiments for generating treatment recommendations.

[0313] Process 1400 begins in block 1402, in which the medical device receives one or more characteristics of a lesion. The medical device may receive characteristics from components of the medical device, for example, by using one or more sensors included in the medical device's invasive probe, and / or by another component (e.g., a lesion analysis facility) that generates characteristics based on data generated by the sensors. In some embodiments, the characteristics may include the composition of the lesion. In addition, or alternatively, the characteristics may include the location of the lesion in the body, one or more dimensions of the lesion (e.g., length, thickness, etc.), the temperature of the lesion, or other information that can be determined based on the type of sensor described above.

[0314] In block 1404, the medical device compares the characteristics(s) received in block 1402 with one or more conditions for one or more treatment options. The medical device may be configured with information on several different available treatment options, each of which may be associated with one or more conditions relating to one or more characteristics of the lesion. For example, the medical device may consist of one or more conditions for treating the lesion by stent implantation, one or more different conditions for the use of a suction catheter, and one or more further different conditions for the use of a stent retriever. Examples of such conditions relating to the composition of the lesion are described above in relation to Figure 13.

[0315] A medical device can compare the characteristics of a lesion(s) with conditions to determine which conditions are met. In some embodiments, the set of conditions for treatment options may be mutually exclusive, such that a lesion may satisfy only one set of conditions, and therefore only one treatment option may be selected. In other embodiments, the set of conditions may not be mutually exclusive, and the medical device can determine which treatment option to recommend by identifying the one that best satisfies the corresponding condition, or the one that most closely satisfies the corresponding condition (for example, if a condition is associated with a range of values, the condition that most closely matches the range, for example, by the value falling in the middle of the range).

[0316] In block 1406, based on the comparison, the medical device can output a recommendation of treatment options via the medical device's user interface, and process 1400 ends.

[0317] Process 1400 is described in relation to generating initial treatment recommendations for the treatment of a lesion based on the characteristics of the lesion, but those skilled in the art will understand how to extend the technique to generating treatment recommendations during the course of treatment, as described above in relation to block 1310. For example, in some embodiments, based on a comparison of the characteristics of the lesion (e.g., the composition of the lesion) with one or more conditions of specific parameters of treatment, such as the rate at which a stent retriever removes the stent, the medical device may output recommendations regarding such parameters.

[0318] Those skilled in the art will understand that there are some methods for setting conditions for therapeutic options that may be used in connection with a process such as process 1400 in Figure 14. For example, values ​​of lesion characteristics for use as conditions can be hardcoded into a medical device following at least some experiments, and a correspondence between the values, the type of lesion, and successful treatment with various therapeutic options can be determined. However, the inventors have recognized and understood the advantages of a system for learning such relationships and conditions based on information, among other information, about lesion characteristics and successful treatment of the lesion. For example, machine learning processes, such as those that may include feature extraction and / or classification, may be implemented in some embodiments.

[0319] Figures 15A and 15B illustrate examples of machine learning processes that may be implemented in some embodiments. Figure 15A shows a process that may be implemented by a medical device, while Figure 15B shows a process that may be implemented by a computing device (e.g., a server) that communicates with multiple different medical devices.

[0320] Process 1500 in Figure 15A begins in block 1502, in which the medical device generates information about the characteristics of the lesion. In blocks 1504 and 1506, the medical device can make recommendations regarding treatment options based on a comparison of the lesion characteristics with the conditions of the treatment options, as well as monitor the progress of treatment and generate status information throughout the treatment. These operations in blocks 1502-1506 can be implemented in the same manner as described above with respect to Figures 13-14, and therefore, for the sake of brevity, will not be described further. In addition, in block 1506, the medical device can generate information about the treatment outcome. The treatment outcome may indicate whether the treatment of the lesion was successful, whether the lesion was removed and released into the subject's body, whether multiple treatments were required, or other information indicating the outcome. Information indicating the outcome can be generated using sensors in the medical device, as can be understood from the foregoing. For example, using data generated by an accelerometer in the handle of the medical device, the medical device may determine whether multiple operations were performed to remove the lesion. As another example, as mentioned above, if the sensor stops detecting a lesion after having detected it, this could be an indicator that the lesion has moved within the subject, including that the lesion has been removed and become an embolism.

[0321] In block 1508, the information generated in blocks 1502-1506 is transmitted from the medical device to a computing device via a network including one or more wired and / or wireless communication connections and / or the Internet. In some embodiments, the computing device may be geographically distant from the medical device. In block 1508, following the transmission in block 1506, the medical device receives one or more updated conditions for treatment options from the computing device (for example, via the network(s) through which the information was transmitted in block 1508). The updated conditions allow for the identification of new values ​​for evaluating the conditions regarding the characteristics of the lesion. The medical device can be configured to apply one or more updated conditions for generating treatment recommendations, for example, by considering one or more updated conditions in the context of a process as described above in relation to Figure 14. Once the medical device is configured with the updated conditions, process 1500 ends.

[0322] Figure 15B illustrates a process that may be implemented by a computing device to perform a learning process on reports of lesion treatment to generate conditions for use in selecting treatment recommendations, such as through the process described above in relation to Figure 14. Specifically, in the example of Figure 15B, the computing device analyzes reports of lesion treatment in relation to information about the characteristics of those lesions so as to identify relationships between successful (and / or unsuccessful) treatments and the characteristics of those lesions. Through identifying such relationships, conclusions may be drawn about which treatment options are best for a particular type of lesion, and based on these conclusions, treatment recommendations for treating a particular lesion can be generated based on the characteristics of that lesion, as in the example of Figure 14. Similarly, as described above, recommendations on how to perform a treatment (e.g., the time or speed of stent removal during stent retrieval) can be determined based on information about the status or performance of the treatment. While the example of Figure 15B is described in the context of generating conditions for initial selection of treatment options for use on a lesion based on the characteristics of the lesion, those skilled in the art will understand from the following description how to extend the technique to be used together with generating recommendations on how to perform a treatment.

[0323] The inventors recognize and understand that the generation of such conditions and the identification of the relationship between successful / failed treatments and lesion characteristics can be favorably determined using machine learning processes. Various machine learning algorithms are known in the art and can be adapted for use in this context. Some classification algorithms can operate on feature extraction and machine learning techniques, where groups (classifications) of units are identified, and an analysis of the unit characteristics is performed to determine which characteristics and / or the values ​​of those characteristics best correspond to the correct membership in the group, or to predict the correct membership in the group. Based on these identified characteristics, subsequently received unclassified units having such characteristics can be “classified” into one of the groups / classifications based on a comparison of the characteristics and / or the values ​​of the characteristics of the unclassified units with the characteristics / values ​​of each group. In some machine learning applications, groups / classifications can be identified manually during the configuration of the machine learning process. In addition, or otherwise, groups / classifications can be determined or adjusted over time by the machine learning process, such as through the creation of new groups / classifications when the machine learning process perceives, through its analysis, that a new grouping can better characterize some units. A complete explanation of machine learning is outside the scope of this document and is not necessary for understanding the techniques described herein. Those skilled in the art will understand how to implement machine learning techniques for use with the information and objectives described herein.

[0324] Here, a group may be defined as a treatment option or treatment outcome, as illustrated in Figure 15B. In this case, a group may be defined by the characteristics of a lesion and / or the status of treatment. In this case, when the characteristics of the lesion and / or the status of treatment match the characteristics of the group, the corresponding treatment option may be selected for output. In addition, or alternatively, in some embodiments, a group may be associated with different types of lesions (each type having one or more characteristics or ranges of characteristics that differ from other types) and / or statuses of treatment, and these different groups may then be associated with a method of operating a particular treatment option or treatment device. In the latter case, when the characteristics of a particular lesion or status of treatment match the group, the corresponding treatment recommendation(s) for the group may be selected for output.

[0325] Process 1520 in Figure 15B begins in block 1522, and a learning facility running on one or more computing devices receives multiple reports over time regarding the treatment of a lesion by a medical device. The medical device may be a medical device operating according to the embodiments described above. The reports may include information about the treated lesion, such as one or more characteristics of the lesion. The reports may also include information about how the lesion was treated, such as one or more therapeutic devices operated to treat the lesion and how those lesions were treated. Information about the treatment outcome, such as whether the treatment was successful, whether multiple treatments were required, whether the lesion was removed and whether it became embolized, or other outcomes, may also be included in the reports.

[0326] The report may include information determined by one or more sensors of the medical device, including examples of the types of sensors and information described above. As described above, various types of sensors, including one or more electrical, mechanical, optical, biological, or chemical sensors, may be included in the embodiment. Specific examples of such sensors include inductance sensors, capacitance sensors, impedance sensors, EIS sensors, electrical impedance tomography (EIT) sensors, pressure sensors, flow sensors, shear stress sensors, mechanical stress sensors, deformation sensors, temperature sensors, pH sensors, chemical composition sensors (e.g., O2 ions, biomarkers, or other compositions), acceleration sensors, and motion sensors. It should be understood that various types of characteristics or other information may be generated from these sensors. Any of this information may be included in the report and used in process 1520 to generate conditions associated with treatment recommendations. For example, as described above, an accelerometer placed in the handle of the medical device may be used to track the movement of the medical device and determine whether multiple treatments have been performed to treat a blood clot. As another example, a force sensor may indicate the force required to remove a stent retriever, or a set of impedance sensors may determine whether a lesion is partially or completely separated from the stent during removal, based on whether the impedance detected by one or more sensors on the stent of the stent retriever changes over time during removal. Those skilled in the art will understand from the above description the different types of data that may be generated by sensors in a medical device for inclusion in such a report.

[0327] The report may also include information that can be entered by a clinician or retrieved from another system that the medical device can interoperate with. For example, the report may include information about the location of the lesion within the anatomical structure of the subject, such as whether the lesion is in the cranial artery, femoral artery, pulmonary vein, common bile duct, or other duct. This information may be entered by a clinician via a user interface or retrieved from another system, such as an angiography device.

[0328] Upon request, the report may include patient information such as age, medical history, and demographics.

[0329] Reports received in Block 1522 may be received over time from multiple medical devices that may be geographically dispersed. By receiving these reports and their contents over time, a set of conditions and treatment recommendations that define recommendations or best practices may be generated.

[0330] Therefore, in block 1524, the learning facility analyzes the information in the report to identify the relationship between lesion characteristics (and / or the way the treatment device operates), the options for treating lesions having those characteristics, and successful treatments. Based on this analysis, the learning facility can learn the relationships between these pieces of information. Such relationships can indicate when a particular treatment option was successful or unsuccessful, or when different treatment options were successful or unsuccessful for which types of lesions. In at least some embodiments where patient information is available, the learning facility can learn the relationship between lesion characteristics, the options for treating lesions having those characteristics, and successful treatments based on patient information. The model can be trained to learn which specific pieces of information obtained about the patient may influence the probability of treatment success. For example, a trained model may identify that a particular treatment is likely to have different success probabilities depending on the patient's age, even if all lesion characteristics are equal. Therefore, different treatment recommendations can be provided for two patients with the same lesion but different ages. As another example, a trained model can learn that, even if the type of lesion is the same, some treatments are less likely to succeed when applied to subjects who have previously suffered from a particular disease compared to subjects who have not suffered from that disease.

[0331] Based on this analysis in block 1524, the learning facility (through the feature extraction and classification processes of the machine learning process) can generate conditions for each of the treatment options in block 1526. The conditions can be associated with lesion characteristics so as to indicate different characteristics or ranges of characteristics of lesions that can be successfully treated with each treatment option. For example, the conditions may be associated with a range of values ​​for the viscoelastic properties of a lesion, where one range of viscoelasticity may be associated with treatment using a suction catheter, and another range of viscoelasticity may be associated with treatment using a stent retriever. In this way, when a lesion with a particular viscoelasticity is detected, it can be determined which treatment option to recommend for that particular lesion using comparisons with these conditions (as in the process in Figure 14).

[0332] In block 1528, once conditions are generated in block 1526, the conditions may be delivered to a medical device, as described above in relation to Figure 15A, so that the medical device may be configured to use those conditions to generate treatment recommendations. Once the conditions are delivered, process 1520 terminates.

[0333] Process 1520 is described as a discrete process in Figure 15B, but it should be understood that in some embodiments, the receiving of reports and the determination of conditions may be processes that are repeated over time, including continuous or discrete intervals. Therefore, in some embodiments, process 1520 may be performed multiple times, or following the delivery of conditions in block 1528, the learning facility may return to block 1522 to receive additional reports and continue the learning process.

[0334] Examples of devices and processes for providing feedback to a clinician during the diagnosis and / or treatment of a lesion, including providing treatment recommendations during the diagnosis and / or treatment of the lesion, are provided above. In some embodiments, in addition to, or as an alternative to, providing such feedback during diagnosis and / or treatment, the medical device may be configured to present information regarding the diagnosis and / or treatment to the clinician following the operation of the medical device in diagnosis / treatment. Figure 16 illustrates an example of such a process.

[0335] Process 1600 is initiated in blocks 1602 and 1604, during which the medical device operates to generate information regarding the characteristics of the lesion and the performance of the treatment, as well as recommendations on how to carry out the treatment. The operation of blocks 1602 and 1604 may be similar to the data generation examples described above.

[0336] In block 1606, following treatment, the information generated in blocks 1602 and 1604 is used by the history generation facility to generate a treatment history. The treatment history may include information on how the device behaved over time, what characteristics of the lesion were detected, what recommendations were made by the medical device, and whether those recommendations were followed by the clinician. For example, if an error is detected in treatment, such as the formation of an embolism or the loss of part or all of the lesion resulting in the need for subsequent treatment, the history generation facility can analyze the error to determine its cause. For example, if a sensor detects at once that part of the lesion has separated from the stent retriever, and another sensor records a sudden application of force to the stent retriever in the time immediately preceding this, the history generation facility can record this in the history. If the force applied to the stent retriever exceeds the maximum force recommendation value from the medical device, or if the medical device is operated in any other way that does not conform to the treatment recommendation value, this can be recorded in the history. When such information is included in the history, recommendations can be made to the clinician on how to avoid errors in future procedures.

[0337] In addition, in some embodiments, the history generation facility can include detailed information about the lesion and its potential cause in the history to assist clinicians in diagnosing the lesion. For example, in some embodiments, a brief characterization of the lesion may be output during treatment (e.g., the lesion is viscous), while the history can output more detailed information about its composition (e.g., the lesion consists mainly of cholesterol). In addition, the history generation facility can analyze the composition in relation to the location of the lesion in the subject to determine whether the lesion was the result of, for example, injury, a thrombus that developed at the site of the lesion, or an embolism that blocked the site of the lesion. For example, if the lesion is mainly composed of smooth muscle cells or tissue such as atheroma, the lesion may be a post-injury growth. As another example, if the composition of the lesion indicates that the lesion formed in an area of ​​anatomical structure with high shear stress, but the lesion is located in an area of ​​anatomical structure with low shear stress, this may indicate that the lesion was an embolism that blocked that site.

[0338] Once the history is generated in block 1606, the history is output for presentation to the user (e.g., via a display, stored in memory, or transmitted over a network), and process 1600 terminates.

[0339] Examples The following are various examples of scenarios in which medical devices and technologies may be used. However, it should be understood that the embodiments are not limited to operating according to any one of these examples.

[0340] Example 1 One example of how the technologies described herein may be used is the use of an invasive smart guidewire. The invasive guidewire may be used to navigate the vascular system. Using the sensor and analytical techniques described herein, the invasive guidewire may characterize the tissue / material it is in contact with and communicate the properties of this tissue / material to the clinician. The invasive guidewire may also help additional devices reach the intervention site within the patient.

[0341] In this example, the guidewire comprises a sensor (preferably an EIS sensor), an impedance spectrometer, and a handle. The guidewire may also include additional components that can be inserted along its length during use. The sensor may be used to detect and characterize the properties of the tissue / material it is in contact with. For example, the sensor may be used to determine the tissue / material composition when used with the impedance spectrometer to perform high-frequency impedance measurements. Both the sensor and the impedance spectrometer are preferentially located at the invasive tip of the guidewire so that tissue adjacent to the tip can be characterized without requiring a long wire connecting the sensor to the impedance spectrometer. This design can reduce electronic noise that may otherwise be introduced into the electrical signal if the impedance spectrometer were located outside the subject.

[0342] The handle may include additional components for communicating with the user, recording and transmitting data both during and after surgery, processing data, and powering the device. Examples of such components include a feedback unit such as a user-readable display or indicator lights, a unit for transmitting data either wirelessly or via cable, a database, a processor, and a battery. The handle may be detachable from other device components and may also be detachably connected to the circuitry on the guidewire itself.

[0343] Example 2 The guidewire described in Example 1 may be used by a clinician to determine the optimal treatment strategy for a patient experiencing arterial occlusion. The clinician can use the guidewire to characterize the tissue / material occluding the artery and then, based on this information, select from among different possible treatments. In some embodiments, the guidewire may provide the clinician with treatment recommendations based on one or more characterizations it has performed, and optionally, on data from previous treatments performed with the assistance of the guidewire.

[0344] In this embodiment, a clinician can use a guidewire to assess and treat arterial lesions. The clinician may, if desired, use a handle to maneuver the guidewire to the site of the thrombus and then penetrate the thrombus to begin. Next, the clinician may use the guidewire to perform measurements of the composition of the thrombus and / or the tissue / material occluding the artery. The clinician can then determine the optimal treatment for the occluded artery based on the results of these measurements. For example, if the occluding tissue consists of cells from the patient's arterial wall, the clinician may decide to use a stent device. If the occluding tissue is a thrombus, the clinician may instead decide to measure its viscoelastic properties and then, based on this information, determine whether to use an aspiration catheter or a stent to remove the blood clot.

[0345] In some embodiments, clinicians may also receive treatment recommendations from the guidewire. These recommendations may be based on characterization of arterial lesions performed by the guidewire and / or on data collected during previous use of the guidewire.

[0346] Once the treatment is complete, the clinician can remove the handle from the guidewire and use the guidewire to insert the appropriate intervention device.

[0347] Example 3 A further example of a device that may be used in accordance with the techniques described herein is a smart stent retriever. A stent retriever can be used to retrieve blood clots from a patient. Using the sensors and analytical techniques described herein, an invasive stent retriever can characterize the blood clot it is in contact with and communicate the properties of this tissue / material to a clinician.

[0348] In this embodiment, the stent retriever comprises at least one sensor (preferably at least one EIS sensor and / or EIT sensor), a measuring unit, and a handle. The stent retriever may be equipped with multiple sensors at multiple strategic locations so that information about the blood clot it is in contact with can be obtained from multiple locations within the blood clot. If the stent retriever includes two or more sensors, the sensors can detect different characteristics of the blood clot it is in contact with. For example, the stent retriever may be equipped with one or more sensors that can detect integration between the blood clot and the stent retriever, one or more sensors that can detect the position of the stent retriever as a function of time, and / or one or more sensors that can detect the force applied to the blood clot. Integration between the stent retriever and the blood clot can be determined by detecting the stent's inductance and / or EIT signal as a function of time. Since the stent's inductance and EIT value change with stent expansion and the surrounding environment, a constant value of these characteristics indicates that the stent has reached its maximum expansion and integration with the blood clot. Motion sensors can be used to detect the position of the stent retriever as a function of time. This feature may allow clinicians to understand the movement of the stent retriever within a patient and determine the number of passes the stent retriever made during blood clot retrieval. Stress sensors may also be included to measure the force applied by the stent retriever to the blood clot or tissue / material.

[0349] The measurement unit for the stent retriever may be an impedance spectrometer and / or a tomography unit. This unit is preferentially located near the tip of the stent retriever so that it can characterize blood clots adjacent to the stent retriever without requiring long wires to connect the sensor to the measurement unit. This design can reduce electronic noise that may otherwise be introduced into the electrical signal if the impedance spectrometer is located outside the subject.

[0350] The handle may include additional components such as those described in Example 1. It may also be equipped with a robotic pulling mechanism to enable precise and automated retrieval of the blood clot.

[0351] Example 4 The guidewire described in Example 1 and the stent retriever described in Example 3 may be used together by clinicians to determine and implement the optimal treatment strategy for patients experiencing arterial occlusion. The clinician can use the guidewire to characterize the tissue / material occluding the artery, and then use the stent retriever to retrieve the blood clot and / or thrombus. Optionally, data may be collected during clot retrieval and uploaded to a database for later analysis.

[0352] In this embodiment, a clinician can use a combination of smart devices to treat a patient experiencing arterial occlusion. The clinician may begin by inserting a guidewire with the sheath and using the guidewire (along with an invasive probe, as described above) to assess the lesion, as described in Example 2. If the clinician decides to use a stent retriever next based on the information and / or recommendations provided by the guidewire, the clinician removes the guidewire, leaves the sheath in place, inserts the stent retriever along the sheath, and maneuvers it into the blood clot and / or thrombus. Once the stent penetrates the blood clot and / or thrombus, sensors incorporated into the stent retriever can detect the characteristics of the blood clot and / or thrombus and provide this information to the clinician as a function of time (e.g., on an external display). For example, EIS and / or EIT sensors can characterize the integration of the stent with the blood clot and / or thrombus, as well as the shape and composition of the blood clot and / or thrombus. Stent retrievers can also provide clinicians with treatment recommendations using data from previous retrievals of blood clots and / or thrombi. These recommendations may include, for example, signals indicating that integration of the stent retriever with the blood clot and / or thrombus is optimal, and / or recommendations regarding the appropriate speed and force for pulling the blood clot and / or thrombus.

[0353] At this point, the clinician can act based on the information and / or recommendations provided by the stent retriever to retrieve the blood clot and / or thrombus. The clinician may decide to use the automatic pulling mechanism built into the stent retriever to retrieve the blood clot. The automatic pulling mechanism can then pull the blood clot and / or thrombus using the speed and force determined by the stent retriever based on data received from a database of previous blood clot and / or thrombus retrievals. If the blood clot and / or thrombus separates from the stent retriever, the stent retriever signals the clinician using an alarm. The clinician can then re-penetrate the blood clot and / or thrombus and restart the retrieval process.

[0354] At the end of the blood clot and / or thrombus retrieval, all data collected during the intervention may be transferred to a database for later analysis.

[0355] Example 5 Another example of a device that may be used in accordance with the techniques described herein is a smart aspiration catheter. A suction catheter may be used to collect blood clots from a patient. Using the sensors and analytical techniques described herein, an invasive aspiration catheter can characterize the blood clot it is in contact with and communicate the properties of this tissue / material to the clinician.

[0356] In this embodiment, the suction catheter comprises at least one sensor (preferably at least one EIS sensor and / or EIT sensor), a measuring unit, and a handle. As in Embodiment 3, the suction catheter may be equipped with multiple sensors at multiple strategic locations so that information about the blood clot it is in contact with can be obtained from multiple locations within the blood clot. If the suction catheter includes two or more sensors, the sensors can detect different characteristics of the blood clot it is in contact with. For example, the suction catheter may be equipped with one or more of the sensors described in Embodiment 3 (i.e., one or more sensors that can detect integration of the blood clot with the suction catheter, one or more sensors that can detect the position of the suction catheter as a function of time, and / or one or more sensors that can detect the force applied to the blood clot). The suction catheter may also be equipped with additional sensors that can monitor blood flow within the suction catheter.

[0357] The measurement unit and handle unit of the suction catheter are the same as those of the stent retriever described in Example 3.

[0358] Example 6 The guidewire described in Example 1 and the suction catheter described in Example 5 may be used together by a clinician to determine and implement the optimal treatment strategy for a patient experiencing arterial occlusion. The clinician can use the guidewire to characterize the tissue / material occluding the artery, and then use the suction catheter to retrieve the blood clot and / or thrombus. Optionally, data may be collected during clot retrieval and uploaded to a database for later analysis.

[0359] In this embodiment, a clinician can use a combination of smart devices to treat a patient experiencing arterial occlusion. The clinician can begin by inserting a guidewire and using it to assess the lesion, as described in Example 2. If the clinician decides to use an aspiration catheter next based on the information and / or recommendations provided by the guidewire, the clinician then inserts the aspiration catheter along the guidewire, maneuvers it into the blood clot and / or thrombus, and begins the aspiration process. During the aspiration of the blood clot and / or thrombus, the external display provides the clinician with information on the progress of removal, the shape and composition of the blood clot and / or thrombus as detected by the EIS sensor and / or EIT sensor, and the passage of the blood clot and / or thrombus through the aspiration catheter. The smart aspiration catheter can also determine the optimal time to begin the removal of the blood clot and / or thrombus based on the integration of the aspiration catheter with the blood clot and signal this condition to the clinician. The clinician can then begin the removal of the blood clot and / or thrombus. If a blood clot and / or thrombus separates from the aspiration catheter, the aspiration catheter may signal to the clinician using an alarm. The clinician can then re-penetrate the blood clot and / or thrombus and restart the retrieval process. If the sensor detects that the thrombus has been completely aspirated and passed along the tube of the aspiration device, another message indicating successful removal may be generated and output.

[0360] At the end of the blood clot and / or thrombus retrieval, all data collected during the intervention may be transferred to a database for later analysis.

[0361] Example 7 The guidewire described in Example 1 may be used to treat a patient experiencing chronic total occlusion (CTO). In this case, the patient's artery is occluded by an old, hard thrombus that may be difficult for the clinician to penetrate in order to re-establish blood flow. The clinician can use the smart guidewire to detect the location of the lesion and to pass through it. During operation, the guidewire can provide the clinician with information about when penetration of the lesion is initiated and when passage through the lesion into the lumen of the artery occurs. If the thrombus is too hard to penetrate, the clinician can instead pass the guidewire through the arterial wall adjacent to the lesion. In this case, the guidewire can provide the clinician with continuous information about its location within the atheroma / plaque. This may help the clinician avoid puncturing the vessel.

[0362] Example 8 The guidewire described in Example 1 may be used by clinicians in the diagnosis and / or treatment of peripheral pathologies. Examples of peripheral pathologies include thrombi forming in deep veins or arteries, or in artificial veins or arteries. The guidewire may be used to determine the optimal treatment strategy for patients experiencing peripheral pathologies. The clinician can use the guidewire to characterize the tissue / material occluding the vascular access and then, based on this information, select from among different possible treatments. In some embodiments, the guidewire may provide treatment recommendations to the clinician based on one or more characterizations it has performed, and optionally based on data from previous treatments performed with the assistance of the guidewire.

[0363] Example 9 As an additional example, the age of a blood clot (e.g., a thrombus) can be estimated using one of the aforementioned invasive probes. The age of a blood clot (i.e., the lifespan of the clot since its formation) can be determined based on one or more characteristics of the clot, such as its composition. Different treatments or combinations of treatments may be provided based on the age of the clot, so that they are determined from these characteristics. For example, if the clot is less than 14 days old, one treatment may be recommended, and if the clot is longer than 14 days old, a different treatment may be recommended.

[0364] In addition, or alternatively, at least some of the devices and techniques described herein may be used to identify whether a biological structure is healthy tissue. For example, a device / technology may be used to determine whether a vascular wall is healthy or whether atherosclerotic plaque or calcification has formed on the vascular wall. In such cases, the biological structure contacted by one of the devices described herein may be a vascular wall or an atherosclerotic plaque (or other lesion), and a technique described herein may be used to determine whether it is one of those biological structures. Based on this identification, different treatment recommendations can be provided.

[0365] How to operate medical devices for use in oncology The inventors have recognized and understood that conventional techniques for examining potentially cancerous cells are often inadequate. For example, one conventional technique for examining potentially cancerous cells uses a needle to remove a tissue sample. Conventional imaging systems such as X-ray, ultrasound, or magnetic resonance imaging (MRI) are used to assist clinicians in guiding needle insertion. However, the images produced using these techniques are often inaccurate or blurry, making it difficult for clinicians to determine whether the needle is in contact with the targeted cells or tissue. As a result, the diagnosis and / or treatment of cancerous cells using such techniques is often inaccurate. Consequently, when attempting to determine whether a particular lesion is cancerous, there is a significant risk that a needle intended to examine a potentially cancerous lesion may not actually come into contact with the lesion, but instead come into contact with nearby healthy tissue, leading to an inaccurate sample and inaccurate medical conclusions. Similarly, when attempting to remove cancerous cells, two undesirable situations can arise: healthy tissue may be removed along with the cancerous cells, or some cancerous cells may remain.

[0366] Accordingly, according to some embodiments described herein, medical devices can be used to determine the presence of cancerous cells / tissues, the characteristics of cancerous cells / tissues, and / or the type of cancerous cells / tissues (e.g., carcinoma, lymphoma, myeloma, neoplasm, melanoma, metastasis, or sarcoma). For example, the machine learning techniques described above may be used to distinguish cancerous cells / tissues from non-cancerous biomaterials and / or to characterize cancerous cells / tissues. Furthermore, the types of techniques described herein (including machine learning techniques) can provide recommendations on how to treat cancerous cells / tissues, at least in part, based on the characteristics of the cancerous cells / tissues. For example, excision or removal of cancerous cells / tissues, and methods of excision or removal, may be recommended in some situations.

[0367] Examples of medical devices, sensors, and methods for detecting cancerous cells in tissue / material are described in detail above with respect to Figures 2 to 11. Examples of technologies that may be implemented by and / or manipulated by such medical devices are described below with respect to Figures 31 to 33.

[0368] Figure 22 shows an exemplary process 2200 that may be carried out by a medical device operating according to some of the techniques described herein. In the example of Figure 22, the sensor may be located within a diagnostic and / or therapeutic device such as a needle, resection catheter, high-frequency probe, robotic probe, laparoscope, or cutting device. In some embodiments, the sensor is located near the distal end of the medical device. The medical device may generate treatment recommendations based on the characteristics of cancer cells determined using the sensor. It should be understood that the processes described herein are not limited to use with invasive probes. In some embodiments, the techniques described herein may not be designed for use inside an animal or for use alone, but may be used in conjunction with systems and devices including non-invasive probes that may be designed for use on biological structures, including tissues outside the animal's body, either additionally or alternatively. For example, in some embodiments, the devices, systems, and techniques described herein may be used for the diagnosis and / or treatment of superficial lesions such as skin cancer or other skin conditions.

[0369] Process 2200 begins in block 2202, in which an invasive probe of a medical device is operated to detect one or more characteristics (e.g., size and / or composition) of a lesion adjacent to the sensor, which may be cancerous tissue or cells. Prior to the start of process 2200, the invasive probe may be inserted into the body of an animal and moved in close proximity to the predicted location of the lesion. The medical device is then operated to detect when the sensor has come into contact with a lesion. Contact with a lesion, or with tissue known to be or potentially cancerous, can be determined by evaluating changes over time (e.g., changes in impedance) of the value output by the sensor, or by using machine learning techniques such as those described in relation to Figure 17C. For example, the medical device may output a result (e.g., to the user via a user interface) when the sensor of the invasive probe has not come into contact with cancerous tissue / cells, or with a type of tissue known to be part of a lesion.

[0370] For example, when a lesion is being investigated, as an invasive probe is moved through the animal toward the lesion, the medical device may output a value indicating the tissue it is in contact with. In some embodiments, this value may be a qualitative value, including a binary value such as yes / no or true / false, indicating whether the invasive probe is in contact with the lesion.

[0371] A medical device can determine whether an invasive probe is in contact with a lesion by analyzing the biomaterial(s) it is in contact with, including the tissue it is in contact with, and thus determine whether the invasive probe is “abnormal” and therefore in contact with any biomaterial that may be part of a lesion. In some embodiments, a medical device can determine whether the biomaterial in contact with the probe is “abnormal” by evaluating the location of the invasive probe within an animal, which may indicate biomaterial that the invasive probe is expected to come into contact with.

[0372] In addition, or alternatively, the medical device may determine whether the invasive probe is in contact with a lesion based on predictions about the lesion that may be entered by a clinician as a result of a preliminary diagnosis. For example, the clinician may enter information that preliminaryly characterizes the lesion, such as whether the lesion is located within a vascular structure or an organ, and if it is an organ, what organ it is, a prediction of the composition of the lesion, or a prediction of the tissue or cellular state of the lesion (e.g., unhealthy, inflammatory, cancerous, morbid, etc.). In embodiments in which such information is entered, the clinician may enter information that preliminaryly characterizes each lesion individually, or may make a selection of preliminary diagnoses of the lesion that can be associated with such preliminary characterizing information (for example, by selecting a specific category of atheroma, other information such as the expected composition of the atheroma and that it is located within a vascular structure may also be selected). As the invasive probe moves through the animal, the medical device may determine whether the invasive probe is in contact with the lesion by comparing the biomaterial in contact with the invasive probe to the preliminary characterization of the lesion. For example, if a lesion is tentatively diagnosed as a brain lesion that may be a brain tumor, the medical device may determine whether the invasive probe has come into contact with abnormal brain tissue and / or cancerous brain tissue, and output this result.

[0373] In other embodiments, instead of simply providing a binary value indicating whether the invasive probe is in contact with a lesion, the medical device may output a value indicating, for example, the identification, quantity, and / or relative abundance of one or more biomaterials in contact with the sensor of the invasive probe, which may change as the probe moves through the body. The value indicating the material(s) may be material identification information, such as a list of materials identified from an impedance spectrum, as determined using the techniques described herein (including the machine learning techniques described above). In other embodiments, the value may be a numerical value, such as a value detected by the sensor (e.g., an impedance value, or an impedance spectrum) or other value.

[0374] The probe and its sensor may be moved until they make contact with the lesion, at which point, once contact is made, the output from the medical device may change. In this way, the location of the lesion can be determined using the invasive probe, and it can be determined that the invasive probe is in contact with the lesion.

[0375] The invasive probe can, in some cases, be manipulated to determine the geometric shape of a lesion. For example, the geometric shape of a lesion potentially containing cancerous tissue (e.g., a tumor) may be determined in some embodiments by moving the invasive probe near the lesion and identifying when the probe's sensors are in contact with or not in contact with the lesion. For example, if analysis of the values ​​output by the invasive probe determines that the lesion contains cancerous tissue, the invasive probe can be moved and, over time, different sensors can be used to determine whether each individual sensor is in contact with the cancerous tissue. The amount of movement of the invasive probe (e.g., measured using an accelerometer as described above) and the position of the sensors on the invasive probe can then be analyzed by a medical device to determine the geometric shape of the cancerous tissue in the animal, including one or more dimensions of the cancerous tissue.

[0376] In some such embodiments, the medical device can determine one or more treatment recommendations for a lesion based on the geometric shape of the lesion.

[0377] In one treatment protocol, which may be implemented in embodiments such as those illustrated in Figure 22, excision may be used as a first option for treating cancerous tissue. Thus, in block 2204, an excision device, such as a needle or a high-frequency probe, is inserted into the animal. In some embodiments, the excision device may include an invasive probe containing a sensor of the type described herein. The excision device may be moved until the excision device determines that contact with cancerous cells or tissue has been formed. (However, it should be understood that embodiments are not limited to working with an excision device including an invasive probe. In other embodiments, the invasive probe is part of a separate medical device, and after the positioning of the invasive probe, the excision device is moved until it is positioned close to the invasive probe, and therefore close to the cancerous cells / tissue).

[0378] In block 2204, after positioning the excision device in close proximity to cancerous cells / tissue, the excision device is activated to excise the cancerous cells / tissue. Following a treatment time interval, the excision device may operate to determine whether the excision device is affecting the cancerous cells / tissue. For example, in some embodiments, treatment recommendations may be generated to guide the clinician in performing the excision, including whether the excision is effective and whether to continue the excision. Thus, in block 2206, the sensor may provide information indicating whether the excision device is still in contact with cancerous cells or cancerous tissue. This decision may be made using techniques described herein (including the machine learning techniques described above). The information may be processed and used to provide treatment recommendations, such as whether to stop or continue the excision, or to check the positioning of the invasive probe before determining whether to stop the excision.

[0379] In some embodiments, the excision device may include multiple different electrodes for excision, such as different electrodes positioned at different locations, and the different electrodes may be individually operable so that others can be operated to excise when some are not being operated to excise. In some embodiments, each excision electrode may be positioned near a sensing electrode, which operates according to the techniques described herein to determine the biomaterial in contact with the sensing electrode. The excision device may use the sensing electrode to determine whether a particular part of the excision device is in ...

Claims

1. A circuit board for use with an invasive probe inserted into an animal tube, wherein the circuit board is The first area is, The interconnection layer, A first polymer layer disposed on the first side of the interconnection layer, A second polymer layer disposed on the second side of the interconnection layer opposite to the first side, A first region comprising, The second area is, One or more integrated circuits, The interconnection layer connected to the one or more integrated circuits, The interconnection layer and the first polymer layer disposed on the first side of the one or more integrated circuits, The interconnection layer on the opposite side of the first side and the second polymer layer disposed on the second side of the one or more integrated circuits, A second area comprising, Equipped with, In the first region, the first thickness of the first polymer layer is equal to the second thickness of the second polymer layer. The first flexibility of the first region is greater than the second flexibility of the second region. Circuit board.

2. The one or more integrated circuits described above are A first integrated circuit arranged to operate one or more sensors to detect one or more values, A second integrated circuit comprising one or more circuits electrically connected to the first integrated circuit and operated by the first integrated circuit, A circuit board according to claim 1, including the following:

3. An invasive probe, Housing and One or more electrical components, A circuit board according to claim 1 or 2, Equipped with, The circuit board is at least partially disposed within the housing, and the one or more electrical components are mounted on the circuit board. The aforementioned circuit board is A region of the circuit board extending from the housing, comprising two or more conductive contacts disposed on the outside of the non-flexible housing, wherein the two or more conductive contacts comprise a first contact and a second contact, At least one interconnection layer that electrically connects the two or more conductive contacts to the one or more electrical components, Equipped with, A first wire is electrically connected to the first contact located outside the non-flexible housing. An invasive probe wherein a second wire is electrically connected to the second contact disposed outside the non-flexible housing.

4. The invasive probe further comprises at least one additional wire, The two or more conductive contacts are three or more conductive contacts, and include one or more additional conductive contacts disposed on the outside of the non-flexible housing. The invasive probe according to claim 3, wherein the first wire, the second wire, and the at least one additional wire are joined together in a ribbon shape, each of the first wire, the second wire, and the at least one additional wire is electrically insulated from the other wires of the ribbon, and each wire of the ribbon is electrically connected to one of the three or more conductive contacts.

5. Each wire in the ribbon is provided with an insulating jacket that electrically insulates the wire within the ribbon. The invasive probe according to claim 4, wherein, for each wire of the ribbon electrically connected to one of the three or more conductive contacts of the circuit board, the insulating jacket of the wire is in contact with another conductive contact of the three or more conductive contacts of the circuit board.

6. The three or more conductive contacts of the circuit board are distributed outside the non-flexible housing over the region of the circuit board that extends from the non-flexible housing, Each wire of the ribbon includes an opening within the associated insulating jacket of the wire at a position corresponding to the location of one of the three or more conductive contacts to which the wire is electrically connected. The invasive probe according to claim 5, further comprising three or more regions of a conductive material for bonding the ribbon to the circuit board, wherein the three or more regions of the conductive material are positioned on the circuit board at positions corresponding to each of the three or more conductive contacts.

7. The circuit board is flexible, The aforementioned ribbon is flexible, The invasive probe according to claim 6, wherein the three or more regions of the conductive material each form three or more non-flexible regions that are positioned on the circuit board.

8. The invasive probe according to any one of claims 3 to 7, further comprising an insulating adhesive disposed in close proximity to the region in which the first wire, the second wire, and / or additional wires are electrically connected to the first contact, the second contact, and / or additional conductive contact.

9. The invasive probe according to any one of claims 3 to 8, wherein the invasive probe is a guide wire including a core wire made of a conductive material, each of the first wire, the second wire, and / or additional wires is arranged on the outer surface of the core wire, and the core wire is connected to a potential reference.

10. The invasive probe according to any one of claims 3 to 9, wherein the first wire, the second wire, and / or additional wires include at least one of a ground wire and a positive potential wire for supplying power to the circuit board, and a signal carrier wire for providing a time-dependent signal to the circuit board, the signal carrier wire being positioned between the ground wire and the positive potential wire.

11. An invasive probe according to any one of claims 3 to 10, wherein at least one integrated circuit is configured to implement a digital communication protocol by supplying a digital time-dependent signal through at least one of the first wire, the second wire, and / or additional wires.

12. The invasive probe according to any one of claims 3 to 11, wherein the first region radially surrounds at least a portion of the second region with respect to the longitudinal direction of the housing.

13. A method for manufacturing an invasive probe according to any one of claims 3 to 12, The housing includes a slot, and the method is A step of positioning the flexible circuit board according to claim 1 or 2 with respect to the housing, wherein the positioning includes positioning the second region of the flexible circuit board within the slot of the housing, The process includes winding the first region of the flexible circuit board around the housing with the second region positioned within the slot, method.

14. The method according to claim 13, wherein the step of winding the first region around the housing includes applying consistent pressure to the first region before and / or during winding.

15. The process further includes joining each of the plurality of wires of the invasive probe to each of the plurality of conductive contacts of the invasive probe, The method according to claim 13 or 14, wherein the plurality of conductive contacts are formed on the flexible circuit board of the invasive probe, the flexible circuit board is partially disposed within the non-flexible housing, and the plurality of conductive contacts are disposed outside the non-flexible housing.

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