Devices and methods for vascular navigation, evaluation and / or diagnosis - Patents.com

Abstract

To provide devices and methods for vascular navigation, assessment, and / or diagnosis.SOLUTION: A location detection system generally includes an elongate body defining a lumen at least partially along a length of the elongate body. One or more sensors 6306 are positioned near or at a distal tip of the elongate body and one or more openings are defined along the elongate body in proximity to the one or more sensors 6306. The one or more openings are configured to control a boundary distance λ between the one or more sensors 6306 and a fluid 6302 with a parameter of a known initial value when emitted from the one or more openings. A controller is in communication with the one or more sensors 6306 and is configured to track a change in the parameter relating to a concentration over the one or more sensors 6306 and determine a position of the one or more sensors 6306 within a body.SELECTED DRAWING: Figure 63ABCD

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 553,023, filed August 31, 2017, U.S. Provisional Patent Application No. 62 / 563,604, filed September 26, 2017, and U.S. Provisional Patent Application No. 62 / 580,238, filed November 1, 2017, each of which is incorporated herein by reference in its entirety.

[0002] The present invention relates to devices and methods for vascular navigation, evaluation, and / or diagnosis.

[0003] Citation by reference All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. [Background technology]

[0004] A central vascular catheter (vascular catheter), also known as a central line, central venous line, or central venous access catheter, is a catheter placed in a large vein in the neck (internal jugular vein), chest (subclavian or axillary vein), arm, or groin (femoral vein). It is primarily used to administer medications or fluids, obtain blood test values ​​(such as central venous oxygen saturation), and measure central venous pressure.

[0005] A peripherally inserted central catheter (PICC, or PIC line) is a form of vascular catheter that can be used for long-term administration of blood and / or substances. It is a catheter that enters the body through the skin (percutaneously) at a peripheral site, extends into the superior vena cava (central vein trunk), and can remain in place for days or weeks.

[0006] Placing a catheter (PICC, central vascular catheter, or related vascular catheters, referred to herein as "vascular catheter" or "catheter") in the ideal location can be difficult. The catheter may be mistakenly inserted into an artery instead of a vein, into the wrong vein or the wrong venous branch, or may be overdone or advanced into / along the vessel wall. Ideally, the catheter tip is placed at the superior vena cava / cavo-atrial junction (SVC-CAJ or CAJ) or in the lower one-third of the superior vena cava.

[0007] Correct placement is currently determined by physically measuring the distance from the catheter entry point to the estimated location of the superior vena cava or the lower third of the CAJ. Current technology presents several challenges. First, the catheter may enter an artery instead of a vein. Second, the catheter may be advanced down the wrong branch of the venous tree. The catheter may be advanced down the azygos, thoracic, or jugular vein, or any number of additional veins in the branches. Third, the catheter may be advanced past the superior vena cava and into the heart or inferior vena cava, which can be a dangerous situation. Fourth, the catheter may be advanced against or embedded in the vessel wall, which can prevent fluid delivery or withdrawal. Fifth, because the criteria for catheter placement are virtually invisible, verification of placement must be corroborated with a chest x-ray, which adds substantial cost and time. Sixth, the estimated distance to the superior vena cava or the lower third of the CAJ may be inaccurate. Summary of the Invention [Problem to be solved by the invention]

[0008] What is needed is a relatively simple and accurate method for navigating a vascular catheter by precisely locating the catheter's tip as it is advanced to its target location. [Means for solving the problem]

[0009] The present invention includes a vascular catheter location and navigation device and method that determines the location of the tip of a vascular catheter using the introduction of a medium (or infusate) having a measurable parameter (temperature, light reflection, sound reflection, conductance, impedance, etc.) and sensing and measuring the measurable parameter as the catheter is advanced within a flowing fluid, e.g., blood flow in a blood vessel. The parameter measurements are tracked, recorded, and analyzed over time. The value of the parameter and / or the shape of the curve of the parameter value versus time may be used in the analysis. For example, the amplitude, variability, pulsatility, phase, standard deviation, slope, etc. of the curve may be used in the analysis of the catheter location.

[0010] The direction, characteristics, profile, and type of flow to the catheter and catheter tip can provide a wide range of information regarding catheter positioning during placement, after initial placement or following placement, after the catheter has been in place for a period of time, and / or when the catheter is withdrawn.

[0011] The devices and methods disclosed herein may be used to alert a user to one or more of the following conditions: insertion, placement, or advancement of a catheter into an artery rather than a vein; insertion, placement, or advancement of a catheter into an undesirable venous branch; placement or advancement of a catheter too close to, into, or past the heart; or placement of the catheter tip against or embedded in the wall of a blood vessel, or insufficient advancement of the catheter. Each of these situations is described in detail herein.

[0012] The characteristics and direction of blood flow can help determine whether a catheter is in an artery or a vein. In veins, blood generally flows more slowly toward the heart, while in arteries, blood generally flows more quickly away from the heart. At least the direction and velocity of blood flow relative to the catheter differ depending on whether the catheter is in an artery or a vein. Other flow parameters may also differ (turbulence, pulsatility, etc.). Furthermore, the flow characteristics of blood in smaller branches of a blood vessel differ from those in larger vessels. For example, blood flow in a venous branch may completely or substantially stop where the catheter tip fully or partially occludes the venous branch. When the catheter tip rests against the vessel wall, the flow pattern around the catheter differs from when the catheter tip is floating freely in the blood.

[0013] As the catheter tip enters the superior vena cava and passes near or into the right atrium or right ventricle, the blood flow characteristics change. For example, the blood flow may become more or less turbulent. More or less turbulent flow results in different flow characteristics, profiles, and flow types, and can be detected by various types of sensors.

[0014] These flow profile changes can be measured using the instruments and methods disclosed herein.

[0015] The devices disclosed herein may include catheters, guidewires, stylets, controllers, communication devices, infusion mechanisms, media sources, one or more media sensors, and the like.

[0016] The devices and methods disclosed herein may involve the introduction of a medium or infusate (e.g., saline, fluid, light, sound, etc.) having measurable parameters (e.g., temperature, conductivity, impedance, opacity, light reflectivity, sound reflectivity, density, viscosity, light absorption capacity, sound absorption capacity, amplitude, etc.), which may be detected using sensors (e.g., sensors, thermocouples, electrodes, light sensors, sound sensors, microphones, etc.). By introducing a medium at or near the tip of the catheter and measuring one or more parameters of the medium over time and possibly over distance, flow parameters, such as flow direction, rate, amount and type, turbulent or laminar flow, may be determined. Based on these determinations, a user can identify whether the catheter tip is progressing via a desired path to a desired location within the vasculature. Blood vessels may be identified by type (e.g., venous vs. arterial, cardiac, etc.), size, shape, etc.

[0017] The measurable parameter of the infusate medium is different from that of blood, either higher or lower. In some embodiments, the measurable parameter of the infusate medium or blood can be zero or substantially zero. For example, if the parameter is conductivity, the infusate medium can be a zero-conductivity fluid, such as distilled water or the like.

[0018] The medium may be infused or introduced as a bolus or drip periodically during all or part of the catheterization, continuously during all or part of the catheterization, or at regular intervals during all or part of the catheterization. The medium may be introduced manually, automatically by a controller, automatically by an intravenous (IV) bag with or without an IV pump, or passively using an IV.

[0019] Measurements of one or more medium parameters may be taken before, during, and / or after medium introduction. For example, room temperature or other non-body temperature saline (or other fluid) may be injected through the catheter or stylet during placement. One or more sensors at or near the distal tip of the catheter / stylet may measure the temperature of the fluid immediately surrounding the sensor over time as the device advances / moves. Based on blood flow characteristics, including direction, pulsatility, and turbulence, the temperature profile over time will be different at different locations, resulting in certain temperature (or parameter) profiles or signatures for different flow types and, therefore, different catheter / stylet tip location scenarios.

[0020] In embodiments where the device is used in, for example, intravascular fluid flow, the medium may be a fluid (first fluid) having a measurable parameter that may be different from the intravascular fluid (second fluid, which may be blood). The sensor in any of the embodiments disclosed herein may measure the parameter of a mixture of the first and second fluids over time and at different locations to determine the location of the device. Note that in some embodiments, the medium parameter level may be negligible and may serve to dilute the parameter of the mixture of the first and second fluids. For example, if the parameter is electrical conductivity, the medium, or infusate, may be distilled water or another infusate, which has negligible conductivity, where blood has a higher conductivity. In these embodiments, the sensor may measure the conductivity of the infused medium / blood mixture to determine the location of the device.

[0021] The temperature sensors may include thermocouples or other temperature sensors, such as fiber optic, resistive, bimetallic, thermometer, change of state, silicon diode, thermistor, optical thermometry (infrared or other), mercury thermometer, pressure gauge, etc. The one or more sensors are in communication with a controller, which records and / or analyzes signals from the sensors. Communication between the sensors and the controller may be wired or wireless.

[0022] By placing a thermocouple, thermistor, or other temperature-sensing device, or array of temperature-sensing devices, on or through the catheter, the direction of flow of a room-temperature fluid bolus injected into the bloodstream can be determined. Since blood temperature is approximately 37°C, a saline (or other) fluid bolus or fluid infusion having a temperature of approximately 20-25°C, or 15-30°C, or 0-35°C, or generally colder than 37°C, can be distinguished from body temperature and can be used to detect the direction and characteristics of blood flow and, therefore, the location of the device.

[0023] Alternatively, the fluid may be above body temperature, optimally about 40°C, but may range from about 39°C to 42°C or from about 37°C to about 45°C.

[0024] In some embodiments, optical sensing may be used: an optical sensor may be used to detect the direction of flow by measuring the amount of dilution of blood with another fluid, such as saline, that has different optical properties.

[0025] Alternatively, sonar or sound can be used as a parameter to detect blood flow direction, velocity, and other blood flow characteristics. Sound waves can be generated by a controller and transmitted to or near the tip of the catheter. A sound detector, or microphone, records sound waves reflected by red blood cells or other components of blood. Saline can also be introduced to produce changes in the detected sound waves.

[0026] In some embodiments, various media and / or parameters may be used in combination. For example, both light (visible and / or invisible) and temperature may be used. Additionally, other sensors may be used to assist in catheter location, including electrocardiogram (ECG), ultrasound, Doppler, x-ray, etc. Pressure may also be used instead of or in combination with these embodiments.

[0027] Embodiments incorporating two or more types of sensors may be used in any of the following situations (vein vs. artery, branch vessel, vessel wall, catheter within or beyond the heart), or different sensors may be used in different situations. For example, pressure may be used to determine when the catheter tip is in the heart, while temperature may be used to determine whether the catheter is in an artery. Or, for example, an ECG may be used to determine whether the catheter is at the cavoatrial junction, while temperature may be used to determine whether the catheter has advanced down the azygos vein or an undesirable venous branch.

[0028] In some embodiments, a camera may be used to optically determine the presence and possibly density or number of red blood cells. If more red blood cells pass, the flow is stronger. If the red blood cells flow in the opposite direction, the flow is reversed and the catheter is going in the wrong direction.

[0029] These sensing modalities may also be combined with one or more (ECG) sensors to detect catheter placement. ECG electrodes may be precisely placed either at the targeted location of the catheter tip (e.g., the upper third of the vena cava) or on the upper side of the heart itself to detect unwanted overextension of the catheter. Alternatively, one or more ECG sensors may be incorporated into the device itself, for example, on the guidewire / stylet. Alternatively, ECG signals may be collected with the same sensors or electrodes used to measure conductivity, temperature, or other parameters. The received signals may alternate, for example, between ECG and conductivity, with or without a break between them.

[0030] In any of the embodiments disclosed herein, the sensor may be placed at or near the distal tip or along the length of a guidewire or stylet that passes through the vascular catheter.

[0031] One objective of some of the embodiments disclosed herein is to locate devices within the vasculature without the use of x-ray and / or fluoroscopy and / or ultrasound and / or magnetic fields and / or other imaging modalities.

[0032] Some embodiments disclosed herein may be specifically designed for use with patients who are sedentary, or who have pacemakers, or who have certain conditions, etc.

[0033] One embodiment of a location detection system may generally include an elongate body defining a lumen at least partially along its length. One or more sensors may be positioned at or near the distal tip of the elongate body, and one or more openings may be defined along the elongate body proximate to the one or more sensors, where the one or more openings are configured to control a boundary distance between the one or more sensors and a fluid having a parameter with a known initial value when released from the one or more openings. A controller may be in communication with the one or more sensors, where the controller is configured to track changes in the concentration-related parameter overlying the one or more sensors and determine the location of the one or more sensors within the subject's body.

[0034] Another embodiment of a location detection system may also generally include an elongate body defining a lumen at least partially along its length. One or more sensors may be positioned at or near the distal tip of the elongate body, and one or more openings may be defined along the elongate body proximate to the one or more sensors, where the one or more openings are sized to control a boundary distance between the one or more sensors and a fluid having a parameter with a known initial value when the fluid is released at a predetermined flow rate. A controller may be in communication with the one or more sensors, where the controller is configured to track changes in the concentration-related parameter overlying the one or more sensors and determine the location of the one or more sensors within the subject's body.

[0035] In one example of a method for determining a location within a subject's body, the method may generally include releasing a fluid of a known initial parameter through one or more openings defined along the elongate body and sensing a change in the parameter of the fluid in terms of concentration via one or more sensors positioned at or near the distal tip of the elongate body and proximate the one or more openings, the one or more openings configured to control a boundary distance between the one or more sensors and the fluid having the parameter when released from the one or more openings. The location of the one or more sensors within the subject's body may be determined based on dilution of the fluid. [Brief explanation of the drawings]

[0036] [Figure 1] 1 illustrates an embodiment of a vascular catheter navigation device for navigating the human anatomy. [Figure 2] 1 illustrates an embodiment of a vascular catheter navigation device placed in the human anatomy. [Figure 3] 1 illustrates an embodiment of a vascular catheter navigation device. [Figure 4A] 10 illustrates the effect of fluid flow direction on the flow properties of an injected fluid bolus relative to the catheter tip before, during, and after injection. [Figure 4B] 10 illustrates the effect of fluid flow direction on the flow properties of an injected fluid bolus relative to the catheter tip before, during, and after injection. [Figure 4C] 10 illustrates the effect of fluid flow direction on the flow properties of an injected fluid bolus relative to the catheter tip before, during, and after injection. [Figure 4D] 10 illustrates the effect of fluid flow direction on the flow properties of an injected fluid bolus relative to the catheter tip before, during, and after injection. [Figure 4E] 10 illustrates the effect of fluid flow direction on the flow properties of an injected fluid bolus relative to the catheter tip before, during, and after injection. [Figure 4F]10 illustrates the effect of fluid flow direction on the flow properties of an injected fluid bolus relative to the catheter tip before, during, and after injection. [Figure 5A] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 5B] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 5C] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 5D] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 5E] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 6A] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 6B] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 6C] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 6D] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 6E] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 7] 1 illustrates an embodiment of a vascular navigation device with two sensors and multiple openings between the two sensors. [Figure 8] FIG. 1 is a schematic diagram illustrating fluid flow in different regions of the vasculature. [Figure 9A] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 9B] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 9C] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 9D] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 9E]1 illustrates various embodiments of a vascular catheter navigation device. [Figure 9F] The distance between the fluid port and the sensor is shown. [Figure 9G] The distance between the fluid port and the sensor is shown. [Figure 9H] The distance between the fluid port and the sensor is shown. [Figure 9I] The distance between the fluid port and the sensor is shown. [Figure 9J] The distance between the fluid port and the sensor is shown. [Figure 10] 1 illustrates an embodiment of a vascular catheter navigation device that can be used with any catheter. [Figure 11A] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11B] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11C] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11D] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11E] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11F] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11G] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11H] 1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 11I]1A-1C show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device. [Figure 12] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 13] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 14] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 15] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 16] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 17] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 18A] Two possible embodiments of the flow director are shown. [Figure 18B] Two possible embodiments of the flow director are shown. [Figure 19A] 10 illustrates another embodiment of an infusion lumen of a vascular catheter navigation device. [Figure 19B] 10 illustrates another embodiment of an infusion lumen of a vascular catheter navigation device. [Figure 19C] 10 illustrates another embodiment of an infusion lumen of a vascular catheter navigation device. [Figure 20] 1 illustrates an embodiment of a vascular catheter navigation device. [Figure 21] Exhibits features that enhance turbulence control. [Figure 22] It exhibits characteristics that result in controlled, laminar (or less turbulent) flow. [Figure 23A] 1 shows a possible graphical user interface for the device. [Figure 23B] 1 shows a possible graphical user interface for the device. [Figure 23C] 1 shows a possible graphical user interface for the device. [Figure 23D] 1 shows a possible graphical user interface for the device. [Figure 23E] 1 shows a possible graphical user interface for the device. [Figure 24A] 1 shows a possible graphical user interface for the device. [Figure 24B] 1 shows a possible graphical user interface for the device. [Figure 24C] 1 shows a possible graphical user interface for the device. [Figure 24D] 1 shows a possible graphical user interface for the device. [Figure 24E] 1 shows a possible graphical user interface for the device. [Figure 25A] 1 illustrates an embodiment of a vascular catheter navigation device that includes a conduit to control fluid flow out of the device. [Figure 25B] 1 illustrates an embodiment of a vascular catheter navigation device that includes a conduit to control fluid flow out of the device. [Figure 25C] 1 illustrates an embodiment of a vascular catheter navigation device that includes a conduit to control fluid flow out of the device. [Figure 26] 1 illustrates an embodiment of a vascular catheter navigation device in which the flow path is within the guidewire / stylet component itself. [Figure 27] 13 shows a variation of the conduit including a proximal flange. [Figure 28] 28 shows a variation of the embodiment shown in FIG. 27 in which the conduit has both a proximal flange and a distal flange. [Figure 29A] 1 illustrates an embodiment of a vascular catheter navigation device in which the conduit comprises a thin-walled inflatable structure. [Figure 29B] 1 illustrates an embodiment of a vascular catheter navigation device in which the conduit comprises a thin-walled inflatable structure. [Figure 29C]1 illustrates an embodiment of a vascular catheter navigation device in which the conduit comprises a thin-walled inflatable structure. [Figure 30] 1 shows an embodiment including a thin-walled "skirt." [Figure 31] 10 illustrates an embodiment in which the conduit includes features that assist in directing the flow of fluid exiting the conduit. [Figure 32] 10 illustrates an embodiment in which the conduit includes features that assist in directing the flow of fluid exiting the conduit. [Figure 33] 10 illustrates an embodiment in which the conduit includes features that assist in directing the flow of fluid exiting the conduit. [Figure 34] 1 shows an embodiment with a deflector. [Figure 35] 1 shows an embodiment of a conical shaped conduit. [Figure 36A] 1 illustrates an embodiment of a vascular catheter navigation device that includes a compressible conduit. [Figure 36B] 1 illustrates an embodiment of a vascular catheter navigation device that includes a compressible conduit. [Figure 36C] 1 illustrates an embodiment of a vascular catheter navigation device that includes a compressible conduit. [Figure 37ABCDEF] 1A-1C illustrate two different cross-sectional views of various embodiments of a vascular catheter navigation device. [Figure 38A] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 38B] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 38C] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 38D] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 38E] 1 illustrates various embodiments of a vascular catheter navigation device. [Figure 39A] 1 is a longitudinal cross-sectional view of an embodiment of a vascular catheter navigation device. [Figure 39B]1 is a longitudinal cross-sectional view of an embodiment of a vascular catheter navigation device. [Figure 39C] 1 is a longitudinal cross-sectional view of an embodiment of a vascular catheter navigation device. [Figure 39D] 1 is a longitudinal cross-sectional view of an embodiment of a vascular catheter navigation device. [Figure 39E] 1A-1C are radial cross-sectional views of an embodiment of a vascular catheter navigation device. [Figure 39F] 1A-1C are radial cross-sectional views of an embodiment of a vascular catheter navigation device. [Figure 39G] 1A-1C are radial cross-sectional views of an embodiment of a vascular catheter navigation device. [Figure 39H] 1 is a cross-sectional view of an embodiment of a vascular catheter navigation device with a fixed conduit. [Figure 39I] 1 is a cross-sectional view of an embodiment of a vascular catheter navigation device with a fixed conduit. [Figure 39J] 1 is a cross-sectional view of an embodiment of a vascular catheter navigation device with a fixed conduit. [Figure 39K] 1 illustrates an embodiment of a vascular catheter navigation device that includes a conduit that extends the length, or substantially the entire length, of the catheter. [Figure 40ABC] 10 illustrates variations in embodiments of different configurations of vascular catheter lumens and vascular catheter navigation devices that work with them. [Figure 41A] 1 illustrates various embodiments of guidewire / stylet components of a vascular catheter navigation device. [Figure 41B] 1 illustrates various embodiments of guidewire / stylet components of a vascular catheter navigation device. [Figure 41C] 1 illustrates various embodiments of guidewire / stylet components of a vascular catheter navigation device. [Figure 41D] 1 illustrates various embodiments of guidewire / stylet components of a vascular catheter navigation device. [Figure 41E]1 illustrates various embodiments of guidewire / stylet components of a vascular catheter navigation device. [Figure 41F] 1 illustrates various embodiments of guidewire / stylet components of a vascular catheter navigation device. [Figure 42A] 1 illustrates an embodiment of a vascular catheter navigation device. [Figure 42B] 1 illustrates an embodiment of a vascular catheter navigation device. [Figure 42C] 1 illustrates an embodiment of a vascular catheter navigation device. [Figure 43] 1 shows data from an embodiment of a vascular catheter navigation device that uses optical reflection. [Figure 44] 1 illustrates an embodiment of a vascular catheter navigation device that uses optical reflection. [Figure 45] A triple lumen device with two fiber optic cables is shown. [Figure 46] A double lumen device with two fiber optic cables is shown. [Figure 47] An embodiment using sonar and sound waves to detect the direction of blood is shown. [Figure 48] 10 illustrates an embodiment in which one or more pressure sensors are used to determine flow directionality using a turbulence inducer. [Figure 49] 10 illustrates an embodiment in which one or more pressure sensors are used to determine flow directionality using a turbulence inducer. [Figure 50] 1 shows an embodiment including a controller and a medium introduction mechanism. [Figure 51] 1 shows an embodiment of an injection mechanism. [Figure 52] FIG. 1 is a block diagram of a data processing system that may be used in conjunction with any embodiment of the present invention. [Figure 53] 1 illustrates an embodiment of a vascular catheter navigation device that includes a sensor, or electrode, and a diffusion exit port for measuring conductivity. [Figure 54]1 shows an embodiment of a pair of electrode sensors and a diffusion outlet port. [Figure 55] 1 shows an embodiment with a diffusion outlet port, where the media infusion lumen extends the length of the guidewire / stylet. [Figure 56] 10 illustrates an embodiment of a vascular catheter navigation device that includes a mesh or braid as a component of the diffusion fluid exit point. [Figure 57] 10 shows an embodiment in which a diffusion outlet port is provided and which includes a spacer. [Figure 58] 10 shows an embodiment in which a diffusion outlet port is provided and which includes a spacer. [Figure 59A] 1 shows some possible embodiments of electrode pairs. [Figure 59B] 1 shows some possible embodiments of electrode pairs. [Figure 60ABC] FIG. 60A shows the distal end of a vascular catheter navigation device with a diffusion outlet port region, FIG. 60B shows a porous sheet used to manufacture an embodiment of a catheter with a diffusion outlet port region, and FIG. 60C shows the distal end of a vascular catheter navigation device with a diffusion outlet port region. [Figure 61A] Some examples with diffusive outlet port designs are shown. [Figure 61B] Some examples with diffusive outlet port designs are shown. [Figure 61C] Some examples with diffusive outlet port designs are shown. [Figure 61D] Some examples with diffusive outlet port designs are shown. [Figure 61E] Some examples with diffusive outlet port designs are shown. [Figure 62A] Some further examples are shown with a diffusive outlet port design. [Figure 62B] Some further examples are shown with a diffusive outlet port design. [Figure 62C] Some further examples are shown with a diffusive outlet port design. [Figure 63ABCD] We show how the infusate outlet flow rate affects the sensor's ability to sense infusate parameters within the vascular bloodstream. [Figure 64A] 1A-1C illustrate several embodiments of a trimmable vascular catheter in which electrodes are integrated into the catheter. [Figure 64B] 1A-1C illustrate several embodiments of a trimmable vascular catheter in which electrodes are integrated into the catheter. [Figure 64C] 1A-1C illustrate several embodiments of a trimmable vascular catheter in which electrodes are integrated into the catheter. [Figure 65] 1 illustrates an embodiment of a vascular navigation device. [Figure 66AB] 1 shows pressure profiles for different blood flow directions. [Figure 67] 1 illustrates various embodiments of a vascular navigation device. [Figure 68] 1 illustrates various embodiments of a vascular navigation device. [Figure 69] 1 illustrates various embodiments of a vascular navigation device. [Figure 70] 1 illustrates various embodiments of a vascular navigation device. [Figure 71] 1 illustrates various embodiments of a vascular navigation device. [Figure 72] 1 illustrates various embodiments of a vascular navigation device. [Figure 73] 1 illustrates various embodiments of a vascular navigation device. [Figure 74] 1 illustrates various embodiments of a vascular navigation device. [Figure 75] 10 shows a graph depicting a pressure balloon priming method according to some embodiments. [Figure 76] 10 shows a graph depicting a pressure balloon priming method according to some embodiments. [Figure 77] 3 shows a flow chart of possible logic in various embodiments of the present invention. [Figure 78]3 shows a flow chart of possible logic in various embodiments of the present invention. [Figure 79] 3 shows a flow chart of possible logic in various embodiments of the present invention. [Figure 80] 1 illustrates an embodiment of a vascular navigation device that includes bladderless pressure sensing capabilities. [Figure 81] 1 illustrates an embodiment of a vascular navigation device that includes bladderless pressure sensing capabilities. [Figure 82] 1 illustrates an embodiment of a vascular navigation device that includes bladderless pressure sensing capabilities. [Figure 83] 1 illustrates an embodiment of a vascular navigation device that includes bladderless pressure sensing capabilities. [Figure 84] 1 illustrates an embodiment of a vascular navigation device that includes bladderless pressure sensing capabilities. [Figure 85] 1 illustrates an embodiment of a vascular navigation device that includes bladderless pressure sensing capabilities. [Figure 86] 1 illustrates an embodiment of a vascular navigation device that uses electrodes as sensors. [Figure 87] 10 illustrates an embodiment of a vascular navigation device in which a stiffener extends beyond the end plug. [Figure 88] 10 illustrates an embodiment of a vascular navigation device in which the stiffeners terminate in a curved portion. [Figure 89] 1 illustrates an embodiment of a vascular navigation device with a small diameter exit port area. [Figure 90A] 1 illustrates an embodiment of a vascular navigation device with a sleeve-type exit port area. [Figure 90B] 1 illustrates an embodiment of a vascular navigation device with a sleeve-type exit port area. [Figure 91] 1 illustrates an embodiment of a vascular navigation device with a dual layer exit port region. [Figure 92] 10 illustrates an embodiment of a vascular navigation device in which the core, or stiffener, contains leads for sensors / electrodes. [Figure 93]10 illustrates an embodiment of a vascular navigation device in which the stiffener is exposed at the distal end to form the most distal electrode. [Figure 94] 1 shows the magnitude of the sensor signal within the anatomy. [Figure 95] The relative magnitude of the signals from the distal and proximal sensors, as well as the pulsatile nature of the signals, are shown. [Figure 96] The relative magnitude of the signals from the distal and proximal sensors, as well as the pulsatile nature of the signals, are shown. [Figure 97] It is shown that signal magnitude, relative signal magnitude, and / or signal pulsatility can be used by a controller of a vascular navigation system to determine the location of the distal end of the device. DETAILED DESCRIPTION OF THE INVENTION

[0037] FIG. 1 illustrates an embodiment of a vascular catheter navigation device or system for navigating the human anatomy. A vascular catheter navigation device 102 is shown within a patient's vein 104. The vascular catheter navigation device is inserted into the patient via an insertion point 106. While the insertion point is shown here in the patient's chest, the insertion point may instead be in the patient's leg, arm, or neck, or elsewhere. To navigate a standard vascular catheter to its desired location, several undesirable obstacles must be avoided and / or overcome. For example, the vascular catheter may be mistakenly placed in an artery instead of a vein, the vascular catheter may be ventured down or up the wrong branch of the vascular system, the vascular catheter may get stuck on a vessel wall, the vascular catheter may be advanced too close to the heart, too far into or beyond the heart, or the vascular catheter may not be advanced far enough to reach its desired location or may only travel to a less-desirable location. Some of these risk areas are labeled 116. The distal tip of the vascular catheter navigation device is indicated as 108. At the proximal end of the vascular catheter navigation device is shown an infusion or sampling lumen 110 in fluid communication with one or more openings at or near the distal end of the vascular catheter navigation device. Also shown is a sensing port 112 in communication with a controller 114. The sensing port 112 is in communication with one or more sensors (not shown here) at or near the distal tip 108 of the vascular catheter navigation device 102. While one infusion / sampling lumen and one sensing port are shown here, multiple infusion / sampling and / or sensing ports may be present. The infusion lumen 110 may also be in communication with the controller 114.

[0038] FIG. 2 illustrates an embodiment of a vascular catheter navigation device where the distal tip is placed at the superior vena cava / caval-atrial junction (SVC-CAJ) 202.

[0039] FIG. 3 illustrates an embodiment of a vascular catheter navigation device. The distal end of the vascular catheter navigation device is inserted into an appropriate access vein and advanced along the vein to its target location. After the vascular catheter navigation device is inserted into the blood vessel, a sensing element 302 typically senses a parameter of blood flowing through the blood vessel through a needle, catheter, or sheath. A medium, such as a fluid, with a measurable parameter, such as temperature or conductivity, is injected through the device and into the blood vessel. The sensor signal is communicated back to the controller, which analyzes the sensor signal based on the sensor data over time, including the slope, magnitude, value, length, variability, pulsatility, phase, standard deviation, shape, pulsatility / Fourier analysis, etc. of the data curve. For example, by measuring and analyzing the measurable parameters, the controller can determine whether the distal end of the vascular catheter navigation device is in an artery instead of a vein based on the magnitude and direction of blood flow around the vascular catheter navigation device. If the controller determines that the distal end of the vascular catheter navigation device is in an undesirable position, an alarm or other indicator can be sent to the user. For example, if the controller determines that the catheter is in an artery instead of a vein, a specific identification signal, including an audible, visual signal, etc., may be signaled to instruct the user to remove the vascular catheter navigation device and any other devices, e.g., sheath, catheter, etc., and to apply pressure to the blood vessel.

[0040] Similarly, the vascular catheter navigation device can sense when its distal end is in the wrong branch of the vein based on the direction of flow and possibly the flow profile and magnitude. When the vascular catheter navigation device is advanced in the correct direction and into the correct vessel (towards the SVC-CAJ in the vein), blood will flow over the vascular catheter navigation device from the more proximal end to the distal end.

[0041] 3 shows one sensor 302, one sensor port 112, and one infusion / sampling lumen 110. However, there may be more than one infusion / sampling lumens and / or more than one sensor. Furthermore, the port to the controller and the sampling lumen may be the same lumen and incorporated into a single-lumen device. The infusion and / or sampling lumens may also be connected to the controller.

[0042] 4A-F illustrate the effect of fluid flow direction on the fluid flow properties relative to the catheter tip before, during, and after injection of a fluid bolus. At time T=0, the device 102 is within a blood vessel 404. The device 102 includes a sensor 302. The sensor 302 is designed to measure parameters of the blood and / or injection medium. A controller (not shown) communicates with the sensor 302 via a connector or lead 402, which in this example extends the length of the catheter to the controller. The sensor 302 and connector 402 may be incorporated into the vascular catheter or into a stylet extending through the catheter. A medium 410 is introduced into the blood vessel at time T=x. For example, the medium may be saline solution at a temperature different from body temperature. In this example, the parameter measured by the sensor is temperature, but any parameter, such as conductivity, may also be used. After injection, at T=x+1, blood flow causes the medium to mix with the blood flow. Figures 4A-C show the device in in-line blood flow conditions. As blood flow 406 flows away from the catheter, a bolus of medium 404 moves away from the catheter tip and away from the sensor. Figures 4D-4F show the device in a retrograde blood flow condition, such as in an artery. As blood flow 408 flows toward the catheter, a bolus of medium 410 flows toward and over the catheter tip. While this example shows a bolus of fluid, a stream of fluid could also be used.

[0043] Depending on the location of the sensor, different temperatures, parameters, or profiles can be measured over time / location. Variations in flow rate, direction, turbulence, etc. affect the mixing of the blood and medium and affect the profile of the parameter, in this example, temperature over time. In this way, the system can determine the direction and characteristics of blood flow at or near the catheter tip.

[0044] Figures 5A-5E and 6A-6E show several exemplary embodiments of a vascular catheter navigation device. Figure 5A shows an embodiment in which the sensor 302 is located at the catheter tip. Figure 5B shows an embodiment in which the sensor is located near, but not at, the catheter tip. This configuration may prevent the sensor from measuring parameters when introducing media from the catheter tip, allowing for better flow direction discrimination. Figure 5C shows an embodiment with two sensors, one at, and one near, but not at, the catheter tip. Sensor readings at different locations may vary depending on the fluid flow direction, characteristics, profile, etc. A sensor located near, but not at, the catheter tip may be located approximately 0.05 cm to approximately 2.0 cm back from the tip. Alternatively, a sensor located near, but not at, the catheter tip may be located approximately 0.75 cm to approximately 1.25 cm back from the tip. Figure 5D shows an embodiment in which the sensor is located on a guidewire or stylet 502. The stylet 502 may be free to move within the catheter, allowing one or more sensors to be placed at a distance from the catheter tip. Additionally, the guidewire / stylet may be removed after placement of the catheter. In this embodiment, the catheter may also include a sensor, as shown here. Figure 5E illustrates an embodiment in which the opening 504 is located near, but not at, the catheter tip. This opening may be in fluid communication with a separate media introduction lumen or infusion lumen, or with the same lumen as the distal opening. This particular media introduction lumen may exit at the catheter tip. An opening located near, but not at, the catheter tip may be located about 0.25 cm to about 2.0 cm back from the tip. Alternatively, an opening located near, but not at, the catheter tip may be located about 0.75 cm to about 1.25 cm back from the tip. Two or more infusate media may be introduced into either the same lumen or separate lumens of the device.

[0045] Figure 6A shows an embodiment with an opening between two sensors, with both sensors located near, but not at, the catheter tip. Figure 6B shows an embodiment with two or more sensors located near, but not at, the catheter tip. Figure 6C shows an embodiment with an opening between two sensors, with one of the sensors at the catheter tip. Figure 6D shows an embodiment with openings proximate to the two sensors. Figure 6E shows an embodiment with a channel 602. The channel 602 allows fluid to flow through the catheter proximate to the sensors within the catheter.

[0046] FIG. 7 shows an embodiment of a vascular navigation device with two sensors and multiple openings between the two sensors.

[0047] Clearly, numerous variations of these and other embodiments of the vascular catheter navigation device are contemplated. For example, sensors, openings, channels, etc. may be located on different sides of the catheter and / or guidewire / stylet. While the sensors, openings, and channels are shown here as being at or near the catheter tip, they may be located anywhere along the catheter and / or guidewire / stylet.

[0048] Different sensor configurations produce different parameter curve signatures at different vascular locations. For example, a single sensor will give a different set of curves than a system with two sensors. The distance of the sensor from the infusion exit site will also provide different curves. Different infusion rates, infusion volumes, infusion types (bolus vs. stream), infusion pressures, infusion velocities, etc. will also provide different curves and therefore different anatomical characteristics. Different aspects of the curves may be analyzed by the controller to determine vascular location. These may include, but are not limited to, slope, magnitude, value, length, variability, pulsatility, phase, standard deviation, shape, area under the curve, Fourier transform, frequency, harmonics, etc. In some embodiments, some frequencies in the data may be removed, including those related to heart rate, system noise, tissue conductance, etc.

[0049] In some embodiments, there is one sensor, and therefore one parameter versus time / location curve. In some embodiments, there are two or more sensors, and therefore two or more parameter versus time / location curves. In some embodiments, the infusion outlet port is near the more proximal sensor or sensors. In some embodiments, the infusion outlet port is more proximal or distal than the sensor or sensors. In some embodiments, the infusion outlet port is between the sensors. In some embodiments, one or more sensors may be used.

[0050] Note that the curve may look different in different anatomies and based on the design of the vascular catheter navigation device. For example, the curve may be different for different sensor locations relative to the fluid exit port. The curve may depend on the type of sensor or the fluid infusion rate. The curve may depend on the initial parameter level of the infused fluid. Other design factors may also result in different parameter versus time / location curve shapes.

[0051] Additionally, calibration of the parameter versus time / location curves can be performed by the controller. For example, a baseline measurement can be derived after insertion of the system or at other times during use of the system. For example, a baseline measurement can be taken in the blood vessel before any infusion fluid is infused or at a particular infusion rate. The baseline measurement (a measurement taken without infusing any fluid into the system) can be used in analyzing the data in the controller to determine the location of the vascular catheter navigation device within the anatomy.

[0052] Various characteristics of the parameter versus time curves may be analyzed to determine the location of the vascular catheter navigation device. For example, the curve amplitude, noise, standard deviation, shape, slope, value, area under the curve, Fourier transform, frequency, harmonics, etc. of one or more curves may be used to determine the location of the vascular catheter navigation device within the vasculature. These same parameters may be compared between multiple parameter versus time / location curves to determine the placement location of the vascular catheter navigation device. For example, the position of the curves, relative position, magnitude, and / or relative magnitude (positive or negative) of the peaks may be used to determine the location of the vascular catheter navigation device. Furthermore, the differences between the amplitude, noise, standard deviation, shape, slope, value, area under the curve, and / or Fourier transform, harmonics, and frequency of data from multiple sensors may be used to determine the location of the vessel. Depending on the droplet size and / or infusion rate, the area under the curve or Fourier transform may be used to analyze the parameter versus time curve and therefore the location of the vessel. Furthermore, a maximum value, or multiple maximum values, may be meaningful.

[0053] As used herein, the term "droplet" can mean a drop, a bolus, a stream, an intermittent stream, etc. when referring to an infusion fluid.

[0054] 8 is a schematic diagram showing fluid flow in different regions of the vasculature, representing desired (correct) and undesired (incorrect) device placement. Arrow 802 indicates the direction of blood flow. Region 804 indicates the infusion of fluid (such as saline). Note how different anatomical locations result in different flow conditions and therefore different dissipation patterns of the fluid infusion. While one sensor 806 is shown here, in this and any other embodiment disclosed herein, two, or three, or four, or five, or six, or more sensors may be used.

[0055] It should be noted that some embodiments disclosed herein may describe a particular type of sensor and measured parameter, e.g., the sensor measures temperature. However, any of the embodiments disclosed herein may use any type of sensor (or more than one type of sensor) that measures the sensor parameter. For example, an embodiment that discloses a sensor that measures temperature may instead or additionally include a conductivity sensor that measures conductivity. An embodiment that describes a controller that uses data from a particular type of sensor may instead or additionally use data from another type of sensor.

[0056] 9A-9E show various embodiments of a vascular catheter navigation device with two sensors, or other types of sensors, on the guidewire / stylet. FIG. 9A shows a stylet 910 with a proximal sensor 902 and a distal sensor 904. In this embodiment, infusate 906 exits at the distal tip of the catheter 908, proximal or close to the proximal sensor 902. Alternatively, infusate can be infused through the lumen of the guidewire / stylet. While two sensors are shown here, one, or more than two sensors can also be used.

[0057] Figure 9B shows an embodiment in which infusate is injected through the stylet / guidewire and exits between two sensors. Figure 9C shows an embodiment in which infusate is injected through the stylet / guidewire and exits near or distal to the distal sensor. If one sensor is used, the fluid injection exit port can be either proximal or distal to the sensor.

[0058] 9D and 9E show an embodiment where there are two sensors on the stylet / guidewire and the guidewire can be moved relative to the end of the catheter. This embodiment can be used to change the sensing and / or infusate outlet location relative to the tip of the catheter.

[0059] For example, in some embodiments, the stylet / guidewire may include both an infusion lumen (i.e., the stylet / guidewire may be hollow) and a sensor, so that it may be positioned initially within the anatomy and / or independently of the vascular catheter, such as when jugular venous access is used for catheter insertion. Once the stylet / guidewire is in place, the vascular catheter may be advanced so that the distal tip of the catheter is in a known position relative to the distal tip of the stylet / guidewire. The stylet / guidewire may then be removed.

[0060] Figures 9F-9H show the distance between the fluid exit port and the sensor, and the distance between the catheter / stylet tip and the sensor / port. Figure 9F shows the axial distance aa between the infusate exit or port and the distal or single sensor. The axial distance bb is the distance between the fluid exit port and the proximal sensor. The axial distance cc is the distance between the distal sensor and the proximal sensor. These distances can be positive or negative. Although two sensors are shown here, the device may have one sensor or more than two sensors.

[0061] Distance aa may be approximately 0 mm. Alternatively, distance aa may be in the range of approximately 0 mm to approximately 0.5 mm, or approximately 0 mm to approximately 1 mm. Alternatively, distance aa may be in the range of approximately 0 mm to approximately 2 mm. Alternatively, distance aa may be in the range of approximately 0 mm to approximately 3 mm. Alternatively, distance aa may be in the range of approximately 3 mm to approximately 5 mm. Alternatively, distance aa may be in the range of approximately 5 mm to approximately 10 mm. Alternatively, distance aa may be in the range of approximately 0 mm to approximately 100 mm. Alternatively, these distances may be negative. For example, distance aa may be approximately 1 mm or approximately -1 mm. At 1 mm, the distal sensor is more distal than the fluid exit port. At -1 mm, the fluid exit port is more distal than the distal sensor. This is true for all dimensions provided in connection with Figures 9F-9H.

[0062] The distance bb may be approximately 10 mm. Alternatively, the distance bb may be in the range of approximately 0 mm to approximately 10 mm. Alternatively, the distance bb may be in the range of approximately 8 mm to approximately 12 mm. Alternatively, the distance bb may be in the range of approximately 5 mm to approximately 15 mm. Alternatively, the distance bb may be in the range of approximately 1 mm to approximately 100 mm. Alternatively, the distance bb may be in the range of approximately 3 mm to approximately 5 mm. Alternatively, the distance bb may be in the range of approximately 5 mm to approximately 10 mm. Alternatively, the distance bb may be in the range of approximately 0 mm to approximately 100 mm. These ranges may also be negative distances.

[0063] The distance cc may be approximately 10 mm. Alternatively, the distance cc may be in the range of approximately 0.0 mm to approximately 5 mm, or the distance cc may be in the range of approximately 5 mm to approximately 15 mm. Alternatively, the distance cc may be in the range of approximately 15 mm to approximately 20 mm. Alternatively, the distance cc may be in the range of approximately 1 mm to approximately 100 mm.

[0064] Distance dd in FIG. 9G is the distance between the fluid exit port and either the distal sensor or the proximal sensor. While the distance is shown here for the proximal sensor, distance dd may apply to either. Alternatively, there may be only one sensor. Distance dd may be approximately 0.75 mm. Alternatively, distance dd may be in the range of approximately 0.25 mm to 1.5 mm. Alternatively, distance dd may be in the range of approximately 0.1 mm to 5 mm.

[0065] FIG. 9H shows the axial distance ee between the fluid exit port and the end of the catheter and / or stylet. The distance ee may be approximately 0 mm. Alternatively, the distance ee may be in the range of approximately 0 mm to approximately 1 mm. Alternatively, the distance ee may be in the range of approximately 0 mm to approximately 3 mm. Alternatively, the distance ee may be in the range of approximately 0 mm to approximately 5 mm. Alternatively, the distance ee may be in the range of approximately 5 mm to approximately 10 mm. Alternatively, the distance ee may be in the range of approximately 0 mm to approximately 100 mm. These distances may be positive or negative.

[0066] 91 shows an embodiment of a vascular catheter navigation device that includes only one sensor and includes a conduit 902 within the system. Various embodiments of systems that include conduits are described in more detail elsewhere herein. The conduit 902 incorporates an infusate exit port, indicated by an X. The distance ff shown here is the longitudinal distance between the conduit's fluid infusate exit port and the sensor.

[0067] FIG. 9J shows an embodiment similar to that of FIG. 9I, where distance gg represents the radial distance between the fluid infusate exit port of the conduit and the sensor.

[0068] FIG. 10 illustrates an embodiment of a vascular catheter navigation device that can be used with any catheter, or in other words, in which the sensor, infusate lumen, controller, and locking mechanism are included in the stylet / guidewire. FIG. 10 illustrates an embodiment with two thermocouples, a distal sensor 1012 and a proximal sensor 1010, and an infusate exit port 1002 as part of the guidewire / stylet 1001. Alternatively, the stylet / guidewire may have only one sensor, or three or more sensors. The stylet / guidewire may include a feature 1014 to assist in aligning the stylet / guidewire with the catheter. This embodiment may include a tip section 1006, such as a molded urethane, nylon, silicone, or other polymer section, for embedding a sensor. Also shown here is an optional guidewire / stylet coil 1008 and the distal tip of the catheter 1018. In cross section, the infusion lumen 1016 may also be shown.

[0069] This embodiment may include a torque or locking device 1022, which may be used to lock the stylet to the proximal end of the catheter, for example, using a luer lock 1020 at the proximal end of the catheter 1018. Because the torque / locking device is locked to the stylet / guidewire, the stylet / guidewire does not move relative to the vascular catheter. A controller (not shown) may include and / or control the infusion mechanism via fluid port 1026 and read data from the sensor via port 1004. The controller may be located near the proximal end of the stylet or may be located a few inches or feet from the proximal end of the stylet. Sensor leads 1024 are also shown. The infusion may be constant, intermittent, or consist of a bolus.

[0070] 11A-11I show various views of various embodiments of a stylet / guidewire version of a vascular catheter navigation device.

[0071] The stylet shown in Figures 11A-11I and some other embodiments serves several functions, including: 1) stiffening the catheter to aid insertion, 2) providing a medium for fluid delivery, and 3) providing channels for one or more sensor leads. Figure 11A is a cross-section of a stylet such as that shown in the embodiment of Figure 10. While two sensors are shown here, the device may include one, or more than two sensors.

[0072] 11B shows an embodiment of a stylet that includes three components in a triple-lumen heat shrink and / or tubing housing 1102, which houses two sensors 1104 and a fluid lumen 1106. Alternatively, there may be one or more than two sensors.

[0073] Figure 11C shows an embodiment in which all or part of the stylet coil is made from sensor wire or lead. Figure 11D is a side view of the embodiment shown in Figure 11C.

[0074] Figure 11E shows an embodiment that includes an extrusion, i.e., a tube (metal or plastic), that houses two sensors and a fluid lumen. Alternatively, there may be one or more than two sensors.

[0075] FIG. 11F shows an embodiment that includes multiple sensor leads bundled together as well as an extrusion, i.e., tubing (metal or plastic), that houses a fluid lumen.

[0076] Figure 11G shows an embodiment comprising a thin-walled extrusion, i.e., a tube, in which the sensor leads are surrounded by a fluid lumen. There may be one, two, three or more sensors.

[0077] 11H shows an embodiment including an extrusion, i.e., a tube (plastic or metal), containing multiple sensors, a fluid lumen, and a stiffener 1108, which may be a wire or rod. There may be one, two, three, or more sensors.

[0078] 11I shows an embodiment including an extrusion, i.e., tubing (plastic or metal), that contains the sensor lead bundle as well as the fluid lumen. The outer surface of the sensor lead bundle may be made of the same material as the outer extrusion, allowing for optional chemically or thermally formed bonds or welds 1106. There may be one, two, three, or more sensors.

[0079] In some embodiments, it is important to either fix or precisely control the distance between the catheter tip and the guidewire / stylet, or to be able to determine the distance between the catheter tip and the guidewire / stylet. It may also be important to be able to fix the location of the infusion relative to the sensor, or to be able to know the distance between the location of the infusion outlet port and the sensor. The distance between the outlet port and the sensor may have an effect on the parameter profile during the fluid infusion. These distances may be fixed across multiple patients and scenarios, or may be different for different patient types and scenarios. For example, the distance may be different depending on the vasculature being accessed. The distance may be different for patients with different weights, sizes, body mass indexes, health conditions, ages, genders, heart conditions, or other patient characteristics. The distance may be different for different catheter sizes, such as catheters with different numbers and shapes of catheter lumens.

[0080] In some embodiments, the stylet / guidewire is secured or locked relative to the catheter tip using a torque device near the proximal end of the catheter, such as that shown in FIG.

[0081] In some embodiments, the user determines the relative alignment of the catheter and stylet / guidewire by visual inspection and then measures the relative distance from the two values.

[0082] 12-17 show various embodiments of vascular catheter navigation devices that include various registration techniques for fixing or knowing the distance between one or more sensors on the stylet and the catheter tip or fluid injection point.

[0083] FIG. 12 illustrates an embodiment with an indicator on the stylet / guidewire at a fixed, known distance from the sensor. In this embodiment, the user aligns the tip of the catheter 1202 with an indicator or marking 1204 on the stylet 1206 before inserting it into the patient. The relative distance 1208 of the catheter tip to the stylet tip can be locked using a torque device, a locking-rotating hemostatic valve, a Tuohy-Borst valve, or other locking mechanism, preferably at the proximal end, before the catheter is inserted into the patient. The indicator on the guidewire / stylet can be a visible marking, such as a red stripe or dot, or a tactile marking, such as a ridge or groove, or other type of indicator.

[0084] 13 shows an embodiment with a protuberance, or projection, 1302 on the stylet at a fixed, known distance from the distal sensor. This allows the user to align the tip of the catheter with the projection on the stylet, either visually or by feel. This alignment can be performed ex vivo or in vivo. In some embodiments, the projection is small or soft enough to allow the stylet to be removed from the catheter after placement within the anatomy.

[0085] FIG. 14 shows an embodiment similar to that shown in FIG. 13 in which the sensor 1104 performs the function of a protrusion on the stylet.

[0086] 15 illustrates an embodiment in which a jig, block, or aligner 1502 is used to align the tip of the catheter a fixed, known distance from the tip of the stylet. The relative position of the catheter to the stylet is then locked at the proximal end using a torque device, a locking and rotating hemostatic valve, a Tuohy-Borst valve, or other locking mechanism, and / or at the distal end using a fixed conduit (disclosed in detail elsewhere herein). The jig or block 1502 may itself be adjustable, allowing the fluid exit port (here, the distal end of the catheter) to be aligned with the sensor at a variety of different lengths.

[0087] FIG. 16 shows an embodiment similar to that shown in FIG. 13 in which an inflatable balloon 1602 is used as a protrusion to align the catheter and stylet. The balloon may be annular or on one or more sides of the stylet. The balloon may be inflated for use during alignment and either remain inflated during placement to lock the stylet in place relative to the catheter, or deflated during placement (where the catheter and stylet are locked together using a torque or valve). In this embodiment, the stylet or catheter includes an inflation lumen to inflate and deflate the balloon. The balloon may be deflated to remove the stylet after placement of the catheter.

[0088] FIG. 17 shows an embodiment of a vascular catheter navigation device that includes a sensor 1702 that can sense when inside the catheter tip during use. For example, the sensor can be magnetic, ultrasound, light, temperature, etc. In some embodiments, a proximal sensor 1704 is used as the sensor that determines when the proximal sensor is inside the catheter tip. The shape of the parameter versus time / location curve after injection of infusate indicates a particular profile when the sensor is just inside the catheter tip and can be used to identify this alignment. This embodiment can include one, two, or more sensors.

[0089] In some embodiments, control of the infusate outlet flow pattern may be important to achieve consistent results. It may also be important to compare the infusate flow to the flow of blood within the vasculature / heart. The infusate flow may be intentionally made either more laminar or more turbulent to achieve these goals. Some embodiments may include features that direct the flow and are part of the catheter or stylet. These features may be surface features such as dimpling or an orange peel finish that alters the surface finish of the catheter or stylet. These features may be part of the OD of the stylet / temperature sensor, or the ID of the fluid lumen, or both.

[0090] Figures 18A and 18B show two possible embodiments for a flow director (to create laminar or turbulent flow) in the infusate lumen 1016 of a vascular catheter navigation device. The flow director 1802 can be at the end of the infusate lumen, as shown in Figure 18A, or recessed from the tip of the lumen outlet, as shown in Figure 18B.

[0091] 19A-19C show another embodiment of a vascular catheter navigation device in which the shape of the infusate lumen controls the type of fluid flow exiting the lumen. Some of the parameters that may be varied include the area, shape, surface condition, etc. of the infusate lumen opening. Sensor leads and / or stiffeners 1902 are also shown.

[0092] Some embodiments vibrate the stylet and / or catheter to create turbulent flow of infusate from the infusate lumen.

[0093] 20 shows an embodiment of a stylet without an infusion lumen. Fluid may be introduced through another catheter lumen (perhaps on a separate catheter) upstream of the catheter tip, closer to the insertion site, or elsewhere. For example, fluid may be infused through a "buddy" catheter 2002, shown here with the vascular catheter. Fluid may also be heated or cooled by a heating / cooling element on the catheter or on the "buddy" catheter. A "buddy" guidewire / stylet for infusion is also envisioned.

[0094] FIG. 21 shows features 2102 within the infusate lumen that enhance turbulence control.

[0095] FIG. 22 illustrates a feature 2202 within the infusate lumen that can result in laminar (or less turbulent) flow control.

[0096] Note that some embodiments disclosed herein show two sensors. In any of these embodiments, one, two, or more sensors may be used.

[0097] In some embodiments, the outer diameter (OD) of the stylet is about 1 mm or less. In some embodiments, the OD of the stylet is about 0.5 mm or less. In some embodiments, the OD of the stylet is about 1.5 mm or less. In some embodiments, the OD of the stylet may be in the range of about 0.2 mm to about 5 mm.

[0098] In some embodiments where the catheter is double or triple lumen, the functionality of the stylet is divided into separate portions (fluid, stiffener, sensing lead, etc.) and multiple stylets can be used within the multiple lumens of the catheter.

[0099] Many types of temperature sensors may be used in any of the embodiments disclosed herein, including thermocouples, fiber optics, resistive, bimetallic, thermometers, change of state, silicon diodes, thermistors, optical thermometry (infrared or otherwise), mercury thermometers, manometers, and the like.

[0100] In addition to infusing fluid, other methods of creating a thermal change at or near the tip of the catheter / stylet can be used, as disclosed elsewhere herein. Fluids at temperatures above body temperature can be introduced, and resistive heating elements, piezoelectric cooling elements, or the like can be included in or on the catheter, on the guidewire / stylet, or in the injector, external to the body. Alternatively, the infused fluid can be at a temperature that is different from body temperature but is not tightly controlled, and this temperature difference (between body temperature and the infusate temperature) is measured and tracked by the controller.

[0101] In embodiments using a resistive heating element, the resistive heating element may be on the catheter or on the stylet. In embodiments on the catheter, the element may be external to the catheter or within one or more lumens of the catheter. Alternatively, the element may be on the guidewire / stylet. In embodiments on the guidewire / stylet, the element may be within the catheter lumen, partially within the catheter lumen, or external to the catheter lumen exposed to the blood. Embodiments that heat / cool blood may not require an injectate fluid.

[0102] As shown in FIGS. 23A-23E and 24A-24E, a graphical user interface may be displayed on a small screen / display 2314, a large screen, in the form of a projection, virtual reality or augmented reality goggles, etc. The main categories of user interaction may include user alerts: 1) icons, 2) icon colors or warning lights, 3) auditory tones accompanying alerts, 4) visual body map that matches the catheter tip location and uses alert types, and 5) any combination of phrases or words written on the display indicating status or alert, vibration, etc. The categories may be: 1) "Keep moving forward," which means the catheter tip is advancing through a peripheral vein or has rounded a curve and reached the superior vena cava. This mode is accompanied by visual and auditory feedback indicating a positive state, such as a green light and icon and a positive tone. 2) "Correct placement," using a checkmark icon, indicates the tip has reached the proper location—the cavoatrial junction for a PICC line, or perhaps another location for another type of catheter insertion. This state may also be accompanied by a positive tone and light. 3) If the catheter encounters opposing flow, a warning, "Turn" may appear. This is a warning if the catheter is advanced down the azygos branch, into the IVC, or is located in an artery. Because this is not a positive state, this state may be accompanied by a red, yellow, or orange light or icon, along with a tone indicating an undesirable state is occurring. This may be accompanied by an unpleasant frequency, pitch, and tone. 4) If the catheter is in the heart, either atrium or ventricle, the user may be alerted by a heart icon and / or an "Intracardiac" warning. This state may be accompanied by a negative color and tone. 5) If the catheter tip is hitting the wall of a vein or has some kind of obstruction, a "Adjust" warning may be displayed. This may be accompanied by a negative color and tone. Also shown in Figures 23A-23E and 24A-24E are a catheter 2302, a stylet 2304, a sensor adapter 2306, a fluid adapter 2308, a primary button 2310, and an insertion / tracking button 2312.

[0103] A graphical user interface (GUI) may display and navigate the location of the catheter tip relative to three-dimensional space in real time. While the graphical user interfaces shown in Figures 23A-23E and 24A-24E are two-dimensional, some embodiments include a three-dimensional display that may also communicate information in three dimensions.

[0104] It should be noted that although some embodiments disclosed herein incorporate sensors into the vascular catheter, the vascular catheter navigation device may be a standalone device that fits within the vascular catheter and can be removed once placement of the vascular catheter is complete. The vascular catheter navigation device may, for example, perform the function of a stylet or guidewire in a standard vascular catheter.

[0105] 25A-25C illustrate an embodiment of a vascular catheter navigation device that includes a conduit for controlling fluid flow out of the device's fluid exit point. In this embodiment, conduit 2502 is attached to a guidewire / stylet 2504, forming a combined stylus / conduit device. Conduit 2502 is designed to fit within the ID of an infusion lumen 2506 of a vascular catheter 2508. In this illustration, vascular catheter 2508 includes only one lumen, the infusion lumen, although multiple lumens may be present in a vascular catheter in addition to the infusion lumen.

[0106] In some embodiments, the guidewire / stylet 2504 includes a core 2510, a coil 2512, an end cap 2514, and a sensor 2516. The core 2510 may include a stiffening wire, which may be tapered and lead to a sensor. The sensor may be integrated into the end cap or may be separate. There may be one or more sensors. The sensor may be a thermocouple. A larger cross-sectional dimension of the sensor attenuates the parameter measurement, where a smaller cross-sectional dimension of the thermocouple may allow for a faster response time. The diameter or cross-sectional dimension 2526 of the sensor may be approximately 0.2 mm to 0.3 mm. Alternatively, the diameter or cross-sectional dimension 2526 of the thermocouple may be approximately 0.02 mm to approximately 0.5 mm.

[0107] In some embodiments, the conduit 2502 has a length 2520 and includes one or more fluid flow channels 2518 with a diameter or cross-sectional dimension 2522. The channels may be circular, oval, or any other cross-sectional shape. The channels may have a diameter or cross-sectional dimension of about 0.4-0.6 mm. Alternatively, the channels may have a diameter or cross-sectional dimension of about 0.1-1.0 mm. Alternatively, the channels may have a diameter or cross-sectional dimension of about 0.01-2.0 mm. The conduit length 2520 may be about 4-8 mm. Alternatively, the conduit length 2520 may be about 0.5 mm-20 mm.

[0108] The cross-sectional area and shape of the flow channels at least partially determine the flow rate of the fluid exiting the conduit. The number of flow channels also affects the flow parameters of the fluid exiting the conduit. Preferably, the fluid infusion rate may be about 2-3 ml / min. Alternatively, the fluid infusion rate may be about 3-5 ml / min. Alternatively, the fluid infusion rate may be about 5-10 ml / min. Alternatively, the fluid infusion rate may be about 1-5 ml / min. Alternatively, the fluid infusion rate may be about 0.5-7 ml / min. The flow rate at the conduit outlet is preferably about 60-100 cm / sec. Alternatively, the flow rate at the conduit outlet is about 1-300 cm / sec.

[0109] The conduit 2502 may serve several purposes: 1) It substantially seals the distal end of the infusion lumen of the vascular catheter while allowing fluid flow through / over the conduit so that when fluid is infused through the infusion lumen of the catheter, the majority of the fluid exits the vascular catheter via flow path 2518. It is important to note that the conduit does not fully occlude the infusion lumen of the catheter, allowing fluid to pass therethrough and, in some cases, through channels around it.

[0110] 2) The distance 2524 between the fluid exit point 2503 and the sensor on the guidewire / stylet is made known and fixable for more controlled parameter measurement within the vasculature. The fluid exit point may be the exit point at the distal end of the conduit flow path or at the distal end of the catheter, depending on whether the conduit partially protrudes beyond the distal end of the catheter. The distance 2524 may be approximately 0.0-1.0 mm. Alternatively, the distance 2524 may be approximately 0.5-1.0 mm. Alternatively, the distance 2524 may be approximately 0.0-2.0 mm. Alternatively, the distance 2524 may be approximately 0.0-5.0 mm. Alternatively, the distance 2524 may be approximately 0.0-10.0 mm. As used herein, "approximately 0.0" or "substantially zero" may mean plus or minus 1 mm, or "substantially zero" may mean plus or minus 2 mm, or "substantially zero" may mean plus or minus 3 mm. This may be true for any of the embodiments disclosed herein.

[0111] 3) Centering or otherwise aligning the fluid exit point of the conduit with the temperature sensor.

[0112] 4) Centering or otherwise aligning the fluid exit point with the catheter tip.

[0113] 5) Controlling the flow characteristics of the fluid exiting the exit point. For example, the size, shape and number of exit ports at least partially control the flow characteristics of the fluid exiting the ports. Parameters such as turbulence, flow rate, volumetric flow rate, and flow volume may be controlled. The cross section of the flow channel 2518 determines the infusion rate of the fluid as well as the infusion rate of the fluid exiting the flow channel 2518. The infusion rate may be matched to the blood flow rate.

[0114] The outer surface of the conduit can be substantially sealed by the inner surface of the vascular catheter's infusion lumen without the need for perfect alignment of the guidewire / stylet with the vascular catheter. Because the vascular catheter is larger and more compressible than the stylet, the relative alignment of their respective distal tips can change during the procedure. If the length of the conduit is longer than this changed value, the conduit still seals the vascular catheter's infusion lumen even if the distal tip of the stylet / conduit combo and the vascular catheter move relative to each other. Alternatively or additionally, the conduit secures the guidewire / stylet to the vascular catheter so that one does not substantially move relative to the other, at least longitudinally.

[0115] The cross-sectional size / diameter of the conduit may be approximately 0.5-1.5 mm. Alternatively, the cross-sectional size / diameter of the conduit may be approximately 0.1-3 mm. In some embodiments, the gap between the outside of the conduit and the inside of the infusion lumen of the vascular catheter is small enough to create a substantial seal between the outside of the conduit and the inside of the infusion lumen of the vascular catheter. This facilitates essentially all of the infused fluid to exit through the flow path 2518, which controls the distance between the fluid outlet and the temperature sensor. The gap between the outside of the conduit and the inside of the infusion lumen of the vascular catheter may also be large enough to allow the stylet / conduit combination to move within the infusion lumen of the vascular catheter for positioning and / or removal. The outer surface of the conduit may be coated with or fabricated from a lubricious material, such as PTFE, a hydrophobic material, a hydrophilic material, or the like. The gap between the outside of the conduit and the inside of the infusion lumen of the vascular catheter may be approximately 0.070-0.080 mm. Alternatively, the gap between the outside of the conduit and the inside of the infusion lumen of the vascular catheter may be about 0.05 to 0.1 mm, or about 0.001 to 1.00 mm.

[0116] It should be noted that the clearance between the outside of the conduit and the inside of the infusion lumen of the vascular catheter may vary for embodiments of expandable / contractable conduits or conduits having expandable / contractable features, such as those shown in Figures 27, 28, 29A-29C, 30, and 36A-36C. For example, the clearance in the contracted state may be larger than that of a conduit that does not expand / contract, and the clearance in the expanded state may be smaller than that of a conduit that does not expand / contract. For example, the clearance in the expanded state may be substantially zero.

[0117] FIG. 25A shows the distal end of the conduit 2502 substantially aligned with the distal end of the catheter 2508 (note that, as used herein, "distal" refers to the end of the vascular catheter navigation device that enters the body; as used herein, "proximal" refers to the end of the vascular catheter navigation device that does not enter the body). FIG. 25B shows an embodiment in which the distal end of the conduit is designed to be mounted inside the distal end of the infusion lumen of a catheter for infusion. FIG. 25C shows an embodiment in which the distal end of the conduit is designed to be mounted outside the distal end of the distal end of the infusion lumen of a catheter for infusion. Note that some embodiments may be designed to be mounted in more than one position.

[0118] Fluid exit point 2503 is shown for the device in Figures 25A-25C and other figures. Note that the exit point can be at the distal end of the conduit or the distal end of the catheter, depending on the alignment of the conduit and the distal end of the catheter.

[0119] During use, a stylet / conduit combination device is inserted (or becomes inserted) into the infusion lumen of a vascular catheter. The catheter is then inserted into and advanced through the vascular system. As the device is advanced, fluid is infused through the infusion lumen. The conduit substantially seals the catheter's infusion lumen, so fluid exits the system through the conduit's flow path, and the fluid flows through the vascular system, and a sensed parameter of the blood / fluid in the vascular system is sensed by the sensor. The distance between the fluid's exit point and the sensor is fixed / known, and a parameter vs. time / location curve is related to the flow characteristics within the vessel. Different signatures of these curves can be used to identify the location of the tip of the vascular catheter navigation device. After the system is navigated to its desired location, the stylet / conduit combination device is removed, and the vascular catheter's infusion lumen functions as a standard infusion lumen. The stylet / conduit combination device can later be reinserted into the vascular catheter's infusion lumen to confirm the location of the vascular catheter's tip.

[0120] 26 illustrates an embodiment of a vascular catheter navigation device in which the flow path is within the guidewire / stylet component itself. In this embodiment, the conduit serves to substantially seal the end of the catheter's infusion lumen, but the flow path flows between the stylet core 2510 and stylet coil 2512 and exits via an opening 2602 between the coils.

[0121] In some embodiments, the seal between the conduit and the catheter may be an O-ring, a bulge, a flange, a flare, a balloon, a compression seal, a hydrophilic material, or other sealing mechanism. The seal may be part of the conduit, e.g., a flare, a bulge, or a flange, or the seal may be a separate component, e.g., an O-ring. The seal may be manufactured by any suitable method, including injection molding. In some embodiments, the seal is on the stylet / conduit, while in some embodiments, the seal is on the catheter. In some embodiments, the seal is on the stylet / conduit and catheter combination.

[0122] FIG. 27 shows a variation of the conduit that includes a proximal flange 2702. The flange can act as a seal, substantially sealing the conduit against the ID of the catheter's infusion lumen when fluid is infused through the catheter's infusion lumen above a certain pressure. The flange can be rigid, semi-rigid, or flexible. When fluid is no longer infused through the infusion lumen or the infusion pressure is reduced below a certain pressure, the flange 2702 collapses slightly, reducing the diameter or cross-sectional area of ​​the conduit at the flange, thereby allowing the combination stylet / conduit device to be removed from the vascular catheter after its location has been established. Alternatively, the flange can fold inward and reverse direction during a withdrawal motion to allow for easy removal of the combination stylet / conduit device.

[0123] Figure 28 shows a variation of the embodiment shown in Figure 27 in which the conduit has both proximal and distal flanges. It should be noted that in these and other embodiments disclosed herein, during use, i.e., during catheter navigation, the distal end of the conduit can be flush with the distal tip of the catheter, distal to the distal end of the catheter, or proximal to the distal end of the catheter.

[0124] 29A-29C illustrate an embodiment of a vascular catheter navigation device in which a conduit includes a thin-walled inflatable structure. FIG. 29A shows a conduit with a thin-walled, inflatable proximal portion 2902 and a distal portion 2904, the distal portion being bonded or otherwise attached to a stylet. The proximal portion 2902 of the conduit includes an opening 2906. The proximal conduit portion 2902 expands when fluid is infused through the infusion lumen of the catheter, substantially sealing the inflatable portion against the inner wall of the infusion lumen. Infusion fluid can also exit the catheter through the opening 2906. The opening must be small enough to allow pressure to build within portion 2902, causing it to "expand" within the infusion lumen. The opening must be large enough to allow adequate fluid to escape into the bloodstream and allow meaningful parameter measurements to be made. The diameter or cross-sectional dimension of the opening may be approximately 0.4-0.06 mm. Alternatively, the diameter or cross-sectional dimension of the opening may be between about 0.05 and 1.0 mm. The length 2910 of the proximal section 2902 of the conduit may be between about 0.3 and 0.5 mm. Alternatively, the length 2910 of the proximal section 2902 of the conduit may be between about 0.3 and 20 mm.

[0125] To remove the stylet / conduit component from the vascular catheter, the fluid infusion is reduced or reversed to "collapse" the proximal section 2902 of the conduit so that the stylet / conduit may be removed. This is shown in FIG. 29B. In some embodiments, collapsing is not required, and the stylet / conduit may be removed from the vascular catheter while the fluid infusion is still occurring.

[0126] FIG. 29C shows a variation of an inflatable conduit with a collar 2912 that can help direct the fluid flow as it exits the conduit.

[0127] One advantage of an "inflatable" conduit is that the shape of the conduit can conform to any shape of infusion lumen, whether round, semicircular, triangular, oval, etc. The difference in cross-sectional area of ​​the deployed versus undeployed conduit can be significant, which is useful in smaller infusion lumen devices.

[0128] Figure 30 shows an embodiment of a conduit having a thin-walled "skirt" 3002. This "skirt" expands and contracts similarly to the "inflatable" portion of the embodiment shown in Figures 29A and 29B.

[0129] Figure 31 shows an embodiment of a conduit that includes features 3102 that help direct the flow of fluid exiting the conduit. The features may direct the flow parallel as shown in Figure 31, inward as shown in Figure 32, outward as shown in Figure 33, or in any other manner.

[0130] 34 shows an embodiment that includes a deflector 3402 that helps keep the system away from the vessel wall. The deflector can be spherical, or substantially spherical, or any other shape. The diameter or cross-sectional dimension of the deflector can be about 0.3-0.4 mm. Alternatively, the diameter or cross-sectional dimension of the deflector can be about 0.01-1.0 mm.

[0131] FIG. 35 shows an embodiment of a cone-shaped conduit that helps to seal within the infusion lumen of the catheter during the infusion period.

[0132] FIGS. 36A-36C show an embodiment of a vascular catheter navigation device including a compressible conduit 3606. The compressible conduit may be made of silicone, polymer, or other suitable material. FIG. 36A shows the conduit in its compressed state. In this state, the conduit substantially seals the infusion lumen of the catheter. FIG. 36B shows the compressible conduit in its uncompressed state, which can be repositioned and / or removed to reduce its diameter / cross-sectional dimension. Compression / decompression of the conduit may be accomplished by a rod or hypotube or tube 3602 connected to the proximal end of the compressible conduit and manipulated (pushed, pulled, twisted, etc.) from the proximal end of the catheter to compress and decompress the conduit. FIG. 36C shows a variation of the system that allows the user to compress / decompress the conduit by rotating a threaded rod / hypotube / tube 3604 that engages the conduit.

[0133] Figures 37A-37F show two different cross-sectional views of several embodiments of a vascular catheter navigation device. Figure 37A shows an embodiment in which a guidewire / stylet 2504 is approximately centered within a conduit 2502 within the infusion lumen of a vascular catheter 2508. The flow channel 2518 can have different cross-sectional shapes, such as spherical, triangular, as shown here, and others. There may be one, two, or more flow channels. The guidewire / stylet can include a sensor lead 3702. The lead can be, for example, copper magnet wire, with a diameter of about 0.001 inch to about 0.005 inch (about 0.0254 mm to about 0.127 mm).

[0134] 37B shows an embodiment of a vascular catheter navigation device in which the guidewire / stylet is off-center. The cross-sectional views show various possible configurations of the guidewire / stylet and flow channels. The flow channels can be circular, crescent-shaped, etc., and there may be one, two, or more flow channels in any of the embodiments disclosed herein. Note that the conduit may simply be a tube, as indicated by 3704.

[0135] 37C shows an embodiment of a vascular catheter navigation device in which the guidewire / stylet is off-center and the tip of the guidewire / stylet is angled to align with the flow path in the conduit so that the sensor 2516 is approximately aligned with the flow path. The tip of the guidewire / stylet may be aligned in other ways, for example, between the flow paths or simply near the center of the catheter. Cross-sectional views show various possible configurations of the guidewire / stylet and the flow paths. The flow paths may be circular, crescent-shaped, etc. The conduit may simply be a tube.

[0136] 37D shows an embodiment of a vascular catheter navigation device in which the conduit is simply a tube and the guidewire / stylet is either floating within the ID of the conduit (where the ID of the conduit is the same as the conduit's flow path) or attached to the inner wall of the conduit. The guidewire / stylet can be angled so that the sensor is more aligned with the center of the conduit flow path, or it can be straight or bent or curved in some other way.

[0137] 37E shows an embodiment of a vascular catheter navigation device that includes a cage or scaffold 3706 that centers the sensor 2516 over a central flow path within the conduit. The cage / scaffold may be made from metal wire, polymer, porous material, etc. The cage / scaffold may be embedded in or attached to the conduit.

[0138] 37F shows an embodiment of the vascular catheter navigation device in which the conduit 2502 has no outer surface. In this embodiment, the flow path is in direct contact with the ID of the catheter 2508.

[0139] 38A-38E illustrate some possible architectures for various embodiments of a vascular catheter navigation device. FIG. 38A shows a vascular catheter 2508, a guidewire / stylet 2504, and a conduit 2502 along with an IV bag 3802, optionally equipped with an infusion pump 3804, where the infusion bag is connected to the vascular catheter's fluid infusion port 2806. The guidewire / stylet is inserted / removed from the catheter via a stylet port 3808. In some embodiments, the catheter's stylet port may be the same port as the infusion port. A stylet / sensing connector 3810 connects to a display 3814 and a controller 3812, which may include one or more controls 3816. In this embodiment, fluid infusion through the vascular catheter and conduit flow paths is controlled by the IV bag / infusion pump. The IV bag may be set for a consistent drip, flow, and / or may be controlled by the infusion pump. In this embodiment, the IV bag and / or infusion pump are connected to the vascular catheter without a controller. FIG. 38B shows a similar embodiment, except that the flow of IV fluid from the IV bag is controlled by a controller. The IV bag 3802 is connected to the controller via an IV fluid line 3818. The controller controls the fluid infusion from the IV bag and delivers the fluid to the catheter via a catheter fluid line 3820. The controller can be disposable or reusable. The kit also comes with a disposable line that attaches to the IV bag or hospital infusion pump.

[0140] 38C shows an embodiment of a vascular catheter navigation device that includes a fluid pump 3822, such as a syringe pump. The fluid pump may be a standard off-the-shelf fluid pump. It may be a peristaltic pump or a lead screw driven pump. Note that in this embodiment, the fluid pump is not connected to a controller.

[0141] 38D shows an embodiment in which a fluid pump 3824 connects to a controller so that the controller can control fluid delivery to the catheter via the fluid pump. The controller may have a module to which a user can attach an off-the-shelf fluid pump, or the controller may require a specific fluid pump. The connection may be by electrical connection, or the controller may control the infusion or fluid pump by wireless protocol, e.g., Bluetooth, Wi-Fi, etc. The fluid pump and / or the syringe cartridge within the fluid pump may be disposable.

[0142] 38E shows an embodiment in which the fluid pump is integrated into the controller 3812. The fluid pump and / or the syringe cartridge within the fluid pump may be disposable.

[0143] FIG. 39A is a longitudinal cross-sectional view of a vascular catheter navigation device including a conduit 2502, a guidewire / stylet 2504, a sensor 2516, and a vascular catheter 2508.

[0144] Figure 39B illustrates an embodiment of a vascular catheter navigation device with multiple conduits along the length of the guidewire / stylet, including 0, 1, 2, 3, 4, 5, 6, or more conduits.

[0145] FIG. 39C illustrates an embodiment of a vascular catheter navigation device comprising a conduit 2502 and a fixed conduit 3902. In some embodiments, these fixed conduits are inflatable, such as a balloon, but can also be compressible, e.g., silicone or another soft / compliant material, such as any suitable polymer. Alternatively, the fixed conduit may be made of a more rigid material, such as epoxy, metal, or polymer. Preferably, the fixed conduit secures the guidewire / stylet to the inner lumen of the catheter so that the stylet does not move significantly longitudinally relative to the catheter. As a result, the distance between the fluid exit point and the sensor is substantially fixed. Movement of the sensor relative to the fluid exit point may be limited to plus or minus 1 mm. Or, movement of the sensor relative to the fluid exit point may be limited to plus or minus 2 mm. Or, movement of the sensor relative to the fluid exit point may be limited to plus or minus 3 mm. Preferably, the fixed conduit also allows fluid to flow past the securing conduit and through the catheter lumen during infusion. There may be zero, one, two, three, four, five, six, or more fixed conduits. In embodiments where the guidewire / stylet includes a balloon, it also includes an inflation lumen. The balloon may be relatively non-compliant or relatively compliant. The advantage of a non-compliant balloon is that it can retain its shape, or roundness, when inflated above a critical pressure. This prevents the balloon from conforming to the infusion lumen and blocking the lumen. Instead, a non-compliant balloon remains relatively round when inflated, and a fluid flow lumen is available between the inner wall of the catheter infusion lumen, the stiffener / electrode, and the fixed conduit, as shown in FIG. 39G.

[0146] FIG. 39D illustrates an embodiment of a vascular catheter navigation device that includes an anchor conduit 3902. In this embodiment, the anchor conduit may function as a conduit. The anchor conduit may be located at the distal end of the catheter or may be located further proximally from the distal end of the catheter by a length 3904. The length 3904 may be approximately 0-0.5 mm. Alternatively, the length 3904 may be approximately 0-1.0 mm. Alternatively, the length 3904 may be approximately 0.5-1.0 mm. Alternatively, the length 3904 may be approximately 0-5 mm. Alternatively, the length 3904 may be approximately 0-10 mm. Alternatively, the length 3904 may be approximately 0-20 mm. Alternatively, the length 3904 may be approximately 0-30 mm. Alternatively, the length 3904 may be approximately 0-40 mm. Alternatively, the length 3904 may be approximately 0-50 mm. Alternatively, the length 3904 may be approximately 0-60 mm. Alternatively, length 3904 can be between about 0 and 70 mm. Alternatively, length 3904 can be between about 0 and 80 mm. Alternatively, length 3904 can be between about 0 and 90 mm. Alternatively, length 3904 can be between about 0 and 100 mm.

[0147] Length 3905 is the length between the sensor and the tip of the catheter, which in this embodiment is the fluid exit point. The fixed conduit secures the guidewire / stylet to the infusion lumen of the catheter, substantially fixing length 3905 during placement. Length 3905 may be approximately 0-0.5 mm. Alternatively, length 3905 may be approximately 0-1.0 mm. Alternatively, length 3905 may be approximately 0.5-1.0 mm. Alternatively, length 3905 may be approximately 0-5 mm. Alternatively, length 3905 may be approximately 0-10 mm. Alternatively, length 3905 may be approximately 0-20 mm. Alternatively, length 3905 may be approximately 0-30 mm. Alternatively, length 3905 may be approximately 0-40 mm. Alternatively, length 3905 may be approximately 0-50 mm. Alternatively, length 3905 may be approximately 0-60 mm. Alternatively, length 3905 can be between about 0 and 70 mm. Alternatively, length 3905 can be between about 0 and 80 mm. Alternatively, length 3905 can be between about 0 and 90 mm. Alternatively, length 3905 can be between about 0 and 100 mm.

[0148] The length of the fixed conduit 3902 can be about 1 mm. Alternatively, the length of the fixed conduit 3902 can be about 1-2 mm. Alternatively, the length of the fixed conduit 3902 can be about 1-3 mm. Alternatively, the length of the fixed conduit 3902 can be about 1-4 mm. Alternatively, the length of the fixed conduit 3902 can be about 0.5-5 mm.

[0149] Figures 39E-39G show radial cross-sections revealing some embodiments of the fixed conduit 3902. In Figure 39E, there are three balloons, or soft ridges, around the guidewire / stylet 2504. Figure 39F shows two balloons / ridges, and Figure 39G shows only one. Note that the flow path 3906 of these fixed conduits is the space between the fixed conduit and the inner lumen of the catheter 2508 and does not have an outer surface, similar to the conduit shown in Figure 37F. In some of these embodiments, the flow path is in direct contact with the ID of the catheter 2508.

[0150] In one embodiment, the fixed conduit 3902 is a small silicone protuberance or inflatable balloon near the distal end of the stylet / guidewire and, as such, may function as a conduit. Prior to insertion, the guidewire / stylet is placed in the desired location so the sensor is properly positioned relative to the distal tip of the catheter. At this point, the fixed conduit may be "activated," for example, by inflating the balloon. The fixed conduit maintains the relative positions of the guidewire / stylet and catheter throughout the placement process. During the placement process, fluid is injected through the catheter, passes through the fixed conduit, and exits the distal tip of the catheter. The fixed conduit may either be collapsed or be sufficiently flexible for removal, allowing the guidewire / stylet to be removed from the catheter. When activated, the sealed conduit 3902 may assume a cross-sectional dimension larger than that of the guidewire / stylet 2504. The cross-sectional dimension of the conduit may be approximately 0.05 mm larger than that of the guidewire / stylet. Alternatively, the cross-sectional dimension of the conduit may be approximately 0.05-0.1 mm larger than that of the guidewire / stylet. Alternatively, the cross-sectional dimension of the conduit may be approximately 0.05-0.5 mm larger than that of the guidewire / stylet. Alternatively, the cross-sectional dimension of the conduit may be approximately 0.5-1.0 mm larger than that of the guidewire / stylet. Alternatively, the cross-sectional dimension of the conduit may be approximately 1.0-2.0 mm larger than that of the guidewire / stylet.

[0151] FIG. 39H shows an embodiment of a vascular catheter navigation device including multiple anchor conduits 3902. Multiple anchor conduits may provide better longitudinal anchoring between the guidewire / stylet and the catheter near their respective distal ends. Note that in this example, the length 3905 is substantially zero, which is the case when the sensor 2516 is substantially at the distal tip of the catheter. "Substantially zero" may mean plus or minus 1 mm, or "substantially zero" may mean plus or minus 2 mm, or "substantially zero" may mean plus or minus 3 mm. This may be the case for any of the embodiments disclosed herein.

[0152] Figure 39I shows an embodiment of a vascular catheter navigation device in which the fixed conduit is helical. The helical conduit stabilizes and centers the guidewire / stylet within the infusion lumen of the catheter while allowing fluid to flow past the conduit. The helical conduit is preferably open at the end to allow fluid to flow therethrough.

[0153] 39J shows an embodiment of a vascular catheter navigation device in which the anchoring conduit 3902 is one or more metal wires or filaments that secure the stylet relative to the catheter lumen through an outward mechanical force. The filaments extend the length of the guidewire / stylet and can be expanded / retracted using a mechanism at the proximal end of the guidewire / stylet. The filaments can be a single piece of metal, or a cage, or a spiral, etc.

[0154] 39K shows an embodiment of a vascular catheter navigation device in which the conduit 2502 extends the length, or substantially the entire length, of the catheter 2508. An optional fixation mechanism 3908 is shown here. The fixation mechanism secures the conduit to the catheter so that one does not move substantially longitudinally relative to the other. In this embodiment, the fixation mechanism does not need to allow fluid to flow past the fixation mechanism because the infusion lumen is incorporated into the conduit.

[0155] Markings or any other mechanism may be used to align the conduit with the distal end of the catheter for catheter navigation. For example, a movable marker may be present on the proximal end of the guidewire / stylet so that the distal tip of the vascular catheter (perhaps after being cut to length) can be aligned with the conduit outside the body, the movable marker moved to fit snugly against the proximal end of the vascular catheter, and the catheter can then be inserted into the body. Other mechanisms include valves, such as a Tuohy-Borst valve, or clamps, torque devices, etc. The length of the conduit may be long enough that precise alignment between the distal tip of the catheter and the conduit is not necessary. For example, the vascular catheter may move approximately 0-2 mm relative to the guidewire / stylet during the placement procedure. Alternatively, the vascular catheter may move approximately 0-4 mm relative to the guidewire / stylet during the placement procedure. The conduit may be longer than this, e.g., approximately 2-12 mm, to accommodate these changes in alignment and ensure that the conduit expands to the distal tip of the catheter.

[0156] Some embodiments of the vascular catheter navigation device can inhibit the conduit from exiting the distal end of the vascular catheter. Some embodiments allow the conduit to exit the distal end of the vascular catheter. The proximal end of the conduit tapers to a smaller cross-sectional area in the proximal direction so that the conduit can be pulled back into the catheter without getting caught.

[0157] FIGS. 40A-40C illustrate several different configurations of vascular catheter lumens and variations in embodiments of vascular catheter navigation devices that work with them. Vascular catheters can have one, two, three, four, five, or more lumens. FIG. 40A illustrates several exemplary configurations of a dual-lumen vascular catheter. These configurations include an infusion lumen 2506 and an auxiliary lumen 4002. The auxiliary lumen may be an additional infusion lumen, a sampling lumen, a pressure lumen, a guidewire / stylet lumen, an instrument lumen, or a lumen used for any other purpose. Shown here are a guidewire / stylet 2504, a conduit 2502, a flow path 2518, and a vascular catheter 2508. Various components of the vascular catheter navigation device, including the stylet, conduit, and flow path, may have different cross-sectional shapes to accommodate differently shaped vascular catheter lumens. While several examples are shown here, others are contemplated. The shape of the conduit may be prefabricated, for example in the form of a polymeric conduit, or may take the shape of a lumen, for example via an inflatable or conformable conduit, as shown, for example, in Figures 27, 28, 29A-29C, 30, and 36A-36C.

[0158] Figure 40B shows some example configurations of a three-lumen angiocatheter, and Figure 40C shows example configurations of a four-lumen angiocatheter.

[0159] In multi-lumen catheters, the vascular navigation device may have different cross-sectional shapes, including round, although some embodiments of the vascular navigation device shown here show a vascular navigation device that matches the shape of the lumen.

[0160] It should be noted that although the embodiments disclosed herein show a vascular catheter navigation device in the infusion lumen of a vascular catheter, it is also possible that a vascular catheter navigation device could be used in any lumen of a vascular catheter, such as the sampling lumen, and it is also possible that more than one vascular catheter navigation device could be used in more than one lumen at a time.

[0161] 41A-41F illustrate various embodiments of the guidewire / stylet component of a vascular catheter navigation device. FIG. 41A shows a guidewire / stylet 2504, including a core 2510, a coil 2512, an end cap 2514, and a sensor 2516. Also shown are a sensor lead 4102, a sensor lead insulation layer 4104, a stiffener 4108, and a core enclosure 4106. The sensor lead connects a sensor on the distal end of the device to a controller on the proximal end of the device. There may be one, two, or more leads. For example, thermocouples typically have two leads. However, some thermocouples may have three leads if one of the leads is a ground wire. The leads are preferably made of metal. The leads may be insulated by an insulation layer 4104 surrounding each lead. In some embodiments, only one of the leads is insulated. The insulation may be made of a polymer such as polyethylene, PTFE, polyimide, or other suitable material, and may or may not be heat-shrinkable. The lead wire may be made of a metal, such as copper, stainless steel, or other suitable material. The stiffener may be made of a metal (such as nitinol or stainless steel) and may taper to a smaller cross-sectional dimension at the distal tip, or the stiffener may have a constant cross-section throughout its length. The stiffener may be round in cross-section or any other shape. Alternatively, the stiffener may be a polymer. In that case, the lead wire may perform the function of the stiffener, and no additional stiffener is present.

[0162] The core, including the leads and additional stiffeners, if present, may be encapsulated by an enclosure 4106. The enclosure 4106 may be a tube made from a polymer such as polyimide, polyethylene, PTFE, or a metal or other suitable material. Alternatively, the enclosure may be dip or spray painted. The enclosure may be heat-shrinkable tubing.

[0163] Figure 41A shows a guidewire / stylet in which the leads are moved to the distal end of the stylet where the sensor 2516 resides separate from and proximal to the end cap 2514. Figure 41B shows an embodiment in which the end cap and sensor are combined. Figure 41C shows an embodiment in which the sensor is distal to the end cap.

[0164] 41D shows an embodiment of a stylet / guidewire in which the coil functions as a lead, where the lead exits the core and is incorporated into the coil proximal to the sensor.

[0165] 41E shows an embodiment in which the leads 4102 are made of conductive ink. In this embodiment, the leads may be external to the enclosure 4106. The ink may be deposited on the enclosure. The conductive ink leads may be sandwiched between two enclosures. Note that conductive ink may be used for any of the sensors, including conductance sensors, thermocouples, ECG sensors, etc., and may be printed on a stylet and / or catheter and / or conduit, or printed on a flexible circuit and wrapped around or applied to the device.

[0166] FIG. 41F illustrates an embodiment of a stylet / guidewire in which the coil runs the entire length, or substantially the entire length, of the stylet / guidewire.

[0167] FIG. 42A shows a stylet / guidewire embodiment in which the leads 4102 also function as stiffeners. The leads are encased in an enclosure 4106 and connected to a sensor 2516. Additional stiffness is added to this embodiment by using larger leads and a thicker / stiffer enclosure, such as a metal braid or coil or a filament-reinforced polyimide or polymer tubing. Alternatively, the gap between the enclosure and the leads may be filled with epoxy or adhesive. The leads may be welded or bonded to each other or to the enclosure. The enclosure may be co-extruded with one or more of the lead insulation layers, as shown in FIG. 42B. Thermosetting polymers and / or metals may be used in the enclosure, insulation, and / or leads. For example, in embodiments in which adhesive or epoxy is used to stiffen the stylet, each lead may include an insulation layer, or only one lead may have an insulation layer, or none of the leads may include an insulation layer. In such embodiments, the diameter, cross-sectional design, and material of the lead wires can be designed to match the desired stiffness of the stiffener, and one or more of the lead wires can be spirally shaped, coiled, or braided to achieve the desired stiffener mechanical properties.

[0168] FIG. 42C shows the embodiment shown in FIG. 42A with the addition of a coil.

[0169] Any of the guidewires / styluses disclosed herein may be used with any of the embodiments disclosed herein, including any of the conduit embodiments.

[0170] Where "sensor" or "sensor" is used herein, other types of sensors may be used that include any measurable parameter including temperature, opacity, light reflectivity, sound reflectivity, density, viscosity, ability to absorb light, ability to absorb sound, pressure, etc.

[0171] Figure 43 shows that an optical signal can provide information about the direction of blood flow and other blood flow parameters. In this embodiment, the medium is light, and the measured parameters are light intensity and / or reflected light. Curve 4302 represents measurements of reflected light over time in a blood vessel where blood flow is toward the device.

[0172] FIG. 44 shows an embodiment of a device using an optical sensor. Fiber optic cables 4402 and 4404 can be used for light transmission and detection. One cable can be used to introduce the medium (light), and the other cable can act as a sensor of a parameter of the medium (light intensity / wavelength). A combination of detector and emitter can be used, or an emitterless photodetector can be used, requiring only a single fiber. In some embodiments, specific wavelengths of light can be used. For example, red light between approximately 620 nm and 750 nm can be emitted, which is more reflected by red blood cells than by saline or blood diluted with saline. Therefore, the response can indicate the direction or characteristics of flow. This same embodiment can be more broadly enabled by other types of visible light between approximately 350 nm and 800 nm and near-infrared light between approximately 400 and 1400 nm. This embodiment can be achieved with a detector and / or emitter placed at the measurement point and potentially used in combination with a flex circuit. Optical measurement embodiments can also be used with the use of optical fibers (plastic, glass, or other) or light pipes, where the actual detectors and emitters are located within the controller and light pipe, or optical fibers communicate information collected at or near the catheter tip to a controller located outside the patient's body. This can be accomplished with fiber optic lines about 0.1 mm to about 0.5 mm in diameter or about 0.5 mm to about 4 mm in diameter. Fiber optic cables can have an insulating jacket. In some embodiments, a single optical fiber can be used.

[0173] Figures 45 and 46 show a triple lumen device and a double lumen device, respectively, with two fiber optic cables.

[0174] Figure 47 shows an embodiment using sonar and / or sound waves to detect the direction of blood. In this embodiment, the introduced medium is sound, and the parameter measured by the sensor is the intensity and / or wavelength of the reflected sound. Sound is introduced through the device, producing sound waves 4702 that are transmitted into the blood vessel. Some sound waves are reflected back as reflected sound waves 4704 and can be measured by a sensor, such as a microphone, on the device.

[0175] 48 and 49 illustrate an embodiment using one or more pressure sensors to determine flow directionality with a turbulence inducer. A single pressure sensor 4804 or multiple pressure sensors may be used to detect flow direction relative to the catheter or pressure sensor. This embodiment may include a mechanism 4802 that induces turbulence 4808, producing different pressures at the reading location depending on whether the flow disruption feature is upstream or downstream of the pressure sensor. Pressure data measured by the pressure sensor 4804 is communicated to a controller (not shown) via a connector 4806. The turbulence inducer may be contained on a stylet and deployed like an umbrella and then retracted. The turbulence inducer may be deployed and pushed through the vasculature as the device reaches the heart, or the turbulence inducer may be deployed at specific times when the device's location needs to be determined. This may be at a predetermined interval, for example, about every 3 seconds (or in the range of 1 to 5 seconds), or simply whenever the operator wishes to take a measurement. Alternatively, the turbulence inducers may be small enough that they may be permanently deployed.

[0176] FIG. 50 illustrates an embodiment including a controller 114 and a medium introduction mechanism 5002 controlled by the controller via a lever or mechanism 5004. The medium introduction mechanism may be a syringe containing saline or other fluid, and the mechanism 5004 may be a lever controlled by a motor within the controller. Alternatively, the controller may be remote from the medium introduction mechanism. Alternatively, the medium introduction mechanism may be manually driven. The controller may be located at the patient's bedside or remotely. The controller may provide real-time feedback if there are any changes in safety issues. Standard PICC, subclavian, and intrajugular canal catheters, and central catheters may be used, regardless of brand.

[0177] controller The controller may control the delivery of media and the detection of media parameters in the bloodstream. Additionally, the controller receives information from one or more sensors and interprets the information to assess location, relative position, and / or risk zones within the vasculature. Sensor signals are communicated via wires, fiber optic cables, or other means back to the controller, where the signals are analyzed based on measured parameters, parameter profiles, parameters of two or more sensors, or parameter changes over time and / or distance. For example, the controller may determine whether the distal end of the vascular catheter navigation device is in an artery instead of a vein based on the magnitude and direction of blood flow near the vascular catheter navigation device and / or other flow parameters. For example, if the controller determines that the distal end of the vascular catheter navigation device is in an artery instead of a vein, a specific identification signal, including an audible, visual, or other signal, may be signaled to instruct the user to remove the vascular catheter navigation device and any other devices, such as a sheath, catheter, or the like, and to apply pressure to the blood vessel. For example, instructions to advance, retract, change direction, stop, or remove the vascular catheter navigation device may be displayed by the controller on a screen connected to either the controller. The connection may be wired or wireless, and the screen may be local or remote. Signals from the controller may be transmitted via Bluetooth or other wireless protocols to a computer, such as a laptop, tablet, phone, watch, or other peripheral device.

[0178] The controller may control the introduction of a medium, including the injection of a temperature-controlled solution such as saline, the introduction of sound, the introduction of light, the introduction of a fluid with a certain level of parameter, etc. Temperature-controlled may mean a temperature different from body temperature.

[0179] Injection mechanism and fluid properties The infusion fluid drop, bolus, droplet, stream, etc. used to detect catheter location can have specific parameters. The infusion fluid can be a drop or a stream. A preferred intermittent volume size (drop, drop, bolus, intermittent stream) can be about 0.5 cc to about 3 cc, but can also range from about 0.1 cc to about 10 cc. Alternatively, the volume can range from about 0.5 cc to about 1 cc. Alternatively, the volume can range from about 0.5 cc to about 2 cc.

[0180] A preferred drip interval may be about every 0.5 seconds to about every 4 seconds, or more broadly, about every 0.25 seconds to about every 10 seconds. If the infusion is a continuous stream, a preferred flow rate is about 4 cc / min, but may range from about 0.25 cc / min to about 15 cc / min, or from about 0.1 cc / min to about 30 cc / min, or from about 0.1 cc / min to about 60 cc / min.

[0181] The pressure applied to the injection mechanism (e.g., syringe) for injection can be about 3 psi (about 30.684 kPa), but may range from about 1 psi to about 5 psi (about 6.894 kPa to about 34.473 kPa), or may range from about 0.1 psi to about 200 psi (about 6.894 kPa to about 1379.31 kPa).

[0182] The controller may control an infusion device or volume transfer device, such as a syringe, so that the infusion device introduces fluid into the catheter or stylet / guidewire at a controlled amount and / or flow rate. The fixed amount and / or flow rate of fluid may be at a controlled temperature, either above or below blood temperature (approximately 37°C), or at a measured known temperature. The infusion device may infuse fluid at a controlled amount and / or flow rate at predetermined intervals, other intervals, or continuously. The controlled amount and / or flow rate of fluid may remain the same throughout the procedure, or the amount and / or flow rate may vary depending on the patient, the location of the catheter / system within the vasculature, etc. For example, the amount and / or flow rate of fluid infused may be increased the closer the tip of the catheter is to the heart. The amount and / or flow rate may be different for different sized vascular catheters or different sized lumens of vascular catheters, such as catheters with multiple lumens.

[0183] The volume and / or flow rate of the fluid being injected may be controlled by a lead screw, cam, linear actuator motor, peristaltic pump, etc. The force of the injection requirement may also be controlled and / or monitored. For example, if too much force is required to inject the fluid, an alarm may indicate to the user that a catheter blockage condition may exist, including a kinked catheter, a blood clot, the catheter tip hitting the vessel wall or in a small vessel, or other catheter patency condition. Injections at higher or lower forces may be used to confirm locations in different regions of the anatomy or within the anatomy. For example, injections at higher force with lower volume and / or flow rate may provide different temperature curve information than injections at higher volume and / or flow rate with lower force. Injections of smaller volumes at higher frequencies may provide different information than injections of larger volumes at lower frequencies, etc.

[0184] The fluid injector may also be configured to withdraw fluid through the catheter / stylet / guidewire to determine the patency of the injection lumen / tip. The controller may evaluate the force of withdrawal to determine that fluid is flowing freely through the catheter / stylet / guidewire. If fluid is not flowing freely, a patency alarm may alert the user. Alternatively, the controller may have a sensor that detects the presence of blood in the system as the injector withdraws fluid through the catheter / stylet / guidewire. This may be done optically or by other means.

[0185] An embodiment of the injection mechanism is shown in FIG. 51. This embodiment may include an automatic injection system for the cartridge / syringe / reservoir, which may be a motor-driven lead screw. A controller controls the infusion delivery parameters, including pressure, volume, frequency, flow rate, etc. The controller may also control the GUI. Buttons shown in FIG. 51 may switch the device on and off, purge air from the catheter before insertion, and / or stop device operation in the event of a detected problem condition. The unit may be fully disposable, partially disposable, or non-disposable, and may be in a sterile or non-sterile field during a procedure.

[0186] The system may be packaged with a prefilled or refillable infusion device. Saline may be used as the fluid. Contrast agents may be used (which have a higher viscosity than saline). Fluids of different viscosities may be used, or fluids may be mixed (e.g., contrast agents and saline) to achieve a desired viscosity or other desired properties. Fluids with different surface tensions, specific heat capacities, acidities, or other different attributes may be used. Fluids with properties different from those of blood will provide different temperatures, parameters, curves, and therefore different information regarding the location of the catheter / guidewire / stylet tip in the vasculature. Some fluids may dissolve in blood, and others may dissolve less in blood. Because the infusion fluid is injected into the bloodstream, the fluids used are preferably biocompatible.

[0187] Additives may be added to the infusion fluid for different results. For example, salts such as NaCl may be added. In embodiments that include ECG electrodes, different salts or other additives may improve the ECG signal. Different fluids (liquids or gases) may be introduced along with the main fluid to modify the fluid properties. For example, a biocompatible liquid or gas may be "bubbled" into the saline solution.

[0188] Two or more infusion fluids may be used, either mixed and infused through the same lumen and outlet port, or infused separately through different lumens and different outlet ports. One or more of the infusion fluids may contain a drug or medication.

[0189] The user interface controlled by the controller may include a display, alarms (audible, visual, light, vibration, etc.), and other information. The user interface may include a display of the anatomy using a virtual reality indicator of the location of the catheter / guidewire / stylet tip within the anatomy. For example, the display may be an image of the human vasculature, and a dynamic indicator, e.g., a light, may indicate where the catheter / guidewire / stylet tip is within the anatomy. The display may be life-size and possibly projected onto the patient, or may be smaller or larger in size, for example, displayed on the controller, tablet, or projected onto a wall. The controller and / or display may include a computer, laptop, tablet, cell phone, virtual reality / augmented reality glasses, etc.

[0190] The system may be completely disposable. The main package of a completely disposable system includes: a syringe, a syringe pump, a syringe filled with the fluid of choice, a controller, a user interface which may be any combination of display, alarm, and light, a catheter, a stylet / guidewire, and an introduction mechanism. All of these elements may be completely disposable. By doing so, the chance of infection is reduced.

[0191] Another embodiment includes all of the items listed above, but the display is non-disposable. The display may be in the non-sterile field and communicate via a cable or wireless communication protocol such as Bluetooth®. Alternatively, the display may be in the sterile field using a wired or wireless connection. Additionally / alternatively, the display may be projected onto glasses—either virtual reality glasses or augmented reality glasses. The glasses may be in the sterile or non-sterile field. Furthermore, a projector may project the display onto a selected surface, and the projector may be in the sterile or non-sterile field.

[0192] Another embodiment consists of two subsystems: the disposable component may include the catheter, stylet / guidewire, and fluid-filled volume displacement device, such as a syringe; the non-disposable component may include the controller within the housing, mechanics / motor for pushing the lead screw on the syringe / cartridge, display, audio, and visual components, and user interaction buttons, etc.

[0193] Any of the catheter / stylet / guidewire placement and / or patency techniques disclosed herein can be used during placement of a device within the vasculature, as well as after placement, to determine if the device has significantly shifted from its placement location over time.

[0194] Any of the embodiments disclosed herein may be used with any type of central vascular catheter, including central venus line, clavicle line, midline, etc. Additionally, any of the embodiments disclosed herein may be used with peripheral vascular catheters, dialysis catheters, and cardiac catheters, including catheters used for coronary arteries, patent foramen ovale, atrial septal defects, etc. Any of the embodiments disclosed herein may be used with any type of urinary catheter. Similar technology may be used in underwater navigation, mining, oil and gas export, utility construction or repair, transportation infrastructure construction and repair, etc.

[0195] Other techniques may also be used in conjunction with sensor readings from the vascular catheter, such as ECG readings, ultrasound readings, Doppler readings, x-ray readings, induced current techniques, pressure readings, etc. Some, all, or none of the readings may be augmented by a turbulence inducer. These and other types of readings may be used in conjunction with the sensor readings by the controller to determine the location of the distal tip of the vascular catheter navigation device. Certain modalities may be better at identifying particular vascular targets or conditions.

[0196] For example, any of the conductive components of the vascular navigation device can be used as an ECG lead. Separate ECG leads can be placed on the patient's skin. For example, guidewire stylet stiffeners, coils, enclosures, thermocouple leads, sensor leads, thermocouples, end caps, conduits, etc. can be used as one or more ECG leads. Alternatively, separate ECG leads can be added to the system.

[0197] Embodiments of the vascular navigation device may include the ability to measure cardiac output or cardiac flow. The parameter versus time / location curve may be analyzed by the controller to determine cardiac output in addition to vascular location, either simultaneously or at separate points in time. Cardiac output may also be used to assist in establishing the location of the vascular navigation device within the vasculature.

[0198] Embodiments of the vascular navigation device may include the ability to measure blood flow in other regions of the body / vasculature.

[0199] Several embodiments are disclosed herein, and it is understood that any feature of any of the embodiments may be combined with any embodiment.

[0200] Some embodiments of the vascular access or vascular navigation device may be used in other applications. For example, the device's controller may include logic for navigating, identifying, and assessing the health of various blood vessels or other anatomical structures. For example, some embodiments may be configured to identify the location of valves within the peripheral vascular (e.g., venous) system. The location of the valve may be identified based on flow characteristics near and within the valve. The health of the valve may be assessed based on flow characteristics near and within the valve. Valve function may be assessed based on flow characteristics near and within the valve. Valve closure may be assessed based on flow characteristics near and within the valve. The flow characteristics of the vessel may be used by the system to navigate near, within, and / or past the valve. Some embodiments of the vascular navigation device may be used in conjunction with therapeutic procedures. For example, the system may be used to assist in the placement of valve prosthetics, valve repair, etc. The system may be used to assess the success of such procedures based on flow characteristics, placement location, etc. The system may also be used to navigate vascular stent placement locations and assess vascular function before and after the procedure. The system may be used to assess the function and / or location and / or health of prostheses (stents, valves, etc.) before and after their placement.

[0201] In some embodiments, the system may be used to diagnose stenosis, blockage, narrowings, or disease of blood vessels based on flow characteristics. The system may be used to classify stenosis, blockage, narrowings, or disease of blood vessels based on flow characteristics. The system may be used to identify the location and amount of spinal fluid leaks.

[0202] In some embodiments of the system, the vasculature is accessed peripherally, such as via the legs, arms, groin, etc.

[0203] Some embodiments of the system may be used to diagnose other diseases or conditions based on the flow characteristics of blood vessels or other organs (eg, sacs, lungs, etc.).

[0204] Some embodiments of the system can be used to assess the health of and navigate through other blood vessels, such as those in the brain. For example, the system can be used to identify, navigate to, and assess the health of aneurysms, occlusions, narrowings, and stenoses in the brain and elsewhere in the body.

[0205] Embodiments of the system may be used for any interventional radiology procedure, including angiography, arteriovenous malformations (AVMs), balloon angioplasty, biliary drainage and stent placement, bleeding internally, central venous access, chemoembolization, embolization, gastrostomy tubes, hemodialysis access maintenance, hypertension, infection and abscess drainage, needle biopsy, radiofrequency ablation, stents, stent grafts, thrombolysis, TIPS (transjugular intrahepatic portovenous shunt), urinary tract obstruction, uterine artery embolization, uterine fibroid embolization, varicocele embolization, varicose vein treatment, vena cava filters, vertebroplasty, deep vein thrombosis, and the like.

[0206] Some embodiments of the system may be used to identify blood flow direction, velocity, flow characteristics, etc. This may be useful not only for navigating the venous system, but also for assessing venous or arterial flow conditions, which may be useful for identifying cardiac disease, chronic venous disorders, venous outflow obstruction, etc.

[0207] Some embodiments of the system can be used to identify changes in blood flow properties in response to medications such as blood thinners (e.g., heparin) either acutely or over time. For example, blood thinning, viscosity, or other properties can be assessed based on the flow properties.

[0208] Some embodiments of the multi-sensor technology may also be included in permanent implants within the body, rather than being used as temporary devices. They may be used to measure cardiovascular performance or health over time, measure post-intervention performance over time, etc. This type of intervention may be surgical only, such as when used in bypass surgery, and may also include monitoring the outcome and / or performance and / or success of interventions such as mechanical valves, stents, balloons, etc. They may also be used for assessments required for interventions.

[0209] In any of the embodiments disclosed herein, in addition to or instead of measuring the temperature of the infused fluid bolus or stream, the system may measure the electrical conductivity of the fluid bolus or stream. As the fluid stream or bolus fluctuates under various flow conditions and flow directions, fluctuations in electrical conductivity may be detected. Furthermore, the fluid may be infused to optimize electrical conductivity. For example, a fluid containing one or more salts may be used to make the fluid more electrically conductive, or a fluid less conductive than blood may be used, such as distilled water or a glucose solution.

[0210] This technology may also be used outside the body, on the skin surface in proximity to one or more veins. This may be done on the skin, just below the skin, across the skin, or within the skin. For example, a temperature sensor may be placed on top of the skin or in several locations within the vein. A heating or cooling event may be administered within the vessel to detect blockages, flow, or navigation requirements. Conversely, heating and / or cooling events may occur external to the skin while the system senses temperature within the vessel. Alternatively, pressure or electrical conductivity may be used. Some embodiments may also detect flow characteristics and diagnose venous or arterial diseases, problems, and disorders, either acute or chronic. Device embodiments on the body surface or within the vein may be temporary assessment tools or more permanently worn biosensors, such as watches, rings, wristbands, necklaces, earrings, contact lenses, etc.

[0211] Data Processing System Example Figure 52 is a block diagram of a data processing system that may be used with any embodiment of the present invention. For example, system 5200 may be used as part of a controller. Note that while Figure 52 illustrates various components of a computer system, it does not represent any particular architecture or manner of interconnecting the components; as such, the details are not directly relevant to the present invention. It should also be understood that network computers, handheld computers, mobile devices, tablets, cellular phones, and other data processing systems having fewer components or perhaps more components may also be used with the present invention.

[0212] As shown in Figure 52, a computer system 5200, in the form of a data processing system, includes a bus or interconnect 5202 coupled to one or more microprocessors 5203 and ROM 5207, volatile RAM 5205, and non-volatile memory 5206. The microprocessor 5203 is coupled to cache memory 5204. The bus 5202 interconnects these various components and also interconnects these components 5203, 5207, 5205, and 5206 to a display controller and display devices 5208, and to input / output (I / O) devices 5210, which may be a mouse, keyboard, modem, network interface, printer, and other devices known in the art.

[0213] Typically, input / output devices 5210 are coupled to the system by an input / output controller 5209. Volatile RAM 5205 is typically implemented as dynamic RAM (DRAM), which requires constant power to refresh or maintain data in memory. Non-volatile memory 5206 is typically a magnetic disk drive, magnetic optical drive, optical drive, or DVD RAM, or other type of memory system that retains data even after power is removed from the system. Typically, non-volatile memory is also random access memory, although this is not required.

[0214] While FIG. 52 illustrates the non-volatile memory as a local device directly coupled to the rest of the data processing system components, the present invention may also employ non-volatile memory located remotely from the system; for example, a network storage device coupled to the data processing system by a network interface such as a modem or an Ethernet interface. Bus 5202 may include one or more buses connected to each other by various bridges, controllers, and / or adapters, as are known in the art. In one embodiment, I / O controller 5209 includes a USB (Universal Serial Bus) adapter for controlling USB peripheral devices. Alternatively, I / O controller 5209 may include an IEEE-1394 adapter, also known as a FireWire® adapter, SPI (Serial Peripheral Interface), I2C (Inter-Integrated Circuit) or UART (Universal Asynchronous Receiver / Transmitter), for controlling FireWire® devices, or any other suitable technology. Wireless communication protocols may include Wi-Fi, Bluetooth, ZigBee, short range, cellular, and other protocols.

[0215] Some portions of the preceding detailed descriptions are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory. These algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art. An algorithm is here, and generally, conceived to be a self-consistent sequence of operations leading to a desired result. These operations require physical manipulations of physical quantities.

[0216] It should be borne in mind, however, that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities. As is apparent from the above description, unless specifically stated otherwise, it will be understood that throughout the description, descriptions using terms such as those set forth in the claims below refer to the actions and processing of a computer system or similar electronic computing device, manipulating data represented as physical (electronic) quantities in the computer system's registers and memory, and converting it into other data also represented as physical quantities in the computer system's memory or registers or other such information storage, transmission, or display device.

[0217] The techniques shown in the figures may be implemented using code and data stored and executed on one or more electronic devices that store and communicate (internally and / or over a network with other electronic devices) the code and data using computer-readable media, such as non-transitory computer-readable storage media (e.g., magnetic disks; optical disks; random access memory; read-only memory; flash memory devices; phase-change memory) and transitory computer-readable transmission media (e.g., electrical, optical, acoustic, or other forms of propagated signals—e.g., carrier waves, infrared signals, digital signals).

[0218] The processes or methods shown in the preceding figures may be performed by processing logic including hardware (e.g., circuit components, dedicated logic, etc.), firmware, software (e.g., implemented on a non-transitory computer-readable medium), or a combination of both. While the processes or methods are described above in terms of several sequential operations, it should be understood that some of the described operations may be performed in a different order. Furthermore, some operations may be performed in parallel rather than sequentially.

[0219] As described herein, localization of blood vessels using fluid injection can also be determined by sensing conductivity or electrical conductivity, for example, where the sensor includes one or more electrodes. In these embodiments, the sensor or electrodes measure the conductivity (or impedance) of the blood / medium mixture, where the medium has a conductivity different from that of the blood. For example, the medium infused into the blood vessel can have a higher or lower conductivity than the blood.

[0220] Because salt is conductive, the salinity of a blood / medium mixture can be determined by the voltage drop across a pair of electrodes. For example, if a fluid less conductive than blood (such as a saline solution with a lower salinity (e.g., 0.45% NaCl saline) or a salt-free solution such as HO or glucose solution) is the medium introduced into the bloodstream, a conductivity sensor can measure the presence of that fluid in the bloodstream by measuring the conductivity of the blood / medium mixture within the bloodstream. Conductivity measurements over time / at the device's location within the blood vessel can be used to determine laminar flow, turbulent flow, flow direction, etc. at the tip of the device or at the location of the sensor. As a reference, the salinity of blood is approximately 0.9%.

[0221] Alternatively, a medium with a higher conductivity than blood may be used. For example, a 3% NaCl solution may be used to detect the flow characteristics of the fluid. Additionally, a hypertonic solution may increase the signal strength of the measured ECG signal. Alternatively, all of the configurations described herein that use temperature or other sensors may use conductivity or impedance sensors. In some embodiments, the electrodes that function as sensors may detect ECG signals without the use of an external (i.e., skin) ground electrode.

[0222] FIG. 53 illustrates an embodiment of a vascular catheter navigation device including sensors, or electrodes, for measuring conductivity. Shown are a distal electrode pair 5302, a proximal electrode pair 5304, a fluid exit point 2503, a conduit 5202, a seal 5306, a catheter 2508, and a guidewire / stylet 2504. A single sensor may include a pair of electrodes. For example, the distal electrode pair 5302 may represent a distal sensor, and the proximal electrode pair 5304 may represent a proximal sensor. The seal 5306 may provide a substantially fluid-tight seal between the conduit and the catheter. The electrodes may be on the surface of the device or, in some embodiments, may be a solid disk. In some embodiments, the fluid exit point 2503 may include multiple small openings in the conduit. The fluid exit point may be forward-facing, as shown in some embodiments herein, or may be side / lateral-facing, as shown herein. Multiple small openings may result in a more diffused infusion of the media fluid, as opposed to a more directional stream that may result from a single opening. The multiple openings may extend substantially circumferentially (360 degrees) around the device, or may be present in less than substantially 360 degrees around the device. Figure 53 shows an embodiment with two pairs of electrodes and a diffusion outlet port. Figure 54 shows an embodiment with only one pair of electrodes. In some embodiments, the sensor or electrode pair is located close (0.05 mm to 1 mm) to the fluid outlet port / hole to increase sensor sensitivity.

[0223] In embodiments using conductivity or impedance to determine the location of the vascular navigation device, a current is applied to an electrode of the sensor, and the conductivity or impedance of the blood / medium mixture between the two electrodes is sensed by a second electrode of the sensor. The driving frequency of the signal may be about 10,000 Hz. Alternatively, the driving frequency may be about 500 Hz to about 100,000 Hz. Alternatively, the driving frequency may be greater than about 100,000 Hz. The sampling frequency may be about 50 Hz. Alternatively, the sampling frequency may be about 25 Hz to about 100 Hz. The sampling frequency may be fixed or variable and may depend on the frequency in the sensed conductivity or impedance signal.

[0224] FIG. 55 shows an embodiment in which the media infusion lumen extends the length of the guidewire / stylet.

[0225] 56 shows an embodiment of a vascular catheter navigation device that includes an open mesh or braid 5702 as a component of the fluid exit point. The mesh / braid may encircle substantially 360 degrees of the conduit, or may encircle less than substantially 360 degrees of the conduit. The mesh / braid may be metallic, polymeric, or other suitable material.

[0226] 57 and 58 show an embodiment including a spacer 5802 that maintains space between the vessel wall and the electrode sensor, preventing the sensor from directly contacting the vessel wall. The spacer may be a simple wire loop, as shown here, or may have two or more loops like a whisk, or may be of any other suitable configuration. Preferably, the spacer can be compressed for introduction into and removal from the vessel. For example, the spacer can be compressed by pulling a guidewire / stylet into the catheter, as shown in FIG. 58.

[0227] 59A and 59B show some possible embodiments of electrode pairs at the distal end of the device. FIG. 59A shows a snake-like or other suitable pattern to increase the surface area of ​​the two electrodes in the electrode pair. The distance between the electrodes within the electrode pair can also be varied to optimize the signal. A connector 5902 can be used to connect the electrodes to wires / leads back to the controller or other conduction mechanisms within the device. For example, the connector 5902 can connect to wires underneath the electrodes that run the length of the device back to the controller. Alternatively, the connector 5902 can connect to tracings internal or external to the device.

[0228] Disclosed herein are various embodiments of vascular catheter navigation devices that rely on the injection of an infusate, or medium, into the bloodstream, where the infusate has parameters whose values ​​differ from those of the blood. For example, the temperature, conductance, or impedance of the infusate differs from the temperature, conductance, or impedance of the blood. Because these embodiments sense and analyze parameters of the infusate to determine the flow characteristics of the blood within the vessel, it is important that the infusate flow characteristics be reproducible and meaningful. Different infusate exit port designs result in different infusate flow characteristics and affect the data collected and analyzed by the controller.

[0229] It is also desirable for the infusate to flow in close proximity to sensors on the device so that the sensors can measure changes in sensed parameters. It may be desirable for the infusate flow to surround the navigation device substantially 360 degrees, or as close to 360 degrees as possible, particularly in laminar or less turbulent blood flow.

[0230] To accomplish this, some embodiments include an infusate outlet or port that diffuses the infusate outlet flow, controlling and / or minimizing the infusate outlet flow rate. These types of infusate port outlet designs are referred to as "diffusing" outlet port designs. Such diffusing outlet ports may incorporate multiple openings or meshes similar to those shown in Figures 53-59B. For further illustration of this type of fluid exit point or port, see Figures 60A-60C.

[0231] Figure 60A shows the distal end of a vascular catheter navigation device with a diffusion exit port region 6002. The exit port includes an opening 6004 and, in this embodiment, is located between two sensors 6006, each of which may be a pair of electrodes. The exit port 6002 shown in this embodiment is fabricated by wrapping a thin, perforated sheet around the opening of the device to create the diffusion exit port. An example of the sheet is shown in Figure 60B. The sheet may be made of polyimide or any other suitable thin, strong material, such as a polymer, metal, etc.

[0232] 60C shows an embodiment in which openings 6004 are incorporated into the surface of the conduit. The conduit can extend through substantially the entire length of the catheter inner lumen or through a portion of the catheter inner lumen. For example, the vascular access device can include a length of polyimide or other material tubing with openings 6004 cut into the wall of the tubing near its distal end. The sensor can be a sheet wrapped around the tubing, as shown here, or can be other types of sensors as disclosed herein. The sensor lead (not shown) can be a wire or tracing that is either inside or outside the tubing.

[0233] By showing the diffusion exit port flattened, we can see that the exit port has a surface area, X x Y. We can also have an aperture area ratio, which is the surface area of ​​the sheet minus the total surface area of ​​the apertures. If the apertures are circular, the area of ​​each aperture is πR 2 If the opening is circular, the total surface area of ​​the opening is n × πR2 where . The sheet shown here also has a thickness, designated z. In some embodiments, the resistance to flow at the exit port can also be increased to minimize and / or control the velocity at the infusate exit port. Flow resistance can be increased by increasing the number of openings (for a given opening area) and / or increasing the circumference of the openings (for a given opening area), and / or increasing the thickness (z) of the openings (for a given opening area). For example, a mesh with small openings will have a higher resistance to flow than a single opening of the same opening area.

[0234] Diffusion outlet port designs can include multiple holes in the conduit, holes in a secondary material attached to the conduit, a mesh (polymer, metal, etc.) incorporated into the conduit, interruptions or openings in the conduit supported by other structures such as a core wire, a sponge (polymer, sintered or 3D printed metal or polymer).

[0235] 61A-61D show several embodiments of diffusion outlet port designs, including mesh (FIG. 61A), porous polymer (FIG. 61B), large outlet port openings with struts 6102 passing through them (FIG. 61C), large outlet port openings with central core wire 6104 passing through them (FIG. 61D), and spiral outlet port openings (FIG. 61E). The material in the outlet port region can be rigid, flexible, or semi-rigid.

[0236] The exit port design and the distance from the port to the sensor are design variables and are optimized so that the sensor performs well in a wide range of conditions, including a range of blood flow velocities (1 cm / sec to 200 cm / sec in both directions), a wide range of vessel and organ diameters, both large and small (0.5 mm diameter to 100 mm diameter), and a wide range of infusion flow rates of infusate (0.001 cc / min to 100 cc / min, or more optimally 0.5 cc / min to 5 cc / min).

[0237] In some embodiments, it may be desirable to limit the velocity of the infusate as it exits the infusate outlet port. This may be done by limiting the injectate flow rate at the proximal end of the device, and may also be done by increasing the area of ​​the opening of the infusate outlet port. Increasing the area of ​​the opening of the outlet port may be done by increasing the percentage of the area that is open within the infusate outlet port and / or by increasing the surface area of ​​the infusate outlet port.

[0238] Some embodiments of the diffusion infusate outlet port may include multiple circumferential openings. FIGS. 62A-62C show an embodiment of a vascular catheter navigation device including a diffusion outlet port region 6202, a sensor 6206, which may be an electrode pair or other sensor, a diffusion outlet port region length 6204, and an opening 6208. Note that the opening outlined in dotted lines is on the back side of the device. FIG. 62A, for example, shows two circumferential openings in the outlet port region length 6204. FIG. 62B also shows two circumferential openings in the outlet port region length 6204, but in FIG. 62B, the openings are circumferentially aligned, while in FIG. 62A, the openings are circumferentially offset.

[0239] As an example, the exit port may have two or more openings within a length of about 0.5 cm. As another example, the exit port may have two or more openings circumferentially aligned within the exit port. As an example, the exit port may have three or more openings within a length of about 0.5 cm. As another example, the exit port may have three or more openings circumferentially aligned within the exit port.

[0240] FIG. 62C shows an embodiment in which the outlet port opening occupies more than 40% of the circumference of the diffusion outlet port. In other embodiments, the outlet port opening occupies more than 30% of the circumference of the diffusion outlet port. In other embodiments, the outlet port opening occupies more than 50% of the circumference of the diffusion outlet port. In other embodiments, the outlet port opening occupies more than 30% of the area of ​​the diffusion outlet port. In other embodiments, the outlet port opening occupies more than 40% of the area of ​​the diffusion outlet port. In other embodiments, the outlet port opening occupies more than 50% of the area of ​​the diffusion outlet port. In other embodiments, the outlet port opening occupies more than 60% of the area of ​​the diffusion outlet port. The open area percentage of the diffusion outlet port can range from 10% to 99%, but more optimally can range from 30% to 80% by area.

[0241] In some embodiments, the length 6204 of the diffusion outlet port is greater than about 0.10 cm. In some embodiments, the length 6204 of the diffusion outlet port is greater than about 0.25 cm. In some embodiments, the length 6204 of the diffusion outlet port is greater than about 0.5 cm. In some embodiments, the length 6204 of the diffusion outlet port is greater than about 0.75 cm. In some embodiments, the length 6204 of the diffusion outlet port is greater than about 1.0 cm.

[0242] FIGS. 63A-63D illustrate how the infusate outlet flow rate affects the sensor's ability to sense infusate parameters within the vascular bloodstream. FIGS. 63A and 63B show two-dimensional representations of the infusate fluid 6302 flow characteristics as it exits the infusate outlet port area 6304 at a higher outlet flow rate. FIGS. 63A and 63B illustrate the infusate flow at a given infusion rate in a reverse blood flow scenario. The distance λ is the approximate distance between the exiting infusate fluid and the sensor 6306 in the plane of the sensor. This distance may also be referred to as the boundary distance. FIGS. 63C and 63D illustrate the infusate fluid flow at the same infusion rate exiting the device at a lower infusate outlet flow rate, e.g., via a diffusion outlet port. Note that the boundary distance λ is much shorter in the slower infusate outlet flow rate scenario. To optimize sensor sensitivity, it is desirable to design the exit port so that λ is zero or near zero under laminar or less turbulent blood flow conditions and can be greater than zero under turbulent blood flow conditions. Using a diffusive exit port design, such as that shown in Figures 63C and 63D, allows the boundary distance λ to be controlled for any given proximal infusate injection rate, and the boundary distance approaches zero under laminar or low-turbulence blood flow conditions. By selecting the appropriate exit port configuration for a given infusate injection rate, the sensor can perform under a range of blood flow rates. The sensor, along with the analytical capabilities of the controller, can detect in-line and countercurrent flow and can detect the difference between laminar and turbulent blood flow conditions.

[0243] For example, at an infusion rate of 3 ml / min, the infusion rate may be approximately 6 cm / sec, and the infusion rate exiting the outlet port may be approximately 1.5 cm / sec. This represents an infusion rate:outlet rate ratio of approximately 4. Alternatively, at an infusion rate of 5 ml / min, the infusion rate may be approximately 10 cm / sec, and the infusion rate exiting the outlet port may be approximately 2.5 cm / sec. This represents an infusion rate:outlet rate ratio of approximately 4. Alternatively, the outlet rate may be in the range of approximately 0-1 cm / sec. Alternatively, the outlet rate may be in the range of approximately 1-3 cm / sec. Alternatively, the outlet rate may be in the range of approximately 1-4 cm / sec. Alternatively, the outlet rate may be in the range of approximately 1-6 cm / sec. Alternatively, the outlet rate may be in the range of approximately 1-8 cm / sec. The ratio of inlet flow rate to outlet flow rate may be about 4. Alternatively, the ratio of inlet flow rate to outlet flow rate may be about 2-5. Alternatively, the ratio of inlet flow rate to outlet flow rate may be about 1-6. Alternatively, the ratio of inlet flow rate to outlet flow rate may be about 5-10. Alternatively, the ratio of inlet flow rate to outlet flow rate may be greater than about 2. Alternatively, the ratio of inlet flow rate to outlet flow rate may be greater than about 5. Alternatively, the ratio of inlet flow rate to outlet flow rate may be greater than about 10.

[0244] In embodiments that include a diffusion outlet port, the distance between the outlet port and the sensor can be measured from the nearest opening to the sensor. For example, in Figure 63D, the distance between the outlet port and the distal sensor is length portion 6308.

[0245] In some embodiments of vascular catheter navigation devices, it may be desirable to incorporate sensors into or on the vascular catheter itself. This feature allows the user to detect whether the catheter has moved over time, even after the guidewire / stylet has been removed. Including sensors and infusion ports on the catheter itself may also obviate the need for a guidewire or stylet. In some of these embodiments, the electrodes are designed so that the vascular catheter can be trimmed at its distal end without sacrificing electrode and / or sensor functionality. For example, electrodes may be printed onto the catheter using 3D printing techniques, conductive ink may be used, metal strips may be attached, or a flex circuit may be affixed to the catheter. Conductive plastic may also be co-extruded to produce separate traces or electrodes.

[0246] Figures 64A-64C show several embodiments of a trimmable vascular catheter with electrodes integrated into the catheter. Figure 64A shows electrodes 6402 and 6404 extending along the length of the catheter. Figure 64B shows an vascular catheter with multiple electrode pair regions that can function as sensors. Figure 64C shows the catheter of Figure 64B after trimming at the arrows. The most distal sensor or sensors can be used for subsequent infusate parameter sensing during catheter placement. The controller can determine which sensor is most distal based on the resistance of the sensor loop. The vascular catheter can range in length from about 42 to about 53 cm, and the trimmed length at the distal end can be up to about 6 cm.

[0247] Any of the conductivity sensors / electrodes disclosed herein can be incorporated into a rolled printed circuit board, which can be wrapped around and attached to a device. Different manufacturing techniques can be used, alone or in combination, including plating, masking, lithography, stamping, soldering, etc.

[0248] The conductivity sensor may also be used to measure the patient's ECG signal. The two techniques may be used together to localize the location of the distal tip of the device within the anatomy.

[0249] 65 illustrates an embodiment of a vascular navigation device that uses pressure to navigate a vessel. The distal end of the vascular navigation device is inserted into a suitable access vein and advanced along the vein to its target location. These embodiments may not require the use of an infusion medium or infusate to determine the device's location. Alternatively, pressure-based vascular navigation embodiments may be combined with other embodiments disclosed herein.

[0250] After the vascular navigation device is inserted into a blood vessel, typically by a needle or sheath, a pressure sensing element, balloon, or bladder 6502 senses pressure within the blood vessel. The pressure signal is communicated back to the controller, where it is analyzed using a pressure transducer based on pressure, a pressure profile, the pressure of two or more pressure bladders, or changes in pressure and / or distance over time. For example, the controller may determine whether the distal end of the vascular navigation device is in an artery instead of a vein based on the magnitude and direction of blood flow around the vascular navigation device. If the controller determines that the distal end of the vascular navigation device is in an artery instead of a vein, a specific identification signal, including an audible, visual, or other signal, may be signaled to instruct the user to remove the vascular navigation device and any other devices, such as a sheath, catheter, or the like, and apply pressure to the blood vessel.

[0251] Similarly, a pressure-based vascular navigation device can sense when its distal end is in the wrong branch of the vein based on the flow direction and possibly the flow profile and magnitude. When advancing the pressure-based vascular navigation device in the correct direction (toward the SVC-CAJ in the vein), a pressure pulse advances up the top of the vascular navigation device from the more proximal end to the distal end. Conversely, when moving the device away from the SVC-CAJ, a pressure pulse advances up the top of the vascular navigation device from the distal end to the more proximal end. Some embodiments described herein utilize multiple pressure bladders to detect flow directionality. Figures 66A and 66B show pressure profiles for these two different flow scenarios. The pressure shown is the pressure difference between the pressure of the sensing bladder (proximal to the reference bladder) and the reference bladder (closest to the distal tip of the vascular navigation device) as measured by a differential pressure transducer. In Figure 66A, the pressure-based vascular navigation device is advanced in the same direction as the flow, so the sensing bladder generates a pressure wave before the reference bladder, resulting in a positive initial spike in pressure. In Figure 66B, the catheter is advanced against the flow, so the initial spike is negative. In this way, placement in the vessel can be monitored to ensure it is being advanced in the direction of the flow.

[0252] While Figures 66A and 66B show differential pressure measurements between two pressure sensors or two pressure lumens, a single lumen could be used and the data analyzed to separate the readings from each pressure sensor. Pressure openings such as those shown in Figures 80-82 could also be used.

[0253] The vascular navigation device can sense when the distal end strikes the vessel wall based on changes in pressure sensed by one or more pressure bladders.

[0254] The spatial resolution of the pressure signal depends on the location of the differential pressure sensor or pressure opening. In some embodiments, the spatial resolution may be about 1-2 cm. Pressure readings may be taken about every 1 second. Alternatively, pressure readings may be taken about every 0.5 seconds. Alternatively, pressure readings may be taken about every 0.5-1.5 seconds.

[0255] Pressure-based vascular navigation devices can detect the shape and magnitude of the heartbeat, which can be used to determine proximity to the heart and therefore the location of the tip of the vascular navigation device.

[0256] Figure 65 shows one pressure bladder 6502, one pressure lumen 6504 and one infusion / sampling lumen 6506. However, there may be more than one infusion / sampling lumens and / or more than one pressure lumen / bladder.

[0257] 67-74 show the distal end of various embodiments of a pressure-based vascular navigation device. Figure 67 shows a pressure-based vascular navigation device in which a pressure bladder 6704 is external to the pressure-based vascular navigation device 6702 and is at or near the distal end of the vascular navigation device. An infusion / sampling lumen opening 6706 allows fluid to be infused into the vessel or a sample to be withdrawn from the vessel.

[0258] Figure 68 illustrates a pressure-based vascular navigation device with a pressure bladder 6802 near the distal end of the device. In this embodiment, the pressure bladder may be recessed from the distal end of the vascular navigation device by about 1 mm to about 10 mm. Alternatively, the pressure bladder may be recessed from the distal end of the vascular navigation device by about 10 mm to about 30 mm.

[0259] FIG. 69 illustrates a pressure-based vascular navigation device with two or more pressure bladders, including a distal pressure bladder 6902 at or near the distal end of the vascular navigation device and a second pressure bladder 6904 spaced from the distal pressure bladder 6902 by about 1 mm to about 10 mm. Alternatively, the second pressure bladder 6904 may be spaced from the distal pressure bladder 6902 by about 10 mm to about 30 mm. While two pressure bladders are shown here, there may be three or more pressure bladders. They may be spaced the same distance from each other, i.e., regularly spaced, or they may be spaced by different distances from each other, i.e., irregularly spaced. The spacing between the pressure bladders may be about 1 mm to about 50 mm. Each pressure bladder may communicate with a separate pressure lumen.

[0260] Figure 70 shows a pressure-based vascular navigation device with two or more pressure bladders, where the pressure bladders are different sizes, including different lengths and / or diameters and / or volumes. Alternatively, the pressure bladders may be the same size, as shown in Figure 69. A more distal pressure bladder 7002 may be larger or smaller than a more proximal pressure bladder 7004.

[0261] 71 illustrates a pressure-based vascular navigation device in which a pressure bladder 7102 is internal to the vascular navigation device and is at or near the distal end of the device. This configuration allows the pressure bladder to sense pressure within the vessel with less interference caused by the pressure bladder contacting the vessel wall. Additionally, a second pressure bladder may be external to the vascular navigation device to detect contact with the vessel wall and / or other pressures.

[0262] 72 illustrates an embodiment of a pressure-based vascular navigation device that includes a pressure bladder 7202 on a shaft 7204. The shaft 7204 may be a guidewire, other wire, thin tubing, stylet, thin multi-lumen tubing, or other elongated member that may pass through the inner lumen of a vascular catheter. The shaft 7204 in combination with the bladder 7202 may be integral with each other, or may be separate from the vascular catheter and inserted into the vascular catheter either before insertion or when needed. The shaft / bladder combination may be movable within the lumen of the vascular catheter or may be fixed within the vascular catheter.

[0263] FIG. 73 shows a shaft / bladder combination positioned within the distal opening of a vascular catheter. This arrangement may be achieved by moving the shaft / bladder combination within the vascular catheter, or the shaft / bladder combination may be fixed to the vascular catheter at this or another location. This location within the distal tip, as opposed to external to the distal tip as shown in FIG. 72, may allow the pressure bladder to sense pressure within the vessel with less interference caused by the pressure bladder contacting the vessel wall. Additionally, a second pressure bladder may be external to the vascular navigation device to detect contact with the vessel wall and / or other pressures.

[0264] FIG. 74 illustrates an embodiment of a pressure-based vascular navigation device that incorporates a spacer, or cage, 7402 in addition to a pressure bladder 7404. The spacer 7402 can help center the vascular navigation device within the vessel without impeding blood flow past the device. While the cage 7402 is shown here proximal to the pressure bladder 7404, other embodiments may include a cage more distal to the pressure bladder and / or multiple cages and / or multiple pressure bladders. While the embodiment shown in FIG. 74 illustrates a cage that allows blood to flow, some embodiments may include spacers in different configurations, such as solid, perforated, grooved, etc. Different spacer configurations can be designed to affect blood flow in predictable ways. The spacer can also be inflatable or collapsible, so the vascular navigation device has a smaller diameter for introduction into the patient's body. The pressure bladder can also be placed within the spacer.

[0265] In some embodiments, the spacer and / or pressure bladder is slidable along a longitudinal axis on or within the vascular navigation device shaft, hi some embodiments, the spacer and / or pressure bladder is rotatable about the exterior or interior of the vascular navigation device shaft.

[0266] Priming In embodiments that include a pressure bladder and obtain sensitive, high-resolution, and accurate pressure measurements from the pressure bladder, it is important that the pressure bladder be properly "primed." This means that the pressure bladder is pressurized to an optimal pressure to obtain the maximum magnitude of pressure readings from blood flow, blood pressure, and vascular pressure. Continuous adjustment and maintenance of pressure balance on both sides of the pressure bladder membrane is necessary and can be controlled by a controller. This pressure balance can be referred to as a pressure differential. In some embodiments, the desired pressure differential is zero or near zero. In some embodiments, the desired pressure differential can be a different value. The pressure acting on the external interface of the pressure bladder (facing the interior surface of the blood vessel) is subject to change according to the patient's physiology. The pressure on the internal interface of the pressure bladder (which is in fluid communication with the fluid column within the vascular navigation device, which is in fluid communication with the controller) can decrease due to fluid leaks and imperfect seals.

[0267] When a vascular navigation device is initially inserted, external pressure is typically applied to the fluid column and to the pressure interface up to a first approximation of the pressure applied to the pressure interface from within the vessel. The pressure signal, as measured across the pressure interface, has a maximum amplitude when the pressure differential is near zero. The amplitude of the pressure signal can therefore be used to adjust the pressure being applied from the fluid column to the pressure interface. This process of applying the appropriate amount of pressure to the interface can be referred to as priming the fluid column or priming the pressure bladder. As mentioned above, because the pressure on both sides of the pressure interface can vary, the fluid column may need to be reprimed or readjusted from time to time. The need for repriming can be monitored by checking for small changes in pressure to achieve a maximum amplitude in the pressure signal profile. Alternatively, priming can occur periodically and automatically via a controller.

[0268] Embodiments of the disclosed systems and methods include automatic pressure adjustment by a controller. Thus, the adjustment system can detect optimal target pressure and volume and inflate the pressure bladder by monitoring the sensed pressure signal and adding or removing air or fluid volumes as needed. For example, upon insertion of a vascular navigation device, a pressure adjustment circuit that adjusts the pressure bladder volume and pressure may inflate the bladder until it detects a pressure rate due to a physiological factor, such as heart rate. Upon sensing that rate, the pressure adjustment controller may add or subtract small amounts of air in a routine sequence until the amplitude of the sensed wave is maximized. A control feedback loop between the optimally adjusted pressure (manifested as pressure and volume of the pressure bladder) and the sensed physiological pressure profile may be repeated continuously and / or as needed to ensure high-fidelity measurement of physiological data. In some embodiments, the automatic pressure adjustment may be performed in an apparent background while physiological data is transmitted and displayed; in other embodiments, the system may pause transmission of physiological data during the pressure adjustment sequence.

[0269] An embodiment of the disclosed technology includes a gas delivery system capable of delivering gas in a priming operation, whereby pressure can be applied to a fluid column proximal to a proximal-facing surface of a pressure interface. A source of gas, such as compressed air, or liquid is held in a storage tank. Using CO2 as an example, CO2 is released in a controlled manner from the storage tank by a pressure regulator that can reduce the pressure within the tank (e.g., a pressure of about 850 psi (about 5862.0689 kPa)) to a range of about 1 psi to about 2 psi (about 6.896 kPa to about 13.793 kPa). The released gas passes through a filter and a pressure relief valve set at about 2.5 psi (about 17.241 kPa). The pressure relief valve is a safety feature that prevents gas levels above 2.5 psi (about 17.241 kPa) from flowing in the event of an upstream regulator failure. The CO2 exiting the pressure relief valve then passes through a first solenoid fill valve, enters the catheter line, and ultimately fills a pressure bladder containing a pressure-sensing interface. The pressure in the pressure bladder is allowed to rise to a level as high as 30 mmHg (approximately 3.999 kPa), whereupon the first solenoid valve closes. A second solenoid valve distal to the first valve acts as a drain valve, which can release pressure to the target pressure. Alternatively, the drain valve can be activated until a pressure waveform is detected, after which the pressure bladder is optimally primed and the valve is closed. The drain valve may be operably proportionally controlled based on voltage or pulse-width modulation (PWM), allowing the drain rate to be sufficiently slowed so that the target pressure is achieved and the valve can be closed before overshooting. Alternatively, a peristaltic or other air pump can be used to fill the pressure bladder with chamber air.

[0270] FIG. 75 shows a graph illustrating a method for priming a pressure bladder in some embodiments. Here, a small burst (approximately about 0.3 cc) of fluid volume is added to the pressure bladder and the pressure within the bladder is measured. The small burst of fluid is introduced until the measured pressure within the bladder settles to a stable pressure 7501. This transition is indicated by inflection point 7502. Multiple bursts of fluid are introduced until, past this point, the measured pressure begins to rise rapidly (e.g., when the slope 7504 of the curve exceeds about 2 mmHg / 10 ms). This inflection point is indicated by 7506. At this point, the pressure within the bladder is reduced to a pressure that is approximately at or slightly above the stable pressure 7501. This pressure represents the prime pressure at which the pressure is measured in some embodiments. This process is also described in the flowchart of FIG. 78.

[0271] The small burst of fluid can be from about 0.2 cc to about 0.4 cc. The small burst of fluid can be from about 0.1 cc to about 0.5 cc. The small burst of fluid can be up to about 0.5 cc. The small burst of fluid can be up to about 1.0 cc.

[0272] FIG. 76 shows a graph illustrating a method for priming a pressure bladder in some embodiments. This method is similar to that shown in FIG. 75, except that the pressure rises more smoothly in the pressure bladder without the burst shown in FIG. 75. A volume of fluid is added to the pressure bladder, and the pressure in the bladder is measured. The bladder pressure is increased until the measured pressure in the pressure bladder settles to a stable pressure 7605. This transition is shown at inflection point 7606. The bladder pressure is increased until, past this point, the measured pressure begins to rise rapidly (e.g., when the slope 7610 of the curve exceeds approximately 2 mmHg / 10 ms). This inflection point is shown at 7608. At this point, the pressure in the bladder is reduced to approximately or slightly above the stable pressure 7605. This pressure represents the prime pressure at which the pressure is measured in some embodiments. This process is also depicted in the flowchart of FIG. 79.

[0273] FIG. 77 shows a flowchart of a pressure bladder priming process in some embodiments. Embodiments of the disclosed systems and methods include automatic pressure adjustment by a controller. Thus, the adjustment system can detect an optimal target pressure and volume for inflating the bladder by monitoring the sensed pressure signal and adding or removing air amounts as needed. For example, upon insertion of a vascular navigation device, the pressure adjustment circuit, which adjusts the pressure bladder volume and pressure, inflates the bladder until it detects a physiologically-driven pressure rate. Upon sensing that rate, the pressure adjustment controller adds or subtracts minute amounts of air or fluid (approximately 0.3 cc) in a routine sequence until the sensed wave amplitude reaches a maximum. The control feedback loop between the optimally adjusted pressure (manifested as pressure bladder pressure and volume) and the sensed physiological pressure profile can be repeated continuously and / or as needed to ensure high-fidelity measurement of physiological data. In some embodiments, the automatic pressure adjustment can be performed in the apparent background while physiological data is transmitted and displayed; in other embodiments, the system can pause transmission of physiological data during the pressure adjustment sequence.

[0274] The trace amount of air or fluid may be from about 0.2 cc to about 0.4 cc. The trace amount of air or fluid may be from about 0.1 cc to about 0.5 cc. The trace amount of air or fluid may be up to about 0.5 cc. The trace amount of air or fluid may be up to about 1.0 cc.

[0275] FIGS. 80-85 illustrate embodiments of a pressure-based vascular navigation device that includes a bladderless pressure sensing feature. These embodiments may also include a pressure bladder. One advantage of a bladderless pressure sensing feature is that priming may not be necessary. FIG. 80 illustrates the distal end of a vascular navigation device with an opening 8002 to an infusion or sampling lumen. Openings 8004 and 8006 connect to two separate pressure lumens, which connect to a differential pressure transducer via a fluid column. Instead of a pressure bladder as shown in other embodiments, the embodiment of FIG. 80 includes a pressure interface at openings 8004 and 8006. This interface may be a meniscus between a gas and a liquid, such as air and blood. Alternatively, this interface may be a meniscus between two different fluids. Alternatively or additionally, this interface may include a membrane separating the two fluids. The membrane may be loose, allowing the interface between the two fluids to move freely depending on the pressure to which it is exposed. The membrane may be impermeable to one or both of the fluids involved.

[0276] For example, if gas is used in the pressure lumen of a pressure-based vascular navigation device and the lumen is narrow enough, the gas will not leak out of the lumen and enter the bloodstream. Instead, the interface between the blood and the gas forms a meniscus, which acts as a pressure interface similar to the pressure bladders disclosed herein but without the need for priming. Alternatively, a liquid, preferably one with different properties than blood, such as a different viscosity, can be used in the pressure lumen.

[0277] 81 shows an embodiment of a pressure-based vascular navigation device with two pressure lumens and a cage 8102 that may assist in centering the device within the vessel. Other centering mechanisms, such as loops, wires, balloons, bumpers, etc., may also be used.

[0278] 82 shows an embodiment of a pressure-based vascular navigation device with two pressure lumens and a pressure bladder 8202. The pressure bladder can serve both to center the device within the vessel and also to sense pressure exerted by the vessel wall to aid in navigation. In this embodiment, three pressure lumens may be present in the device.

[0279] Alternatively, the membrane may act as a pressure bladder similar to other pressure bladders disclosed herein. In these embodiments, priming may still be required.

[0280] FIGS. 83-85 show various cross sections of a pressure-based vascular navigation device. These configurations may be used with any of the embodiments disclosed herein. FIG. 83 shows infusion / sampling lumen 8302 and pressure lumens 8304, 8306, and 8308. This configuration may be particularly useful in the embodiments shown in FIGS. 80-82, where it may be advantageous to have two pressure lumens near each other on one side of the catheter wall. For example, two or more pressure interface openings may be located on the same half of the circumference of the vascular navigation device catheter shaft, allowing for detection of pressure differences between pressure along one side of the catheter versus pressure on different sides of the catheter. For example, lumen 8304 may connect to one pressure interface opening, and lumen 8306 may connect to another pressure interface opening. Optionally, pressure lumen 8308 may connect to a pressure bladder, such as that shown in FIG. 82. Alternatively, three or more pressure interfaces may be present in the vascular navigation device.

[0281] There are advantages to a small cross-sectional area and / or small volume pressure lumen. The smaller the volume, the less fluid / gas that needs to be moved to convey the pressure sensed at the catheter tip through the fluid column within the device to a pressure transducer connected to or integrated into the controller. Additionally, the smaller the pressure interface opening, the greater the likelihood of a meniscus forming between the fluid in the pressure lumen and the blood in the vessel. For clarity, "fluid" can include either a gas or a liquid.

[0282] Figure 84 shows an infusion / sampling lumen 8402 and pressure lumens 8404, 8406, and 8408. In this example, pressure lumens 8404 and 8408 may be connected to pressure interface openings, and pressure lumen 8406 may be connected to a pressure bladder. In this configuration, lumens 8404 and 8408 have a larger cross-sectional area and volume than the configuration of Figure 83, but still allow the two pressure interface openings to be closer together on either side of the catheter wall.

[0283] 85 shows another cross-sectional view that may be used with any of the embodiments disclosed herein. This embodiment shows infusion / sampling lumen 8502 and pressure lumens 8504, 8506, and 8508.

[0284] It should be noted that while many of the figures shown herein incorporate a pressure lumen into a vascular catheter, the vascular navigation device may be a standalone device that fits within the vascular catheter and can be removed once placement of the vascular catheter is complete. For example, the vascular navigation device may function as a stylet for a standard vascular catheter.

[0285] In some embodiments of pressure-based vascular navigation devices, one or more pressure bladders may be used, one or more pressure interface openings may be used, a combination of pressure bladders and pressure interface openings may be used, etc. Other pressure measurement mechanisms may also be used, including miniature pressure transducers on the catheter, piezoelectric pressure sensors, etc.

[0286] Disclosed herein are embodiments comprising different types of sensors. It is understood that any type of sensor may be used with any of the embodiments disclosed herein. For example, any of the embodiments disclosed herein may use a sensor that senses an electrical property, such as conductance or resistance.

[0287] FIG. 86 shows an embodiment of a vascular navigation device that uses electrodes as sensors to sense the conductance of blood and / or blood / infusate mixtures flowing between electrode pairs, where an electrode pair may be considered one sensor. In this embodiment, a stylet 8604 is configured to fit into a catheter 8602. The stylet 8604 includes a proximal electrode pair or sensor 8606 and a distal electrode pair or sensor 8608. Infusate is infused through the lumen of the catheter or stylet and exits the stylet via an opening 8610 in the diffusion exit port region 8612. In this embodiment, an electrode lead 8614 is wrapped around a stylet stiffener 8616. A stylet end plug 8618 is also shown. The stylet end plug may have a rounded tip as shown here or may incorporate a soft ridge. Although four electrode leads are shown here, fewer leads may be used. For example, a single lead may connect to both ground electrodes of the two sensors, resulting in three leads instead of four.

[0288] 87 shows an embodiment of a vascular navigation device in which a stiffener 8616 exits past an end plug 9618. The stiffener may assist in guiding the device through the vascular system. The end plug may be made from an adhesive, polymer, metal, or other suitable material.

[0289] FIG. 88 shows an embodiment of a vascular navigation device in which the stiffener 8616 terminates in a curved portion. The curved portion may be rigid or more flexible than the more proximal section of the stiffener. The curved portion may be passive, i.e., a set curve of the device, or the curved portion may be active, where the user can change the shape or amount of curvature of the curve at the tip of the device to assist in navigating the vasculature. The change in curve may occur from the proximal end during the procedure or may occur before the procedure. The curve may be smooth or abrupt, i.e., a bend. The curve may be any suitable angle, for example, about 120 degrees, or from about 100 degrees to about 140 degrees.

[0290] 89 illustrates an embodiment of a vascular navigation device with a small diameter exit port region 8612. For example, the outer diameter of the exit port region 8612 may be smaller than the outer diameter of the electrode / sensor region of the device. This embodiment allows for different fluid flow dynamics of the infusate exiting the exit port through the opening. Alternatively, the outer diameter of the exit port region may be larger than the outer diameter of the electrode / sensor region of the device.

[0291] FIG. 90A shows an embodiment of a vascular navigation device including a sleeve-type exit port region. In this embodiment, infusate exits the stylet through a proximal opening 9002 and / or a distal opening 9004. The openings may be annular or may include one or more openings around the circumference of the device. This embodiment allows for different fluid flow dynamics of the infusate exiting the exit port through the openings. Other embodiments may include baffles or skirts adjacent to the openings to direct the flow of infusate as it exits the exit port.

[0292] FIG. 90B shows an embodiment of a vascular navigation device with a small-diameter, sleeve-type exit port region. In this embodiment, the exit port is recessed. In other words, fluid exiting the exit port exits within a recess in the outer surface of the device. Similar to the embodiments shown in FIGS. 89 and 90A, this allows infusion fluid to exit the device in situations where the device is against the vessel wall or in other restrictive situations. Embodiments with recessed exit ports may also help reduce the boundary distance λ, as shown in FIGS. 63A-63D. Embodiments with diffusion, sleeve, and recessed exit ports may reduce the boundary distance λ.

[0293] 91 shows an embodiment of a vascular navigation device with a dual-layer exit port region. In this embodiment, an inner exit port region 9102 is coaxial with and inside an outer exit port region 9104. This embodiment allows for different flow dynamics of infusate exiting the exit port regions.

[0294] 92 shows an embodiment of a vascular navigation device in which the core or stiffener contains the leads for the sensors / electrodes. Shown here are four insulated leads 9202 within an outer sheath 9204. Additional stiffening cores may or may not be included in the bundle that makes up the stiffener. In some embodiments, the insulated leads are stripped at their distal ends and coiled to create a coiled electrode 9206 on the exterior of the stylet.

[0295] FIG. 93 shows an embodiment of a vascular navigation device in which the stiffener is exposed at the distal end to form the most distal electrode 9302.

[0296] In these and other embodiments, the space between the OD 9304 of the stiffening cord and the ID 9306 of the outer tube of the device can be significant. This defines an infusion area for fluid infusion along at least a portion of the device. The ratio of the tube ID to the stiffener OD can be approximately 0.4. Alternatively, the ratio of the tube ID to the stiffener OD can be approximately 0.3-0.5. Alternatively, the ratio of the tube ID to the stiffener OD can be approximately 0.2-0.6. Alternatively, the ratio of the tube ID to the stiffener OD can be approximately 0.1-0.7. In some embodiments, the OD of the stiffening cord is zero or substantially zero, thereby making this ratio at or near infinity.

[0297] In these and other embodiments, the total area of ​​the outlet port opening (e.g., port length 6204 * % port opening area * tube ID 9306 * π) versus the cross-sectional area defining the space between the stiffener OD and tube ID (π(tube ID 9306 / 2) 2 -π (stiffener OD9304 / 2) 2 ) may be significant. This ratio may be about 4.5. Alternatively, this ratio may be about 1.8 to 14. Alternatively, this ratio may be about 1.4 to 20. Alternatively, this ratio may be about 1.2 to 30. In embodiments where the stiffener OD is zero, this ratio may be about 4. Alternatively, in embodiments where the stiffener OD is zero, this ratio may be about 1.6 to 13. Alternatively, in embodiments where the stiffener OD is zero, this ratio may be about 1.2 to 30.

[0298] Figure 94 shows the relationship between the magnitude of the sensor signal and the location of the navigation device. Figure 94 shows conductivity data collected from a distal sensor of a vascular navigation device that includes a conductivity sensor. These data represent the signal from the vascular navigation device during a constant infusion of infusion fluid, as opposed to an intermittent or bolus infusion of infusion fluid, where the conductivity of the infusion fluid is lower than that of blood.

[0299] This signal has been attenuated / filtered to more clearly show the signal magnitude as the navigation device is navigated through the vasculature. The distal tip of the device is navigated through the SVC, into the CAJ, into the heart, and then retracted through the CAJ and SVC. The baseline conductivity signal, without infusion of infusate medium, is shown by the dotted line. This is generally what the conductivity signal would be if the device were advanced through the vasculature without any infusion of infusate. However, when infusate is continuously infused through the device and allowed to exit the device opening near the distal tip, the sensor (electrode in this case) will detect a different conductivity signal depending on the location of the device in the anatomy.

[0300] While the device is in the upper part of the SVC, the conductivity is generally below the baseline due to the infusion of infusate, which has a lower conductivity than blood. Because there is less turbulence and less mixing in this region of the vasculature, the signal magnitude, or the difference between the signal and baseline, is relatively large in this region. This signal magnitude can vary with vessel size and / or anatomy. As shown here, there is also a fairly large signal magnitude when the device enters the CAJ. The signal magnitude decreases as the device crosses the superior vena cava / caval-atrial junction (SVC-CAJ) and enters the right atrium. In other words, the signal reaches baseline. This is due to increased flow, turbulence, and mixing of the blood in the atrium, which quickly dilutes and eliminates the lower conductivity infusate, so the sensor does not detect the presence of infusate. Because the ideal location for the catheter tip is within the CAJ, the user withdraws the catheter until the conductivity signal magnitude increases again, typically to the point represented by an "X" on the curve. In this way, the magnitude of the conductivity signal can be used to locate a navigation device within the CAJ.

[0301] Figures 95 and 96 show how the relative magnitude of the signals from the proximal and distal sensors can be used to determine the direction of blood flow. Figure 95 shows the conductivity signal of a vascular navigation device in the external jugular vein of a pig. Figure 96 shows the conductivity signal of a vascular navigation device in the brachiocephalic vein of a pig. Signals from both the distal and proximal sensors are shown. Note that blood flows in the same direction as the advancement of the device, along with the device, in the brachiocephalic vein, and against the device in the external jugular vein. It is important to be able to identify blood flowing against the device, as this indicates that the device is in the wrong vessel and needs to be retracted.

[0302] In a situation where the device is in the wrong place, with blood flowing against the device, the signal from the proximal sensor will have a larger magnitude from baseline (lower conductivity) than the signal from the distal sensor. This is shown in Figure 95. In a situation where the device is in a blood vessel, with blood flowing with the device, the signal from the proximal sensor will have a smaller magnitude from baseline (higher conductivity) than the signal from the distal sensor. This is shown in Figure 96. By analyzing the relative magnitudes of the distal and proximal sensors, the controller can determine if the device is in a vessel where blood is flowing in the wrong direction (either the wrong vein or artery).

[0303] Figure 96 also clearly shows the pulsatility of the signal at some locations within the vasculature. Here, in the brachiocephalic vein, the pulsatility of both the proximal and distal sensor signals can be seen. Both respiratory and cardiac pulses can be seen in these signals, each with its own frequency. The cardiac frequency has a pulse length 9602, and the respiratory frequency has a pulse length 9604. A Fourier transform or other mathematical method can be used by the controller to extract the various frequencies from the sensor signals and determine the magnitude and relative magnitudes of the sensor signals as well as the heart rate and respiratory rate.

[0304] A constant infusion of infusate was used to obtain these data in pigs. Constant, variable, or intermittent infusion of infusate may be used.

[0305] The pulsatility of the sensor signal depends on the location of the device within the vasculature. For example, smaller blood vessels may produce a more pulsatile signal than very large blood vessels or the heart. Therefore, the pulsatility of the sensor signal may also be used to locate a vascular navigation device. The pulsatility of the signal, the signal magnitude, and / or the relative signal magnitude may be used to locate the device within the anatomy.

[0306] Figure 97 illustrates different types of flow that may be encountered within the vasculature when placing a vascular catheter: in-line flow, reverse flow, highly turbulent bidirectional flow, and highly turbulent multidirectional flow. Figure 97 also illustrates different types of signals that a vascular navigation device may sense or monitor, including signal magnitude, signal pulsatility, signals due to electrical activity, and other signal types. The controller of the vascular navigation system uses one or more of these signal types to identify the location of the device within the anatomy and also communicates instructions to the user based on the sensed location.

[0307] While several examples are provided herein, it is understood that the signal signature may vary from the examples and may incorporate fewer, more, or different signal types. The controller may incorporate one or more signal types as absolute or relative values. The relative values ​​may be relative to another time point, or to another signal type, or to the same signal type from a different sensor. For example, a controller of a vascular navigation device may determine that the distal tip of the device is in an artery based on a high magnitude of the proximal sensor signal. Alternatively or additionally, the determination may be based on an increase in the magnitude of the proximal sensor signal from a previous time point / location of the device. Alternatively or additionally, the determination may be based on the magnitude of the proximal sensor signal relative to the magnitude of the distal sensor signal, where the magnitude of the proximal sensor signal may be higher in an artery. Any of the signal types disclosed herein may be similarly analyzed, either absolute or relative, or both.

[0308] The anatomical diagram shows the location of the ostium vein (A), SVC (B), contralateral vein (C), artery (D), CAJ (E), and right atrium (F). As the device is advanced through the vasculature, ideally it passes through an ostium vein and enters the SVC and CAJ. The vascular navigation system may detect where the tip of the device is located based on one or more signal signatures. The vascular navigation system may also be able to detect the transition of device location from one anatomical region to another. For example, the vascular navigation system may detect when the device has moved past the CAJ and entered the right atrium to be advanced from the CAJ, and instruct the user to slightly retract the catheter / device so that it is again in or near the CAJ. The navigation system may detect when the device has passed back into or near the CAJ, and instruct the user that the device is now in the desired location.

[0309] During navigation, it is also possible that the catheter / instrument may enter either an artery or a contralateral vein with blood flow, such as at location (C) or (D). When this occurs, the system may detect that the instrument is in the wrong place based on one or more signal signatures and instruct the user that they should withdraw the instrument until the system signals that the instrument is no longer in the wrong place.

[0310] A representation of the vascular navigation device is shown with catheter 9702, proximal sensor 9704, distal sensor 9706 and infusion port area 9708.

[0311] The table in Figure 97 shows several different types of signals sensed by sensors at different locations in the vasculature and received by the system's controller. These signal types include: 1. Signal size The signal magnitude is the magnitude of the sensor signal relative to a reference. The signal magnitude used by the controller may be the absolute signal magnitude or the relative signal magnitude. The relative signal magnitude may be relative to the signal magnitude at another time / location within the vasculature or relative to the magnitude signal of another sensor. For example, the controller may use the absolute signal, i.e., the increase or decrease in signal as the device is advanced through the vasculature. Alternatively, or in addition, the controller may use the relative magnitude of the signal between the distal and proximal sensors—in other words, whether and by how much one is a higher magnitude signal than the other. 2. Pulsatility of the signal The signal pulsatility used by the controller may be absolute signal pulsatility or relative signal pulsatility, which may be relative to the signal pulsatility at another time / location within the vasculature or relative to the pulsatile signal of another sensor. 3. Signals resulting from the electrical activity of the heart The signal resulting from the heart's electrical activity can be sensed by a sensor. Either one sensor or two or more sensors can pick up the heart's electrical activity. The relative signal resulting from the heart's electrical activity can be relative to time / location or between two sensors. Generally, the signal resulting from the heart's electrical activity is stronger closer to the sinoatrial node in the pathway to the heart.

[0312] Other signal types may be used instead or as well, for example, signal phase (e.g., the relative phase of the signal between two sensors).

[0313] The following is an example of how a vascular access device may use signal signatures to locate the device within the anatomy. When the device / catheter is properly advanced through the vein and SVC, blood flow is in-line, the proximal sensor signal magnitude may be small or negligible, and the distal sensor signal magnitude may be relatively large (although this may vary depending on the size of the vein). In other words, the ratio of distal to proximal signal magnitude will generally shift to a ratio greater than 1. The pulsatility of the sensor signal may also be relatively large. The signal due to cardiac electrical activity may be relatively low. From one of these signal types or a combination of two or more of them, the controller may determine that the device is in the proper vein and instruct the user to continue advancing the device.

[0314] When the device enters the wrong vessel, such as an artery or a vein with contralateral blood flow, the magnitude of the proximal sensor signal may be relatively large while the magnitude of the distal sensor signal may be relatively small; in other words, the ratio of the distal signal magnitude to the proximal signal magnitude generally shifts to a ratio less than one. The pulsatility of the signal may be large when the device is in an artery or small when the device is in a vein with contralateral blood flow. The signal due to the cardiac electrical activity may remain relatively low. Based on one or more of these signals, the controller of the vascular navigation system may determine that the device is in the wrong place and can determine whether the device is in an artery or a vein. The controller instructs the user that the device should not be advanced further and that the device should be retracted until the sensor signals again indicate that the device is in a vein with in-line blood flow.

[0315] As the user continues to advance the device through the SVC and into the CAJ, the system instructs the user to continue advancing until the CAJ or the right atrium is detected. At the CAJ, the magnitude of the distal sensor signal may be relatively high, while the magnitude of the proximal sensor signal may vary. The pulsatility of the signal may be relatively high, and the signal due to the electrical activity of the heart may be relatively high. The controller may determine that the device is now in the CAJ and instruct the user to stop advancing. Alternatively, the user may be instructed to continue advancing the device so that it enters the right atrium.

[0316] Blood flow within the right atrium is highly turbulent and multidirectional, causing significant mixing and rapid dilution of the infusate. In this region, the signal magnitudes of both the distal and proximal sensors may be reduced, and the pulsatility of the signals may be reduced. Signals due to cardiac electrical activity may be relatively low. One or more of these signals may be used by the controller to determine that the device has entered the heart. At this point, the controller signals the user to cease advancing the device and retract it until the controller detects that the device is again approximately at or near the CAJ. The vascular navigation system may automatically control the distance the device / catheter is retracted to ensure proper location of the distal catheter tip within or near the CAJ. In some embodiments, the vascular navigation device extends a known distance beyond the tip of the catheter, and in this case, when the distal tip of the vascular navigation device is within the heart, the distal tip of the catheter may be within the CAJ, and the device / catheter may not need to be retracted.

[0317] After the navigation device / catheter is properly positioned, the navigation device may be disengaged from the lumen of the catheter and removed.

[0318] The controller may determine the location of the device within the vasculature based on the signal signature. One or more of the signal types may be used to locate the device. The signal type or combination of signal types used at one location may differ from that used at another location in the anatomy. The controller may also, or in addition, analyze the signal for specific frequencies indicative of heart rate, respiratory rate, or other factors. This information may also be factored into the controller logic used to locate the device or for other purposes.

[0319] Embodiments of the vascular navigation device may use a constant infusion rate, intermittent infusion, a variable infusion rate, or varying infusion rates of infusate depending on the anatomy, the patient, the location within the anatomy, etc. For example, a constant infusion rate may be used for navigation until the device detects turbulence. The device then either signals the user or automatically increases or otherwise modifies the infusion rate of infusate. The resulting sensor data may be used to verify the location of the device within the heart versus the thoracic junction or other bifurcation or other point within the anatomy.

[0320] In some embodiments, the infusion rate of the infusion fluid may be continually changed so that more data at different infusion rates is continually collected and analyzed. For example, the infusion rate may vary as a sine wave, a constant increase or decrease, or other function.

[0321] In some embodiments, the infusion rate of the infusate may be automatically adjusted so that the sensor signal is maximized. This "adjusted" infusion rate may be determined by the patient, by the anatomy, by location within the anatomy, or any combination thereof.

[0322] In some embodiments, the infusion rate of the infusate can be varied and tracked so that the signal from the sensor is constant. In this manner, the infusion rate can be used to determine vessel parameters including diameter, device location, etc.

[0323] In some embodiments, the signal signature and / or signal magnitude may be used to determine the diameter of the vessel, where a larger signal magnitude generally indicates a vessel with a smaller diameter.

[0324] In some embodiments, vascular health may be determined based on the sensor signal, the infusion rate, or both.

[0325] In some embodiments, the controller of the vascular navigation system may use sensor data to collect patient health data. For example, the system may assess the patient's hydration level based on the salt concentration of the patient's blood. The device may also determine respiratory rate, heart rate, and blood flow based on the sensor data.

[0326] Some embodiments of the vascular navigation system use the collected data to diagnose the patient's health condition, such as cardiac arrhythmia, valve problems, pulmonary hypertension, deep vein thrombosis, bradycardia or heat block, various types of congenital heart disease, ventricular arrhythmia, supraventricular tachycardia, atrial fibrillation, atrial flutter, tachycardia, re-entrant tachycardia, premature atrial contractions (PACs), premature ventricular contractions, junctional arrhythmias, tricuspid regurgitation, tricuspid stenosis, pulmonary regurgitation, pulmonary stenosis, mitral or aortic stenosis, mitral or aortic regurgitation, atrial septal defect, patent ductus arteriosus, systolic heart failure (or HFrEF), diastolic heart failure (HFpEF), right heart failure, cardiogenic shock, distributive shock, hypovolemic shock, obstructive / restrictive shock, and the like. shock, pulmonary embolism, cardiac effusion, cardiac tamponade, paravalvular regurgitation, subclavian stenosis, jugular venous stenosis, pulmonary vascular shunt, hepatorenal syndrome, hypokalemia, hyperkalemia, digitalis toxicity, superior vena cava syndrome, inferior vena cava syndrome, pneumothorax, pulmonary or mediastinal mass, pleural disease or effusion, diaphragmatic paralysis, compartment syndrome, cirrhosis, angioplasty, aortic aneurysm, arterial bypass, cardiac catheterization, cardiac device monitoring The controller may assess the presence or status of: cardiac monitoring, cardiomyopathy, carotid artery stenting, carotid endarterectomy, computed tomography, congestive heart failure (CHF), constrictive pericarditis, coronary artery bypass surgery, dilated cardiomyopathy, echocardiography, heart transplant, hypertrophic cardiomyopathy, implantable cardioverter defibrillator (ICD), varicose vein treatment, mitral valve prolapse, pericardial effusion, restrictive cardiomyopathy, stroke, thrombectomy, ventricular assist device (VAD), etc. Machine learning and / or neural networks may be used within a single patient or may use data from two or more patients to correlate signature signals received and analyzed by the controller with specific disease states or risks.

[0327] Some embodiments of the vascular navigation system may assist in identifying the location or malposition of devices such as pacemakers, ECMO (extracorporeal membrane oxygenation) circuits, intra-aortic balloon pumps, impellor-based heart pumps, IVC filter placement, and umbilical vascular catheters.

[0328] Some embodiments of the vascular navigation system are designed to automatically calibrate the system. For example, when initially inserted, the device may be able to assess the relative salinity of the patient's blood, the size of the patient's relative vasculature, blood flow rate, blood viscosity, etc. The system may automatically operate over a range of infusate infusion flow rates to maximize the sensor signal for a given patient. The system may collect sensor data at zero infusate infusion and at set or variable infusate infusion flow rates. The calibration process may be performed at the beginning of a procedure or at any time during a procedure. The calibration process may also be performed manually, with or without a prompt from the controller.

[0329] Some embodiments of the vascular navigation system use device vibration data to assist in determining the location of the device. Some embodiments control the vibration of the device.

[0330] Some embodiments disclosed herein can be used to determine a patient's fluid level, or hydration level. Fluid level is especially important when a patient has congestive heart problems. Low fluid levels can result in low amplitude pulses in the bloodstream, while high fluid levels can result in large amplitude blood flow pulses. Other flow patterns can differ between hydrated and less hydrated patients. These flow patterns can be detected using embodiments disclosed herein. Hydration levels can be monitored in patients over time or compared between patients.

[0331] Some embodiments of the vascular navigation system use controller logic to identify signal signatures characteristic of certain conditions, including conditions where the sensor area of ​​the device is against the wall of a vessel or is in a bend in the vessel. In this condition, the sensor may not be properly or circumferentially exposed to the infusion fluid. It is also possible that the sensor may sense tissue in the wall of the vessel itself instead of fluid within the vessel. The controller may identify these situations based on changes in any of the sensor signals disclosed herein and perform one or more of several functions to change the condition, such as: instructing the user to move the device forward, backward, or rotate; automatically moving the device; moving the device relative to the catheter; increasing or decreasing the infusion rate of the infusate; changing the infusion rate from pulsatile to continuous or from continuous to pulsatile; changing the sampling and / or drive frequency; etc.

[0332] Some embodiments of the vascular navigation system include sensors for sensing other patient parameters, such as chemical sensors (O2, glucose, electrolytes, etc.), temperature sensors, viscosity sensors, blood viscosity sensors, pressure sensors, ECG, etc. For example, blood clotting time may be able to be determined after the introduction of an anticoagulant. These sensors may sense these parameters in real time.

[0333] Some embodiments of the vascular navigation system may include algorithms that use different types of signals and / or determinations. For example, by measuring vessel diameter and blood flow and determining the location of a device, some embodiments may perform real-time estimation of how well a medication is mixed or infused into the bloodstream. In some embodiments, the medication may be the infusion fluid. Midline catheter placement may be more affordable and easier to install than PICCs and central catheter lines, but PICCs and central catheter lines differ from PICC lines in that they are not placed at the CAJ. By determining the mixing ratio or mixing results of two infusion media, the vascular navigation system may determine the location of a device based on this mixing outside the CAJ.

[0334] Infusion fluids in embodiments using conductance / resistance sensors / electrodes may be higher or lower in salinity (i.e., higher or lower conductivity) than blood. For example, the infusion fluid may be distilled water, 5% dextrose in water (D5W), etc.

[0335] The controller may also be integrated with other systems, such as electronic medical systems, electronic health systems, etc. This integration may be wired or wireless, and may be local or remote. Integration may also be via an "EMR sniffer."

[0336] From the foregoing, it will be understood that, although specific embodiments of the present invention have been described herein for purposes of illustration, various modifications may be made without departing from the spirit and scope of the various embodiments of the present invention. For example, some embodiments may include various suitable combinations of components, devices, and / or systems from any of the embodiments described herein. Furthermore, while various advantages associated with some embodiments of the present invention have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments necessarily need to exhibit such advantages in order to fall within the scope of the present invention.

Claims

1. an elongate body defining a lumen at least partially along a length of the elongate body; one or more sensors positioned at or near the distal tip of the elongate body; one or more openings defined along the elongate body proximate the one or more sensors; a fluid having known initial parameters when released from said one or more openings; a controller in communication with the one or more sensors, the controller configured to track changes in the parameter related to the concentration of the fluid as it is released through the one or more openings and passes over the one or more sensors, the controller further configured to determine a position of the one or more sensors within the subject based on a dilution of the fluid after it is released; A location detection system comprising:

2. The system of claim 1 , wherein the one or more openings include a diffusion outlet port.

3. The system of claim 1 , wherein the one or more openings include a plurality of openings adjacent to one another.

4. The system of claim 1 , further comprising a stiffening member extending at least partially through the lumen.

5. The system of claim 4 , wherein the ratio of the inner diameter of the elongate body to the outer diameter of the stiffening member is in the range of 0.1 to 0.

7.

6. 5. The system of claim 4, wherein the one or more openings are defined such that a ratio of a total area of ​​the one or more openings to a cross-sectional area between an inner diameter of the elongate body and an outer diameter of the stiffening member is in a range of 1.2 to 30.

7. 5. The system of claim 4, wherein the one or more openings are defined such that a ratio of a total area of ​​the one or more openings to a cross-sectional area of ​​an inner diameter of the elongate body is in the range of 1.2 to 30.

8. The system of claim 1 , further comprising a sleeve positioned proximate to the one or more sensors such that the one or more openings define an annular or circumferential opening.

9. The system of claim 1 , wherein the one or more openings are defined along a portion of a smaller diameter relative to the one or more sensors.

10. 10. The system of claim 9, further comprising a sleeve positioned proximate to the one or more sensors such that the one or more openings define an annular or circumferential opening along the minor diameter.

11. The system of claim 1 , wherein the initial known value of the fluid comprises a conductivity.

12. The system of claim 11 , wherein the conductivity of the fluid is selected to be lower than the conductivity of a second fluid surrounding the one or more sensors.

13. The system of claim 1 , wherein the one or more sensors include at least two sensors.

14. The system of claim 1 , wherein the one or more openings are positioned between at least two sensors along the elongate body.

15. The system of claim 1 , wherein the one or more openings are sized and positioned to minimize a boundary distance when the fluid is released at a predetermined flow rate.

16. The system of claim 1 , further comprising one or more electrocardiogram (ECG) sensors in communication with the controller.

17. 17. The system of claim 16, wherein the one or more electrocardiogram (ECG) sensors are positioned at the distal tip of the elongate body.

18. 17. The system of claim 16, wherein the controller is further configured to receive electrocardiogram (ECG) signals from the one or more electrocardiogram (ECG) sensors and determine a location of the one or more sensors within the body of the subject.

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