Patent Application
20170354357
The present disclosure relates to analyzing anatomical structures within the body. More specifically, the present disclosure relates to systems, methods, and devices for monitoring and assessing tissue ablation using fluorescence.
In ablation therapy, it is often necessary to determine various characteristics of body tissue at a target ablation site within the body. In interventional cardiac electrophysiology procedures, for example, it is often necessary for the physician to determine the condition of cardiac tissue at a target ablation site in or near the heart.
In Example 1, a catheter system includes a catheter with an elongate catheter body, a catheter tip coupled to a distal end of the catheter body, and at least one light-emitting element configured to emit light to excite flavin adenine dinucleotide (FAD) molecules. The catheter system further including at least one light sensor configured to sense a light emitted by the excited FAD molecules.
In Example 2, the catheter system of Example 1, wherein the at least one light-emitting element is a light-emitting diode.
In Example 3, the catheter system of Example 1, wherein the at least one light-emitting element is an optical fiber.
In Example 4, the catheter system of Example 3, wherein the optical fiber is communicatively coupled to a light source.
In Example 5, the catheter system of any of Examples 1-4, wherein the at least one light-emitting element is at least partially positioned within the catheter tip.
In Example 6, the catheter system of any of Examples 1-5, wherein the catheter tip includes at least one window or optically-transparent balloon.
In Example 7, the catheter system of any of Examples 1-6, wherein the at least one light sensor is at least partially positioned within the catheter tip.
In Example 8, the catheter system of any of Examples 1-7, further comprising control circuitry configured to assess lesion formation in response to receiving a signal indicative of an intensity of the sensed light emitted by the excited FAD molecules.
In Example 9, the catheter system of Example 8, wherein the control circuitry assesses lesion formation by determining the intensity of the sensed light is greater than a threshold.
In Example 10, the catheter system of Example 8, wherein the control circuitry assesses lesion formation by determining that a rate of change in intensity of the sensed light is greater than a threshold.
In Example 11, the catheter system of Example 8, wherein the control circuitry assesses lesion formation by determining that a difference in intensity of the sensed light is greater than a threshold.
In Example 12, a method for assessing tissue damage includes receiving an indication of intensity of FAD fluorescence of a section of tissue; and in response to the received indication of intensity, determining whether the section of tissue is damaged by an ablation catheter.
In Example 13, the method of Example 12, further comprising: determining, based on the received indication of intensity, whether an ablation catheter has contacted the section of tissue.
In Example 14, the method of any of Examples 12-13, wherein determining whether the section of tissue is damaged further comprises determining that the intensity is greater than a threshold.
In Example 15, the method of any of Examples 12-14, wherein determining whether the section of tissue is damaged further comprises determining that a rate of change of intensity is greater than a threshold.
In Example 16, a system includes a catheter with an elongate catheter body, a catheter tip coupled to a distal end of the catheter body, and at least one optical fiber partially positioned within the catheter tip and configured to emit light to excite flavin adenine dinucleotide (FAD) molecules. The system further includes at least one light sensor communicatively coupled to the at least one optical fiber and configured to sense a light emitted by the excited FAD molecules.
In Example 17, the system of Example 16, wherein the catheter further comprises at least one ablation electrode coupled to a catheter tip.
In Example 18, the system of any of Examples 16-17, wherein the catheter tip includes at least one window coupled to the at least one optical fiber.
In Example 19, the system of Example 18, wherein the at least one window is positioned on a distal end of the catheter tip.
In Example 20, the system of any of Examples 16-19, wherein the catheter further includes a plurality of optical fibers.
In Example 21, the system of any of Examples 16-20, wherein the catheter further includes a lumen extending within and along the catheter body, wherein the plurality of optical fibers are wound around the lumen.
In Example 22, the system of any of Examples 16-21, wherein at least a portion of the plurality of optical fibers are positioned radially around a circumferential wall of the catheter tip.
In Example 23, the system of any of Examples 16-22, wherein at least one of the plurality of optical fibers terminates at a distal end of the catheter tip.
In Example 24, the system of any of Examples 16-23, wherein at least one of the plurality of optical fibers terminates at a circumferential wall of the catheter tip.
In Example 25, the system of any of Examples 16-24, further comprising: control circuitry configured to assess lesion formation in response to receiving a signal indicative of an intensity of the sensed light emitted by the excited FAD molecules.
In Example 26, the system of any of Examples 16-25, wherein the control circuitry is configured to assess lesion formation by determining the intensity of the sensed light is greater than a threshold.
In Example 27, the system of any of Examples 16-25, wherein the control circuitry is configured to assess lesion formation by determining that a rate of change in intensity of the sensed light is greater than a threshold.
In Example 28, the system of any of Examples 16-25, wherein the control circuitry is configured to assess lesion formation by determining that a difference in intensity of the sensed light is greater than a threshold.
In Example 29, the system of any of Examples 16-28, wherein the at least one light sensor in one of a photodetector, spectrophotometer, camera, semiconductor, and photomultiplier tube.
In Example 30, a method for assessing tissue damage includes receiving an indication of intensity of flavin adenine dinucleotide (FAD) fluorescence near a section of tissue; and in response to the received indication of intensity, determining whether the section of tissue is damaged.
In Example 31, the method of Example 30, further comprising: receiving an indication of intensity of nicotinamide adenine dinucleotide hydrogen (NADH) fluorescence near a section of tissue; and in response to the received indication of NADH fluorescence intensity, determining whether the section of tissue is damaged.
In Example 32, the method of any of Examples 30-31, further comprising: exciting FAD molecules by directing light towards the section of tissue; and detecting FAD fluorescence intensity of the excited FAD molecules.
In Example 33, the method of any of Examples 30-32, wherein determining whether the section of tissue is damaged includes: determining the intensity of the sensed light is greater than a threshold.
In Example 34, the method of any of Examples 30-33, wherein determining whether the section of tissue is damaged includes: determining that a rate of change in intensity of the sensed light is greater than a threshold.
In Example 35, the method of any of Examples 30-34, wherein determining whether the section of tissue is damaged includes: determining that a difference in intensity of the sensed light is greater than a threshold.
In Example 36, a method includes receiving an indication of intensity of FAD fluorescence of a section of tissue. In response to the received indication of intensity, the method further includes determining whether an ablation catheter has contacted the section of tissue.
While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
While the disclosure is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the disclosure to the particular embodiments described. On the contrary, the disclosure is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.
Various cardiac abnormalities can be attributed to improper electrical activity of cardiac tissue. Such improper electrical activity can include, but is not limited to, generation of electrical signals, conduction of electrical signals, and/or compression of the tissue in a manner that does not support efficient and/or effective cardiac function. For example, an area of cardiac tissue may become electrically active prematurely or otherwise out of synchrony during the cardiac cycle, causing the cardiac cells of the area and/or adjacent areas to contract out of rhythm. The result is an abnormal cardiac contraction that is not timed for optimal cardiac output. In some cases, an area of cardiac tissue may provide a faulty electrical pathway (e.g., a short circuit) that causes an arrhythmia, such as atrial fibrillation or supraventricular tachycardia. In some cases, inactive tissue (e.g., scar tissue) may be preferable to malfunctioning cardiac tissue.
Cardiac ablation is a procedure by which cardiac tissue is treated to inactivate the tissue. The tissue targeted for ablation may be associated with improper electrical activity, as described above. Cardiac ablation can lesion the tissue and prevent the tissue from improperly generating or conducting electrical signals. For example, a line, a circle, or other formation of ablated cardiac tissue can block the propagation of errant electrical signals. In some cases, cardiac ablation is intended to cause the death of cardiac tissue and to have scar tissue reform over the lesion, where the scar tissue is not associated with the improper electrical activity. Ablation therapies include radiofrequency ablation, cyroablation, microwave ablation, laser ablation, and surgical ablation, among others.
When the element 112 is an optical fiber, the system 100 can include at least one sensor 114 that is coupled to the at least one optical fiber and that is configured to sense light transmitted by the at least one optical fiber. Such a configuration can also include a light source 116 (e.g., laser(s)) coupled to the at least one optical fiber to supply light to the at least one optical fiber, which transmits the supplied light through the catheter 102.
The system 100 also includes control circuitry 118 (including a memory 120, processor 122, measurement sub-unit 124, analyzer sub-unit 126, mapping sub-unit 128, and display controller 130) and a display 132. As will be explained in more detail below, the system 100 and its various components are configured to utilize fluorescence to assess and monitor tissue ablation (e.g., lesion formation).
In cardiac tissue, mitochondria assist in meeting energy demands of a beating heart. Nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD) are two elements of aerobic energy production within the mitochondria and have an intrinsic fluorescence. In addition to assisting with meeting energy demands, mitochondria assist with cell death mechanisms. In necrosis, the cell death mechanism associated with ablation, swelling and destruction of intracellular organelles leads to an increase in cell death signaling, among other things—culminating in a collapse of the mitochondrial membrane and oxidation of NADH and FADH2. Oxidized FADH2 (i.e., FAD) emits light when excited by light, and the intensity of the emitted light can be an indicator of the metabolic state of the tissue. The intensity of the emitted light thus can be an indicator of tissue health for real-time assessment and monitoring of tissue ablation (e.g., lesion formation). Certain embodiments of the present disclosure are accordingly directed to utilizing FAD and its fluorescence to assess and monitor lesion formation and therefore assist with tissue ablation.
The catheter 200 includes a light-emitting element, which can be an optical fiber 210 and/or a catheter-based light source 218. In certain embodiments, the optical fiber 210 extends through the catheter tip 206 (e.g., from a proximal end 212 to a distal end 214 of the catheter tip 206) and is coupled to a window 216 positioned at the distal end 214 of the catheter tip 206. Although only one optical fiber is shown in
The optical fiber 210 is configured to direct light (e.g., ultraviolet light) through the window 216. The window 216 can comprise glass, acrylics, silicone, polycarbonate (Lexan), plexiglass, fluorinated ethylene propylene (FEP), optically-clear epoxies, and the like. In certain embodiments, the optical fiber 210 is communicatively coupled to a light source (like the light source 116 shown in
The light-emitting element (e.g., optical fiber 210 or catheter-based light source 218) can be coupled to a steering mechanism (not shown), which can articulate either the optical fiber 210 or the catheter-based light source 218 in different directions such that the light emitted from the optical fiber 210 or the catheter-based light source 218 can be directed in a specific direction. For example, the optical fiber 210 or the catheter-based light source 218 can be rotated to direct light through different sections of the window 216 and at different directions. Although the window 216 is shown as being positioned at the distal end 214 of the catheter tip 206, the window 216 could cover a larger portion of the catheter tip 206 to provide a larger range of directions at which the optical fiber 210 or the catheter-based light source 218 can direct light. In some embodiments, the window 216 does not cover the entire distal end 214 of the catheter tip 206. In certain embodiments, the catheter 200 includes a balloon (e.g., optically-transparent balloon) in place of or in addition to the catheter tip 206. An optically-transparent balloon can provide a large range of directions at which the optical fiber 210 or the catheter-based light source 218 can direct light.
The light source (e.g., light source 116 in
In certain embodiments, the optical fiber 210 is communicatively coupled to at least one sensor 220 such that the optical fiber 210 transmits light (e.g., FAD fluorescence) to the at least one sensor 220, which is configured to sense the transmitted light (e.g., FAD fluorescence, optical data). For example, the sensor 220 can be but is not limited to a photodetector, spectrophotometer, camera (e.g., MEMS-based camera), semiconductor (e.g., CMOS), photomultiplier tube, among other imaging and light detection devices and/or circuitry. The sensor 220 can be coupled to one or more filters 222 such as a filter designed to filter out wavelengths outside the emission range of FAD and/or NADH.
In certain embodiments, the catheter 200 includes a sensor 224 that is positioned on or within the catheter tip 206. The sensor 224 can be photodetector, spectrophotometer, camera (e.g., MEMS-based camera), semiconductor (e.g., CMOS), photomultiplier tube, among other imaging and light detection devices and/or circuitry sized to fit onto or within the catheter tip 206. Embodiments utilizing the catheter-based light source 218 and the sensor 224 may not need to use the optical fiber 210, the light source 116, and/or the sensor 220.
During an ablation procedure, the catheter 200 is positioned adjacent tissue that is to be ablated. If the optical fiber 210 or the catheter-based light source 218 were to direct light towards the tissue before ablation, the sensor 220 or 224 would sense little to no intensity of FAD fluorescence because, before being ablated, little to no FAD molecules would be produced from FADH2 oxidation. However, once the ablation electrode 208 is energized and moved into contact with the tissue, FADH2 begin to oxidize into FAD molecules. When light from the optical fiber 210 or the catheter-based light source 218 is directed towards the tissue, the FAD molecules become excited and emit light. More specifically, when the optical fiber 210 or the catheter-based light source 218 directs light with a wavelength of 405-500 nm, FAD emits light (e.g., FAD fluorescence) between approximately 500-600 nm, which is detected by the at least one sensor 220 or 224.
The intensity of the emitted light (e.g., FAD fluorescence intensity) can be measured, analyzed, and/or used to assess and monitor ablation of the tissue. For example, various thresholds can be predetermined or dynamically varied and used to determine when a catheter's ablation electrode has contacted tissue and/or ablation of the tissue has started, is occurring, is successful, and/or has ended. The thresholds can be based on parameters such as a levels of intensity, rates of increase in intensity (e.g., slopes), timing of events involving intensity and/or in combination with other physiological parameters, and levels of intensity changes (e.g., deltas), etc. In certain embodiments, an increase in the level of intensity can indicate that tissue ablation has started because FAD fluorescence intensity generally increases once ablation has started. In certain embodiments, certain rates of increase in the level of intensity can indicate that tissue ablation has started. In certain embodiments, an increase and subsequent plateau in a level of intensity can indicate that the target tissue is fully ablated. For example, a plateau of the level of intensity for a certain amount of time (e.g., 15, 30, 45, or 60 seconds) can indicate that the target tissue is fully ablated. In certain embodiments, FAD fluorescence intensity can be synchronized with other physiological parameters. For example, levels of FAD fluorescence intensity can be synchronized, and plotted against, ECG signals and local electrograms, among other physiological parameters.
Optical data, such as fluorescence intensity, can be used to normalize FAD fluorescence intensity by using a broader range of light reflected from the excitation source. For example, when the optical fiber 210 or the catheter-based light source 218 emits light at the peak excitation wavelength (e.g., 460 nm), the measured FAD fluorescence intensity resulting from tissue ablation can be divided by the measured fluorescence intensity outside the FAD wavelength band (e.g., outside 500-600 nm). The optical data can also be used to generate “smart tags” within an electro-anatomic mapping system. For example, during or after creating a map of portions of a heart (e.g., an electro-anatomic shell), a tag can be automatically placed on the map at areas where FAD fluorescence intensity (or another fluorescence-related parameter) is determined to be greater than a threshold, such as the various thresholds discussed above. In certain embodiments, the tag can be automatically created by setting a threshold on cumulative FAD fluorescence over time (e.g., fluorescence-time integral). The tag may be visually encoded with the maximum FAD fluorescence intensity or cumulative FAD fluorescence over time.
Although the description above primarily discusses using FAD fluorescence intensity, parameters other than or in addition to intensity can be used. These other parameters can include parameters that characterize how fluorescence changes over time. For example, lifetime characteristics of fluorescence (e.g., how quickly fluorescence changes, how does fluorescence recover after photo-bleaching) can be measured and controlled by timing of excitation light (e.g., pulsing excitation light) and timing of light collection.
Assessment and monitoring of tissue ablation can be carried out using various components of the system 100. The control circuitry 118 includes memory 120, processor 122, measurement sub-unit 124, analyzer sub-unit 126, mapping sub-unit 128, and display controller 130. The control circuitry 118 and its components are configured to carry out the various functions of the system. In operation, FAD fluorescence detected by the at least one sensor 220 or 224 is communicated to the measurement sub-unit to determine the intensity of the FAD fluorescence. Once the FAD fluorescence intensity is determined, the analyzer sub-unit 126 compares the intensity to certain predetermined or dynamic thresholds (as mentioned above) to assess whether the ablation electrode 208 has contacted issue and/or whether tissue ablation has started, is occurring, is successful, and/or has ended. The mapping sub-unit 128 receives mapping/positioning signals from mapping and/or navigation sensors coupled to the catheter 200 and determines physiological mapping and catheter position information. The display controller 130 outputs the results of the various sub-units to the display 132. For example, the display controller 130 can combine mapping, positioning, and FAD fluorescence intensity information and output such information to the display 132, which can indicate that certain portions of a targeted ablation site are not fully ablated. Such information can be gathered and displayed in real-time to assist with monitoring and assessing lesion formation. In some embodiments, the display controller 130 synchronizes, in time, signals associated with the determined FAD fluorescence intensity and signals associated with other physiological parameters such that the display 132 displays the synchronized signals.
The control circuitry 118 can include a computer-readable recording medium or “memory” 120 for storing processor-executable instructions, data structures and other information. The memory 120 may comprise a non-volatile memory, such as read-only memory (ROM) and/or flash memory, and a random-access memory (RAM), such as dynamic random access memory (DRAM), or synchronous dynamic random access memory (SDRAM). In some embodiments, the memory 120 may store processor-executable instructions that, when executed by a processor 122, perform routines for carrying out the functions related to assessing and monitoring tissue ablation.
In addition to the memory 120, the control circuitry 118 may include other computer-readable media storing program modules, data structures, and other data described herein for assessing and monitoring tissue ablation. It will be appreciated by those skilled in the art that computer-readable media can be any available media that may be accessed by the control circuitry 118 or other computing system for the non-transitory storage of information. Computer-readable media includes volatile and non-volatile, removable and non-removable recording media implemented in any method or technology, including, but not limited to, RAM, ROM, erasable programmable ROM (EPROM), electrically-erasable programmable ROM (EEPROM), FLASH memory or other solid-state memory technology, compact disc ROM (CD-ROM), digital versatile disk (DVD), BLU-RAY or other optical storage, magnetic tape, magnetic disk storage or other magnetic storage devices and the like.
It will be appreciated that the structure and/or functionality of the control circuitry 118 may be different than that illustrated in
The catheter 400 includes multiple optical fibers 410, 412, and 414. Alternatively, or in addition, the catheter 400 could include one or more or the catheter-based light sources such as the catheter-based light source 218 shown in
The optical fibers are communicatively coupled to a light source (like the light source 116 shown in
In certain embodiments, one of the optical fibers 608 is configured to emit light at a wavelength that excites FAD molecules, as discussed in detail above. The other fiber 610 is configured to emit UV light at a wavelength that excites NADH molecules. For example, the optical fiber 610 can emit UV light at a wavelength at or between 300-400 nm, which excites NADH molecules. When excited, NADH molecules emit light between 435-485 nm. But, unlike FAD, intensity of NADH fluorescence decreases as tissue is ablated. For example, a high NADH fluorescence intensity corresponds to unablated tissue. Thus, it can be challenging to determine whether a decrease in NADH fluorescence is due to ablation (e.g., increased lesion formation) or due to a catheter being moved away from tissue intended to be ablated. However, exciting FAD in addition to NADH and detecting their respective fluorescence can provide information to offset the certain disadvantages mentioned and associated with using NADH as an indicator of tissue ablation.
The optical fibers 608,610 can be communicatively coupled to at least one sensor 628 such that one or more of the optical fibers transmit light to the at least one sensor 628, which is configured to sense the transmitted light (e.g., optical data). When a single light sensor is used, the sensed light from the single light sensor can multiplexed. In certain embodiments with more than one sensor, signals from each sensor can be multiplexed and directed to the control circuitry 118 for analysis. The at least one sensor 628 can be coupled to one or more filters 630 such as a filter designed to filter out certain wavelengths.
Although certain embodiments of the disclosure feature an ablation electrode, monitoring and assessment of tissue ablation via optical fibers, sensors, control circuitry, etc. could be used with devices such as accessary and/or therapeutic catheters that do not include an ablation electrode. For example, an accessory or therapeutic catheter could monitor FAD fluorescence (and therefore tissue ablation) by positioning the catheter near the ablation site during ablation. In certain embodiments, the catheter includes a balloon (e.g., optically-transparent balloon) that facilitates transmission of light between the catheter and tissue. Moreover, features of the present disclosure are applicable to all ranges of ablation targets (e.g., atrial fibrillation, ventricular tachycardia) and ablation techniques (e.g., cyroablation, microwave ablation). For example, in certain embodiments, FAD fluorescence is enhanced at colder temperatures like those used with cryoablation.
Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. For example, while the embodiments described above refer to particular features, the scope of this invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.
This application claims priority to Provisional Application No. 62/348,901, filed Jun. 11, 2016, which is herein incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62348901 | Jun 2016 | US |
