System for optical analysis and prediction of lesions using an ablation catheter - Patents.com

Abstract

Described herein are systems and methods for performing optical signal analysis and lesion prediction in ablation. The system includes a catheter coupled to multiple optical fibers via a connector that interfaces with a computing device. The computing device includes a memory and a processor, and the processor is configured to receive optical measurement data of a portion of tissue from the catheter. The processor analyzes the optical measurement data to identify one or more optical properties of the portion of tissue and determine a time of degeneration of the portion of tissue based on the one or more optical properties. A model is generated to represent the correlation between lesion depth and ablation time using the time of degeneration, the one or more optical properties, and a predetermined time period. A predicted lesion depth over the predetermined ablation time is generated using the model.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to EP Application No. 20382014.7, filed January 13, 2020, the disclosure of which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates to components, systems, and methods for using catheter and console devices to perform tissue ablation, to perform optical signal analysis, and to predict lesion depth for ablation. [Background technology]

[0003] Ablation is a medical technique for producing tissue necrosis. It is used to help treat various pathologies, including cancer, Barrett's esophagus, or cardiac arrhythmias, among others. For radio frequency (RF) ablation, the application of an alternating current with an oscillation frequency above several hundred kHz avoids the stimulation of excitable tissues while delivering heat by the Joule effect. The increase in tissue temperature produces the denaturation of biomolecules, including proteins (such as collagen, myosin, or elastin). Traditionally, RF ablation is performed by placing an external electrode on the patient's body and applying an alternating potential to the tip of a catheter that is placed in contact with the tissue to be treated in the patient's body.

[0004] A variety of energy sources may be utilized for ablation, including cryogenic cooling for cryoablation, radio frequency, microwave, laser, and photoacoustic / ultrasound, etc. In some cases, cryoablation can use extremely low temperatures to ablate tissue, while electroporation ablation can use pulsed electric fields to ablate specific tissue for the treatment of atrial fibrillation.

[0005] The ablation effect depends on many factors, including the applied power, the quality of the electrical contact, the local tissue properties, the presence of blood flow near the tissue surface, and the effectiveness of irrigation. Due to the variability of these parameters, it can be difficult to obtain consistent results and to understand the ablation effect in tissue using current systems and methods for ablation.

[0006] Thus, such systems and methods may be limited due to difficulties and challenges in evaluating the results of ablation in tissue, such as, for example, identifying lesions formed in the tissue and determining various characteristics of the lesions through the catheter. Summary of the Invention

[0007] Thus, a need may exist to provide new methods, devices, and systems for performing tissue ablation, for tracking scar formation (e.g., the formation and progression of lesions in tissue), and for predicting lesion depth.

[0008] In the embodiments presented herein, the optical system, console or processing device, and catheter are capable of providing optical measurements to understand optical properties (e.g., tissue birefringence, polarization, and / or phase retardation, etc.) to monitor changes in optical properties over time and to predict lesion depth within tissue.

[0009] In an embodiment, an exemplary method is described. The method includes performing ablation by applying energy from a catheter to a portion of tissue for a predetermined period of time, the catheter including a proximal section, a distal section including a plurality of optical ports, and a sheath coupled between the proximal and distal sections. The method further includes acquiring optical measurement data from the portion of tissue using at least one optical port in the catheter, identifying one or more optical properties of the portion of tissue by analyzing the optical measurement data using a processing device coupled to the catheter, and determining a time of alteration of the portion of tissue based on the one or more optical properties of the portion of tissue.

[0010] In another embodiment, the system includes a catheter with a proximal section, a distal section, and a sheath coupled between the proximal and distal sections. The system further includes a plurality of optical fibers positioned in the catheter and a computing device coupled to the plurality of optical fibers through a connector. The computing device includes a memory and a processor, the processor configured to receive optical measurement data of a portion of tissue from the optical fibers during or after ablation. The processor of the computing device is further configured to identify one or more optical properties of the portion of tissue by analyzing the optical measurement data, is further configured to determine a time of modification of the portion of tissue based on the one or more optical properties of the portion of tissue, is further configured to generate a model representing a correlation between lesion depth and ablation time using the time of modification, the one or more optical properties, and a predetermined period of time, and is further configured to generate a predicted lesion depth over a predetermined ablation time using the model.

[0011] In another embodiment, a computing device is described that includes a memory and a processor coupled to the memory, The processor of the computing device is configured to receive optical measurement data of the portion of the tissue from the catheter after application of energy to the portion of the tissue for a predetermined period of time during ablation, is configured to identify one or more optical properties of the portion of the tissue by analyzing the optical measurement data, is configured to determine a time of modification of the portion of the tissue based on the one or more optical properties of the portion of the tissue, is configured to generate a model expressing a correlation between lesion depth and ablation time using the time of modification, the one or more optical properties, and the predetermined period of time, and is configured to generate a predicted lesion depth over the predetermined period of time using the model.

[0012] Further features and advantages, as well as the structure and operation of various embodiments, are described in detail below with reference to the accompanying drawings. It is noted that the specific embodiments described herein are not intended to be limiting. Such embodiments are presented herein for illustrative purposes only. Additional embodiments will be apparent to those skilled in the art based on the teachings contained herein.

[0013] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate embodiments of the present disclosure and together with the description, further serve to explain the principles of the present disclosure and to enable those skilled in the art to make and use the present disclosure. [Brief description of the drawings]

[0014] [Figure 1] 1 is an exemplary diagram of a catheter according to an embodiment of the present disclosure. [Diagram 2] 1 illustrates a cross-section of a catheter according to an embodiment of the present disclosure. [Diagram 3]1 is an exemplary diagram of a system for ablation and lesion prediction according to an embodiment of the present disclosure. [Figure 4] 1 is an exemplary diagram of an optical system for imaging a sample, according to an embodiment of the present disclosure. [Diagram 5] FIG. 1 is an exemplary block diagram illustrating a full chain of integration of data collection of optical signals, according to an embodiment of the present disclosure. [Figure 6] 1 is an exemplary diagram of a cross section of a connector according to an embodiment of the present disclosure. [Figure 7A] 1 is an exemplary diagram of a multi-fiber connector design according to an embodiment of the present disclosure. [Figure 7B] 1 is an exemplary diagram of a multi-fiber connector design according to an embodiment of the present disclosure. [Figure 7C] 1 is an exemplary diagram of a multi-fiber connector design according to an embodiment of the present disclosure. [Figure 8] 1 is a graph illustrating exemplary results from optical measurements of tissue, according to an embodiment of the present disclosure. [Figure 9] 1 is a graph showing exemplary results and analysis of optical signals obtained by Polarization-Sensitive Optical Coherence Reflectometry (PS-OCR) from tissue, according to an embodiment of the present disclosure. [Figure 10] 10A and 10B are exemplary diagrams illustrating a lesion formed in tissue at a catheter tip and measurement of the lesion, respectively, according to an embodiment of the present disclosure. [Figure 11] 1 is a diagram illustrating an exemplary regression model for predicting maximum lesion depth, according to an embodiment of the present disclosure. [Figure 12] 1 is a diagram illustrating an exemplary model of lesion depth analysis, according to an embodiment of the present disclosure. [Figure 13]13A and 13B are diagrams illustrating exemplary lesion depth and lesion width, respectively, as a function of ablation time, according to an embodiment of the present disclosure. [Figure 14] 1 is a diagram of an exemplary catheter tip geometry and orifice location for contact with tissue, according to an embodiment of the present disclosure. [Figure 15] 1 is a diagram of an exemplary contact between a catheter and tissue and beam direction at the catheter tip according to an embodiment of the present disclosure. [Figure 16] FIG. 1 illustrates an exemplary graphical user interface (GUI) showing predicted lesion depth, according to an embodiment of the present disclosure. [Figure 17] 1 illustrates an exemplary method for predicting lesion depth for ablation, according to an embodiment of the present disclosure. [Figure 18] FIG. 2 is a block diagram of exemplary components of a computer system according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Embodiments of the present disclosure will be described with reference to the accompanying drawings.

[0016] While specific configurations and arrangements are discussed, it should be understood that this is done for illustrative purposes only. Those skilled in the art will recognize that other configurations and arrangements can be used without departing from the spirit and scope of the present disclosure. It will become apparent to those skilled in the art that the present disclosure can also be used in a variety of other applications.

[0017] It is noted that references herein to "one embodiment," "an embodiment," "an exemplary embodiment," and the like, indicate that the embodiment being described may include a particular feature, structure, or characteristic, but that all embodiments do not necessarily include that particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Furthermore, when a particular feature, structure, or characteristic is described in connection with an embodiment, it will be within the knowledge of one of ordinary skill in the art to implement such feature, structure, or characteristic in connection with other embodiments, whether or not explicitly described.

[0018] It should be noted that although this application may refer specifically to cardiac ablation, the embodiments described herein may also be used to target other conditions with additional energy sources for ablation, including but not limited to cryogenic, radio frequency (RF), microwave, laser, ultrasound, and pulsed electric fields. The principles of using energy to treat other conditions are similar, and thus the techniques used to apply energy are similar.

[0019] In this specification, the terms "electromagnetic radiation," "light," and "beam of radiation" are all used to describe the same electromagnetic signal that propagates through the various described elements and systems.

[0020] Exemplary Catheter Embodiments FIG. 1 illustrates a catheter 100 according to an embodiment of the present disclosure. The catheter 100 includes a proximal section 102, a distal section 104, and a sheath 106 coupled between the proximal section 102 and the distal section 104. In an embodiment, the sheath 106 includes one or more radiopaque markers for navigation purposes. In one embodiment, the catheter 100 includes a communication interface 110 between the catheter 100 and a processing device 108. The communication interface 110 can include one or more optical fibers and connectors between the processing device 108 and the catheter 100. In other examples, the communication interface 110 can include an interface component that enables wireless communication (e.g., Bluetooth, WiFi, cellular, etc.) to communicate with the catheter 100 or other processing components in the catheter system.

[0021] In one embodiment, the sheath 106 and the distal section 104 are disposable. As such, the proximal section 102 may be reused by attaching a new sheath 106 and proximal section 104 each time a new procedure is to be performed. In another embodiment, the proximal section 102 is also disposable.

[0022] The proximal section 102 can house various electrical and optical components used in the operation of the catheter 100. A first optical source can be included in the proximal section 102 and generate a source beam of radiation for optical evaluation. The first optical source can include one or more laser diodes or light emitting diodes (LEDs). The beam of radiation generated by the optical source can have a wavelength in the infrared range. In one example, the beam of radiation has a central wavelength of 1.3 μm. The optical source can be designed to output a beam of radiation at only a single wavelength, or it can be a swept source and can be designed to output a range of different wavelengths. The generated beam of radiation can be guided toward the distal section 104 via an optical transmission medium connected between the proximal section 102 and the distal section 104 within the sheath 106. Some examples of the optical transmission medium include single mode optical fiber and / or multimode optical fiber. In one embodiment, the electrical transmission medium and the optical transmission medium are provided by the same hybrid medium that allows the propagation of both electrical and optical signals.

[0023] In some embodiments, the proximal section 102 includes a second optical source (such as, for example, a laser energy source) capable of generating laser energy applied at the distal section 104 for tissue ablation. In some embodiments, the laser energy source can emit an ablative beam of laser energy at a wavelength of 980 nm or at a wavelength of 1060 nm. Laser energy from the source at the proximal section 102 can propagate through the catheter 100 via an optical transmission medium connected between the proximal section 102 and the distal section 104 in the sheath 106, and the laser energy can be output from the distal section 104 of the catheter 100 to the target tissue. For example, the laser energy from the source can produce 5W to 12W of optical power applied to the target tissue for 20-30 seconds to create a transmural lesion in cardiac tissue. In another example, the laser energy from the source can produce 30W to 50W of optical power applied to the target tissue for 60-90 seconds. In some embodiments, the processing device 108 can include one or more components, such as detectors, electronics, and / or other components of an optical circuit / system as described herein. In other embodiments, these one or more components (e.g., detectors, electronics, and / or other components of an optical circuit / system) can be included within the proximal section 102.

[0024] In one embodiment, the proximal section 102 includes one or more components of an interferometer to perform low coherence interferometry (LCI) using light generated from a second optical source. Due to the nature of the data analysis of the interferometer, in one embodiment, the optical transmission medium used to guide the light to and from the distal section 104 does not affect the state and degree of polarization of the light. In another embodiment, the optical transmission medium affects the polarization in a fixed, reversible manner.

[0025] The proximal section 102 can include additional interface elements by which a user of the catheter 100 can control the operation of the catheter 100. For example, the proximal section 102 can include a deflection control mechanism that controls the deflection angle of the distal section 104. The deflection control mechanism can require mechanical movement of elements on the proximal section 102 or the deflection control mechanism can use an electrical connection to control the movement of the distal section 104. The proximal section 102 can include various buttons or switches that allow a user to control when laser energy is applied at the distal section 104 or when a beam of radiation is transmitted from the distal section 104, allowing for the acquisition of optical data. In some embodiments, the proximal section 102 can include a deflection control mechanism for controlling one or more pull wires coupled to the distal section 104. In some embodiments, the deflection control mechanism and one or more pull wires allow steering of the distal section of the catheter 100 to steer and target within specific tissue regions for ablation.

[0026] The distal section 104 includes multiple optical viewports. In some embodiments, the multiple optical viewports may be referred to herein as orifices in the catheter tip. In an embodiment, one or more of the optical viewports are machined into the outer body of the distal section 104. The optical viewports are distributed across the exterior of the distal section 104, resulting in multiple distinct viewing directions. In some embodiments, the optical viewports are capable of transmitting and collecting light (e.g., optical signals) at various angles from the distal section 104. The optical viewports also enable multiple directions (e.g., beam directions) in which laser energy may be directed for tissue ablation through one or more of the optical viewports. In an embodiment, each of the multiple viewing directions is substantially non-coplanar. The optical viewports may also be designed with irrigation functionality to cool the distal section 104 and surrounding tissue during ablation.

[0027] 2A and 2B illustrate cross-sectional views of a sheath 106 according to an embodiment of the present disclosure. The sheath 106 can include all of the elements interconnecting the proximal section 102 with the distal section 104. The sheath 106a illustrates an embodiment housing the irrigation channel 202, the deflection mechanism 206, the electrical connection 208, and the optical transmission medium 210. FIG. 2A illustrates a protective cover 212 wrapped around both the electrical connection 208 and the optical transmission medium 210. The electrical connection 208 can be used to provide a signal to an optical modulation component located in the distal section 104. In other embodiments, the optical transmission medium 212 and components can be located in a protective cover separate from the protective cover 212 in which the electrical connection 208 is housed. One or more optical transmission media 210 guide light generated from an optical source (exposure light) towards the distal section 104, while another subset of the optical transmission media 210 guides light returning from the distal section 104 (scattered or reflected light) towards the proximal section 102. In another example, the same one or more optical transmission media 210 guide light in both directions. In some embodiments, the optical transmission medium 210 includes one or more single-mode and / or multimode optical fibers.

[0028] The irrigation channel 202 can be a hollow tube used to guide the cooling fluid towards the distal section 104. The irrigation channel 202 can include heating and / or cooling elements disposed along the channel to affect the temperature of the fluid. In another embodiment, the irrigation channel 202 can also be used as a passageway to draw fluid surrounding the distal section 104 back towards the proximal section 102.

[0029] The deflection mechanism 206 can include electrical or mechanical elements designed to provide signals to the distal section 104 to change the deflection angle of the distal section 104. The deflection system allows for the guidance of the distal section 104 by actuating a mechanical control installed in the proximal section 102, according to an embodiment. This system can be based on a series of aligned and evenly spaced cutouts in the sheath 106 intended to provide unidirectional deflection of the distal section 104, combined with wires connecting the deflection mechanism control in the proximal section 102 with the catheter tip in the distal section 104. In this way, a certain movement of the proximal section can be projected to the distal section. Other embodiments including a combination of several control wires attached to the catheter tip can allow deflection of the catheter tip along different directions.

[0030] 2B illustrates a cross section of sheath 106b. Sheath 106b shows an embodiment having most of the same elements as sheath 106a from FIG. 2A, except that electrical connections 208 are not present. Sheath 106b may be used in situations where modulation (e.g., multiplexing) of the generated beam of radiation is performed in the proximal section 102. In some embodiments, sheath 106b may be implemented into a diagnostic catheter used for laser or cryogenic ablation.

[0031] Exemplary Catheter System and Console Embodiments Disclosed herein are embodiments of ablation catheters and console systems that use Optical Coherence Tomography (OCT) and / or Optical Coherence Reflectometry (OCR), refractometry, or other methods to perform tissue ablation, track scar formation in real time, and monitor / verify lesion geometry and isolation by directly observing scar patterns in the tissue. To assess whether scarring is forming, the methods, devices, and systems described herein acquire optically reflected / refracted light from the tissue, determine the optical properties of the reflected light (e.g., by measuring intensity and polarization, and by computing the phase delay and / or birefringence of the tissue based on the measurements), and monitor the changes, since these optical properties change when the tissue is scarred when compared to healthy tissue. By identifying the changes in the optical properties of the tissue, the lesion depth and degeneration time in the tissue can be predicted for various ablation times, as described herein.

[0032] FIG. 3 illustrates an exemplary diagram of a system 300 for performing ablation and lesion prediction, according to an embodiment of the present disclosure. The system 300 includes a catheter 302, a console 310, a signal generator 320, a display 325, and an irrigation pump 330. The catheter 302, the console 310, the signal generator 320, the display 325, and the irrigation pump 330 may be communicatively coupled together via wired and / or wireless connections. In some embodiments, the catheter 302 may represent an exemplary embodiment of the catheter 100 shown in FIG. 1. In some embodiments, a distal section of the catheter 302 is positioned in a portion of tissue of a patient 304. It is understood that the embodiments described herein may be used in vivo and / or ex vivo.

[0033] In some embodiments, the catheter 302 can be positioned at a portion of tissue targeted for ablation using energy generated by a signal generator 320. In some embodiments, the signal generator 320 can be an electronic device configured to generate radio frequency (RF), cryogenic, or electroporation (e.g., pulsed electric field) signals for ablation. The signal generator 320 can be coupled to the catheter 302 directly or via a console 310 and can deliver energy to the catheter 302 to ablate a portion of tissue at a selected tissue site. In some embodiments, the portion of tissue can include myocardial tissue, cardiac muscle tissue, or skeletal tissue, etc. Energy can be applied to the portion of tissue through an optical viewport in a distal section of the catheter 302. After applying the energy, structural changes in the tissue can be observed by acquiring optical signals through one or more optical viewports of the catheter 302.

[0034] The console 310 may include a computing device configured to acquire optical signals from the catheter 302 and to analyze the optical signals and detect changes in optical properties of the tissue. In some embodiments, the console 310 may include hardware (e.g., circuitry), firmware, software, or any combination thereof, to perform analysis of the optical signals and generate models to predict lesion depth and ablation time, as described herein. In some embodiments, the console 310 may send light through optical circuitry within itself and within the catheter 302 into the tissue to monitor scar progression, contact between the tissue and the catheter 302, and other properties of the tissue. In some embodiments, the console 310 may be referred to herein as a control console, a processing device, and / or a controller. The console 310 may be coupled to a display 325, which may present results from the optical signal analysis and lesion prediction, and may allow a user to select / view, modify, and / or control parameters related to the operation of the catheter 302, the console 310, the signal generator 320, and / or the irrigation pump 330.

[0035] In some embodiments, irrigation pump 330 may be coupled to catheter 302 via tubing. In some embodiments, irrigation pump 330 may allow fluid to be pumped through the tubing and released at the tissue site through catheter 302 (e.g., through an optical viewport or through a separate irrigation slit in the distal section of catheter 302). Fluid from irrigation pump 330 may cool the distal section of catheter 302 and the surrounding tissue during ablation and may also flush away any debris during and / or after ablation.

[0036] In some embodiments, the catheter 302 may be coupled to the console 310 via one or more optical connections 312 and one or more electrical connections 314. The optical connections 312 may include single mode and / or multimode optical fibers that allow for the acquisition and / or transmission of optical signals from the catheter 302 and the console 310 for further analysis. The electrical connections 314 may include wires, pins, and / or components used to provide power and energy from the signal generator 320 to the catheter 302 for ablation.

[0037] In some embodiments, the optical connection 312 and the electrical connection 314 may be connected to the console 310 via a communication interface 316. The communication interface 316 may allow for the transmission of various signals (e.g., optical and electrical signals) between the catheter 302 and the console 310. In some embodiments, the communication interface 316 may include a connector that facilitates proper alignment of the optical fibers between the catheter 302 and the console 310. In some embodiments, the connector design may include both electrical and optical extension lines.

[0038] Exemplary Optical System and Console Embodiments 4 illustrates a diagram of an exemplary optical system 401 for imaging a sample 420, according to an embodiment of the present disclosure. In some embodiments, the components of the optical system 401 are implemented in a console 310 and can acquire optical measurements of the sample 420 using a catheter 302. In some embodiments, the sample 420 can be a tissue surface within a patient's body.

[0039] In some embodiments, the optical system 401 can perform imaging using low coherence interferometry (LCI), optical coherence tomography (OCT), and / or optical coherence refractometry, or other optical modalities. The optical system 401 can include an optical source 402, a polarization splitter 403, a coupling / splitting element 404, a sample arm 406, a polarization switch 407, a reference arm 408, an optical switch 409, an output fiber 410, a delay unit 412, and a detector 414. It should be understood that the optical system 401 can include any number of other optical elements not shown for clarity. In some embodiments, the optical system 401 can include mirrors, lenses, gratings, splitters, micromechanical elements, and the like along the path of the sample arm 406 or the reference arm 408.

[0040] In some embodiments, the optical source 402 can generate a source beam of radiation that is coupled to the coupling / splitting element 404 via one or more fibers. The coupling / splitting element 404 is used to direct light received from the optical source 402 to both the sample arm 406 and the reference arm 408. The coupling / splitting element 404 can be, for example, a coupling element (e.g., a bidirectional coupler), an optical splitter, a coupler with an adjustable splitting ratio, or any other modulating optical device that converts a single beam of light into two or more beams of light. In some embodiments, the light from the optical source 402 can also pass through an optical attenuator.

[0041] Light traveling down sample arm 406 travels through a polarization switch 407 and an optical switch 409 to eventually impinge on sample 420. In some embodiments, the polarization switch 407 can be included on the sample arm 406, but can also be at the input of the LCI system (e.g., before the splitting / coupling element 404). In some embodiments, after passing through the polarization switch 407, the optical switch 409 can direct the light to one or more of a number of output fibers 410. In some embodiments, the number of output fibers 410 represent fibers in the console 310 that are coupled to the fibers of the catheter 302 via connectors.

[0042] In some embodiments, the sample 420 can be any suitable sample to be imaged (e.g., tissue, etc.). The light is scattered and reflected back from various depths in the sample 420, and the scattered / reflected radiation is collected back into the sample arm 406. The scan depth can be selected via a delay imposed on the light in the delay unit 412.

[0043] In some embodiments, the delay unit 412 can include various light modulation elements. These modulation elements can perform phase and / or frequency modulation to counteract undesired optical effects in the light and select one or more depths of the sample 420 to be imaged. In some embodiments, the delay unit 412 can also control the polarization of the light in the reference arm and modulate the polarization. In some embodiments, the modulation scheme on the reference arm 408 can simplify the need for switching elements in the reference arm and can allow a shift from time multiplexing to frequency / phase / code / polarization multiplexing. The use of the term "light" can refer to any range of the electromagnetic spectrum. In some embodiments, the term "light" refers to infrared radiation at a wavelength of about 1.3 μm.

[0044] In the illustrated embodiment, the delay unit 412 is positioned in the reference arm 408. However, it should be understood that the delay unit 412 may instead be positioned in the sample arm 406. Alternatively, various elements of the delay unit 412 may be present in both the sample arm 406 and the reference arm 408. For example, elements of the delay unit 412 that introduce a variable delay to the light may be positioned in the sample arm 406, while elements that modulate different polarization modes of the light may be positioned in the reference arm 408. In another example, elements of the delay unit 412 that modulate different polarization modes of the light may be positioned in the sample arm 406, while elements that introduce a variable delay to the light may be positioned in the reference arm 408. In one example, the sample arm 406 and the reference arm 408 are optical fibers. Other implementations may be considered as well, such as, for example, optical fiber systems, free space optical systems, photonic integrated circuits, etc.

[0045] In one embodiment, light may be coupled from the optical source 402 to the coupling / splitting element 404 via one or more fibers, and light may be coupled from the splitting element 404 to the polarization splitter 403 and to the detector 414 via one or more fibers or by direct free space coupling.

[0046] In some embodiments, an optical switch 409 allows for the selection of one or more beams through multiple output fibers 410. In some embodiments, one beam can be active at a time, such that the signal returning from the sample 420 can be combined with the reference arm 408 and then split into different channels in the detector 414 using a polarization splitter 403. In some embodiments, this can allow tissue birefringence and other optical properties to be measured from one channel at a time. In other embodiments, several beams can be active simultaneously and split by a multiplexer or other type of beam splitter, where each beam from each path is distinguished by their frequency, wavelength, amplitude, or other optical property of the light of the beam.

[0047] In some embodiments, the light in the sample arm 406 and the reference arm 408 is recombined by the coupling / splitting element 404 (or by a different optical coupling element) and then split by the polarization splitter 403 before being received at the detector 414. In some embodiments, the light may be polarized before coupling by the coupling / splitting element 404. In other embodiments, the light may be split in the reference arm 408. The detector 414 may include any number of photodiodes, charge-coupled devices, and / or CMOS structures and may convert the received light into an electrical signal. The electrical signal includes depth-resolved optical data related to the sample 420 and may be received by a processing device for further analysis and signal processing procedures. As used herein, the term "depth-resolved" defines data in which one or more portions of the data related to a particular depth of the sample being imaged may be identified.

[0048] In one embodiment, the optical source 402, the detector 414, and the delay unit 412 are located in the proximal portion 102 of the catheter 100. In another embodiment, the optical source 402, the detector 414, and the delay unit 412 are located in the processing device 108. The coupling / splitting element 404, the polarization splitter 403, the polarization switch 407, the optical switch 409, and at least a portion of one or both of the sample arm 406 and the reference arm 408 may be located in the processing device 108 or may be located in either the proximal portion 102 or the distal portion 104 of the catheter 100. In another embodiment, any of the elements of the optical system 401 are located in the processing device 108 or in the console 310 of the catheter system 300 shown in FIG. 3. In some embodiments, the detector 414 may be located in the handle of the catheter 100, while the optical source 402 may be located in the processing device 108. The optical source 402 may include one or more light emitting diodes (LEDs) or laser diodes. For example, LEDs may be used when performing time-domain and / or spectral-domain analysis, while a tunable laser may be used to sweep the wavelength of light over a range of wavelengths. In another embodiment, any of the components of the optical system 401 are located outside the catheter 100 or catheter 302 (e.g., in the processing device 108 or in the console 310). In some embodiments, the optical system 401 is illustrated as an interferometer design similar to a Michelson interferometer. However, other interferometer designs are possible as well, including a Mach-Zehnder interferometer design or a Mireau interferometer design. In some embodiments, the components in the optical system 402 may be adapted for a spectral-domain OCT configuration.For example, the optical source 402 can be a superluminescent diode (SLED) or a light emitting diode (LED), and the detector 414 can be a spectrometer to perform optical spectroscopy of tissue.

[0049] FIG. 5 illustrates an exemplary block diagram showing a full chain of data collection integration of optical signals according to an embodiment of the present disclosure. Data collection and processing of optical signals may be implemented by the console 310. In some embodiments, multiple single-ended signals may be digitized and read by the console 310 in parallel or a single processing stage along with a reference interferometer for signal processing purposes. In some embodiments, processing may be implemented in real-time or near real-time (e.g., about 50 ms or similar). In some embodiments, any number of signals may be digitized. These signals may be combined and processed to measure optical properties of tissue (e.g., birefringence, tissue stability, dragging speed, etc.). The processed signals may be shown on a graphical user interface (GUI) presented on a display (e.g., display 325). In some embodiments, the GUI may be refreshed such that multiple channels (e.g., 15 channels) of the detector are represented at one time. In some embodiments, the console 310 may buffer optical data from all or multiple channels, and once the data is processed, the data may be refreshed and presented in the GUI.

[0050] In some embodiments, data transfer and data processing may be optimized at different software abstraction layers to maintain data integrity while improving refresh times in the GUI. Once optical data (e.g., OCT structural / polarized data) is acquired, tissue detection algorithms using clustering or other methods may be implemented to separate tissue from other artifacts. In some embodiments, a 3D model of the lesion formed from the ablation may be acquired from each of the individual beams from the optical fiber. In some embodiments, the dragging algorithm is combined with the lesion model algorithm to allow for proper prediction of the lesion as the catheter is moving.

[0051] Moreover, optimization algorithms can be applied to compensate for the nonlinearity and phase noise of the optical source while switching using an external reference interferometer at different optical path delays. In some embodiments, additional auto-calibration methods are implemented to optimize the polarization state without manual interaction and to automatically adjust the optical fiber length using motors and retroreflectors so that the coherence range is optimized for each fiber.

[0052] Exemplary Connector Embodiments FIG. 6 illustrates an exemplary diagram of a cross section of a connector 600 according to an embodiment of the present disclosure. The connector 600 shown in FIG. 6 may be used in a face-to-face connector for connecting fibers between a console and a catheter (e.g., in the communication interface 316 between the console 310 and the catheter 302). In some embodiments, at the console-catheter interface, a fiber with a small cross section (e.g., 50-80 um) may be spliced ​​to another fiber with a larger cross section (e.g., 125 um) to be used by a standard size connector (e.g., configured to fit a 125 um fiber) between the catheter and the console. However, splicing the fibers individually can be time consuming and expensive. Therefore, a custom connector (e.g., connector 600 with the cross section shown in FIG. 6) may be used to link the fibers together. In some embodiments, the connector 600 may be a multi-fiber connector with multiple V-shaped grooves 602 that help align the fibers at the connection between the catheter and the console. The V-shaped grooves 602 can be shaped and configured such that each individual fiber is aligned and positioned within the groove 602 with an accuracy of + / - 1 um. In some embodiments, each fiber can be placed into the bottom of each V-shaped groove 602 with a lid that presses the fiber down into the groove.

[0053] In some embodiments, the two connectors 600 can be mated with a male-female connection to allow for proper alignment of the fibers between the console and the catheter. In some embodiments, the two connectors 600 (e.g., the connector in the catheter and the connector in the console) can use alignment pins so that the cores of the fibers meet each other. In some embodiments, the connectors 600 can be formed by an etching process from silicon, glass (e.g., quartz, etc.), or polymeric materials. The connectors 600 can ultimately enhance the alignment and positioning of the fibers and improve the precision of the optics in the catheter and optical system.

[0054] 7A-7C illustrate example diagrams of a multi-fiber push-on (MPO) connector design according to an embodiment of the present disclosure. The MPO connector design shown in FIGS. 7A-7C can be utilized to replace a single connector to ease manufacturing and connectivity to the console. FIG. 7A illustrates the gluing process for the MPO connector, while FIG. 7B illustrates the connector assembled with a glass ferrule. As shown in FIG. 7C, the MPO connector design can include a custom component with a smaller hole (e.g., 54 um) in front of it. In some embodiments, the custom component can be compatible with both the catheter side and the console side, and this design can further facilitate the fiber threading and gluing process. In some embodiments, the additional connector design can include using an MPO connector and adding a custom section with a smaller hole on the front panel of the connector ferrule. In some embodiments, this method can improve the coupling efficiency of using non-standard fiber diameters, but can also benefit from the use of existing multi-fiber connector options.

[0055] Exemplary embodiments of optical analysis and lesion prediction In some embodiments, the optical signal may be acquired by the catheter, and an optical system in the console may perform an analysis of the optical signal and generate a model for predicting lesion depth and ablation time, as described herein, In some embodiments, the predicted lesion depth may represent the height and width of a lesion formed by the energy applied to a portion of tissue by the catheter.

[0056] An exemplary study was performed to develop a lesion depth prediction algorithm using optical property measurements from ablated tissue. In that study, tissue samples were removed from pig hearts and the distal end of a catheter was positioned perpendicular to the endocardial surface of the tissue using a micro-positioner. The tissue samples included the right atrial free wall, superior vena cava, left atrial roof, mitral annulus, and left atrial appendage, and the catheter was suspended above the tissue from a spring to maintain a constant contact force and to reduce the effect of external mechanical vibrations on the contact force recordings. The micro-positioner was adjusted to achieve the desired contact force value and the force was measured using a weighing scale.

[0057] In some embodiments, contact between the catheter and tissue can be analyzed by direct visualization (e.g., using optical system 401) and a change in weight on a scale. In some embodiments, a contact force of 0 g, 2 g, or 10 g or more can indicate no contact, soft contact, or strong contact, respectively, between the catheter and tissue. In some embodiments, a positive distance measured by the micro-positioner can indicate that the tissue is not in contact with the catheter tip, while a negative distance measured by the micro-positioner can indicate that the catheter tip has been introduced into the tissue.

[0058] In some embodiments, RF energy from the distal end of the catheter was applied to the tissue samples with power at a level between 20W and 40W and RF ablation times ranging between 5 seconds and 45 seconds. In some embodiments, focal RF ablation was performed in both the right and left atria under various parameters (including, for example, various power values, times, irrigation flow rates, and catheter contact force values). To identify optical parameters of interest for predicting lesion depth, optical measurements of the tissue were obtained using interferometry, OCT, and / or OCR techniques. In some embodiments, the optical measurements may be obtained by using the optical system 401 of FIG. 4 as described herein.

[0059] 8A and 8B illustrate graphs showing exemplary results from optical measurements of tissue, according to embodiments of the present disclosure. In particular, FIG. 8A illustrates a graph of an exemplary structural image calculated as an average of AM scans in a 5 second time window, according to embodiments of the present disclosure. In some embodiments, optical power as a function of tissue depth is analyzed from the optical measurements, and catheter tip (e.g., end of the distal section of the catheter) and tissue distance and optical signal quality at different locations in the tissue can be further assessed based on catheter irrigation flow rate and incidence angle values ​​(e.g., beam direction of the beam exiting one or more of the optical viewports in the distal section of the catheter).

[0060] In some embodiments, the tissue surface is detected and the lens and tissue interface distance can be estimated based on the distance of the two peaks, as shown by the two vertical dashed lines in FIG. 8A. In some embodiments, the maximum image depth (e.g., optical penetration into the tissue) can be calculated as a function of the distance between the first tissue interface with respect to the depth at which the optical power is 5 dB above the noise background, as shown by the third vertical line shown in FIG. 8A. In some embodiments, a linear regression model (e.g., locally estimated scatterplot smoothing (LOESS) curve fitting regression, etc.) can be applied to the data.

[0061] 8B illustrates an exemplary average phase delay graph calculated as an average of A-scans of a structural image, according to an embodiment of the present disclosure. In some embodiments, the phase delay slope can correspond to the slope measured from the tissue interface (as indicated by the two perpendicular lines shown in FIG. 8B) having the maximum phase delay.

[0062] In some embodiments, the system (e.g., catheter system 300 and optical system 401) measures the intensity and polarization of the tissue, and phase delay data and tissue properties (e.g., birefringence, etc.) can be extracted therefrom. In some embodiments, structural changes in the tissue can be correlated to the A-scan and / or intensity measurements. The phase delay data can provide information about the tissue, including information about lesion depth and structural changes in the tissue (e.g., necrosis and tissue degeneration, etc.). In particular, the heart wall includes three layers (the outer epicardium, the middle myocardium, and the inner endocardium), of which the myocardium is the muscle tissue of the heart and is composed of cardiac muscle cells (cardiomyocytes). Cardiac muscle cells have a highly organized cellular structure with branched myofibrils and sarcomeres. Microscopically, the arrangement of sarcomeres and myofibrils in the cardiac muscle results in a streaky appearance. In some embodiments, unablated untreated myocardial tissue can have a high level of cellular organization, which shows significant phase delay (PR) between antiparallel polarization states. A high level of cellular organization can lead to reflecting polarized light that phase wraps around π on top of the cumulative phase retardation. In some embodiments, the phase retardation can accumulate as the light travels deeper through the myocardial tissue at a rate proportional to the magnitude of birefringence. Thus, less organization within the muscle structures of cardiac muscle tissue can have a direct effect on the properties of tissue birefringence.

[0063] 8B shows the accumulated phase delay at each depth relative to the tissue surface between 0 and π (phase wrapping). In some embodiments, the average phase delay can be calculated as the average of the A-scans in a 5 second time window. The information acquired in the average PR can then be related to the amount and arrangement of collagen and cells within the cardiac tissue.

[0064] In some embodiments, an inflection point in the slope of the phase delay data can be identified several hundred microns after the tissue surface. In some embodiments, this depth can correspond to the transition between the endocardium (collagen) and myocardium (mainly cardiomyocytes) in the tissue. In some embodiments, the average PR slope, R 2 The value, the root mean square error (RMSE) value, and the ratio between the maximum and minimum PR calculated from the end of the endocardial wall estimate to the maximum value may be related to the arrangement of the cardiomyocytes within the myocardium.

[0065] In some embodiments, histological analysis of the tissue (e.g., using staining techniques) can be performed to correlate polarization-sensitive optical coherence reflectometry (PS-OCR) with the arrangement of muscle fibers within the tissue, such as to identify collagen and cardiomyocytes in PS-OCR images and to exclude any abnormal microanatomy from the measurements used in the linear regression model.

[0066] In some embodiments, the R associated with the linear regression model 2 The values ​​and root mean square error (RMSE) can be related to the cellular organization within the tissue, and therefore a small R 2 Values ​​below 0.05 (e.g., <0.8) or high RMSE values ​​(e.g., >0.025) may indicate excess collagen in the extracellular matrix or thick endocardial walls, which may reduce cellular organization.

[0067] 9A, 9B, and 9C illustrate graphs showing exemplary results and analysis of optical signals acquired by polarization-sensitive optical coherence reflectometry (PS-OCR) from tissue, according to embodiments of the present disclosure. In particular, FIG. 9A shows the time progression of a PS-OCR optical signal acquired during an ex vivo RF ablation procedure.

[0068] In some embodiments, after the first instance of heating, a sudden change can be observed in FIG. 9A when there is a large dynamic range of periodic fluctuations in the PR between orthogonal polarization states, thus reducing the dynamic range to the background noise level. This PR change can be approximately monotonic in optimal contact conditions, such that a threshold can be estimated when fiber degeneration occurs. For this phase delay measurement, the A-scan lines can be grouped together and filtered as a 2D signal, to exploit the depth and time coherence. First, the signal can be convolved with a Gaussian kernel with a standard deviation of 30 samples. The resulting smoothed signal can then be processed by a median filter of smaller support (e.g., 3x3) to remove local inhomogeneities.

[0069] Finally, the signal may be binarized (e.g., converted to binary) by a fixed pre-defined threshold equal to 80% of the maximum phase delay within the considered time frame. In some embodiments, the pre-defined threshold may be chosen since a loss of about 20% of the protein denaturation fraction may result in protein denaturation and reduced cell viability. The resulting signal is illustrated in FIG. 9B as a data cluster for tissue from the tissue surface to almost 1 mm depth. In particular, FIG. 9B illustrates an exemplary diagram showing the binarized phase delay of the optical signal as a function of time and depth. In some embodiments, the denaturation time (t D ) may be assumed as the instant at which the birefringence becomes smaller than a certain predetermined threshold equal to 80% of the maximum phase delay. In some embodiments, the acquisition system (e.g., optical system 401) and the RF optical signal can be synchronized to an external clock to guarantee the time base.

[0070] Once the signal has been successfully binarized, the total number of points for each scan can be projected onto the x-axis and an Arrhenius fit can be applied to the result. Figure 9C shows an example graph of an Arrhenius fit curve of the result of Figure 9B, according to an embodiment of the present disclosure. In some embodiments, ,strange Sex time (t D ) and the rate at which the tissue is degenerated can be calculated according to the slope of the Arrhenius equation according to the following formula:

[0071]

number

[0072] In some embodiments, C and C T are the initial number of viable cells and the number of viable cells at temperature T after heating at a constant heating rate B, respectively. In some embodiments, A and Ea are the frequency factor and activation energy values, respectively, for the cell death process. As a result, the denaturation time (t D ) can be inferred from the transition between two clusters of data in time. In some embodiments, fiber degeneration can occur at the minimum time that the Arrhenius curve reaches the y offset in a 0.01 second time window. In some embodiments, the vertical dashed line in FIG. 9C represents the estimated t D It is possible to show that t D The slope of the gradient can be the rate at which tissue degeneration is reached.

[0073] In some embodiments, statistical analysis may be performed on the optical measurement data obtained (e.g., FIGS. 8A-9C), including applying power analysis, T-tests, and linear regression to analyze variance (ANOVA) of the data and model relationships between variables. In some embodiments, optical measurement data indicative of losses in birefringence corresponding to tissue degeneration and necrosis may be included in the development of regression models to predict lesion depth, as described herein.

[0074] In some embodiments, the predictive lesion depth model may be useful in understanding lesion progression in tissue during or after performing RF ablation. In some embodiments, hyperthermia may destroy tissue at temperatures ranging from 50°C to 90°C. At temperatures around 43°C to 45°C, irreversible cell damage (e.g., membrane disruption, protein denaturation, and mitochondrial dysfunction) may destroy cells after longer exposure times (e.g., 30-60 minutes). At higher temperatures (e.g., above 60°C), rapid protein denaturation and cell death may occur, often within seconds.

[0075] To characterize the shape of the lesion and to correlate the biophysical parameters measured in real time with the optical measurements acquired by the optical system, the tissue may be further stained (e.g., with tetrazolium chloride (TTC)) and analyzed via visual inspection and imaging after RF ablation is performed. FIG. 10A and FIG. 10B illustrate exemplary diagrams showing a lesion formed in tissue at a catheter tip and measurements of the lesion, respectively, according to an embodiment of the present disclosure. In some embodiments, the lesion size may be measured by obtaining one or more of the measurements represented by labels A-G in FIG. 10B. In some embodiments, the lesion size may be represented by at least one of the following: maximum lesion depth (A), maximum lesion width (B), depth at maximum lesion width (C), cross-sectional diameter or lesion diameter at the surface (D), tissue depth or thickness (E), catheter indentation depth of the lesion or depth of tissue deformation after ablation (F), lesion depth at -45° from axis (G), and lesion depth at 45° from axis (H). In some embodiments, there may be a high correlation between lesion depth and lesion width, which may allow for estimation of lesion width values. In some embodiments, lesion size measurements may be used in generating a lesion depth model, and image processing may be performed to estimate optical parameters and optical tissue properties as a function of depth-resolved tissue structure.

[0076] In some embodiments, the predictive lesion model may be generated from an analysis of optical measurement data obtained from performing multiple RF ablations using a catheter with various parameters. As an example, RF ablations may be performed with the following parameters: power at a level between 20W and 60W, ablation time between 10 seconds and 50 seconds, irrigation flow rate fixed at 8mL / min, and catheter contact force fixed at 20g. In some embodiments, optical measurement data may be obtained from the RF ablations and analyzed (e.g., using the optical system 401) to detect loss of birefringence, which may be correlated with necrosis and muscle fiber degeneration. In some embodiments, loss of birefringence may be detected in at least one of the beams output from the catheter (e.g., one of the beams exiting one or more of the optical viewports in the distal section 104 of the catheter 100). In some embodiments, one or more optical viewports of the catheter may be in contact with tissue, and one or more beams may be output at a time for optical interrogation of the tissue.

[0077] In some embodiments, the catheter may be positioned in the tissue in a variety of configurations, including a vertical orientation (where the catheter tip is perpendicular to the tissue), a 45° angle (where the catheter tip is at a 45° angle to the tissue), a parallel orientation (where the catheter tip is parallel to the tissue), or other orientations. Exemplary different orientations of the catheter tip are shown in FIG. 14 and will be described in further detail below. Based on the positioning of the catheter in the tissue, one or more beams from the optical viewport may be switched on or off (e.g., using optical switch 409 in optical system 401) to obtain optical measurements from the tissue.

[0078] In some embodiments, the ratio of the ablation time to the modification time at various angles of incidence of the beam (t A / t D ) may be calculated and represented as a logarithmic regression model. In some embodiments, the beam incidence angle can indicate various beam directions in which one or more beams exit the optical viewport at the catheter tip. In an example, RF ablation performed with a catheter positioned in a vertical configuration in tissue with a 45° incidence angle can result in a deeper lesion than other orientations.

[0079] In some embodiments, additional factors for the regression model may be included, such as, for example, the initial impedance associated with the surface of the tip in contact with the tissue (e.g., before RF ablation) and the drop in impedance value during RF ablation, etc. In some embodiments, machine learning algorithms (e.g., support vector machines and / or neural networks, etc.) may be applied to construct the regression model.

[0080] 11 illustrates a diagram showing an exemplary regression model for predicting maximum lesion depth according to an embodiment of the present disclosure. In some embodiments, the regression model can be calculated from a neural network with 10 hidden layers with inputs of correlation between ablation time and time to degeneration, initial impedance, and beam detecting fiber degeneration.

[0081] FIG. 12 illustrates a diagram showing an exemplary model of lesion depth analysis according to an embodiment of the present disclosure. In particular, FIG. 12 illustrates different in vitro measurements of the lesion depth model for catheter ablation with various temperatures. In some embodiments, the optical system of the catheter may have a physical limitation of 1.5 mm in terms of depth due to light scattering, and the catheter system may not be able to evaluate a deeper depth beyond 1.5 mm. However, the methods, devices, and systems described herein may enable measurement of optical properties (e.g., tissue birefringence, polarization, and phase retardation, etc.) to monitor changes in optical properties over time and to predict lesion depths beyond 1.5 mm. In some embodiments, a portion of the tissue at a particular tissue site may be thicker than 1.5 mm, which may require obtaining optical information from 2-5 mm deep into the tissue. Thus, the in vitro model (as shown in FIG. 12) takes into account the estimated time (e.g., denaturation time) required to reach 1.5 mm of denatured tissue after ablation, and further evaluates how energy is applied to the tissue at deeper lesion depths.

[0082] By correlating lesion depth to ablation time and by assessing lesion progression to different sizes, an in vitro model can be constructed using the optical measurement data and correlations. In some embodiments, optical signals providing information at a depth of 1.5 mm can be extrapolated to predict lesion depth data at deeper tissue levels.

[0083] 13A and 13B illustrate diagrams showing exemplary lesion depth and lesion width, respectively, as a function of ablation time, according to embodiments of the present disclosure. In some embodiments, FIGS. 13A and 13B show lesion depth and lesion width, respectively, for ablations performed at temperatures of 50° C. and 70° C. In some embodiments, the lesion depth and lesion width may be obtained by analyzing optical measurement data and using a regression model to predict lesion depth, as discussed with reference to FIGS. 8A-12.

[0084] FIG. 14 illustrates an exemplary diagram of catheter tip geometry and orifice location for contact with tissue according to an embodiment of the present disclosure. In some embodiments, FIG. 14 shows the orientation of the catheter tip at various angles of incidence, including 0°, 29°, 45°, 62°, and 90°. The top panel in FIG. 14 illustrates multiple orifices or optical viewport locations in the catheter tip, where three orifices may be positioned to contact tissue. The bottom panel in FIG. 14 illustrates the orifice locations in the top panel displaced by 50 um in the catheter tip. In some embodiments, the number of orifices in contact with tissue may be determined based on signals detected from the corresponding light beams. Based on the determination, the contact force may be calculated by a direct mathematical relationship or statistical extrapolation. In some embodiments, the orifices in the catheter tip may be utilized to acquire optical signals and to determine lesion progression in tissue from multiple different angles relative to the positioning of the catheter tip in the tissue.

[0085] FIG. 15 illustrates an exemplary diagram of catheter-tissue contact and catheter tip beam direction according to an embodiment of the present disclosure. The diagrams in the top row of FIG. 15 illustrate exemplary diameters and exemplary values ​​of catheter tip-to-tissue distances that indicate different levels of contact. For example, catheter-tissue distances of approximately 0.32 mm, 0.73 mm, and 1.15 mm can represent soft, medium, and strong contact between the catheter and tissue, respectively. In some embodiments, the middle row of FIG. 15 illustrates a lateral view of the catheter tip, where one to three beams from the optical viewport at the catheter tip are in contact with the tissue and can be used to optically evaluate the tissue. In some embodiments, the bottom row of FIG. 15 illustrates a front view of the catheter tip, where one to three beams from the optical viewport are in contact with the tissue and can be used to optically evaluate the tissue. In some embodiments, there may be 15 optical ports at the catheter tip, and any number of optical ports may be selected to provide one or more beams to the tissue. In some embodiments, four or more beams may be used for optical analysis, and using one or more beams from multiple optical viewports may provide more accurate models for predicting lesion depth and for understanding the progression of lesion shape and size in tissue.

[0086] 16 illustrates an exemplary graphical user interface (GUI) 1600 showing predicted lesion depth, according to an embodiment of the present disclosure. In some embodiments, the GUI 1600 may be presented on a display 325 coupled to the console 310, in which optical measurement data may be acquired by the optical system 401. The GUI 1600 provides the optical measurement data (e.g., as processed by the console 310) in real-time or near real-time for the ablation process. In some embodiments, the GUI 1600 includes a front view 1602 of the catheter tip showing different sections 1604-1606 corresponding to various optical viewports at the catheter tip.

[0087] In some embodiments, the front view 1602 of the GUI 1600 can indicate which optical viewports of the catheter tip are in contact with the tissue and which beams from the different optical viewports are active. For example, the dark gray section 1604 of the front view 1602 can indicate strong contact between the catheter and the tissue, the light gray section 1605 can indicate minimal or medium contact between the catheter and the tissue, and the white section 1606 can indicate no contact. In some embodiments, the different sections 1604-1606 can also indicate which beams are switched on or off to obtain optical measurements from the tissue. In some embodiments, the dark gray section 1604 and the light gray section 1605 can indicate that the beams from the corresponding optical viewports are turned on, while the white section 1606 can indicate that the corresponding optical viewports are turned off.

[0088] In some embodiments, the GUI 1600 may further include a plurality of tiles 1608 showing optical readings for respective optical viewport sections in the catheter. In some embodiments, the plurality of tiles 1608 may each correspond to a different section 1604-1606 in the front view 1602. Each tile 1608 may represent an image resulting from processing by the console the optical signals and / or optical measurements obtained from the respective optical viewport sections in the catheter. In some embodiments, individual tiles 1608 may be switched on or off (or may appear or disappear) based on which particular optical viewport section is active at a given time. In some embodiments, the GUI 1600 may include one or more graphs 1610 showing ablation energy data (e.g., RF power), birefringence data, phase data, and predicted lesion depth data. In some embodiments, the GUI 1600 may include one or more panels or indicators 1612 that indicate the occurrence of stable contact between the catheter tip and the tissue, loss of birefringence, ablation energy status (e.g., on / off), and predicted lesion depth. In some embodiments, the GUI 1600 may include one or more buttons or text boxes that allow user selection and / or customization of parameters selected for operating with the catheter for or during ablation.

[0089] Exemplary embodiments of the method of operation The catheters, consoles, and systems described herein can be used to perform optical analysis of tissue and lesion depth prediction. By utilizing the optical analysis and lesion prediction methods described herein, the catheters and optical systems disclosed herein (e.g., catheter system 300 and optical system 401) can enable assessment of lesion formation in tissue in real-time or near real-time with accuracy, sensitivity, and specificity values ​​of 93.5%, 92.9%, and 96.6%, respectively.

[0090] The various methods and other embodiments of the catheters and systems described thus far may be implemented using, for example, the catheter 100 shown in FIG. 1, the system 300 (including the catheter 302 and the console 310) shown in FIG. 3, the optical system 401 shown in FIG. 4, and the embodiments shown in FIGS. 5-16.

[0091] 17 illustrates an exemplary method 1700 for predicting lesion depth for ablation according to an embodiment of the present disclosure. In some embodiments, the method 1700 may be performed by the console 310 of FIG. 3, the catheter 302, and / or the optical system 401 of FIG. 4, as described herein.

[0092] At block 1702, ablation may be performed by applying energy from a catheter to a portion of tissue for a predetermined period of time. In some embodiments, the catheter may include a proximal section, a distal section including multiple optical ports, and a sheath coupled between the proximal and distal sections. In some embodiments, the energy applied by the catheter may be at least one of a pulsed electric field, radio frequency (RF) energy, laser energy, cryogenic energy, or ultrasound energy.

[0093] At block 1704, optical measurement data may be acquired from the portion of the tissue using at least one optical port in the catheter. In some embodiments, the optical measurement data may include one or more optical coherence tomography (OCT) and / or optical coherence reflectometry (OCR) signals acquired from the portion of the tissue. In some embodiments, the optical measurement data may be acquired by the components shown in the block diagram of FIG. 5, by the optical system 410, and / or by the console 310.

[0094] At block 1706, one or more optical properties of the portion of the tissue may be identified by analyzing the optical measurement data using a processing device coupled to the catheter. In some embodiments, the one or more optical properties include at least one of polarization or spectral information (e.g., spectroscopic or imaging information from the tissue).

[0095] At block 1708, a time of modification of the portion of the tissue may be determined based on one or more optical properties of the portion of the tissue. In some embodiments, the time of modification of the tissue may be related to the phase delay measurement and a loss of birefringence in the tissue below a predetermined threshold.

[0096] At block 1710, a model expressing the correlation between lesion depth and ablation time may be generated using the time of degeneration, the one or more optical properties, and the predetermined time period. In some embodiments, the model may be a linear regression model and may be generated using a machine learning algorithm (e.g., a support vector machine and / or a neural network, etc.).

[0097] At block 1712, a predicted lesion depth may be generated over a predetermined period of time using the model. In some embodiments, the predicted lesion depth may represent at least one of a depth and a width of a lesion formed by energy applied to a portion of tissue by the catheter. In some embodiments, the predicted lesion depth may be a function of a ratio of a predetermined period of time to a time of degeneration. In some embodiments, the lesion progression of the lesion may be determined by acquiring optical measurement data at a plurality of different angles relative to the portion of tissue using a plurality of optical ports in a distal section of the catheter, each optical port being positioned at a different location corresponding to a respective angle in the distal section of the catheter.

[0098] Exemplary Computing Embodiments 18 is a block diagram of exemplary components of a computer system 1800. One or more computer systems 1800 may be used to implement, for example, any of the embodiments discussed herein, as well as combinations and subcombinations thereof. In some embodiments, one or more computer systems 1800 may be used to implement the method 1700 shown in FIG. 17 and / or the console 310, signal generator 320, and display 325 as described herein. The computer system 1800 may include one or more processors (also referred to as central processing units or CPUs) (e.g., processor 1804, etc.). The processor 1804 may be connected to a communication infrastructure or bus 1806.

[0099] The computer system 1800 may also include a user input / output interface 1802 (e.g., a monitor, keyboard, pointing device, etc.), which may communicate with a communications infrastructure 1806 through a user input / output interface 1803.

[0100] One or more of the processors 1804 may be a graphics processing unit (GPU). In one embodiment, a GPU may be a processor that is a specialized electronic circuit designed to process mathematically intensive applications. GPUs may have a parallel structure that is efficient for parallel processing of large blocks of data (e.g., mathematically intensive data common to computer graphics applications, images, video, etc.).

[0101] The computer system 1800 may also include a main or primary memory 1808 (e.g., random access memory (RAM), etc.). The main memory 1808 may include one or more levels of cache. The main memory 1808 may have control logic (i.e., computer software) and / or data stored therein. In some embodiments, the main memory 1808 may include optical logic configured to perform analysis of optical measurements obtained from tissue by the catheter and to determine lesion predictions.

[0102] The computer system 1800 may also include one or more secondary storage devices or memory 1810. The secondary memory 1810 may include, for example, a hard disk drive 1812 and / or a removable storage drive 1814.

[0103] The removable storage drive 1814 can interact with a removable storage unit 1818. The removable storage unit 1818 can include a computer usable or readable storage device having computer software (control logic) and / or data stored therein. The removable storage unit 1818 can be a program cartridge and cartridge interface (such as those found in video game devices), a removable memory chip (such as an EPROM or PROM) and associated socket, a memory stick and USB port, a memory card and associated memory card slot, and / or any other removable storage unit and associated interface. The removable storage drive 1814 can read from and / or write to the removable storage unit 1818.

[0104] The secondary memory 1810 may include other means, devices, components, conveniences, or other approaches for allowing computer programs and / or other instructions and / or data to be accessed by the computer system 1800. Such means, devices, components, conveniences, or other approaches may include, for example, removable storage units 1822 and interfaces 1820. Examples of removable storage units 1822 and interfaces 1820 may include program cartridges and cartridge interfaces (such as those found in video game devices), removable memory chips (such as, for example, EPROMs or PROMs) and associated sockets, memory sticks and USB ports, memory cards and associated memory card slots, and / or any other removable storage units and associated interfaces.

[0105] The computer system 1800 may further include a communication or network interface 1824. The communication interface 1824 may enable the computer system 1800 to communicate and interact with any combination of external devices, external networks, external entities, etc. (individually and collectively (referenced by reference numeral 1828)). For example, the communication interface 1824 may enable the computer system 1800 to communicate with external or remote devices 1828 via a communication path 1826, which may be wired and / or wireless (or a combination thereof), which may include any combination of a LAN, a WAN, the Internet, etc. Control logic and / or data may be transmitted to and from the computer system 1800 via the communication path 1826. In some embodiments, the computer system 1800 may be coupled to a catheter via connectors and optical and electrical connections (including optical fibers and electrical wires, pins, and / or components) in the communication interface 1824.

[0106] Additionally, computer system 1800 may be a personal digital assistant (PDA), a desktop workstation, a laptop or notebook computer, a netbook, a tablet, a smartphone, a smart watch or other wearable, a consumer electronics device, part of the Internet of Things, and / or an embedded system, or any combination thereof, to name a few non-limiting examples.

[0107] Computer system 1800 can be a client or a server and can access or host any application and / or data through any delivery paradigm, including, but not limited to, remote or distributed cloud computing solutions, local or on-premise software ("on-premise" cloud-based solutions), "as-a-service" models (e.g., Content as a Service (CaaS), Digital Content as a Service (DCaaS), Software as a Service (SaaS), Managed Software as a Service (MSaaS), Platform as a Service (PaaS), Desktop as a Service (DaaS), Framework as a Service (FaaS), Backend as a Service (BaaS), Mobile Backend as a Service (MBaaS), Infrastructure as a Service (IaaS), etc.), and / or hybrid models including any combination of the foregoing examples or other service or delivery paradigms.

[0108] Any applicable data structures, file formats, and schemes in computer system 1800 may be derived from standards, including but not limited to JavaScript Object Notation (JSON), Extensible Markup Language (XML), Yet Another Markup Language (YAML), Extensible Hypertext Markup Language (XHTML), Wireless Markup Language (WML), MessagePack, XML User Interface Language (XUL), or any other functionally similar representations, alone or in combination. Alternatively, proprietary data structures, formats, or schemes may be used, either exclusively or in combination with known or open standards.

[0109] In some embodiments, a tangible, non-transitory apparatus or article of manufacture including a tangible, non-transitory computer usable or readable medium having control logic (software) stored thereon may also be referred to herein as a computer program product or program storage device. This includes, but is not limited to, computer system 1800, main memory 1808, secondary memory 1810, and removable storage units 1818 and 1822, as well as tangible articles of manufacture embodying any combination of the foregoing. Such control logic, when executed by one or more data processing devices (such as, for example, computer system 1800), can cause such data processing devices to operate as described herein.

[0110] It should be appreciated that the Detailed Description section (and not the Summary and Abstract sections) are intended to be used to interpret the claims. The Summary and Abstract sections may describe one or more (but not all) example embodiments of the present disclosure as contemplated by the inventors, and thus are not intended to limit the scope of the disclosure and the appended claims in any way.

[0111] The embodiments of the present disclosure have been described above with the aid of functional building blocks illustrating the implementation of certain functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of description. Alternative boundaries may be defined so long as the certain functions and relationships thereof are appropriately implemented.

[0112] The foregoing description of the specific embodiments will fully and completely reveal the general nature of the present disclosure, so that others, by applying knowledge within the skill of the art, can easily modify and / or adapt such specific embodiments for various applications without undue experimentation and without departing from the general concept of the present disclosure. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed embodiments, based on the teaching and guidance presented herein. It should be understood that the phraseology or terminology in this specification is for the purpose of description and not of limitation, and that the terminology or terminology in this specification is as it should be interpreted by those skilled in the art in light of the teaching and guidance.

[0113] The breadth and scope of the present disclosure should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.

[0114] Moreover, the following aspects are explicitly disclosed:

[0115] 1. performing ablation by applying energy from a catheter to a portion of tissue for a predetermined period of time, the catheter including a proximal section, a distal section including a plurality of optical ports, and a sheath coupled between the proximal and distal sections; acquiring optical measurement data from a portion of the tissue using at least one optical port in the catheter; identifying one or more optical properties of a portion of the tissue by analyzing the optical measurement data using a processing device coupled to the catheter; determining a time of denaturation of the portion of the tissue based on one or more optical properties of the portion of the tissue; A method comprising:

[0116] 2. The method of aspect 1, wherein the energy applied by the catheter includes at least one of a pulsed electric field, radio frequency (RF) energy, laser energy, or cryogenic energy.

[0117] 3. The method of claim 1 or 2, wherein the optical measurement data includes an optical coherence tomography (OCT) signal or an optical coherence reflectometry (OCR) signal obtained from a portion of the tissue, and the one or more optical properties include at least one of polarization or spectral information.

[0118] 4. generating a model expressing a correlation between lesion depth and ablation time using the time of alteration, the one or more optical properties, and the predetermined time period; using the model to generate a predicted lesion depth over a predetermined period of time; The method of any one of aspects 1 to 3, further comprising:

[0119] 5. The method of aspect 4, wherein the predicted lesion depth represents at least one of the depth and width of a lesion formed by energy applied to a portion of tissue by the catheter.

[0120] 6. The method of embodiment 5, wherein the predicted lesion depth is a function of the ratio of a predetermined period of time to the time of degeneration.

[0121] 7. The method of embodiment 5, further comprising the step of determining lesion progression of the lesion by acquiring optical measurement data at multiple different angles relative to a portion of the tissue using multiple optical ports, each optical port being positioned at a different angle in the distal section of the catheter.

[0122] 8. The method of aspect 4, further comprising the step of selecting at least one optical port in the catheter for acquiring optical measurement data.

[0123] 9. The method of aspect 8, wherein the plurality of optical ports includes 15 optical ports and the at least one optical port includes three or more optical ports.

[0124] 10. determining a portion of the distal section of the catheter in contact with a portion of tissue during ablation based on identifying optical signals received from the three or more optical ports; estimating a contact force between a portion of the distal section of the catheter and a portion of the tissue based on the determining step; and determining a time to denaturation of the portion of the tissue based on the contact force. 10. The method of embodiment 9, further comprising:

[0125] 11. A system comprising: a catheter including a proximal section, a distal section, and a sheath coupled between the proximal and distal sections; a plurality of optical fibers positioned within the catheter; a computing device coupled to a plurality of optical fibers through a connector, the computing device including a memory and a processor; Including, The processor: configured to receive optical measurement data of the portion of the tissue from the optical fiber during or after ablation; configured to identify one or more optical properties of a portion of the tissue by analyzing the optical measurement data; configured to determine a time of denaturation of the portion of the tissue based on one or more optical properties of the portion of the tissue; and configured to generate a model representing a correlation between lesion depth and ablation time using the time of alteration, the one or more optical properties, and the predetermined time period; The system is configured to use the model to generate a predicted lesion depth over a given ablation time.

[0126] 12. The system of aspect 11, wherein the optical measurement data includes an optical coherence tomography (OCT) signal or an optical coherence reflectometry (OCR) signal obtained from a portion of the tissue, and the one or more optical properties include at least one of polarization or spectral information.

[0127] 13. The system of aspect 11 or aspect 12, wherein the predicted lesion depth represents at least one of a depth and a width of a lesion formed by energy applied to a portion of the tissue by the catheter, and the predicted lesion depth is a function of a ratio of a predetermined period of time to a time of degeneration.

[0128] 14. The system of aspect 13, wherein the distal section of the catheter includes multiple optical ports, and the processor of the computing device is further configured to determine lesion progression of the lesion by acquiring optical measurement data at multiple different angles relative to a portion of the tissue using the multiple optical ports, each optical port being positioned at a different angle in the distal section of the catheter.

[0129] 15. The system of any one of aspects 11 to 14, wherein the connector includes a plurality of V-shaped grooves for alignment of respective optical fibers for connection between the catheter and the computing device.

[0130] 16. A computing device comprising: Memory and A processor connected to memory Including, The processor: configured to receive optical measurement data of the portion of tissue from the catheter after applying energy to the portion of tissue for a predetermined period of time during ablation; configured to identify one or more optical properties of a portion of the tissue by analyzing the optical measurement data; configured to determine a time of denaturation of the portion of the tissue based on one or more optical properties of the portion of the tissue; and configured to generate a model representing a correlation between lesion depth and ablation time using the time of alteration, the one or more optical properties, and the predetermined time period; A computing device configured to use the model to generate a predicted lesion depth over a predetermined period of time.

[0131] 17. The computing device of aspect 16, wherein the optical measurement data includes an optical coherence tomography (OCT) signal or an optical coherence reflectometry (OCR) signal obtained from a portion of the tissue, and the one or more optical properties include at least one of polarization or spectral information.

[0132] 18. The computing device of aspect 16 or aspect 17, wherein the predicted lesion depth represents at least one of a depth and a width of a lesion formed by energy applied to a portion of the tissue by the catheter, and the predicted lesion depth is a function of a ratio of a predetermined period of time to a time of degeneration.

[0133] 19. The computing device of aspect 18, wherein the catheter includes a plurality of optical ports in a distal section of the catheter, and the processor is further configured to determine lesion progression of the lesion by acquiring optical measurement data at a plurality of different angles relative to a portion of the tissue using the plurality of optical ports, each optical port being positioned at a different angle in the distal section of the catheter.

[0134] 20. The processor: and further configured to determine a portion of the distal section of the catheter in contact with a portion of tissue during ablation based on identifying an optical signal received from at least one optical port in the plurality of optical ports; and further configured to estimate a contact force between the portion of the distal section of the catheter and the portion of the tissue based on the determining. 20. The computing device of embodiment 19, further configured to determine a time of denaturation of the portion of the tissue based on the contact force. [Explanation of symbols]

[0135] 100 Catheters 102 Proximal Section 104 Distal Section 106 Sheath 106a Sheath 106b Sheath 108 Processing Device 110 Communication Interface 202 Irrigation Channel 206 Deflection Mechanism 208 Electrical Connections 210 Optical transmission media 212 Protective cover 300 Systems 302 Catheter 304 patients 310 Console 312 Optical Connection 314 Electrical Connections 316 Communication Interface 320 Signal Generator 325 Display 330 Irrigation Pump 401 Optical System 402 Optical Source 403 Polarization Splitter 404 Coupling / Splitting Elements 406 Sample Arm 407 Polarization Switch 408 Reference Arm 409 Optical Switch 410 Output Fiber 412 Delay Unit 414 Detector 420 Samples 600 Connector 602 V-shaped groove 1600 Graphical User Interface (GUI) 1602 Front view 1604 Dark Gray Section 1605 Light Gray Section 1606 White Section 1608 tiles 1610 Graph 1612 Panel, indicator 1800 Computer Systems 1802 User Input / Output Interface 1803 User Input / Output Devices 1804 processor 1806 Communications Infrastructure 1808 Main Memory 1810 Secondary Memory 1812 Hard Disk Drive 1814 Removable Storage Drive 1818 Removable Storage Unit 1820 Interface 1822 Removable Storage Unit 1824 Communication Interface 1826 Communication Path 1828 Remote Devices, Networks, and Entities

Claims

1. 1. A system comprising: a catheter including a proximal section, a distal section, and a sheath coupled between the proximal section and the distal section; a plurality of optical fibers positioned within the catheter; a computing device coupled to the plurality of optical fibers through a connector, the computing device including a memory and a processor; Including, The processor, receiving optical measurement data of a portion of tissue from the optical fiber after applying energy to the portion of tissue for a predetermined period of time during ablation; analyzing the optical measurement data to identify one or more optical properties of the portion of the tissue; determining a time of denaturation of the portion of tissue based on the one or more optical properties of the portion of tissue; generating a model expressing a correlation between lesion depth and ablation time using the time of alteration, the one or more optical properties, and the predetermined time period; The system is configured to use the model to generate a predicted lesion depth over the predetermined period of time.

2. 2. The system of claim 1, wherein the optical measurement data comprises an optical coherence tomography (OCT) signal or an optical coherence reflectometry (OCR) signal acquired from the portion of the tissue, and the one or more optical properties comprise at least one of polarization or spectral information.

3. 2. The system of claim 1, wherein the predicted lesion depth represents at least one of a depth and a width of a lesion formed by the energy applied to the portion of the tissue by the catheter, the predicted lesion depth being a function of a ratio of the predetermined period of time to a time of the alteration.

4. 4. The system of claim 3, wherein the distal section of the catheter includes a plurality of optical ports, and the processor of the computing device is further configured to determine lesion progression of the lesion by acquiring the optical measurement data at a plurality of different angles relative to a portion of the tissue using the plurality of optical ports, each optical port being positioned at a different angle in the distal section of the catheter.

5. The system of claim 1 , wherein the connector includes a plurality of V-grooves for alignment of respective optical fibers for connection between the catheter and the computing device.

6. 1. A computing device comprising: Memory and a processor coupled to the memory; Including, The processor, receiving optical measurement data of the portion of tissue from the catheter after applying energy to the portion of tissue for a predetermined period of time during ablation; analyzing the optical measurement data to identify one or more optical properties of the portion of the tissue; determining a time of denaturation of the portion of tissue based on the one or more optical properties of the portion of tissue; generating a model expressing a correlation between lesion depth and ablation time using the time of alteration, the one or more optical properties, and the predetermined time period; A computing device configured to use the model to generate a predicted lesion depth over the predetermined period of time.

7. 7. The computing device of claim 6, wherein the optical measurement data comprises an optical coherence tomography (OCT) signal or an optical coherence reflectometry (OCR) signal acquired from the portion of the tissue, and the one or more optical properties comprise at least one of polarization or spectral information.

8. 7. The computing device of claim 6, wherein the predicted lesion depth represents at least one of a depth and a width of a lesion formed by the energy applied to the portion of the tissue by the catheter, the predicted lesion depth being a function of a ratio of the predetermined period of time to a time of the alteration.

9. 10. The computing device of claim 8, wherein the catheter includes a plurality of optical ports at a distal section of the catheter, and the processor is further configured to determine lesion progression of the lesion by acquiring the optical measurement data at a plurality of different angles relative to a portion of the tissue using the plurality of optical ports, each optical port being positioned at a different angle at the distal section of the catheter.

10. The processor, determining a portion of the distal section of the catheter in contact with a portion of the tissue during the ablation based on identifying an optical signal received from at least one optical port in the plurality of optical ports; estimating a contact force between the portion of the distal section of the catheter and a portion of the tissue based on the determining; The computing device of claim 6 , further configured to further determine a time for the denaturation of the portion of the tissue based on the contact force.

11. A method for operating a system according to any one of claims 1 to 5, comprising: the processor acquiring optical measurement data from the portion of the tissue using at least one optical port in the catheter; identifying one or more optical properties of the portion of the tissue by analyzing the optical measurement data using a processing device coupled to the catheter; determining a time of denaturation of the portion of tissue based on the one or more optical properties of the portion of tissue; A method comprising:

12. The method of claim 11, wherein the energy applied by the catheter includes at least one of a pulsed electric field, radio frequency (RF) energy, laser energy, and cryogenic energy.

13. The method of claim 11, wherein the optical measurement data includes an optical coherence tomography (OCT) signal or an optical coherence reflectometry (OCR) signal obtained from a portion of the tissue, and the one or more optical properties include at least one of polarization or spectral information.

14. The step of the processor generating a model representing a correlation between lesion depth and ablation time using the time of alteration, the one or more optical properties, and the predetermined time period; the processor using the model to generate a predicted lesion depth over the predetermined period of time; The method of claim 11 further comprising:

15. The method of claim 14, wherein the predicted lesion depth represents at least one of a depth and a width of a lesion formed by the energy applied to a portion of the tissue by the catheter.

16. The method of claim 15, wherein the predicted lesion depth is a function of the ratio of the predetermined period of time to the time of the degeneration.

17. The method of claim 15, further comprising the step of: the processor determining lesion progression of the lesion by acquiring the optical measurement data at a plurality of different angles relative to a portion of the tissue using the plurality of optical ports, each optical port being positioned at a different angle in the distal section of the catheter.

18. The method of claim 14, wherein at least one optical port in the catheter is selected to acquire the optical measurement data.

19. The method of claim 18, wherein the plurality of optical ports includes 15 optical ports and the at least one optical port includes three or more optical ports.

20. The method of claim 1, further comprising: determining, based on identifying optical signals received from the three or more optical ports, a portion of the distal section of the catheter that is in contact with a portion of the tissue during the ablation; estimating, by the processor, a contact force between the portion of the distal section of the catheter and a portion of the tissue based on the determining step; the processor further determining a time of the denaturation of the portion of the tissue based on the contact force; 20. The method of claim 19, further comprising:

Images