Method for evaluation of a tubular structure and associated devices and systems

Abstract

Methods of evaluating a tubular structure and associated systems and devices are described herein. An example endoscopic system includes an electrical module including an electrical probe configured for functional assessment of tissue of a gastrointestinal (GI) tract and an optical module including an optical probe configured for optical assessment of the tissue of the GI tract. Optionally, the endoscopic system may include a delivery module configured to deliver the electrical probe and the optical probe to the GI tract. The methods, systems, and devices are useful for acquiring measurements, including multi-modal measurements of function, physiology and structure aligned in space or time, of a tubular structure like a GI tract.

Description

METHOD FOR EVALUATION OF A TUBULAR STRUCTURE AND ASSOCIATED DEVICES AND SYSTEMSRELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 665,072, filed on June 27, 2024. The entire teachings of the above application are incorporated herein by reference.BACKGROUND

[0002] Proper function of the gastrointestinal (GI) tract may be dependent upon a number of its tissue components, which include, among others, the enteric nervous system and smooth muscles, and their coordinated physiological functions, which include, among others, neuromuscular control of motility and communication with the brain via the gut-brain axis. There is an unmet need for a minimally-invasive endoscopic device to image morphology of those tissues and monitor their function and underlying physiology in vivo. Existing standards of care with respect to morphology currently rely upon camera endoscopy for visual inspection only of an inner surface of the GI tract walls. With regards to function, available techniques today rely mostly on GI manometry, which measures pressure exerted by walls of the GI tract with limited temporal and spatial resolution and may not capture underlying coordinating mechanisms.SUMMARY

[0003] Endoscopic tools for improving understanding of the gut or other tubular structures may benefit from modalities investigating morphology, for example, using optical modalities like optical coherence tomography (OCT), and functionality with its underlying physiology, using modalities like electrophysiology. Such tools may be useful for direct analysis of gut status in various digestive disorders, as well as diagnostic or therapeutic gut stimulation, and could also be indirectly used to make inferences about the brain’s influence on the gut or stimulate a brain response via a gut-brain axis. Such tools may have potential in introducing novel diagnosis and treatment paradigms in disorders of the gut-brain interaction (DGBI), irritable bowel syndrome, inflammatory bowel disease and neurological diseases like Parkinson’s disease or Alzheimer’s disease.

[0004] More advanced optical techniques, such as optical coherence tomography (OCT), may offer imaging capabilities that allow assessment of gastrointestinal (GI) tissue morphology at higher resolution and at greater depths in the tissue than those of existing standard-of-care approaches, while electrophysiological techniques may afford high resolution information on the GI tract’s electrical activity that underlies its motor function. A device combining both modalities may provide the richest diagnostic or measurement information by allowing assessment of tissue function directly in the context of tissue morphology. Additionally, stimulating the GI tract’s electrically active tissues may offer further diagnostic modes of interrogating the tissue while monitoring its responses as well as electroceutical therapeutic possibilities.

[0005] In an example embodiment, a multi-modal endoscopic system includes an electrical module including an electrical probe configured for functional assessment of tissue of the GI tract and an optical module including an optical probe configured for optical assessment of tissue of the GI tract. The multi-modal endoscopic system optionally further includes a delivery module configured to deliver the electrical and optical probes to the GI tract. Functional assessment may include electrical assessment.

[0006] The optical probe may be configured for micro-anatomical assessment, functional or physiological assessment of the tissue of the GI tract. The optical module may be configured to acquire optical coherence tomography (OCT) measurements or to deliver energy in the form of light to the tissue, for example, for optogenetic control. The optical probe may comprise an OCT sensor. The optical probe may also be configured for modulating tissue responses through optical means, such as optogenetic activation.

[0007] The optical probe may include one or more optical fibers optically coupled to a light source or to a detector of the optical module, the one or more optical fibers configured to transmit at least one light from the light source or light reflected from the tissue. The one or more optical fibers may include a double clad fiber, wherein a first portion of the double clad fiber is configured to transmit light from a first light source and a second portion of the double clad fiber is configured to transmit light from a second light source. A given fiber of the one or more optical fibers may be optically coupled to an optical element configured to change a direction of light transmitted through the given fiber.

[0008] The optical probe may be configured to move with respect to the delivery module. The movement of the optical probe with respect to the delivery module may include at least one of translational movement along a longitudinal axis of the delivery module or rotationalmovement around the longitudinal axis. The optical module may be configured to acquire measurements while the optical probe undergoes the translational movement or the rotational movement.

[0009] The optical assessment may include at least one of a volumetric OCT scan, a radial OCT scan, a longitudinal OCT scan, an en-face OCT image, a circumferential OCT scan, or time-series OCT imaging of a single point acquisition or multipoint acquisition.

[0010] At least one of the electrical module or the optical module may be configured to deliver energy to the tissue. The electrical module may be configured for stimulation of the tissue to elicit, inhibit or alter function of the tissue and the optical module may be configured for activation of the tissue to elicit, inhibit or alter function of the tissue. The electrical module may be configured to deliver at least one of a time-varying electrical signal or a spatially-varying electrical signal. The optical module may be configured for activation of the tissue to elicit, inhibit or alter its function by activating an optogenetic sensor, for example, by delivery optical power to the tissue.

[0011] The electrical probe may include a plurality of electrodes on a carrier. The plurality of electrodes may be configured to acquire electrical measurements of tissue of the GI tract, to deliver electrical signals to the tissue, or a combination thereof. The plurality of electrodes may be configured to acquire the electrical measurements and to deliver the electrical signals at a plurality of positions of the GI tract, the plurality of positions including at least a circumferential portion of the tissue or a longitudinal portion of the tissue. A given electrical signal of the electrical signals delivered by a given electrode of the plurality of electrodes may be determined by a corresponding position of the given electrode. The carrier may include a flexible, non-conductive substrate and respective leads of the plurality of electrodes may be configured to extend through the non-conductive substrate or along a surface of the non-conductive substrate. The delivery module may be in coupled arrangement with the carrier. At least a portion of the carrier may be configured to cause the plurality of electrodes to contact the tissue. The carrier may include a plurality of members configured to project radially relative to a longitudinal axis of the carrier, the plurality of members in coupled arrangement with the electrodes and further configured to cause the plurality of electrodes to contact the tissue. The plurality of members may include a flexible substrate configured to form a plurality of repeating arches projecting radially outward relative to the longitudinal axis of the carrier. The carrier may define one or more apertures between or below the one or more arches and wherein the optical probe is configured toextend through the one or more apertures. A member of the plurality of members may be configured to be a flexible protrusion and at least one electrode of the plurality of electrodes may be positioned on the flexible protrusion. The carrier may include a flexible substrate configured to be attached to the tissue. The carrier may include at least one inflatable balloon and inflating the at least one inflatable balloon may cause the plurality of electrodes to extend radially from the longitudinal axis of the carrier. The carrier may further include a semi-rigid cage configured to surround the at least one inflatable balloon and to define one or more apertures, wherein inflating the at least one inflatable balloon causes the at least one inflatable balloon to extend through the one or more apertures. The carrier may include a sleeve, wherein the sleeve in an inverted collapsed state is configured to be contained in a channel of the carrier and wherein filling the sleeve causes the sleeve to evert beyond a distal tip of the carrier. The sleeve may be a compliant sleeve and may or may not be stretchable or inflatable. The sleeve may be a closed-end sleeve. The carrier may include one or more clips, a clip of the one or more clips in coupled arrangement with at least one electrode of the plurality of electrodes. The carrier may include an ellipsoid structure configured to adhere to the tissue of the GI tract and the electrodes may be in coupled arrangement with a surface of the ellipsoid structure.

[0012] The carrier may be configured to be removable from the delivery module. In some embodiments, the carrier may be configured to mount on an elongated device, for example, a catheter, an endoscope, or a cylindrical probe. The carrier may be configured to be transparent to light.

[0013] At least a portion of the delivery module may be configured to be substantially transparent to light. For example, the delivery module may include a transparent glass or polymer material.

[0014] The delivery module may include a hollow channel, and the optical module may be configured to pass through the hollow channel. The optical module may acquire optical measurements through the delivery module.

[0015] The multi-modal endoscopic system may include a processing module communicatively coupled to the electrical module and the optical module, the processing module configured to acquire electrical measurements of the tissue using the electrical module and to acquire optical measurements of the tissue using the optical module. The processing module may be further configured to cause at least one of an electrical stimulation to elicit, inhibit or alter function of the tissue and an optical activation to elicit, inhibit or alterthe function of the tissue in response to at least one of the electrical measurements and the optical measurements acquired. The processing module may be still further configured to coregister the electrical measurements and the optical measurements using features of the electrical measurements or the optical measurements.

[0016] In another example embodiment, a multi-modal endoscopic device includes a plurality of electrodes on a carrier, the plurality of electrodes configured to record electrical activity of tissue of an intestinal wall. The multi-modal endoscopic device further includes an optical fiber configured to deliver light into the tissue and to collect light reflected from the tissue. Optionally, the multi-modal endoscopic device may further include a conduit configured to enclose the optical fiber, the conduit further configured to deliver and to deploy the electrode carrier.

[0017] The plurality of electrodes may be configured to deliver an electrical stimulus to the tissue. The plurality of electrodes is configured to acquire the electrical measurements and to deliver the electrical signals at a plurality of positions on the tissue of the GI tract, the plurality of positions including at least a circumferential portion of the tissue and a longitudinal portion of the tissue. The plurality of positions may also include at least one of a circumferential portion of the tissue or a longitudinal portion of the tissue.

[0018] The carrier may include a flexible, non-conductive substrate and respective leads of the plurality of electrodes may be configured to extend through the non-conductive substrate or along a surface of the non-conductive substrate.

[0019] At least a portion of the carrier may be configured to cause the plurality of electrodes to contact the tissue. The carrier may include a plurality of members configured to project radially relative to a longitudinal axis of the carrier, the plurality of members in coupled arrangement with the electrodes and further configured to cause the plurality of electrodes to contact the tissue. The plurality of members may include a flexible substrate configured to form a plurality of repeating arches projecting radially outward relative to the longitudinal axis of the carrier. The carrier may be configured to define one or more apertures between or below the one or more arches and the optical probe may be configured to extend through the one or more apertures. A member of the plurality of members may be configured to be a flexible protrusion and at least one electrode of the plurality of electrodes may be positioned on the flexible protrusion. The carrier may include at least one inflatable balloon and inflating the at least one inflatable balloon may cause the plurality of electrodes to extend radially from the longitudinal axis of the carrier. The carrier further may include a semi-rigidcage configured to surround the at least one inflatable balloon and to define one or more apertures, wherein inflating the at least one inflatable balloon causes the at least one inflatable balloon to extend through the one or more apertures. The carrier may include at least one sleeve, wherein the at least one sleeve in an inverted collapsed state is configured to be contained in a channel of the carrier and wherein filling the at least one sleeve causes the sleeve to evert beyond a distal tip of the carrier. The at least one sleeve may be a compliant sleeve and may or may not be stretchable or inflatable. The at least one sleeve may be a closed-end sleeve. The carrier may include one or more clips, a clip of the one or more clips in coupled arrangement with at least one electrode of the plurality of electrodes. The carrier may include an ellipsoid structure configured to adhere to the tissue of the GI tract and the electrodes may be in coupled arrangement with a surface of the ellipsoid structure.

[0020] The multi-modal endoscopic device may be configured for imaging tissue structures in the intestinal wall using optical coherence tomography or another optical modality with endogenous and / or exogenous contrast to achieve penetration depth of at least 2 mm, spatial resolution of less than 100 microns, and axial resolution of less than 10 microns for analysis of morphology of the tissue structures.

[0021] The optical fiber may be a double-clad optical fiber, a first portion of the double clad fiber configured to transmit light from a first light source and a second portion of the double clad fiber configured to transmit light from a second light source.

[0022] The optical fiber may be a first optical fiber and the multi-modal endoscopic device includes at least one additional optical fiber configured to deliver light into the tissue or to collect light reflected from the tissue.

[0023] A given fiber of the one or more optical fibers may be optically coupled to an optical element, the optical element configured to change a direction of light transmitted through the given fiber.

[0024] The optical fiber may be configured to move with respect to the conduit. Movement of the optical fiber with respect to the conduit may include at least one of translational movement or rotational movement.

[0025] At least a portion of the conduit may be configured to be substantially transparent to light. The conduit may be constructed at least in part using a transparent polymer or glass material.

[0026] In another example embodiment, a method for multi-modal evaluation of a tubular structure includes inserting a measurement device into a lumen of the tubular structure andacquiring a first measurement of the tubular structure along a first length of the measurement device using a first measurement modality, the first measurement including data representative of electrical activity of the tubular structure. The method further includes acquiring a second measurement of the tubular structure along a second length of the measurement device using a second measurement modality, the second measurement occurring with the first measurement. The method further includes co-registering the first measurement and the second measurement to generate multi-modal measurement data and analyzing the multi-modal measurement data generated to characterize one or more properties of the tubular structure. In some embodiments, the second measurement occurs consecutively or simultaneously with the first measurement.

[0027] The one or more properties characterized may include structural integrity, architecture, patency, responsivity, or function of the tubular structure. Co-registering the first measurement and the second measurement includes aligning the first measurement and the second measurement temporally, spatially, or spectrally. The first measurement and the second measurement may be co-registered using features of the first measurement and the second measurement or using parameters of acquisition of the first measurement and the second measurement.

[0028] The multi-modal measurement data may include, for the first measurement, identifying and characterizing spike patterns of the electrical activity, further wherein characterizing the spike patterns includes determining spike morphology, intensity, rhythmicity or spatiotemporal synchronicity of spiking activity.

[0029] The method may further include introducing a stimulus to the tubular structure, the stimulus being temporally correlated with the first measurement or the second measurement. Analyzing the multi-modal measurement data may include characterizing a response of the tubular structure to the stimulus introduced. The stimulus introduced may include an optical stimulus, an electrical stimulus, a magnetic stimulus, a mechanical stimulus, an acoustic stimulus, or a chemical stimulus. The stimulus may be delivered after the first measurement and the second measurement, the method further including determining a type of the stimulus based on the first measurement or the second measurement. The method may further include acquiring additional measurements of the tubular structure after delivering the stimulus and delivering a subsequent stimulus based on the additional measurements acquired.

[0030] The method may further include co-registering the multi-modal measurement data with data acquired from an additional measurement modality. The additional measurement modality may include magnetic resonance imaging. The method may further include acquiring at least one additional measurement using the first measurement modality or the second measurement modality.

[0031] The second measurement may include data representative of a functional parameter or an architecture of the tubular structure.

[0032] The second measurement may be acquired using an optical, acoustic, mechanical, opto-acoustic, electrical, or magnetic measurement modality.

[0033] Aligning the first measurement acquired and the second measurement acquired may include aligning within the measurement device a first instrument configured to acquire the first measurement and a second instrument configured to acquire the second measurement.

[0034] Aligning the first measurement acquired and the second measurement acquired may occur after acquiring the first measurement and acquiring the second measurement.

[0035] Analyzing the multi-modal measurement data may include applying a correction for one of the first measurement or the second measurement based on the other of the first measurement or the second measurement.

[0036] The first measurement and the second measurement may overlap at least in part in space or in time.

[0037] The tubular structure may be tissue of a GI tract. The measurement device may be an endoscopic device, the endoscopic device including an electrical module for acquiring the first measurement, the electrical module comprising an electrical probe configured for functional assessment and stimulation of the tissue to elicit, inhibit, or alter function of the GI tract, and an optical module for acquiring the second measurement, the optical module comprising an optical probe configured for micro-anatomical, functional assessment and activation of the tissue to elicit, inhibit or alter the function of the GI tract. The optical probe may include an optical coherence tomography (OCT) sensor and the electrical probe may include a plurality of electrodes on a carrier.

[0038] The multi-modal endoscopic system or device may include a sensor in coupled arrangement with the carrier. The sensor may be configured to acquire data representative of at least one of a position, motion, or orientation of the carrier.

[0039] In another example embodiment, a device for measuring properties of a gastrointestinal tract of a human or animal includes a plurality of electrodes configured to acquire electrical measurements of a tissue of the gastrointestinal tract and a carrier including one or more protruding flexible members configured to extend with respect to a longitudinal axis of the carrier. An electrode of the plurality of electrodes is in coupled arrangement with a member of the one or more protruding flexible members and the one or more protruding flexible members are further configured to cause the electrode to contact the tissue.

[0040] In another example embodiment, a device for measuring properties of a GI tract of a human or animal includes a plurality of electrodes configured to acquire electrical measurements of a tissue of the GI tract and one or more carriers. A carrier of the one or more carriers includes a substrate in coupled arrangement with at least one electrode of the one or more electrodes, the substrate or the at least one electrode configured to attach the electrode to a surface of the tissue.

[0041] In another example embodiment, a device for measuring properties of a GI tract of a human or animal includes a plurality of electrodes configured to acquire electrical measurements of a tissue of the GI tract using a carrier including one or more inflatable balloons in coupled arrangement with the plurality of electrodes. The one or more inflatable balloons are configured to expand radially from a longitudinal axis of the carrier and the one or more inflatable balloons expanding cause the plurality of electrodes to contact the tissue of the GI tract of the human or animal.

[0042] In another example embodiment, a device for measuring properties of a gastrointestinal tract of a human or animal includes a plurality of electrodes configured to acquire electrical measurements of a tissue of the GI tract and a carrier. The carrier includes an ellipsoid structure in coupled arrangement with the plurality of electrodes, the plurality of electrodes disposed on a surface of the ellipsoid structure.

[0043] The devices may include an optical module configured to acquire optical measurements of the tissue of the GI tract, the optical module including an optical fiber configured to transmit light to the tissue or to transmit light collected from the tissue.

[0044] The devices may include a sensor in coupled arrangement with the carrier. The sensor may be configured to acquire data representative of at least one of a position, motion, or orientation of the carrier and / or the device.

[0045] The device may be configured to be delivered to the gastrointestinal tract via an endoscopic procedure and at least the electrodes and the carrier may be configured to residein the gastrointestinal tract for a period of time beyond a duration of the endoscopic procedure. The electrodes may be communicatively coupled to a monitoring device positioned external to the human or the animal.

[0046] The carrier may be configured to be moved along a length of the GI tract by natural processes of the GI tract.BRIEF DESCRIPTION OF THE DRAWINGS

[0047] The foregoing will be apparent from the following more particular description of example embodiments, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments.

[0048] FIG. 1 A illustrates schematically an example embodiment of a multi-modal endoscopic system configured for acquiring electrical and optical signals in an anatomical lumen.

[0049] FIG. IB illustrates schematically an example embodiment of a multi-modal endoscopic system configured for acquiring electrical and optical signals and for delivering electrical and optical energy in an anatomical lumen.

[0050] FIG. 2A illustrates an exploded view of an example embodiment of a multi-modal endoscopic device configured for acquiring or delivering electrical and optical signals in an anatomical lumen of a small animal.

[0051] FIG. 2B illustrates an example system that includes the multi-modal endoscopic device of FIG. 2 A.

[0052] FIG. 2C is a detailed view of a high-density matrix of the electrode array of the device of FIG. 2 A.

[0053] FIG. 2D illustrates an example embodiment of an optical probe with a delivery mechanism compatible with the multimodal endoscopic device of FIG. 2A.

[0054] FIG. 2E illustrates an example embodiment of an optical probe compatible with the multimodal endoscope of FIG. 2 A.

[0055] FIG. 3 illustrates a time trace plot of electrical signals measured by an electrode positioned in a mouse colon, according to an example embodiment. An inset shows a transient spike (action potential) in the electrical signal.

[0056] FIG. 4 illustrates average actional potential (spike) recorded in a mouse colon with a device, demonstrating high spatial resolution, i.e., an ability to record signals of localorigin, as demonstrated by the average spike’s steep amplitude attenuation with distance, according to an example embodiment.

[0057] FIG. 5A illustrates spatiotemporal patterns of spikes in electrophysiological activity detected in mouse colon, the spatiotemporal patterns including ~10 s-long bursts of spiking approximately 2 times per minute, according to an example embodiment. An arrow indicates a zoomed-in view of the dark grey box showing intraburst patterns of activity, composed of periodic (~1 per second) burstlets frequently forming propagating anterograde waves.

[0058] FIG. 5B illustrates spatiotemporal patterns in root-mean-squared (RMS) envelopes spiking activity detected in the electrophysiological activity, according to an example embodiment.

[0059] FIG. 5C illustrates Fourier spectral analysis of RMS envelopes of electrophysiological spiking activity (calculated with a 100 ms window) of 30 minutes of signals, according to an example embodiment.

[0060] FIG. 6 illustrates measurements of electrophysiological activity, the measurements including responses to pharmacological intervention with a cholinesterase inhibitor (Donepezil) and a cholinergic antagonist (atropine), according to an example embodiment.

[0061] FIGS. 7A-7D illustrate similarity of spatiotemporal patterns of electrophysiological measurements from each quadrant of a probe, each quadrant of an endoscope including 32-channels, according to an example embodiment.

[0062] FIG. 7E illustrates cross-channel correlation RMS envelopes of the electrophysiological measurements of the quadrants of FIGS. 7A-7D, demonstrating similarity of spatiotemporal patterns of electrophysiological around, but not along, the endoscope.

[0063] FIG. 8A illustrates schematically an example OCT probe 812 with an endoscope 818, the OCT probe 812 configured for radial scans, according to an example embodiment. An inset shows an example single OCT measurement that creates a radial scan for OCT imaging.

[0064] FIG. 8B illustrates a radial OCT B-scan of a mouse colon with visible anatomical layers, the radial B-scan being compared with ex-vivo histology and light-sheet imaging of a mouse gut, according to an example embodiment.

[0065] FIG. 9A illustrates a representation of volumetric scanning by translating consecutive radial B-scans longitudinally (L) using an OCT probe, according to an example embodiment.

[0066] FIG. 9B illustrates OCT volumetric data obtained in a wild-type mouse by rotation and translation of an optical probe, according to an example embodiment.

[0067] FIG. 9C illustrates OCT volumetric data processed by virtually reslicing data in different orthogonal planes, according to an example embodiment.

[0068] FIG. 9D illustrates a longitudinal reslice of volumetric OCT data flattened to myenteric plexus for en-face reconstruction, according to an example embodiment.

[0069] FIG. 9E illustrates an en-face reslice of volumetric OCT data for analysis of thin layers of a gut, for example, an enteric nervous system, according to an example embodiment.

[0070] FIG. 10A illustrates radial motility OCT data obtained at a given longitudinal position in a distal colon of a mouse over a period of time, the radial motility OCT data including en-face radial imaging and axial time-series data, according to an example embodiment.

[0071] FIG. 10B illustrates a plot of tissue motility over time for a point extracted from the OCT axial time-series data in FIG. 10 A.

[0072] FIG. 10C illustrates variability of motility patterns at different OCT en-face reslice depths, with high uniformity of patterns in a circumferential direction, according to an example embodiment.

[0073] FIG. 10D illustrates in a line plot of extracted tissue layer thickness changes as a function of motility over time at locations between mucosa to submucosa and between mucosa to serosa in one radial location and the cross-graph.

[0074] FIGS. 11 A-l IE illustrate OCT axial time-reslices of radial data obtained over 2 minutes, the axial-time reslices showing various motility patterns in different sections of a gut including wild-type distal colons (FIGS. 11 A and 1 IB), a lesioned distal colon (FIG. 11C), a wild-type transitional region between a colon and a rectum (FIG. 1 ID), and a wild-type rectum (FIG. 1 IE).

[0075] FIG. 12 illustrates 1 -dimensional (ID) OCT data recorded without external actuation, wherein tissue motility is a source for changes in detected OCT signals when imaging a gut of wild-type mice, according to an example embodiment.

[0076] FIG. 13 illustrates an overlay of three different OCT longitudinal scanning speeds on 5 minutes of raw spiking activity electrophysiology data from 128 channels spanning 24.8 mm of mouse colon, showing a variety of underlying electrophysiological activity that may be captured by varying OCT longitudinal scanning speeds and showing that a very slow translation of an optical probe may capture both morphology and motility, according to an example embodiment.

[0077] FIG. 14A illustrates a cross-sectional B-scan (left) and orthogonal views (right) of volumetric OCT data obtained at 0.9mm / s longitudinal scanning speed with minimal motion in a colon of a mouse, according to an example embodiment.

[0078] FIG. 14B illustrates a cross-sectional B-scan (left) and orthogonal views (right) s of volumetric OCT data obtained in the mouse of FIG. 14A along the colon at O.lmm / s longitudinal scanning speed, the longitudinal scanning speed acquiring morphology and motility, according to an example embodiment.

[0079] FIG. 14C illustrates an overlay of three different OCT longitudinal scanning speeds on 5 minutes of raw spiking activity electrophysiology data from 128 channels spanning 24.8 mm of mouse colon, wherein an OCT scan is triggered to start after an end of an electrophysiology burst recorded with electrodes to optimize the capture of morphology and motility with the OCT modality, according to an example embodiment.

[0080] FIG. 14D illustrates schematically a multi -velocity volumetric OCT scan with a longitudinal morphological scan interwoven in an OCT radial motility scan with velocity changes driven by physiology of a gut, according to an example embodiment.

[0081] FIG. 15A illustrates an unwrapped circumferential OCT scan continuously recorded in a location and an en-face series of OCT data, according to an example embodiment. An artifact is induced to facilitate co-regi strati on of OCT and electrophysiology (Ephys) recordings.

[0082] FIG. 15B illustrates an OCT time series (top) extracted from an OCT circumferential time series recorded at a position inside of a gut, according to an example embodiment. Corresponding electrophysiology data recorded simultaneously with 128 electrodes is also illustrated in a bottom panel.

[0083] FIG. 16A illustrates an en-face OCT reslice in a mucosa layer of a gut, the en-face reslice showing an effect of electrophysiological paths on an outer sheath of an endoscope on the en-face OCT reslice, according to an example embodiment. Dark areas (black shadows) indicate a full pattern of electrodes and paths, and tissue is not visible in the dark areas.

[0084] FIG. 16B illustrates a longitudinal reslice of OCT data, which may be similar to the OCT data used to generate the en-face OCT reslice of FIG. 16 A, showing the full pattern of electrodes and paths including thin dark lines from paths and thicker lines from electrodes, according to an example embodiment.

[0085] FIG. 16C illustrates OCT images showing an impact of partial blocking of light transmission to tissue due to an electrical array on an outer sheath of a mini endoscope, according to an example embodiment.

[0086] FIGS. 17A and 17B illustrate raw electrophysiological measurements (FIG. 17 A) and aggregate RMS envelopes from aboral channels together with their spectra (FIG. 17B) of a healthy gut and a gut including lesions in a gut wall induced by benzalkonium chloride and show changes in electrophysiology caused by the lesions in the gut wall, according to an example embodiment.

[0087] FIGS. 17C and 17D illustrate Fourier spectral analysis of RMS envelopes frequency maps of complex electrophysiology patterns recorded across channels (vertical axis) in healthy (FIG. 17C) and benzalkonium chloride-lesioned animals (FIG. 17D) , according to an example embodiment. Loss of spiking frequencies as well as frequency specificity is observed in benzalkonium chloride-lesioned animals compared to healthy controls.

[0088] FIGS. 17E and 17F illustrate longitudinal reslices of volumetric OCT data from a healthy colon (FIG. 17E) and a benzalkonium chloride-lesioned distal colon (FIG. 17F) , according to an example embodiment. Sawtooth patterns may represent tissue motility, which may be visibly disturbed in the lesioned distal colon.

[0089] FIG. 18A illustrates an example embodiment of bipolar stimulation with 0.5ms biphasic pulses at 10Hz with an amplitude of 300mA between the most distal eight most distal contacts and a next eight contacts on one quadrant of an endoscope.

[0090] FIG. 18B illustrates electrophysiological measurements showing an exemplary stimulus which may be used to generate bursts of activity in a gut of a wild-type mouse, according to an example embodiment.

[0091] FIG. 18C illustrates an electrophysiology recording acquired in a wild-type mouse in a colon silenced by isoflurane anesthesia acquired over a time period including two stimulations with incorrect parameters in a colon silenced by isoflurane anesthesia, according to an example embodiment.

[0092] FIG. 18D illustrates an electrophysiological recording acquired in a wild-type mouse under isoflurane anesthesia, with a silenced gut generating bursts of activity following correctly parametrized electrical stimulation, according to an example embodiment.

[0093] FIG. 19A illustrates time series data of aggregate RMS envelopes of electrophysiological signals, the electrophysiological signals including baseline measurements with sparse, irregular stimulation, followed by 10 minutes of repeated bipolar stimulation at a rate of 3 cycles per minute, and followed again by baseline measurements with sparse, irregular stimulation, according to an example embodiment.

[0094] FIG. 19B illustrates a zoomed in section of the time series data of aggregate RMS envelopes of FIG. 19 A.

[0095] FIG. 19C illustrates a running spectrogram of the time series data of aggregate RMS envelope of FIG. 19 A.

[0096] FIG. 19D illustrates a shift of frequency of electrophysiology spike burst recorded before, during and after the 10 minutes of the 3-cycle-per-minute stimulation in wild-type mice.

[0097] FIG. 20A illustrates a raw electrophysiology recording in a gut of a mouse, the electrophysiological recording including a spontaneous burst followed by a stimulus and an evoked burst of increased intensity, according to an example embodiment.

[0098] FIG. 20B illustrates aggregate RMS values showing peak amplitudes of stimulation-evoked bursts in comparison to spontaneous bursts before stimulation and interburst background activity as a function of refractory period (time since last burst) before the stimulation, demonstrating that the efficacy of the stimulation depends on real-time background activity of the tissue, according to an example embodiment.

[0099] FIGS. 21A-21D illustrate exemplary stimulation modes of operation for a device configured to stimulate and to acquire measurements of a GI system, the stimulation modes including stimulation with set parameters (FIG. 21 A), stimulation with parameters optimized based on a baseline measurement of an individual human or animal (FIG. 2 IB), stimulation with closed-loop operation for real-time feedback (FIG. 21C), or stimulation with long-term correction (FIG. 2 ID), according to an example embodiment.

[0100] FIGS. 22A-22G illustrate example configurations for light delivery various light delivery configurations and optogenetic sensors for optogenetic activation of the tissue to elicit, inhibit or alter its function, according to example embodiments.

[0101] FIGS. 23A-F illustrate example micro-optics configured for delivery of light to tissue that may be used by example embodiments of devices and systems.

[0102] FIG. 24A illustrates example embodiments of configurations for circumferential contact with a tissue using an endoscopic device, including continuous circumferential contact, local circumferential contact, and multi-local circumferential contact configurations.

[0103] FIG. 24B illustrates example embodiments of configurations for longitudinal contact with a tissue using an endoscopic device, the configurations including continuous longitudinal contact, local longitudinal contact.

[0104] FIGS. 25A-25D illustrate example embodiments of configurations for inserting a measurement device into a luminal organ with or without an endoscope.

[0105] FIGS. 26A-26D illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as rows of radially protruding arches.

[0106] FIGS. 27A-27D illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as rows of radially protruding arches including longitudinal lumens for the optical probe.

[0107] FIGS. 28A-28D illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as one row of radially protruding arches.

[0108] FIGS. 29A-29G illustrate example embodiments of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as rows of radially protruding arches in coupled arrangement with apertures for a retractable optical probe.

[0109] FIGS. 30A-30G illustrate example embodiments of a carrier in coupled arrangement with electrodes, the carrier configured for direct attachment of the electrodes to a surface of a tissue.

[0110] FIGS. 31 A and 3 IB illustrate an example embodiment of a carrier including an electrode, the carrier configured to attach the electrode to a surface of a tissue through surface adhesion.

[0111] FIGS. 32A-32C illustrate example embodiments of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as compliant, flexible radial protrusions.

[0112] FIG. 32D illustrates an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a plurality of carriers with members configured as compliant, flexible radial protrusions.

[0113] FIGS. 33A-33C illustrate example embodiments of an endoscopic device including an endoscope in coupled arrangement with a carrier with radially protruding members configured as paddles.

[0114] FIG. 33D illustrates an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a plurality of carriers with radially protruding members configured as paddles.

[0115] FIGS. 34A-35C illustrate example embodiments of a carrier including an electrode configured as a clip.

[0116] FIGS. 36A-36D illustrate an example embodiment of an endoscopic device including an endoscope and a carrier, the carrier including an inflatable balloon.

[0117] FIGS. 37A-37C illustrate an example embodiment of a device including a carrier, the carrier including a compliant closed-end sleeve.

[0118] FIGS. 38A-38D illustrate an example carrier that may be used by an embodiment of an endoscopic device, the carrier including a sleeve configured to be deployed.

[0119] FIG. 39 illustrates an example carrier that may be used by an embodiment of an endoscopic system, the carrier having an ellipsoid and electrodes in coupled arrangement with the ellipsoid.

[0120] FIGS. 40 A and 40B illustrate an example carrier that may be used by an embodiment of an endoscopic device, the carrier including a balloon and electrodes in coupled arrangement with the balloon.

[0121] FIG. 41 illustrates an example embodiment of a method for processing electrophysiology data.DETAILED DESCRIPTION

[0122] A description of example embodiments follows.

[0123] As disclosed herein, example embodiments of the present invention relates to systems and methods for the endoscopic evaluation of gastrointestinal (GI) tissues, with particular focus on both structural and functional assessment in vivo. The physiological function of the GI tract relies on multiple coordinated subsystems, including but not limited to the enteric nervous system (ENS) and smooth muscle layers. These tissue components playcritical roles in neuromuscular control of GI motility and in maintaining bidirectional communication with the central nervous system via the gut-brain axis.

[0124] Currently available diagnostic tools for GI disorders may lack the ability to comprehensively and simultaneously or consecutively assess both tissue morphology and functional physiology. Morphological analysis is typically performed via standard camerabased endoscopy, which may provide only surface-level visualization and lacks the capacity to resolve subsurface architectural features. Functional assessment, such as that conducted by GI manometry, measures intraluminal pressure to infer motility but may be constrained by limited spatial and temporal resolution and do not directly access the underlying electrophysiological mechanisms.

[0125] Accordingly, there is an unmet need for a minimally invasive endoscopic platform capable of integrated assessment of GI tissue structure and function. Example embodiments of the invention disclosed herein may address this need by combining high-resolution optical imaging — such as optical coherence tomography (OCT) — with electrophysiological sensing to monitor bioelectrical activity associated with motor function.

[0126] Furthermore, mechanical deployment of OCT imaging components within the dynamic and anatomically complex GI environment may present an additional technical hurdle. To address this, example embodiments of the present invention may incorporate innovative mechanical designs — such as flexible tethered capsules, articulated catheters, or deployable scanning modules — engineered to maintain consistent tissue contact and precise imaging alignment, even during peristaltic motion or complex curvature of the GI tract. In parallel, the acquisition of high-fidelity electrophysiological signals from within the gut lumen may also be mechanically challenging. Ensuring stable and reproducible contact between recording electrodes and the highly mobile, mucus-covered intestinal lining is critical for signal integrity. Example embodiments of the invention described herein may address this challenge through novel electrode designs and adaptive deployment mechanisms that conform to intestinal contours, reduce motion artifacts, and enhance coupling with electrically active tissue layers. Such solutions may include expandable electrode arrays, anchoring modules, or biocompatible adhesion interfaces optimized for endoluminal environments.

[0127] By enabling complementary acquisition and analysis of structural, functional, and neurophysiological data, example embodiments of the present invention may provide a comprehensive diagnostic tool for evaluating GI health and pathology, includingneurogastroenterology disorders. The ability to apply targeted optogenetic and / or electrical stimulation to GI tissues may further open the potential for electroceutical therapies and the exploration of gut-brain interactions through induced neural responses. Such a platform is anticipated to support novel diagnostic and therapeutic strategies for conditions including, but not limited to, inflammatory bowel disease (IBD), Parkinson’s disease, Alzheimer’s disease, and disorders of gut-brain interaction (DGBI).Understanding gastrointestinal function with electrophysiology recording

[0128] While gold-standard methods for measuring neuronal activity — for example, electrode-based recordings — are effective in organs such as the brain and heart, such methods may be impractical for enteric neurons due to inaccessibility or poor accessibility, tissue motion, and signal interference from surrounding muscle. As a compromise, endoscopic recordings of smooth muscle action potentials from the inner surface of body lumens may serve as an indirect measure of enteric nervous system (ENS) activity, since this myographic activity may largely be ENS-driven and its abnormalities may reflect ENS dysfunction.Understanding gastrointestinal function by modulating the nervous system with optogenetics

[0129] Optogenetics may enable precise control of neuronal activity using light-sensitive opsins introduced via genetic or viral methods. These opsins can activate or inhibit neurons (e.g., ChR2) or allow activity recording through calcium or voltage indicators. The technique may offer millisecond-level temporal resolution and single-cell spatial precision, achieved through targeted opsin expression or focused light delivery. Visible light is typically delivered via optical fibers with micro-optics, allowing stimulation in live, freely moving animals. In addition to brain applications, optogenetic tools are increasingly used in the gastrointestinal tract to study and modulate enteric nervous system (ENS) function, offering a minimally invasive approach to probe gut-brain interactions and GI motility. However, these methods so far may rely on invasive techniques such as surgical interventions of intravital windows to gain access to the GI tract, thus significantly disrupting systemic physiology under study.

[0130] Fiber-optic optogenetics may also be coupled with functional Magnetic Resonance Imaging (fMRI), an established method for brain imaging.Imaging gastrointestinal morphology intraluminally with optical coherence tomography

[0131] Optical Coherence Tomography (OCT), including angiographic OCT, is a highspeed, 3D imaging technique that visualizes tissue microstructure and blood flow using lightscattering and interferometry. By analyzing echo time delays and applying Fourier transforms, OCT generates depth-resolved images (A-lines) sensitive to structural and motion-related changes. It has been used to monitor optogenetic stimulation in the brain and heart of animal models, and to assess vascular and functional responses such as oxygenation. In addition, OCT has advanced imaging of the human digestive systems, including diagnosing Barrett’s esophagus. OCT catheters may be introduced into the GI tract via an endoscope’s working channel. An alternative may include capsule OCT endomicroscopy, which may benefit from peristalsis-driven motion and consistent tissue contact, enabling high-quality imaging. Capsules typically use a 1300 nm wavelength, offering 10 pm axial and 30 pm transverse resolution — sufficient to visualize the esophageal wall up to the adventitia and observe functions like gland emptying. In contrast, OCT catheters using an 800 nm wavelength may provide higher resolution (1.7 pm axial, 6 pm transverse) while maintaining good penetration, particularly in small animal models like the mouse colon.

[0132] Imaging the enteric nervous system (ENS) may be challenging due to microscopic structures of the ENS being located hundreds of microns deep and organization of the ENS as a thin, ganglionated network embedded between two muscle layers. Standard OCT, which acquires radial cross-sections with limited longitudinal sampling, may be poorly suited for reconstructing such complex and sparse architecture. As a result, most current knowledge of the ENS comes from ex vivo studies using cultured cells, animal models, or human biopsies. However, recent advances include in vivo imaging of the ENS using needle-based confocal endomicroscopy, where a needle is inserted into the gut wall to access deeper structures.

[0133] Examples embodiments of the invention as described herein may overcome such limitations through customized OCT imaging trajectories and resolution settings optimized for reconstructing ENS microstructures in longitudinal and circumferential scans. The resulting data may be correlated with electrophysiological signals or evoked responses following optogenetic or electrical stimulation, thereby facilitating functional characterization of enteric neuronal circuits. When enhanced with angiographic or functional OCT capabilities, the system may detect vascular and dynamic tissue changes linked to neuronal activity and vasomotor responses.

[0134] Systems and methods are described herein for evaluating morphology, vasculature, physiology, and function of a digestive system, including complementary analysis of one or more of the aforementioned characteristics. Such systems and methods may be useful for assessing status of gut physiology and function, solve open questions aboutgut-brain axis implication in disease, and help in finding new ways of diagnosing and treating disorders of the gut, disorders of the gut-brain interaction (DGBI), obesity, and neurodegenerative diseases, for example, Parkinson’s disease.Miniature multi-modal endoscope

[0135] FIG. 1 A illustrates schematically an example embodiment of a multi-modal endoscopic system 100a configured for acquiring electrical and optical signals in an anatomical lumen 102. The multi-modal endoscopic system 100a comprises an electrical module 104a including an electrical probe, for example, electrodes 108a, configured for functional assessment of tissue, which may include signal collection of an electrical recording 110a using the electrodes 108a, of the anatomical lumen 102, e.g., a gastrointestinal (GI) tract. The multi-modal endoscopic system 100a further comprises an optical module 106a including an optical probe, e.g., micro optics 112a, configured for optical assessment, which may include signal collection of an optical recording 114a using the optical probe, of the tissue of the GI tract. The multi-modal endoscopic system 100a further comprises a delivery module configured to deliver the electrical probe and the optical probe to the GI tract. The delivery module is not illustrated in FIG. 1 A but is described herein at least with reference to FIGS. 1C, IF, and 1G.

[0136] In some embodiments, the multi-modal endoscopic system 100a may further comprise a processing module 192a communicatively coupled to the electrical module 104a and the optical module 106a. The processing module 192a may be configured to acquire the electrical recordings 110a or measurements using the electrical module 104a and to acquire the optical recordings 114a or measurements using the optical module 106a. The processing module 192a may be further configured for control and synchronization of acquiring signals with the electrical module 104a and the optical module 106a.

[0137] FIG. IB illustrates schematically an example embodiment of a multi-modal endoscopic system 100b configured for acquiring electrical and optical signals and for delivering electrical and optical energy in an anatomical lumen 102. The multi-modal endoscopic system 100b may be similar to the multi-modal endoscopic system 100a described herein with reference to FIG. 1 A. The multi-modal endoscopic system 100b comprises an electrical module 104b configured for electrical recording and stimulation 110b using an electrical probe, which may include an electrode array 108b. The multi-modal endoscopic system 100b further comprises an optical probe configured for optical recording114b and optical stimulation 116b using an optical probe, which may include micro optics 112b. The electrical module 104b and the optical module 106b may be communicatively coupled to a processing module 192b, the processing module 192b configured to perform the electrical recordings and stimulation 110b, to acquire the optical recordings 114b, to perform the optical stimulation 116b, and to control the electrical module 104b and the optical module 106.Mechanisms for delivery or deployment

[0138] According to some example embodiments, delivery mechanisms may be used to overcome challenges of deployment of an endoscopic system to animals or humans based on a respective colon morphology. Two example embodiment categories may include (i) devices that are deployed within the body lumen for a duration of standard of care acute endoscopic assessments and (ii) devices that are deployed within the body lumen for sub-chronic durations to capture activity over extended numbers of hours / days.

[0139] FIG. 24A illustrates example embodiments of configurations for circumferential contact with a tissue 2402a using an endoscopic device, the configurations including continuous circumferential contact 2460a- 1, local circumferential contact 2460a-2, or multisite local circumferential contact, e.g., 2460a-3. Tissue contact may occur around a full circumference, at one local point of contact in the circumference or at multiple local points of contact around the circumference.

[0140] FIG. 24B illustrates example embodiments of configurations for longitudinal contact with a tissue 2460b using an endoscopic device, the configurations including continuous longitudinal contact 2460b- 1 and local longitudinal contact, e.g., 2460b-2. In addition, longitudinal contact may be continuous or at multiple local points of contact along the length of the tissue.

[0141] Deployment categories may further be subdivided into methods of insertion.

[0142] FIGS. 25A-25D illustrate example embodiments of configurations for inserting a measurement device into a luminal organ with or without an endoscope. As illustrated, methods of insertion may include, for example, (a) an endoscope accessory 2562a inserted into a lumen 2502 using an endoscope 2518a (the endoscope 2518a may serve as a delivery module) with a main body of the endoscope accessory 2562a mounted over or along a length of the endoscope 2518a (FIG. 25 A), (b) a delivery module 2519a with an endoscope accessory 2562b inserted into a lumen 2502 through a working channel of an endoscope2518b (FIG. 25B), (c) a delivery module 2519b with a flexible endoscope accessory 2562c inserted into a lumen 2502 using an over-sleeve, which may allow for full autonomy of a working channel of an endoscope 2518c (FIG. 25C), and (d) a self-navigated and deployed delivery module 2519c with a device 2562d configured for insertion into a lumen 2502 (FIG. 25D). The endoscope accessories 2562a, 2562b, 2562c or the device 2562d may be a carrier as described herein at least with reference to FIGS. 26A-37E.

[0143] FIGS. 26A-40B generally illustrate example embodiments of an intraluminal measurement device configured to cause electrodes to come into contact with tissue of a lumen, for example, a gastrointestinal tract.

[0144] FIGS. 26A-26D illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as rows of radially protruding arches.

[0145] FIG. 26A illustrates an isometric diagram of an example embodiment of an endoscopic device 2600 including an endoscope 2618 for example, a colonoscope, in coupled arrangement with a carrier 2664 with members configured as radially protruding members configured as arches, e.g., 2666. In some embodiments, the carrier 2664 may be a collapsible and expandable accessory for existing endoscopic devices and may be configured to be slidably mounted or unmounted from the endoscope 2618. In other embodiments, the carrier 2664 may be fixedly mounted on the endoscope 2618. The carrier 2664 may include an anchoring feature 2668 configured to affix the carrier 2664 with respect to the endoscope 2618. The carrier 2664 may be a flexible tube sleeve over an endoscope and may include a plurality of members configured to form arches, e.g., 2666, the arches, e.g., 2666, protruding radially with respect to a longitudinal axis 2646 of the carrier 2664. The arches, e.g., 2666, may comprise a flexible substrate and may be configured to be deformable. The arches, e.g., 2666, may be arranged longitudinally, circumferentially, or a combination thereof and may vary in size, number, length, or shape to optimize contact with tissue. Each arch of the arches, e.g., 2666, may include one or more electrodes, e.g., 2608, configured to acquire electrophysiological signals. In some embodiments, the endoscope 2618 may be configured to define at least one additional lumen, e.g., 2670, positioned in a center or outer section of the endoscope 2618. The at least one additional lumen, e.g., 2670, may be useful for guiding other devices, for example, optical probes or other endoscopic tools. The carrier 2664 may further include a connector 2680 to an acquisition system, which may be configured to carry electrical leads coupled to the electrodes to the acquisition system.

[0146] The members may be configured to form a series of repeating, uniform, wave-like arches, for example the arches, e.g., 2666. In other embodiments, the arches may vary by size, length, curvature, width, cross-section or other parameters. Additionally, spacing between arches may be varied as well.

[0147] Flexibility of the arches, e.g., 2666, may be helpful for ensuring conformity of at least a portion of the arches, e.g., 2666, to an internal shape a lumen, for example, a colon, and for ensuring contact between tissue an electrodes for electrophysiological recordings or stimulation. The flexibility of the arches, e.g., 2666, may be due to their shape or materials ,e.g., silicone rubber, latex rubber, polyurethane, and the flexibility of the arches, e.g., 2666, may be helpful for advancing the endoscopic device 2600 through the lumen. For example, the arches may be configured to deform at least in part radially (e.g., collapse or expand) to facilitate movement along a tract.

[0148] FIGS. 26B and 26C illustrate longitudinal and axial cross-sections of the endoscopic device 2600 of FIG. 26A. The axial cross-section also illustrates radial axes, e.g., 2672-1, 2672-2, along which a member or an arch may protrude. FIG. 26D illustrates a zoomed-in longitudinal cross section of the endoscopic device 2600 of FIG. 26A. Corresponding components are labeled with like reference numbers.

[0149] FIGS. 27A-27D illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as rows of radially protruding arches including longitudinal lumens for the optical probe.

[0150] FIG. 27A illustrates an isometric diagram of an example embodiment of an endoscopic device 2700 including an endoscope 2718 for example, a colonoscope, in coupled arrangement with a carrier 2764 with members configured as radially protruding arches, e.g., 2766, and external lumens, e.g., 2774. The endoscopic system 2700 may be similar to the endoscopic system 2600 of FIGS. 26A-26D and corresponding features are labeled with like reference numbers but incremented by 100. The carrier 2764 includes one or more members configured to form a plurality of arches, e.g., 2766, which may be arranged longitudinally and circumferentially and may be configured to extend radially with respect to a longitudinal axis 2746 of the carrier 2764. One or more electrodes, e.g., 2708, may be positioned on each arch of the plurality of arches, e.g., 2766. The carrier may further define one or more exterior lumens, e.g., 2774, which may be disposed on an outer surface of the carrier 2764. The one or more exterior lumens may be useful for guiding a device or a probe, for example, an OCT probe.

[0151] FIG. 27B illustrates a zoomed-out isometric view of the endoscopic device 2700 of FIG. 27A. FIG. 27C illustrates an axial cross-section of the endoscopic device 2700 of FIG. 27A. The axial cross-section also illustrates radial axes, e.g., 2772-1, 2772-2, along which a member or an arch may protrude. FIG. 27D illustrates a zoomed-in longitudinal cross section of the endoscopic device 2700 of FIG. 27A. Corresponding components are labeled with like reference numbers.

[0152] FIGS. 28A-28D illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as one row of radially protruding arches. Soft flexible protrusions arranged in a row may be helpful for ensuring contact with the colon through simple controlled deformation, i.e., material intelligence, of the protrusions without need for complex designs like inflatable balloons. The soft flexible protrusions distributed on a carrier as one row may be attached to an endoscope as an accessory and may provide flexibility of placement for the endoscope operator. Restated, the operator may choose where and how to place the contacts by manipulating the endoscope.

[0153] FIG. 28A illustrates an isometric diagram of an example embodiment of an endoscopic device 2800 including an endoscope 2818 for example, a colonoscope, in coupled arrangement with a carrier 2864 with members configured as a row of radially protruding arches, e.g., 2866. The endoscopic system 2800 may be similar to the endoscopic system 2600 of FIGS. 26A-26D and corresponding features are labeled with like reference numbers but incremented by 200. Unlike the carrier 2664 described herein with reference to FIG. 26A, the carrier 2864 includes members configured to form arches, e.g., 2866, protruding radially from a longitudinal axis 2846 of the carrier 2864, the arches, e.g., 2866, arranged longitudinally with respect to the carrier 2864 as opposed to longitudinally and circumferentially. One or more electrodes, e.g., 2808, may be in coupled arrangement with each arch of the arches, e.g., 2866. The carrier 2864 may further include an anchoring mechanism 2868 for affixing the carrier 2864 with respect to the endoscope 2818. The carrier 2864 may further include an inflatable balloon or plurality of balloons arranged longitudinally in respect to the axis 2846 on a side opposite to the members, e.g., the arches 2808 to assure contact of the electrodes, e.g., 2808 with the tissue.

[0154] FIGS. 28B and 28C illustrate longitudinal and axial cross-sections, respectively, of the endoscopic device 2800 of FIG. 28 A. The axial cross-section also illustrates radial axes, e.g., 2872, along which a member or an arch may protrude. FIG. 28D illustrates azoomed-in longitudinal cross section of the endoscopic device 2800 of FIG. 28 A. Corresponding components are labeled with like reference numbers. In some embodiments, the carrier 2864 may include external lumens similar to the external lumens, e.g., 2774, described herein with reference to FIGS. 27A-27D.

[0155] FIGS. 29A-29G illustrate an example embodiment of an endoscopic device including an endoscope in coupled arrangement with a carrier with members configured as rows of radially protruding arches in coupled arrangement with apertures for a retractable optical probe.

[0156] FIG. 29A illustrates an isometric diagram of an example embodiment of an endoscopic device 2900a including an optical probe 2912 in coupled arrangement with a carrier 2964a. The endoscopic system 2900a may be similar to the endoscopic system 2600 of FIGS. 26A-26D and corresponding features are labeled with like reference numbers but incremented by 300. The carrier 2964a may be configured to define one or more apertures, e.g., 2976a, which may be positioned between or under protruding members configured to form arches, e.g., 2966a. The arches, e.g., 2966a may be configured to extend radially with respect to a longitudinal axis 2946a of the carrier 2964a and one or more electrodes, e.g., 2908a may be in coupled arrangement with each arch of the arches, e.g., 2966a. The carrier 2964a may further include a connector 2980 to an acquisition system, which may be configured to carry electrical leads coupled to the electrodes to the acquisition system.

[0157] The optical probe 2912, which may be an OCT probe configured to acquire OCT data of tissue of a GI tract, may include an OCT probe 2942a (or an optical fiber), and a protective lumen 2978a. The OCT probe 2942a may be configured to extend through the one or more apertures, e.g., 2976a, of the carrier 2964a to acquire measurements or to deliver light to tissue. The OCT probe 2942 may also be configured to be retracted. In some embodiments the optical probe 2912 may be configured to contain a light source and an endoscopic camera for real-time visualization and positioning of the optical probe 2912.

[0158] FIG. 29B illustrates a zoomed-in isometric view of the endoscopic device 2900a of FIG. 29A with the OCT probe 2942a extended. FIG. 29C illustrates a zoomed-in isometric view of the endoscopic device 2900a of FIG. 29 A with the OCT probe 2942a retracted. FIG. 29D illustrates a longitudinal cross-section of the endoscopic device 2900a of FIG. 29 A with the OCT probe 2942a extended. FIG. 29E illustrates a longitudinal cross-section of the endoscopic device 2900a of FIG. 29 A with the OCT probe 2942a retracted. Corresponding components are labeled with like reference numbers.

[0159] FIGS. 29F and 29G illustrate isometric diagrams of an example embodiment of an endoscopic device including an optical probe in coupled arrangement with a carrier 2964b with apertures positioned below and between protrusions. The endoscopic system 2900b may be similar to the endoscopic system 2900a of FIGS. 29A-29E and similar components are labeled with corresponding reference numbers. The endoscopic system 2900b further defines apertures, e.g., 2976b, between the protrusions, e.g., 2966b, in addition to below the protrusions, e.g., 2966b. The apertures, e.g., 2976b, may provide advantages including enabling an OCT probe 2942b (or optical fiber for another optical sensing modality) to have a less obstructed view of tissue. FIG. 29F illustrates the endoscopic device 2900b with the OCT probe 2942b extended and FIG. 29G illustrates the endoscopic device 2900b with the OCT probe 2942 retracted. The apertures, e.g., 2976b, may be configured to be a single long slot or aperture beneath a plurality of arches or a series or row of individual slots or apertures aligned along a longitudinal axis. In some embodiments, the protrusions, e.g., 2966b, may be retracted into the apertures, e.g., 2976b.

[0160] Soft flexible protrusions, for example, the protrusions described herein with reference to FIGS. 26A-27D and FIGS. 29A-29G may be in contact with the colon through simple controlled deformation, i.e., material intelligence, without needing complex designs including, for example, inflatable balloons. The protrusions may be distributed radially and may be used to mechanically assure centering of the device in the colon and to ensure contact. Flexible arches with electrode contacts and leads may be mass manufactured in a flat state and formed into a final shape, which may reduce cost and manufacturing time. Devices or carriers may be attached to existing colonoscopes, which may help reduce cost and complexity, need for skilled personnel and training requirements other than such as are already routine for endoscopists. Additional advantages of the endoscopes and carriers described herein may include an unobstructed illumination or camera view by the endoscope or the carrier, which may be helpful for visual inspection for lesions or peristaltic waves.

[0161] FIGS. 30A-30G illustrate example embodiments of a carrier in coupled arrangement with electrodes, the carrier configured for direct attachment of the electrodes to a surface of a tissue. Carriers as described herein may enable a device to be left attached to an internal wall of a colon for extended periods of time (for example, periods of time longer than a standard colonoscopy procedure), which may provide more data and better diagnosis, especially since gastrointestinal processes may be best observed over full dietary cycles, which are much longer than an endoscopic procedure and require normal eating. Suchdevices may also provide minimal contact footprint on the colon wall and minimize impact on natural peristaltic processes.

[0162] FIG. 30A illustrates schematically an example embodiment of a carrier 3064a in coupled arrangement with electrodes, e.g., 3008a, the carrier 3064a configured for direct attachment of the electrodes, e.g., 3008a, for example by surface adhesion, to a surface of a tissue, for example, a wall of a colon. The carrier 3064a may comprise a soft, flexible, or, optionally, stretchable material, or a combination thereof and may be configured for mounting the electrodes, e.g., 3008, to a surface of a tissue. The carrier 3064a may be mounted e.g. by fabricating or coating it with materials that exhibit surface adhesion to mucosa, or by using adhesives, e.g., glues or gels, fasteners, e.g., tape or sutures, mechanical pinning, or other methods for mounting. Deploying and attachment of the carrier 3064a to tissue may be achieved through a standard colonoscope with accompanying accessories. The carrier 3064a may further include a connector 3080 to an acquisition system, which may be configured to carry electrical leads coupled to the electrodes 3008a and to the acquisition system. The connector 3080 may be further configured to include a fiber optic for optical sensing or activation of the tissue. According to some embodiments, the carrier 3064a may include a lumen configured for passing an optical probe, e.g., an OCT probe, to obtain additional information about the tissue. The carrier 3064a may be in coupled arrangement with a sensor 3099, which may be configured to acquire data representative of a position, motion, or orientation of the carrier 3064a and may be similar to other sensors described herein. Additional reference motion sensor(s) may be worn on the outside of the body, but in proximity to sensor 3099, to be used to subtract with mathematical models general body movements from any motion registered by sensor 3099, thus capturing only motion local to sensor 3099, such as may be caused by peristalsis.

[0163] FIG. 30B illustrates a zoomed-in isometric diagram of the carrier 3064a of FIG. 30 A. FIG. 30C illustrates a longitudinal cross-section of the carrier 3064a of FIG. 30 A. FIG. 30D illustrates a rendering of the carrier 3064a of FIG. 30A positioned in a lumen 3002, which may be an intestine. The carrier 3064a may be attached to a wall of the lumen 3002.

[0164] FIG. 30E illustrates a rendering of a carrier 3064b positioned in a lumen 3002. The carrier 3064b may be similar to the carrier 3064a described herein with reference to FIG. 30A but includes electrodes, e.g., 3008a, spatially arranged in a matrix. The carrier 3064b may be attached to the lumen 3002 using mechanical fastening 3082, for example, pinning, taping, or suturing.

[0165] FIG. 3 OF illustrates another example embodiment of a carrier 3064c in coupled arrangement with spikey electrodes, e.g., 3008b. The carrier 3064c may be similar to the carrier 3064a described herein with reference to FIG. 30 A. The spikey electrodes may be helpful for improving adherence of the carrier 3064c to a wall of a gastrointestinal tract. FIG. 30G illustrates a longitudinal cross-section of the carrier 3064c of FIG. 3 OF.

[0166] FIG. 31 A illustrates an example embodiment of a carrier 3164 including an electrode 3108, the carrier 3164 configured to attach the electrode 3108 to a surface of a tissue, for example, a wall of a colon. The electrode may be adhered to the surface of the tissue using a gel or glue. The carrier 3164 may further include a connector 3180 to an acquisition system, which may be configured to carry electrical leads coupled to the electrodes and to the acquisition system. According to some embodiments, the carrier 3164 may include a lumen configured for passing an optical probe, e.g., an OCT probe, to obtain additional information about the tissue. The carrier 3164 may be in coupled arrangement with a sensor 3199, which may be configured to acquire data representative of a position, motion, or orientation of the carrier 3164 and may be similar to other sensors described herein.Additional reference motion sensor(s) may be worn on the outside of the body, as described herein, which may be useful for mathematical models for subtracting general body movements from any motion registered by the sensor 3199.

[0167] FIG. 3 IB illustrates an example embodiment wherein the carrier 3164 of FIG. 31 A is a first carrier 3164-1 and a device further includes at least one additional carrier 3164- 2. The carriers 3164-1, 3164-2 may include respective electrodes 3108-1, 3108-2 and connectors 3180-1, 3180-2. FIG. 3 IB further illustrates another technique of attachment wherein the carrier 3164 of FIG. 31 A is a first carrier 3164-1, and the first carrier 3164-1 and at least a second carrier 3164-2 are attached to a wall of an intestine 3102. The first carrier 3164-1 is attached with a mechanical fastener 3182.

[0168] Direct recording of motility may be integrated in embodiments attached to the gut wall (for example, the example embodiments including the sensors 3099, 3199 described herein with reference to FIGS. 30A-3 IB) for extended time recordings by incorporating tools for monitoring the embodiments’ orientation and angular velocity that may be complemented with external motion sensors to correct for external body movements not related to gastrointestinal motility.

[0169] FIG. 32A illustrates an isometric diagram of an example embodiment of an endoscopic device 3200 including an endoscope 3218 for example, a colonoscope, in coupledarrangement with a carrier 3264 with radially protruding members configured as spikes, e.g., 3266, protrusions, whiskers, or bristles. One or more electrodes, e.g., 3208, may be in coupled arrangement along a length or at a tip of each spike of the spikes, e.g., 3266. The spikes, e.g., 3266, may be configured to protrude radially, for example, along a radial axis, with respect to a longitudinal axis 3246 of the carrier 3264. The spikes, e.g., 3266, may be soft, flexible protrusions and may comprise materials such as silicone rubber, latex rubber, polyurethane, nylon, or a similar material. The members (the spikes, e.g., 3266) may be fixedly or removably attached to the carrier 3264, which may include a soft, flexible core sleeve. In some example embodiments, deployment of the carrier 3264 may be achieved by sleeving the carrier 3264 in an outer wall (e.g., a sheath) of an endoscope 3218, for example, a colonoscope, and advancing the colonoscope through a colon. The endoscope 3218 may be configured to define one or more lumens, e.g., 3270 and may be configured to enable a connector 3280, e.g., a wire, to be positioned along a length of the endoscope 3218 or within a lumen, e.g., 3270, within the endoscope 3218. According to some embodiments, at least one of the spikes, e.g., 3266 or the carrier 3264 may include a lumen configured for passing an optical probe, e.g., an OCT probe, to obtain additional information about the tissue.

[0170] Flexible members or protrusions may be manufactured in various shapes or sizes (for example, the spikes, e.g., 3266). The flexible members may be helpful for conforming electrodes to an internal morphology of a lumen, for example, a colon, during longitudinal or circular advancement. For example, the spikes may be configured to deform at least in part radially (e.g., collapse or expand) to facilitate movement along a tract. In some embodiments, the circumference of the tract may be smaller than an outer circumference of the spikes, e.g., 3266, of the carrier.

[0171] FIGS. 32B and 32C illustrate longitudinal and axial cross-sections, respectively, of the endoscopic device 3200 of FIG. 32A. Corresponding components are labeled with like reference numbers. FIG. 32C further illustrates radial axes 3272-1, 3272-2, 3272-3, 3272-4 along which a spike of the spikes, e.g. 3266, protrude. As illustrated in the axial crosssection, the spikes, e.g., 3266, may be arranged at fixed intervals or at varying intervals circumferentially and longitudinally. In some embodiments, eight spikes, e.g., 3266, may be arranged circumferentially with 45° spacing. FIG. 32D illustrates an example embodiment of an endoscopic device 3200 with a plurality of carriers 3264-1, 3264-2 similar to the carriers 3264 of FIGS. 32A-32C. In some embodiments, the carriers 3264-1, 3264-2 may be manufactured in smaller sections and stacked up along the endoscope 3218 to form arecording array. In such embodiments, each carrier 3264-1 may include one or more spikes of the spikes, e.g., 3266. The endoscopic device 3200 may offer advantages. For example, soft flexible protrusions, for example, the spikes, e.g., 3266, may achieve contact with colon wall through controlled deformation (material intelligence) without the need for much more complex designs like inflatable balloons. The flexible protrusions with electrode contacts and leads may be mass manufactured in segments or in a full or complete state, which may be helpful for reducing time or cost. The endoscopic device 3200 may also be attached to existing colonoscopes, which may reduce cost or complexity, need for skilled personnel, and training requirements.

[0172] FIG. 33A illustrates an isometric diagram of an example embodiment of an endoscopic device 3300 including an endoscope 3318, for example, a colonoscope, in coupled arrangement with a carrier 3364 with radially protruding members configured as arms, e.g., 3366, pads, or petals. The arms may be similar to the spikes, e.g., 3366, described herein with reference to FIG. 32A-D, for example, with respect to material, flexibility, and construction. The arms, e.g., 3366 may include a large electrode pads, e.g., 3308 on one or both sides an arm of the arms, e.g., 3366. The endoscopic device 3300 may further be similar to the endoscopic device 3200 described herein with reference to FIG. 32A, for example, with respect to the endoscope 3318, which may be a colonoscope defining one or more lumens 3370. The arms, e.g., 3366, may be configured to extend with respect to a longitudinal axis 3346 of the carrier 3364 and may be configured to move radially. For example, the arms may be configured to deform at least in part radially (e.g., collapse or expand) to facilitate movement along a tract. In some embodiments, the circumference of the tract may be smaller than an outer circumference of the arms, e.g., 3366, of the carrier. The device 3300 may include a connecter 3380, e.g., a wire, configured to run along a length of or within a lumen, e.g., 3370, defined by the endoscope 3318.

[0173] FIG. 33B and FIG. 33C illustrate longitudinal and axial cross-sections, respectively, of the endoscopic device 3300 of FIG. 33 A. Corresponding components are labeled with like reference numbers. FIG. 33C further illustrates radial axes 3372-1, 3372-2, 3372-3 along which a spike of the spikes, e.g. 3266, protrude. As illustrated in the axial cross-section, the arms, e.g., 3366, may be arranged at fixed intervals or at varying intervals circumferentially and longitudinally. In some embodiments, six arms, e.g., 3366, may be arranged circumferentially with 60° spacing. FIG. 33D illustrates an example embodiment of an endoscopic device 3300 with a plurality of carriers 3364-1, 3364-2 similar to the carriers3364 of FIGS. 33A-33C. Each carrier of the carriers 3364-1, 3364-2 may include one or more arms of the arms, e.g., 3266 and the endoscopic device 3300 may include a plurality of the carriers 3364-1, 3364-2.

[0174] FIGS. 34A and 34B illustrate an electrode 3408 realized as a clip that may be configured to attach to a surface 3402, which may include the inner, mucosal surface of the colon in a manner similar to a conventional endoclip (or endoscopic clip), which is a mechanical device used via endoscopy to hold together two mucosal surfaces. The electrode 3408 may be used by embodiments of a device for studying a GI system. The electrode 3408, or at least surfaces of the electrode 3408 in direct contact with the surface 3402 of the tissue, may be conductive, enabling the electrode 3408 to register biopotentials. The electrode 3408 may be attached to a mucosal surface of the colon using conventional endoscopic techniques. The electrode 3408 may be attached to a wire 3480, which may be configured to be a thin or flexible wire, with a breakaway connection, which may disengage before excessive force may be transmitted though the wire 3480 to the clip. The wire may extend down the colon, through the rectum, to the outside of a body where it may be connected to a portable biopotential acquisition device, for example, a Holter monitor. Differential recording from the electrode 3402 may be made against another clip electrode or another sticky patch reference electrode placed in an appropriate place on the body. A number of clip electrodes may be used together and attached to the same biopotential acquisition device. The electrode 3408 configured as the clip may be in coupled arrangement with a sensor 3499, which may be configured to acquire data representative of a position, motion, or orientation of the electrode 3408. Additional reference motion sensor(s) may be worn on the outside of the body, as described herein, which may be useful for mathematical models for subtracting general body movements from any motion registered by the sensor 3499.

[0175] The electrode 3408 may have an advantage of recording for extended periods of time, for example, 24 hours, which may be unattainable for recordings done during a standard colonoscopy procedure. Measuring over extended periods of time may also provide more data and improved diagnosis, particularly as gastrointestinal processes may be best observed over a normal dietary cycle. The electrode 3408 may also provide minimal contact footprint on the colon wall, which may be helpful for minimizing impact of the electrode 3408 on natural peristaltic processes. In embodiments using the electrode 3408, an endoscope may also be freely moved in the body lumen, for example, the colon, and probes or cameras may be deployed in the colon.

[0176] FIG. 35 A illustrates another example electrode 3508 configured as a clip that may be used by embodiments of a device for evaluating a GI system. The electrode 3508 may be similar to electrode 3408 described herein with reference to FIGS. 34A and 34B, with corresponding elements labeled with like reference numbers but incremented by 100. The electrode 3508 may be in coupled arrangement with a cap 3582, which may be a protective cap, and a connector 3580. According to some embodiments, the connector 3580 may include a lumen configured for passing an optical probe, e.g., an OCT probe, to obtain additional information about the tissue. The electrode 3508 configured as the clip may be in coupled arrangement with a sensor 3599, which may be configured to acquire data representative of a position, motion, or orientation of the electrode 3508. Additional reference motion sensor(s) may be worn on the outside of the body, as described herein, which may be useful for mathematical models for subtracting general body movements from any motion registered by the sensor 3599.

[0177] FIG. 35B illustrates a longitudinal cross section of the electrode 3508 of FIG. 35 A. FIG. 35C illustrates the electrode 3508 of FIG. 35 A attached to a surface 3502 of a lumen, for example, a wall of a colon. Corresponding elements are labeled with like reference numbers.

[0178] Direct recording of motility may be integrated in embodiments configured to be attached to the gut wall (for example, the example embodiments described herein with reference to FIGS. 34A-35C) for extended time recordings by incorporating tools for monitoring the embodiments’ orientation and angular velocity that may be complemented with external motion sensors to correct for external body movements not related to gastrointestinal motility. For example, the sensors 3499, 3599, which may be similar to other sensors described herein, may be used to acquire measures of motility of the gut wall.

[0179] FIG. 36A illustrates an isometric view of an example embodiment of an endoscopic device 3600 including an endoscope 3618 and a carrier 3664, the carrier 3664 including a balloon 3684. One or more electrodes (not shown in FIG. 36A but described herein with reference to FIG. 36B) may be in coupled arrangement with the balloon 3684, and the balloon 3684 may be configured to inflate and to deflate. Deployment or inflation of the balloon 3684 may be achieved using gases, fluids or liquids, pastes, or soft beads, for example, by injection into the balloon 3684. The carrier 3664 may further include a cage 3686 configured to be flexible, rigid, or semi-rigid and to define one or more apertures, e.g., 3688. The one or more apertures, e.g., 3688, may be configured to provide an opening for orto constrain the balloon 3684 when inflated, which may be advantageous for controlling the diameter of the ballon a procedure using the device 3600. In some embodiments, the carrier 3664 may be manufactured and placed inside a lumen, for example, a colon, as a standalone device while the carrier 3664 may be inserted with an endoscope 3618, e.g., a standard colonoscope, in other embodiments. In some embodiments, additional measurement modalities, e.g., OCT measurements, may be implemented by incorporating an additional lumen in the cage 3686 for passing measurement probes.

[0180] FIG. 36B illustrates an isometric view of the endoscopic device 3600 of FIG. 36A, wherein the balloon 3684 is in a deployed state. In the deployed state, the balloon 3684 may extend radially with respect to a longitudinal axis 3646 of the carrier 3664 and may protrude through and be constrained by the one or more apertures, e.g., 3688. Inflating the balloon 3684 may cause the electrodes, e.g., 3608, to extend and to come into contact with tissue. In some embodiments, the cage 3686 may be configured as a constraining member and may be used to define a number of ballooning elements. In other embodiments, the balloon 3684 may include one or more balloon elements. FIG. 36C illustrates an axial cross-section of the endoscopic device 3600 of FIG. 36A in a collapsed state, including a radial axis 3672 along which the balloon 3684 may extend. FIG. 36D illustrates a longitudinal cross-section of the endoscopic device 3600 of FIG. 36A in a collapsed state.

[0181] FIG. 37A illustrates an example embodiment of a device 3700 including a carrier 3764 having a sleeve 3784, e.g., a close-end sleeve, configured to be deployed. FIG. 37A illustrates the sleeve 3784 in a collapsed state. Electrodes may be in coupled arrangement (e.g., positioned in a pattern) on the sleeve 3784, which may include a soft conformable tube. A rim of the sleeve 3784 may be attached, e.g., bonded, to a rim of a deployment tube 3790. In the collapsed state, the sleeve 3784 may be contained in the deployment tube 3790, for example, wherein the sleeve 3784 is collapsed and inverted within the deployment tube 3790 as illustrated in FIG. 37A. The deployment tube 3790 may be positioned at a desired location, for example, within a lumen 3702. The balloon 3784 may be deployed by filling the deployment tube 3790 and the sleeve 3784 with an appropriate medium, such as gases, fluids or liquids, pastes, or soft beads.

[0182] FIG. 37B illustrates the device 3700 of FIG. 37A, wherein the closed-end sleeve 3784 is in a partially deployed state. Expansion of the sleeve 3784 may cause the sleeve 3784 to roll inside-out from the inverted collapsed state of FIG. 37A. The sleeve 3784, when deployed, may be configured to extend past a tip or rim of the deployment tube 3790 and tocontinue everting thus penetrating further the body lumen. FIG. 37C illustrates the device 3700 of FIG. 37A, wherein the sleeve 3784 is in a fully deployed state.

[0183] The device 3700 may offer advantages such as reduced sheer forces applied to a colon due to the deployment mechanisms relying upon the eversion process. The device 3700 may further provide steerability due to inherent material intelligence of the device and may enable self-deployment without the need for an endoscope for guidance.

[0184] FIG. 38A illustrates an example carrier 3864 that may be used by an embodiment of an endoscopic device, the carrier 3864 including a sleeve 3884, e.g., a close-end sleeve, configured to be deployed. The sleeve 3884 may be configured to be compliant, inflatable, or a combination thereof, and may be deployed by filling the sleeve with an appropriate medium, for example, gas, fluid or liquid, paste, or soft beads. Electrodes, e.g., 3808, may be in coupled arrangement with the sleeve 3884 and may be positioned along a surface of the sleeve 3884. Electrical leads, e.g., 3881, (which may also be described as signal paths) may be positioned along a length or on a surface of the sleeve 3884 and may be connected to a signal cable 3880, the signal cable configured to connect the electrodes, e.g., 3808, to a data acquisition device.

[0185] The sleeve 3884, in an undeployed state, may be configured to be stored in an inverted arrangement, wherein a portion, e.g., an inverted portion 3883, of the sleeve 3884 is contained within another portion, e.g., an everted section 3885, of the sleeve 3884. Restated, the sleeve may include a distal end that may be stored within portions of an interior of the sleeve. Deploying the sleeve 3884 may cause the sleeve 3884 to evert. The sleeve may be stretchable or inflatable or may be compliant but not stretchable.

[0186] FIG. 38B illustrates a device 3800 including the carrier 3864 of FIG. 38 A. As further illustrated in FIGS. 38C and 38D, the device 3800 may be configured to contain the carrier 3864, including a storage component configured to store at least a portion of the sleeve 3884 when the sleeve is in an undeployed, for example, inverted, state.

[0187] FIGS. 38C and 38D illustrate a cross-section view of the device 3800 of FIG. 38B, the device 3800 including the carrier 3864 of FIG. 38A in an undeployed state and a deployed state, respectively. A coiled carrier 3887 may be configured to store the sleeve 3884 in the inverted arrangement. The signal cable 3880 may be coupled with the electrical leads, e.g., 3881, of the electrodes, e.g., 3808, at a location within the coiled carrier 3887. A pump 3889 may be configured to deploy the sleeve 3884, causing the sleeve 3884 to evert, which may further cause the sleeve 3884 to extend at a distal end 3891 of the sleeve. Everting thesleeve 3884 may cause the electrodes, e.g., 3808, to become exposed along an outer surface of the sleeve 3884.

[0188] In some embodiments, a sleeve may be configured to collapse and to expand, the sleeve including circumferentially spaced ribs enabling predictable collapse or expansion. The ribs may be placed at fixed or variable intervals and may enable the sleeve to collapse flatly.

[0189] FIG. 39 illustrates an example carrier 3964 that may be used by an embodiment of an endoscopic device or system, the carrier 3964 including an ellipsoid 3993 and electrodes, e.g., 3908, in coupled arrangement with the ellipsoid 3993. In some embodiments, the ellipsoid 3993 may be a sphere, as shown in FIG. 39. The electrodes, e.g., 3908, may be positioned on a surface of the ellipsoid 3993 and may be spatially arranged or patterned on the surface. The ellipsoid 3993 may comprise a polymeric material, for example, plastic, and may include a recessed edge 3995 (e.g., a handle or a gripping structure), which may be useful for grabbing with forceps. The carrier 3964 may further include a cable 3980, which may be a thin, flexible cable and which may be configured to extend along a colon and through a rectum to the outside of a body. The cable 3980 may be further configured to connect to a portable biopotential acquisition device, which may be similar to a Holter monitor. Differential recordings from an electrode of the electrodes, e.g., 3908, on the ellipsoid 3993 may be made against another electrode on the ellipsoid (in such a way, every other electrode on the balloon may be configured to be a reference, which may be helpful for ensuring that at least one reference is in contact with the tissue), against an electrode on another ellipsoid similar to the ellipsoid 3993, or a reference electrode placed at an appropriate place on the body, for example, using a sticky patch reference electrode. An orientation of the ellipsoid 3993 may be rotatable. The carrier 3964 may further include a sensor 3999 in coupled arrangement with the carrier 3964. The sensor 3999 may be configured to acquire data representative of at least one of a position, motion, or orientation of the carrier 3964. For example, the sensor 3999 may be useful for direct measurement of peristaltic motion of a colon or passage of the carrier 3964 through the colon.

[0190] The carrier 3964 may have the advantage of recording for extended periods of time, for example, with respect to standard colonoscopy procedures, as the ellipsoid is naturally passed down the colon. Because the entirety of the ellipsoid 3993 is patterned with electrodes, e.g., 3908, at least a portion of the electrodes, e.g., 3908, may keep contact withthe tissue even if the carrier changes orientation over time. Passage of the device along the colon may allow monitoring of activity along a natural passage through the entire colon.

[0191] In another embodiment, the carrier may not have the cable 3980 and may include a minimized, onboard battery-powered biopotential acquisition device, which may be positioned inside the ellipsoid. The data may be either transmitted to an external unit storage unit, e.g., using Bluetooth or Wi-Fi on the fly, or recovered from onboard memory of the device after the device is passed from the colon via a waterproof connector.

[0192] In some embodiments, a carrier or a device used by an example embodiment of an endoscopic system may include an elongated or tubular structure, for example, in the shape of an inflated balloon as illustrated in FIG. 40B. The carrier may include a rigid or semi-rigid material and may be of a size that enables insertion of the carrier through a natural orifice. The carrier may further be in coupled arrangement with electrodes and may include a tube or connector, which may be used for deploying probes or for passing leads electrically coupled to the electrodes.

[0193] FIGS. 40 A and 40B illustrate an example carrier 4064 that may be used by an embodiment of an endoscopic device or system, the carrier including a balloon 4084 and electrodes, e.g., 4008, in coupled arrangement with the balloon 4084. FIG. 40A illustrates the carrier 4064 in a collapsed or undeployed state and FIG. 40B illustrates the carrier 4064 in a deployed state. The balloon 4084 may be an oblong balloon and the electrodes, e.g., 4008, may be positioned on a surface of the balloon 4084. The carrier 4064 may further include a tube 4080, which may be a thin, flexible tube, configured to house cables that may be used for acquiring signals from the electrodes, e.g., 4008, and to serve as a conduit for filling the balloon. The balloon 4084 and the tube 4080 may extend along a common longitudinal axis. The tube 4080 may further configured to include a lumen for passage of an optical probe. The carrier 4064 may further include a loop or handle 4095 (or a gripping structure), which be useful for manipulating, e.g., grabbing, the balloon 4084 using instruments such as forceps. The carrier 4064 may further include a sensor 4099 configured to detect data representative of at least one of a position, motion, or orientation of the carrier 4064. The sensor may be similar to other sensors described herein.

[0194] Placement of the carrier 4064 in a colon may include, for example, insertion through a conventional colonoscope. The carrier 4064 may be grabbed at the loop or handle by forceps of the colonoscope and the balloon 4084 may be filled with fluid to a low pressure, which may be helpful for ensuring that the balloon 4084 is soft and compliant. Thetube 4080 may extend down the colon and through a rectum to an outside of a body and the cables within the tube 4080 may connect to a biopotential acquisition device, which may be similar to a Holter monitor. Differential recordings from an electrode of the electrodes, e.g., 4008, on the balloon may be made against another electrode on the balloon (in such a way, every other electrode on the balloon may be configured to be a reference, which may be helpful for ensuring that at least one reference is in contact with the tissue), against an electrode on another balloon similar to the balloon 4084, or a reference electrode placed at an appropriate place on the body, for example, using a sticky patch reference electrode. The carrier 4064 may have the advantage of recording for extended periods of time as the balloon 4084 is naturally passed down the colon.

[0195] Direct recording of motility may be integrated in embodiments configured to be attached to or in contact with the gut wall (for example, the example embodiments including the sensors 3999, 4099 described herein with reference to FIGS. 39-40B) for extended time recordings by incorporating tools for monitoring the embodiments’ orientation and angular velocity that may be complemented with external motion sensors to correct for external body movements not related to gastrointestinal motility. The sensors 3999, 4099 may be in coupled arrangement with a carrier, e.g., the carrier 3964, 4064, such as on an internal surface or an external surface. Additional reference motion sensor(s) may be worn on the outside of the body, as described herein, which may be useful for mathematical models for subtracting general body movements from any motion registered by the sensor 3999, 4099. Tools for monitoring position, motion, orientation and angular velocity, which may be similar to the sensor 3999, 4099, may include, for example, gyroscopes, accelerometers, or inertial measurement units (IMUs).Example embodiments for small animal experiments

[0196] FIG. 2A illustrates an exploded view of an example embodiment of a multi-modal endoscopic device 200 configured for acquiring or delivering electrical and optical signals in an anatomical lumen of a small animal. The multi-modal endoscopic device 200 comprises an endoscope 218a, which may be a construct with a semi-rigid cylindrical shape having a 2 mm diameter and 30 mm length. A substrate of the endoscope 218a may include a transparent nylon tube with a hemispherical end cap. The multi-modal endoscopic device 200 also comprises an electrode array 208, which may include a custom electrode matrix . The electrode array 208 may include a 10 pm -thick polyimide film 220 with an electrode matrixbearing 208 electrode contacts wrapped and epoxied to a substrate of the endoscope 218a and connected to external readout contacts 222 through isolated conducting paths (not shown but described herein with reference to FIG. 2C). The electrode array 208, readout contacts 222, and conducting paths may be constructed from a conductive material, for example, platinum. According to an example embodiment, the electrode contacts may have a diameter of 200 pm and may additionally be coated with iridium oxide for improved impedance and charge injection capacity. The electrode contacts, for example, the electrode array 208, may be arranged in a 32-by-4 grid with a 0.8 mm pitch along a shaft of the endoscope 218a (thus longitudinally covering 24.8 mm of a colon) and 1.57 mm pitch (= 2 mm x 7t / 4) along a circumference of the shaft of the endoscope 218a. The polyimide electrode matrix, which may include the polyimide film 220, the readout contacts 222, and the electrode array 208, may be configured to be L-shaped so that after wrapping the longer arm of the L wraps longitudinally around the nylon tube, the shorter arm of the L forms a freely floating tab bearing the readout contacts 222 for connection to a custom printed circuit board (PCB) 224. Precise alignment may be achieved with a custom build fixture, which may include a housing including a top enclosure 226, a bottom enclosure 228, and fasteners, for example, screw 230. Connector ports, e.g., 235, may be used to communicatively couple measurement modalities, for example, the electrode array 208, to connectors for transmitting data to a system or a computer. The custom build fixture may be assembled with use of micro positioners and cameras and connection pads of the PCB 224 may be bonded, for example to the readout contacts 222, using conductive epoxy. The custom build fixture may be a 3-dimensional (3D) printed enclosure, which may also clamp the endoscope 218a containing a central channel for introduction of an optical device. The multi-modal endoscopic device 200 further comprises a reference electrode 232 and a ground electrode 234.

[0197] FIG. 2B illustrates an example system that includes the multi-modal endoscopic device 200 of FIG. 2A. The system may include connectors, e.g., 236, configured to couple to the connector ports, e.g., 235, and to transmit measurement data. The PCB 224, as illustrated in FIG. 2A, of the endoscopic device 200 may include pin outs for a plurality of channels to the connectors, e.g., 236, for connection to downstream recording / stimulating equipment.

[0198] An example embodiment of a distal end of an endoscope similar to the endoscope 218a that may be included in a multi-modal endoscopic device or system is described hereinbelow with reference to FIG. 8A. FIG. 8B further illustrates example OCT data acquired using the multi-modal endoscopic device or system.

[0199] FIG. 2C is a detailed view of an electrical probe 206 including a high-density matrix of the electrode array 208 of the device 200 of FIG. 2 A. The polyimide film 220 bearing electrode contacts, e.g., the electrode array 208, and electrical paths, e.g., path 238, may be wrapped around a device and may also be transparent enough to allow for transmission of light through the combination of the polyimide film, electrical paths, and electrode matrix.

[0200] Multi-modal endoscopic systems and devices described herein, for example the systems and devices of FIGS. 1A, IB, and 2A-2C, may provide high spatial resolution and coverage and enable direct measurement of important features of colonic electrophysiology, e.g., spatial spread and coordination of action potentials, as well as direct assessment of complex patterns formed by the action potentials in great in detail. Spatial oversampling of action potential sources may also be useful for minimizing missed signals or patterns in an area covered by an endoscope.

[0201] FIG. 2D illustrates an example embodiment of an optical probe 212a with a torque delivery compatible with the multimodal endoscopic device 200 of FIG. 2 A. The optical probe 212a, which may be similar to the micro optics 112a, 112b described herein with respect to FIGS. 1 A and IB, respectively, may be configured to pass through at least a portion of an endoscope 218b. The optical probe 212a may include a probe tube 240a, an optical fiber 242a enclosed in a torque coil 240a, and a light refracting element 244a. The optical probe 212a may be protected by a housing 245a. The optical probe 212a is connected to an optical module, for example, the optical module 106a described herein with reference to FIG. 1 A, with an optical connector 250a. The optical probe 212a may be configured for translation, e.g., pullback, along or rotation around a longitudinal axis 246a of the endoscope 218b. The translation may be actuated by a translation actuator 248a with a pullback connector 247a to accommodate for displacement of the probe inside of the probe tube 240a. The rotation may be actuated by a rotational actuator 249a.

[0202] FIG. 2E illustrates an example embodiment of an optical probe 212b compatible with the multi-modal endoscopic device 200 of FIG. 2 A. The optical probe 212b may be similar to the optical probe 212a of FIG. 2D and may comprise an optical tube 240b, an optical fiber 242b, and a light refracting element 244b protected by a housing 245b. The optical probe 212 b may be further configured to pass through an endoscope 218c. The optical probe 212b may further be configured to deliver light through the endoscope 218c and the electrode array, not illustrated, but similar with respect to the electrode array 208illustrated in FIG. 2C. The optical probe may also be configured for translational or rotational movement, as described herein with respect to FIG. 2D.

[0203] Spike detection algorithm may reveal altered shapes of action potentials. Altered smooth muscle action potential shapes may be caused by aberrations changes in ion channel activity and the influence of local factors like disruptions in neurotransmitters, hormones, toxins, or genetic disorders, and may be related to gut disorders. .

[0204] Example multi-modal measurements of morphology, motility, and function of tissue of a gastrointestinal tract acquired using a multi-modal endoscopic device is described hereinbelow with reference to FIG. 15B. The multi-modal endoscopic device may be similar to or contain components similar to at least a portion of the device 200 of FIGS. 2A and 2B, the electrical probe 206 of FIG. 2C, and the optical probe 212a, 212b of FIGS. 2D and 2E.

[0205] FIG. 3 illustrates a time trace plot of electrical signals measured by an electrode positioned in a mouse colon, according to an example embodiment. An inset shows a transient spike (action potential) in the electrical signal.

[0206] Electrophysiological recordings from moving tissue may be susceptible to motion artifacts. These artifacts may introduce spurious waveforms into the data, with time courses that may reflect the physical displacement of tissue rather than genuine neural or myogenic activity. To mitigate this, analysis of electrophysiological signals may be restricted to high- frequency events, specifically action potentials, with time constants in a range of 10-20ms, according to some example embodiments, which are much faster than the motion of the gut.Spatiotemporal selectivity for electrophysiological recording

[0207] A critical design consideration with respect to concepts of intraluminal recordings may include whether the electrodes could maintain spatial selectivity or whether physiological fluid between them would create a common electrical environment, blurring spatial resolution.

[0208] FIG. 4 illustrates average actional potential (spike) recorded in a mouse colon with a device, demonstrating high spatial resolution, i.e., an ability to record signals of local origin, as demonstrated by the average spike’s steep amplitude attenuation with distance, according to an example embodiment. The detected action potentials that were most prominent on a given contact, for example, the measurement at 0° and 0 mm, were recorded in neighboring contacts of the endoscope with less than half the amplitude, for example, at 0° and +0.8 mm, 0° and -0.8 mm, -90° and 0 mm, and 90° and 0 mm. Such steep spatial decaysmay indicate sufficient ability to spatially capture or localize signals of very local origin using intraluminal recordings. Simultaneously, the detected action potentials may verify, for the example embodiment, optimal contact pitch of the endoscope as sources of electrophysiological activity may be somewhat oversampled spatially, which may be helpful in ensuring that there are no blind spots along a length of the endoscope.

[0209] FIG. 5A illustrates spatiotemporal patterns of spikes in electrophysiological activity detected in mouse colon, the spatiotemporal patterns including ~10 s-long bursts of spiking approximately 2 times per minute, according to an example embodiment. An arrow indicates a zoomed-in view of the dark grey box showing intraburst patterns of activity, composed of periodic (~1 per second) burstlets frequently forming propagating anterograde waves. Use of chemical agents or stimuli, for example, ketamine / medetomidine anesthetized animals, may be expected to change electrophysiological properties and patterns of a gut.

[0210] FIG. 5B illustrates spatiotemporal patterns in root-mean-squared (RMS) envelopes spiking activity detected in the electrophysiological activity, according to an example embodiment.

[0211] Manifest periodicities in spiking activity may be quantified and less conspicuous rhythms may be identified using Fourier analysis of an RMS envelope. According to an example embodiment, the Fourier analysis of the RMS may be calculated with 100 ms windows using 30 minutes of recorded signal.

[0212] FIG. 5C illustrates Fourier spectral analysis of RMS envelopes, which may be similar to the RMS of FIG. 5B, of electrophysiological spiking activity (calculated with a 100 ms window) of 30 minutes of signals that shows orally located anterograde bursts occurring at 2.2 cycles per minute (c.p.m.), retrograde bursts at 4.4 cycles per minute, and anterograde burstlets occurring at 60 cycles per minute, according to an example embodiment. Additional frequency hotspots within second and third bands may be visible (oral 18 c.p.m., aboral 30 c.p.m.), that may not be easily distinguishable by eye in the raw electrophysiology signal.In vivo measurement of response to pharmacological modulation

[0213] Sensitivity of an example embodiment of a multi-modal endoscopic device to pharmacological intervention in real-time and to a physiological nature of observed spiking activity may be evaluated by modulating a GI system with injections, for example, intraperitoneal injections, of well-known pharmacological agents.

[0214] FIG. 6 illustrates measurements of electrophysiological activity, the measurements including responses to pharmacological intervention with a cholinesterase inhibitor (donepezil) and a cholinergic antagonist (atropine), according to an example embodiment. Donepezil may be used to enhance cholinergic tone, which may rapidly and significantly upregulate spiking activity. Atropine may have a reversing effect by producing a rapid, shortlived significant reduction of spiking activity. FIG. 6 illustrates time points at which pharmacological agents are applied for an example experiment, including donepezil at 7 min and atropine at 17 min. Areas of statistically significant change in activity are outlined by a solid black line (upregulation) and a dotted black line (downregulation). Rapid onset and decay of pharmacological effects may be most evident in oral regions, which may primarily exhibit anterograde propagation of activity. An exception may include prolonged upregulation of activity at an aboral end of the colon, which may appear to be resistant to the cholinergic antagonism of atropine. Furthermore, decay of atropine downregulation may be followed by a localized (across 7 channels) increase in spiking activity lasting ~3 minutes, which may be interpreted either as a post-atropine rebound or continued donepezil effects, temporarily masked by atropine.Spatial variability of electrophysiological patterns

[0215] Observations of identified spatial patterns may indicate that the spatial patterns evolve and differentiate to a great extent longitudinally in a colon as opposed to around (circumferentially) a colon. This trend may be visible even in raw data.

[0216] FIGS. 7A-7D illustrate similarity of spatiotemporal patterns of electrophysiological measurements, the electrophysiological measurements lasting ~10 s, of quadrants of a probe, each quadrant of an endoscope including 32-channels, according to an example embodiment. A scalebar for the electrophysiological measurements of FIGS. 7A-7D is present in FIG. 7D. The spatiotemporal patterns of FIGS. 7A-7D appear similar while channels, capturing signals longitudinally in a colon, within each of FIGS. 7A-7D vary and complement each other.

[0217] FIG. 7E illustrates cross-channel correlation 100 ms window RMS envelopes of raw signals of the quadrants of FIGS. 7A-7D, the cross-channel correlation indicating that channels located at similar longitudinal positions may correlate highly despite being on different quadrants of an endoscope while correlation between channels shifted along thecolon even by 2 mm may drop off steeply. The cross-channel correlation may be used to quantify correlation between quadrants and between channels within quadrants.OCT scanning patterns for morphology and motility

[0218] OCT uses near-infrared light to recover cross-sectional images of tissue architecture without a need for contrast agents. Locations of internal structures of the tissue may scatter or reflect light and the scattered and recovered light may be measured in a manner similar to that of ultrasound imaging. Intensities of recovered signals may depend upon gradients of endogenous optical properties of tissue constituents. In a single measurement, OCT may collect a one-dimensional (ID) measurement over depth of the tissue from a single location on a surface of the tissue. To achieve volumetric scanning of the tissue, optical beam positions may be translated over the tissue. In the digestive system, which may include tubular organs, volumetric OCT measurements may be obtained by rotation (either on a proximal or a distal side) of an optical probe for a circumferential / radial scan and translation of the optical probe to create a helical volumetric scan. As well as morphology, a motility of a gut wall may be mapped by recording OCT signals as a onedimensional measurement or as a volumetric scan in vivo.

[0219] FIG. 8A illustrates schematically an example embodiment of an OCT probe 812 with an endoscope 818, the OCT probe 812 configured for radial scans, according to an example embodiment. An inset shows an example 1-D depth scan of OCT imaging, which may be called an A-line measurement. A multi-modal endoscopic device 800 may include the OCT probe 812, an electrode array 808, and the endoscope 818. A radial scan, or a B-scan 848, is also illustrated.

[0220] FIG. 8B illustrates a radial OCT B-scan of a mouse colon with visible anatomical layers, the radial B-scan being compared with ex vivo histology and light-sheet imaging of a mouse gut, according to an example embodiment. As shown in FIG. 8B, features of a GI system wall captured by ex vivo histology and light-sheet imaging may be present in OCT imaging, which may be performed in vivo.Morphology of the gastrointestinal wall

[0221] Morphological heterogeneity of a gut may be evident in a helical OCT scan that may provide a 3D volume of OCT data with spatial (e.g., x-y) resolution on an order of tens of microns and depth (axial) resolution on an order of a few microns. A dense scan in bothradial and longitudinal directions may be needed to sufficiently sample data and enable en- face reconstruction for mapping morphological changes as a function of neuromuscular function. With near-infrared light centered at 1300 nm, penetration depth may be sufficient to pass through a mucosa of a mouse gut and visualize changes as an orientation of other organs in the cavity.

[0222] The enteric nervous ganglia morphology may create a thin sheath of net-like network embedded in between circular and longitudinal muscles. The ENS may have a thickness of up to 20 microns and thus may only occupy 2-3 pixels in an axial (z) direction of OCT data. The data may be thus flattened to the circular and / or longitudinal muscle before en-face reslicing in order to reconstruct neuromuscular morphology. The muscle layers may be detected in OCT data using attenuation changes or via polarization properties. En-face reconstruction at a depth of just below the longitudinal muscle may provide information about orientation of a mesentery line, which may be important for analysis of functional electrophysiology and motility signals. The mesentery line and orientation of other organs in a body cavity as well as vasculature patterns in OCT data may be used to reposition a probe during experiments or in between experiments in longitudinal studies.

[0223] FIG. 9A illustrates a representation of volumetric scanning using an OCT probe, according to an example embodiment. The volumetric scanning may include rotating the OCT probe to acquire circumferential measurements (0) and translating the OCT probe ( / .) to acquire longitudinal measurements.

[0224] FIG. 9B illustrates volumetric data obtained in a wild-type mouse by rotation and translation of an optical probe, according to an example embodiment. For example, the volumetric data of FIG. 9B may be acquired using the volumetric scanning illustrated in FIG. 9A.

[0225] FIG. 9C illustrates OCT data processed by virtually re-slicing data in different planes, according to an example embodiment. En-face reslices and longitudinal reslices may be extracted from volumetric data, for example, the volumetric data of FIG. 9B.

[0226] FIG. 9D illustrates an OCT longitudinal reslice of volumetric OCT data flattened to myenteric plexus for en-face reconstruction, according to an example embodiment. A depth for en-face reconstruction may be identified using the longitudinal reslice. Additional anatomical features, for example, internal organs, mucosa, or sheath, may be helpful in identifying the depth for en-face reslice reconstruction.

[0227] FIG. 9E illustrates an en-face reslice of volumetric OCT data of a mouse colon for analysis of thin layers of a gut, for example, an enteric nervous system, according to an example embodiment. The en-face reslice may be reconstructed from a depth level of a myenteric plexus.Radial motility acquisition

[0228] Continuous radial scanning at a given longitudinal position may enable recording of dynamic changes of tissue position that may correspond to mechanical displacement due to gut activity. Motility recording may be driven by knowledge of electrophysiology of gut activity. Radial motility, which may be characterized in some embodiments by a number of cycles per minute, for example, 2 cycles per minute of peristaltic burst in healthy animals, may undergo recording for 2-3 minutes to capture a plurality of bursts; thus, it may not be possible to sample a colon at multiple longitudinal positions due to time constraints of imaging. Radial motility acquisition may allow for verification of activity as a function of morphology (per anatomical layer) and may be helpful in studying features of gut morphology with respect to electrophysiology, for example, whether mechanical changes of gut tissue are more variable around a circumference of the gut tissue than electrophysiological changes. En-face radial patterns may indicate an amount of contact between a probe and gut tissue during peristalsis and en-face radial patterns may be different when re-slices are extracted at different tissue layers, for example, at a muscle layer. The radial motility acquisition may provide 2D mapping of mechanical activity at high resolution with extracted frequency of motility.

[0229] Example OCT data collected of gut motility in colons of healthy mice and in colons of mice with lesions induced using benzalkonium chloride are described hereinbelow with reference to FIGS. 17E and 17F.

[0230] FIG. 10A illustrates radial OCT motility data obtained at a given longitudinal position in a distal colon of a mouse over a period of time, the radial OCT motility data can be post-processed to give access to en-face radial imaging and axial time-series data at a certain radial location, according to an example embodiment. In the radial motility data, the longitudinal axis may represent radial B-scans acquired at specific points in the period of time.

[0231] FIG. 10B illustrates a plot of tissue motility over time for a point extracted from the OCT axial time-series data in FIG. 10A. The plot may indicate tissue motility of a given position along the radial B-scan over the period of time.

[0232] FIG. 10C illustrates variability of motility patterns at different en-face reslice depths, with high uniformity of patterns in a circumferential direction, according to an example embodiment. Reslice depths are indicated by intersections of lines in radial B-scan images (left).

[0233] FIG. 10D illustrates in a line plot of extracted tissue layer thickness changes as a function of motility over time at locations between mucosa to submucosa and between mucosa to serosa in one radial location and the cross-graph.Axial motility acquisition

[0234] Using radial motility datasets, for example, the data described herein with reference to FIGS. 10A-10E, changes of the tissue thickness over time may be investigated.

[0235] FIGS. 11 A-l IE illustrate OCT axial time-reslices of radial data obtained over 2 minutes, the axial-time reslices showing various motility patterns in different sections of a gut including wild-type distal colons (FIGS. 11 A and 1 IB), a lesioned distal colon (FIG. 11C), a wild-type transitional region between a colon and a rectum (FIG. 1 ID), and a wild-type rectum (FIG. 1 IE). Significantly lower motility may be observed in a mouse with a lesioned colon, as illustrated in FIG. 1 IE, where tissue layers may be predominantly flat. With high penetration depth of near-infrared light into the tissue, influence of other organs on mechanical displacement of the gut may also be investigated.

[0236] Electrophysiology recordings may indicate that longitudinal changes of signals may be more significant in comparison to circumferential changes of signals; a plurality of ID recordings over time at given points positioned longitudinally rather than circumferentially in the tissue may be sufficient for characterizing mechanical tissue changes driven by motility.

[0237] FIG. 12 illustrates ID OCT data recorded without external actuation, wherein tissue motility is a source for changes in detected OCT signals when imaging a gut of wildtype mice, according to an example embodiment. In the example embodiment, external actuation may include rotation of an optical probe or translation of the optical probe. As shown in FIG. 12, non-actuated, static OCT probes may be able to record OCT B-scans of endogenous tissue displacement.Simultaneous motility and morphology optical recordings

[0238] Continuous radial scanning of an OCT probe in one location may provide high spatial and temporal resolution information on motility changes, which may occur at various cycles per minute. According to some example embodiments, electrophysiological measurements may be used to identify rates of oscillation within a gut. For example, in some embodiments, measurements over several minutes may be needed to capture at least 5 cycles of slowest oscillations present in the gut. However, using such approaches, only a few longitudinal positions may be sampled within an acceptable experimental time frame. Experimental time for capturing overall morphological status may be a factor as well. One technique that may be useful for assuring acquisition of oscillations of interest may include decreasing pullback speed of an optical probe.

[0239] FIG. 13 illustrates an overlay of three different OCT longitudinal scanning speeds on 5 minutes of raw spiking activity electrophysiology data from 128 channels spanning 24.8 mm of mouse colon, showing a variety of underlying electrophysiological activity that may be captured by varying OCT longitudinal scanning speeds and showing that a very slow translation of an optical probe may capture both morphology and motility, according to an example embodiment.

[0240] Pullback speed may need to be optimized based upon rates or time periods of motility. According to an example embodiment, a pullback speed may be 5 times slower than motility of 2 cycles per minute to cover all oscillations present. As can be seen below in longitudinal reslices from a normal (WT) mouse and mice with lesioned colon (BAC) the motility captured with a slow pullback has a typical sawtooth pattern, whereas in the lesioned gut there are areas of the gut where the sawtooth pattern is not visible.Distinguishing motion from morphological features

[0241] According to some example embodiments, a very fast pullback OCT scan (e.g., faster than 0.9mm / s pullback speed) may be useful for acquiring OCT data of tissue morphology, the very fast pullback OCT scan being further useful for identifying whether patterns in a scan are caused by motion of tissue. In other embodiments, pharmacological or optogenetic methods may be used to temporarily inhibit muscles of a gut, and OCT scans of the inhibited muscles may be useful as a baseline measurement of morphological variabilityof tissue. The baseline measurement may be subtracted from slow pullback datasets to recover morphology-corrected motility.

[0242] FIG. 14A illustrates a cross-sectional B-scan (left) and orthogonal views (right) of volumetric OCT data obtained at 0.9mm / s longitudinal scanning speed with minimal motion in a colon of a mouse, according to an example embodiment.

[0243] FIG. 14B illustrates a cross-sectional B-scan (left) and orthogonal views (right) s of volumetric OCT data obtained in the mouse of FIG. 14A along the colon at O.lmm / s longitudinal scanning speed, the longitudinal scanning speed acquiring morphology and motility, according to an example embodiment. In some embodiments, morphology-corrected motility OCT data may be generated by subtracting the OCT data acquired at 0.9 mm / s longitudinal scanning speed of FIG. 14A from the OCT data acquired at 0.1 mm / s longitudinal scanning speed of FIG. 14B.

[0244] In some embodiments, electrophysiology recordings may be used to trigger OCT volumetric scans to start following a feature of the electrophysiological recordings, for example, after a burst of peristalsis has completed.

[0245] FIG. 14C illustrates an overlay of three different OCT longitudinal scanning speeds on 5 minutes of raw spiking activity electrophysiology data from 128 channels spanning 24.8 mm of mouse colon, wherein an OCT scan is triggered to start after an end of an electrophysiology burst recorded with electrodes to optimize the capture of morphology and motility with the OCT modality, according to an example embodiment.

[0246] In other embodiments, multi-velocity scans may be performed, wherein scan velocities may be determined based on baseline electrophysiology recordings that may be used to calculate rhythmicity of a gut.

[0247] FIG. 14D illustrates schematically a multi -velocity volumetric OCT scan protocol with a longitudinal morphological scan interwoven in an OCT radial motility scan with velocity changes driven by physiology of a gut, according to an example embodiment. Motility may be captured over periods of 5 bursts of activity and longitudinal pullback, as denoted by OCT probe translation FQCT transi and OCT probe position in time ZQCT, may be actuated in times between bursts, which may be ~20 s in some example embodiments.Minimal distances of longitudinal translation may be defined by a number of OCT frames to be collected and framerate of an OCT system. In the exemplary embodiment of FIG. 14D, an OCT probe with a 30 Hz framerate and with 20 micron spot size allows for 6 cm translation at 0.3 mm / s for achieving optimal sampling. Actuation can be stopped to collect motility at astep before a subsequent morphological pullback is achieved. Real-time closed loop operation may be implemented to trigger OCT scanning by real-time feedback from electrophysiology recordings.Consecutive electrophysiology, morphology, and motility recording

[0248] Combining multiple modalities in consecutive recordings of the same animal or human may provide valuable information relating to the dynamics of GI tissue function, morphology and motility. Disease-associated mechanisms including inflammation may lead to changes in GI function, morphology or motility with varying dynamics that may be captured through consecutive measurements. With combined analysis, this may enable highly sensitive diagnosis of disease status in the GI tract including multi-physiological system observation and understanding of progression of dysfunction.

[0249] FIGS. 17A illustrates raw electrophysiological signals, with visible clusters of spikes, from 128 channels recording from healthy guts and guts with lesions induced by benzalkonium chloride, according to an example embodiment. The records of FIG. 17A demonstrate changes in electrophysiology caused by the lesions in the gut wall detected by the example embodiment.

[0250] FIGS. 17B illustrates power spectral densities (right) from RMS envelopes (left) of the raw electrophysiological signals of FIG. 17A, including recordings from healthy guts and a gut with lesions induced by benzalkonium chloride. FIG. 17B demonstrates changes in spiking rhythms caused by the lesions in the gut wall detected by the example embodiment. Most conspicuous is the missing ~2 c.p.m. peak, seen in normal colons, and representing regular peristaltic waves seen in Figure 17A.

[0251] FIGS. 17A and 17B illustrate raw electrophysiological measurements (FIG. 17 A) and aggregate RMS envelopes from aboral channels together with their spectra (FIG. 17B) of a healthy gut and a gut including lesions in a gut wall induced by benzalkonium chloride and show changes in electrophysiology caused by the lesions in the gut wall, according to an example embodiment. The electrophysiological measurements indicate that raw action potentials are no longer patterned in periodic propagating waves in lesioned tissue as compared to a healthy control animal. Insets illustrating spike frequency patterns also indicate disruptions in mice with the lesions in the gut wall.

[0252] FIGS. 17C and 17D illustrate Fourier spectral analysis of RMS envelopes frequency maps of complex electrophysiology patterns recorded across channels (verticalaxis) in healthy (FIG. 17C) and benzalkonium chloride-lesioned animals (FIG. 17D) , according to an example embodiment. Loss of spiking frequencies as well as frequency specificity is observed in benzalkonium chloride-lesioned animals compared to healthy controls. Top, middle, and bottom panels of FIGS. 17C and 17D may indicate spectral analysis from electrophysiological recordings of different healthy and lesioned mice, respectively. Spiking frequency spectral analysis may indicate loss of frequency bands in BAC -lesioned animals that may be seen commonly in healthy mice (e.g., 18-30 c.p.m. and 60 c.p.m bands), as well as alterations in other frequency bands, for example, broadening of ~2 c.p.m. bands (which may indicate “arrythmia”, as described hereinbelow).

[0253] Various aberrant activity patterns may be observed in the guts of the BAC- lesioned animals. For example, one mouse exhibits consistent chirp-like frequency sweeps, as seen in FIG. 17B, which may be organized in a repetitive pattern. The chirp-like frequency sweeps may correlate with trains of spikes with near-perfect steady linear decrease in rate occurring once per minute on a few channels, which may be interpreted as local spasms.

[0254] At an oral end of an endoscope of the multi-modal endoscopic device, where the propagating waves of spike bursts occur at 2 c.p.m. in healthy controls, summed spiking activity plots may reveal global loss of rhythmicity and amplitude of spike bursts in BAC- lesioned animals compared to non-lesioned controls (described herein with reference to the “Spike frequency” plots of FIGS. 17A and 17B). In BAC animals, a larger spread of spiking frequency with no prominent peak may be seen in Fourier frequency plots comparing the healthy and the BAC -treated groups. Interestingly, each BAC animal may exhibit different profiles of dysfunction, which may be illustrated in FIGS. 17C and 17D. This may be due to variations in effects that BAC exposure may have on tissue as a result of inherent variability in physiology, i.e., a complex system.

[0255] FIGS. 17E and 17F illustrate longitudinal reslices of volumetric OCT data from a healthy colon (FIG. 17E) and a benzalkonium chloride-lesioned distal colon (FIG. 17F). Sawtooth patterns may represent tissue motility, which may be visibly disturbed in the lesioned distal colon.Simultaneous electrophysiology, morphology, and motility recording

[0256] Simultaneous acquisition of electrophysiology with concurrent optical motion tracking of a gut using OCT may be helpful for distinguishing and discerning motion artifacts (e.g., mechanical tissue displacement) from genuine slow wave activity. Such simultaneousacquisitions may be achieved by example embodiments of a multi-modal endoscopic system or device as described herein, which may enable electrical measurements of the gut and, concurrently, optical measurements through transparent walls of an endoscope. Such an approach may also provide morphological context of tissue changes over time. 2D radial motility scans may be acquired at a certain longitudinal position simultaneously with electrophysiological recordings. In order to precisely synchronize both datasets, a motor responsible for radial scanning of an OCT probe may be turned into an OFF state and then back into an ON state. The state change of the OCT probe may cause an electrical artifact in recorded electrophysiology signals.

[0257] FIG. 15A illustrates an unwrapped circumferential OCT scan continuously recorded in a location (left) and an en-face series of OCT data (right), according to an example embodiment. An artifact is induced to facilitate co-regi strati on of OCT and electrophysiology (Ephys) recordings, for example, by aligning the artifacts in the electrophysiological and optical measurements in time. The artifact is visible and annotated by an arrow on the en-face reslice of the OCT radial timeseries.

[0258] FIG. 15B illustrates an OCT axial time series extracted from circumferential time series data recorded at a position inside of a gut (top), according to an example embodiment. Corresponding electrophysiology data recorded simultaneously with 128 electrodes is also illustrated in a bottom panel. As can be seen on the OCT axial timeseries data (top), continuous oscillation at a frequency of about 2.7Hz may be captured. Changes in rhythm of tissue motion may be observed in the OCT measurements, which may correlate with activity bursts recorded with electrophysiology.

[0259] FIG. 16A illustrates an en-face OCT reslice in a mucosa layer of a gut, the en-face reslice showing a shadowing effect of electrophysiological paths on an outer sheath of an endoscope on the en-face OCT reslice, according to an example embodiment. Dark areas (black shadows) indicate a full pattern of electrodes and paths, and tissue is not visible in the dark areas. As illustrated in FIG. 16A, the electrodes and the paths of an electrical probe may partially block light transmission. In comparison with areas of the B-scan obtained at a distal tip of an endoscope (far left), a lack of electrode matrix may allow normal transmission of light to a tissue layer. B-scan acquired through an electrode matrix may show areas where tissue is not visible (black shadow in B-scan) in comparison to B-scans obtained at a distal tip of an endoscope (far left), which may extend beyond a front of the electrode matrix.

[0260] FIG. 16B illustrates a longitudinal reslice of OCT data, which may be similar to the OCT data used to generate the en-face OCT reslice of FIG. 16 A, showing the full pattern of electrodes and paths including thin dark lines from paths and thicker lines from electrodes. The longitudinal reslice of the OCT data may show the repeating thin dark lines fand the thicker lines, but overall, the tissue morphological changes can be appreciated. The en-face reslice of the OCT data at mucosa layer shows the full pattern of the electrodes and the paths though a shadow cast by the electrodes and the paths. A wavy line seen on the bottom may corresponding to the edge of the electrode matrix. Static patterns of the electrodes may be used to correct for motion artefacts correction in the OCT data as well as for precise coregistration of OCT and electrophysiology data.

[0261] FIG. 16C illustrates OCT radial B-scans comparing areas without (top) and with (bottom) an electrode array on an outer sheath of a mini-endoscope and an effect of partial blocking of light transmission to tissue due to a presence of an electrical array (bottom).Electrical Stimulation

[0262] According to some example embodiments of the invention disclosed herein, contacts (e.g., electrical contacts or electrodes) of an endoscope may be configured not just for recording, but also for electrical stimulation. Each contact of the contacts of an electrode matrix may be configured to generate specific stimulation patterns, which may include replaying normal activity patterns. Generated stimulation patterns may vary with respect to time or position along the electrode matrix, which may enable generation of spatially, temporally, or spatiotemporally varying patterns. Tuning electrical stimulation parameters may be useful for eliciting functional peristaltic activity patterns in vivo in colons, particularly abnormally functioning colons, e.g., pharmacologically silenced colons.

[0263] FIG. 18A illustrates an example embodiment of bipolar stimulation with trains of biphasic pulses at 10 Hz with an amplitude of 300 mA A between a most distal eight contacts and a next eight contacts on one quadrant of an endoscope. Restated, the most distal eight contacts on one quadrant may be configured to deliver the biphasic pulses and the next eight contacts may be configured to deliver a polarity-inverted signal based on the biphasic pulses to generate a spatiotemporally varying stimulation signal. The example embodiment of the bipolar stimulation may be an example set of electrical parameters that may typically be effective in mice.

[0264] A capacity to stimulate a gut, e.g., in a silent gut, may be important for enabling assessment of stimulation-evoked activity instead of collecting sufficient spontaneous activity over time, which may be too burdensome in subjects with a slow peristalsis (sparse activity) seconds.

[0265] FIG. 18B illustrates electrophysiological measurements showing an exemplary stimulus which may be used to generate bursts of activity in a gut of a wild-type mouse, according to an example embodiment.

[0266] FIG. 18C illustrates an electrophysiology recording acquired over a time period including two stimulations with incorrect parameters in a colon silenced by isoflurane anesthesia, according to an example embodiment. The two stimulations occur at -10.4 and -11.9 seconds, which may be indicated by the vertical wide black line or dot patterns. As used herein, the “incorrect” patterns may be ill-suited for stimulating activity, for example peristaltic activity, within the colon or other section of a gastrointestinal tract of an animal or human.

[0267] FIG. 18D illustrates an electrophysiological recording acquired in a wild-type mouse of FIG. 18C in a colon silenced by under isoflurane anesthesia, with a silenced gut bursts of activity generating bursts of activity following electrical stimulation, according to an example embodiment. Electrical stimulation may be identified by black vertical lines.

[0268] Activity within a gastrointestinal system may be modulated using electrical stimulation. In an example embodiment, a healthy wild-type mouse may be held under ketamine / medetomidine anesthesia and pacing or modulation of activity within a GI system of the mouse may be performed.

[0269] Following a first electrical recording of a typical activity of 2 peristaltic bursts per minute, repeating bipolar stimulation at 3 cycles per minute for 10 minutes may be used to increase frequency of peristalsis bursts to 3 per minute. Once stimulation was turned off the gut function returned to its normal frequency of 2 per minute. This shows that intraluminal stimulation can be used to control the rhythm and possible to increase and / or stabilize frequency of bursts in a gut with abnormal function.

[0270] FIG. 19A illustrates time series data of RMS envelopes of electrophysiological signals, the electrophysiological signals including baseline measurements from 0 to 12 min, followed by optimization of stimulation parameters randomly spaced from 12 min to 40 min, followed by 10 minutes of repeated bipolar stimulation at a rate of 3 cycles per minute, according to an example embodiment. Measurements of a gut of a mouse underketamine / medetomidine anesthesia may indicate typical activity of ~2 peristaltic bursts per minute. The repeated bipolar stimulation occurs between 43 min and 53 min and may cause an increase in frequencies of burst activity to ~3 peristaltic bursts per minute. After stimulation is turned off, gut function may return to the typical activity of ~2 peristaltic bursts per minute. Such results may indicate that stimulation may be used to control rhythms or patterns of gut function and that frequency of bursts in a gut with abnormal function may be controlled, for example, increased, decreased, or stabilized, using electrical stimuli.

[0271] FIG. 19B illustrates a zoomed in section of the time series data of aggregate RMS envelopes FIG. 19 A.

[0272] FIG. 19C illustrates a running spectrogram of the time series data of aggregate RMS envelope of FIG. 19 A. Roughly between 43 and 49 minutes, a notable shift towards a 3 cycles per minute band may be evident.

[0273] FIG. 19D illustrates shifts in frequency of spike bursts recorded in the RMS of electrophysiological signals of FIG. 19A during stimulation in wild-type mice, according to an example embodiment.

[0274] In addition to eliciting stimulation in a silent gut, also frequency modulation of gut activity, as well as amplitudes of gut activity, e.g., peristaltic waves, may potentially be modulated or controlled using exogenous signals as well. In an example embodiment, a healthy wild-type mouse may be held under ketamine / medetomidine anesthesia.

[0275] Amplitudes of a stimulated burst may be dependent upon a refractory period between a stimulus and a prior spontaneous burst. Applying stimulation just after a spontaneous burst may result in no activity being recorded. If a stimulus is applied 5 to 12 seconds after the spontaneous burst, the amplitudes of the stimulated burst may be similar to amplitudes of the spontaneous bursts. Stimulations applied 15 to 30 seconds after the spontaneous bursts may generate stimulated activity with amplitudes approximately 30% higher than the amplitudes of the spontaneous bursts.

[0276] FIG. 20A illustrates a raw electrophysiology recording in a gut of a mouse, the electrophysiological recording including a spontaneous bursts followed by a stimulus and an evoked burst of increased intensity, according to an example embodiment. The stimulus may be identified by the dark gray / black vertical band.

[0277] F FIG. 20B illustrates aggregate RMS values showing peak amplitudes of stimulation-evoked bursts in comparison to spontaneous bursts before stimulation and interburst background activity as a function of refractory period (time since last burst) before thestimulation, demonstrating that the efficacy of the stimulation depends on real-time background activity of the tissue, according to an example embodiment. Greater peak amplitudes may be recorded for stimulations occurring at longer time gaps from a prior spontaneous burst, demonstrating refractory dynamic of intraluminal gut stimulation.Optogenetic modality for cell-specific modulation of activity

[0278] Optical stimulation of gut tissue may be achieved using optogenetics, for example, using genetic manipulation techniques to express chanelrhodopsin (ChR) proteins in selected cell types. ChRs may cause the selected cell types to be sensitive to optical activation at specific wavelengths, which may enable wavelength- and cell type-specific depolarization of cells.

[0279] Modification of components of optical designs for optogenetic stimulation may add multiple layers of selectivity for modulating cells in a gut wall. Such modifications may contribute significantly to customization capabilities of optogenetic control.

[0280] FIGS. 22A-22G illustrate modifications of components of optical designs and optogenetic sensors for optogenetic stimulation, according to example embodiments.

[0281] FIGS. 22 A and 22B illustrate example embodiments of widefield illumination, which may be used to optogenetically stimulate multiple ENS neurons (Nj... N ) within a large field of view, which may encompass a tissue’s circumference. FIG. 22A illustrates an endoscopic device 2200a configured to shine a widefield illumination in a forward facing direction 2252a and FIG. 22B illustrates an endoscopic device 2200b configured to shine a widefield illumination in a side-facing direction 2252b. The endoscopic devices 2200a, 2200b may be multi-modal endoscopic devices configured to acquire electrophysiology, morphology, or motility recordings, or a combination thereof.

[0282] In FIGS. 22 A and 22B opsin expression may be pan-neuronal, meaning different type of neurons may be activated by light. In a similar biological context, spatially-selective illumination may be achieved with focused light wit a ball lens or another focusing micro- optical design (e.g. meta lens, free-form lens, GRIN lens).

[0283] FIG. 22C illustrates endoscopic device 2200c and the use of spatially selective side-viewing illumination to optogenetically stimulate ENS neurons (Nj... NN) within the focal area of the laser the endoscopic device 2200c includes a ball lens 2254a configured to illuminate a smaller field-of-view 2252c. The endoscopic device 2200c may therefore beuseful for pan-neuronal, spatially selective stimulation. The device may be scanned along the lumen axis or circumferentially.

[0284] In tissues expressing several varieties or populations of opsins, which may have different functions (for e.g. excitatory or inhibitory), multiple wavelengths may be used to enable complex coordination of local function. As mentioned earlier, combining Cre recombinase expression with a neuronal subtype promoter may enable cellular subtypespecific optogenetic manipulation. As such, spatial illumination selectivity may be combined with cell subtype opsin expression for cell subtype selectivity. Cell subtypes may include neuronal cell subtypes or other cell subtypes, for example, Cajal cells.

[0285] FIG. 22D illustrates use of spatially selective side-viewing illumination to optogenetically stimulate a subtype of neurons in an ENS (A2). An endoscopic device 2200d of FIG. 22D may be similar to the endoscopic device 2200c described herein with reference to FIG. 22C and may include a ball lens 2254b and a smaller field-of-view 2252d. By utilizing a variety of opsins with different activation wavelengths, only the subset or subtype of neurons of (A2) may be excited using a given illumination wavelength. Further, if multiple opsins differing in excitatory or inhibitory effect are expressed, multiple light sources matching opsin activation wavelengths may be applied to tissue for complex coordination of local function.

[0286] In addition, the optical components may be designed to modify the beam profile and the axial light propagation.

[0287] FIG. 22E illustrates an endoscopic device 2200e configured for spatially selective side-viewing illumination with axial specificity to optogenetical stimulation of targeted regions within the gut wall containing pan-neuronal opsin expression. The device may include a ball lens 2254c configured to transmit converging light directed toward a desired location 2252e. The ball lens 2254c may be adjustably positioned to modify the focal point and intensity distribution, providing variable depth penetration and selective activation of opsin-expressin cells. The convergent illumination configuration produces a focused beam with defined divergence characteristics allowing controlled activation volumes while minimizing off-target effects in adjacent tissue layers.

[0288] Other cell types, for example, Interstitial cells of Cajal or smooth muscle cells of circular or longitudinal layers of a gut wall, may be also targeted using such optogenetic approaches.

[0289] FIG. 22F illustrates use of spatially selective side-viewing illumination to optogenetically stimulate interstitial cells, for example, Interstitial cells of Cajal(C), embedded in muscle layers of the gut wall. FIG. 22G illustrate use of spatially selective sideviewing illumination to optogenetically stimulate smooth muscle cells (M) that make up the muscle layers of a gut wall. For FIGS. 22F and 22G, optogenetic stimulation of Interstitial cells of Cajal and smooth muscle cells may be achieved by changing a promotor in a Cre recombinase construct to unlock opsin expression.

[0290] Although specific embodiments have been described herein, it will be appreciated by those skilled in the art that various modifications and combinations of optical components, opsin proteins and cellular targets may be implemented without departing from the scope of the present design. Such variations may include alternative arrangements of optical elements, different opsin variants, or cell populations selected according to particular experiments protocols or diagnostic and therapeutic procedures required by the intended application. FIGS. 23A-F illustrate example embodiments of micro-optics configured for delivery of light to tissue. The light delivered to the tissue may be configured for optical imaging, e.g., optical coherence tomography or fluorescence imaging, or optogenetic illumination. The example embodiments of FIGS. 23A-F may be similar, and similar elements may be labeled with similar reference numbers.

[0291] FIG. 23A illustrates an endoscopic device 2300a including a dual fiber probe configuration. The dual fiber probe configuration of the endoscopic device 2300a may include a first optical fiber 2342a- 1 coupled to first ball lens 2254a- 1 and a second optical fiber 2342a-2 coupled to a second ball lens 2354a-2. The first fiber 2342a- 1 and the second fiber 2342a-2 may carry light of a same wavelength or of different wavelengths; light emitted from the first fiber 2342a- 1 and the second fiber 2342a-2 may be focused with different spot sizes, at different depths, or a combination thereof. The first fiber 2342a- 1 and the second fiber 2342a-2 may be housed in a protective tubing 2356a. The endoscopic device 2300a may further including a sheath 2318a, which may be transparent, configured to enable intralumenal insertion. FIG. 23B illustrates an endoscopic device 2300b including another dual fiber probe configuration. The endoscopic device 2300b may include a gradient-index (GRIN) lens 2356 and a prism 2354b-l in addition to an optical fiber 2342b and a ball lens 2354b-2. The GRIN lens 2356 and the prism 2354b- 1 may be used for optogenetic stimulation. The GRIN lens 2356 may further be coupled to another optical fiber (not shown). Optical fibers, e.g. the optical fiber 2342b, may be housed individually within protectivetubings 2356b-l, 2356b-2. The endoscopic device 2300b may further including a sheath 2318b, which may be transparent, configured to enable intralumenal insertion. Generally, any combination of lenses or fibers, including the configurations described herein with reference to FIGS. 23A and 23B may be used.

[0292] FIG. 23 C illustrates an endoscopic device 2300c including a side-viewing illumination system. The endoscopic device may include an optical element 2354c, for example, an axicon or a tapered fiber, configured to shine light in a variety of patterns in a side-firing configuration. Axicon lenses may be useful for optogenetic stimulation as axicon lenses may shape light beams into a ring-like profile for circumferential tissue stimulation. FIG. 23D illustrates an endoscopic device 2300d including a dual fiber endoscopic probe, the dual fiber endoscopic probe including an axicon lens 2354d-l. A given fiber of the dual fiber endoscopic probe may be optically coupled to the axicon lens 2354d-l while another fiber of the dual fiber endoscopic probe may be optically to another lens time, for example, a ball lens 2354d-2. According to some example embodiments, more than two fibers may be used in an endoscopic probe.

[0293] FIG. 23E illustrates an endoscopic device 2300e incorporating a dual-clad fiber (DCF) 2342c configured for multi -wavelength light delivery. The dual-clad fiber 2342c comprises a cladding layer operable to transmit light at a first wavelength, which may be a shorter wavelength, and a core to transmit light at a second wavelength, which may be a longer wavelength, distinct from the first wavelength. The first wavelength may also be equal to the second wavelength. .In some embodiments, light for OCT may be carried in the core or the second layer and light for optogenetic stimulation may be carried in the cladding or vice versa. The DCF 2342c may be coupled to a single ball lens 2354e. FIG. 24F illustrates an endoscopic device 2300f with a DCF coupled to a prism 2354f.

[0294] Choice of optics, for example, GRIN lenses, prisms, ball lenses, axicon lenses, or other optical elements, may be determined by desired illumination profiles of light on tissue of a gastrointestinal system.Closed loop neuromodulation

[0295] Simultaneous recording and stimulation of gut function may enable closed-loop neuromodulation of a gut wall in vivo and may provide high temporal sensitivity personalized modulation of gut function.

[0296] FIGS. 21A-21D illustrate exemplary stimulation modes of operation for a device configured to stimulate and to acquire measurements of a GI system, the stimulation modes including stimulation with set parameters (FIG. 21 A), stimulation with parameters optimized based on a baseline measurement of an individual human or animal (FIG. 2 IB), stimulation with closed-loop operation for real-time feedback (FIG. 21C), or stimulation with long-term correction (FIG. 2 ID), according to an example embodiment. Thus, the exemplary stimulation modes may be used for open-loop or closed-loop (i.e. self-regulating feedback) architectures for colonic stimulation.

[0297] With regard to individually optimized stimulation (FIG. 2 IB) or long time scale self-correction (FIG. 2 ID), the available parameter space for stimulation (pulse width, shape, amplitude / power and intra-burst frequency, burst duration, etc.), especially with a high resolution electrode matrix (large number of anode-cathode combinations) or a scanning optogenetic probe, may be very large. Furthermore, there may be variability between gut muscle, ENS architecture, or gut activity in between subjects. A closed-loop operation may be used to converge on a most optimal set of stimulation burst parameters to restore normal function and may further be useful for subsequently adjusting the parameters if effectiveness of stimulations drifts from an optimum.

[0298] With regard to closed-loop operation for fast real-time feedback (FIG. 21C), as described hereinabove, innate colonic rhythms may vary substantially among individuals while effectives of stimulation may be strongly dependent upon refractory dynamics of the colonic rhythms. Thus, a closed-loop operation, wherein each stimulation burst may be triggered by ongoing activity a statistical model trained to recognize an optimal temporal window in the ongoing activity, may be more likely to be effective than an open-loop scheme. Alternatively, frequencies of stimulation bursts may be set to best address individual innate colonic rhythms based on baseline spontaneous activity. Effectiveness of the frequencies of stimulation bursts may be monitored to periodically adjust as needed; this may form a long-term feedback scheme.Data Flow

[0299] FIG. 41 illustrates an example embodiment of a method 4101 for processing electrophysiology data. The method may be similar to methods used to analyze electrophysiology data described hereinabove, including, for example, the measurements of FIGS. 5A-5C, 6, 13, 14D, and 17A-17F. The method 4101 includes raw data 4103, whichmay be sampled at 2kHz. The raw data 4103 undergoes preprocessing 4105, which may include high-pass filtering 4107, noisy channel elimination 4109, artifact elimination 3911, and comparing with a common-ground reference 4113 to generate preprocessed data 4115.

[0300] The preprocessed data 4115 may be evaluated for spike morphology 4117, which may include finding a signal minimum 4119 less than a threshold (the threshold may be, for example, < 150 pV) and excluding data 4121 within 25 ms of the signal minimum found. The process of finding the signal minimum 4119 and excluding data 4121 may be repeated until exhaustion (or until no minima under a threshold is found). Further evaluating for spike morphology 4117 may further include excluding exclude cases 4123 with < 100 pV local minima within 50 ms 4123 and excluding cases 4125 with halfwidth outside of a desired bound 4125, for example, less than 10 ms or greater than 50 ms. Further evaluating for spike morphology 4117 may further include extracting 4127 epochs of a desired duration, e.g., 100 ms, centered on remaining minima to generate a dataset 4129 of individual spike morphology and variance. The dataset 4129 may be used with a benchmark 4131 spike morphology and variance from normal population to compare 4133 spike waveform peak values and latencies to find statistical anomalies.

[0301] The preprocessed data 4115 may also be evaluated for spike envelope 4135, which may include splitting 4137 data into segments, e.g., 100 ms segments, and calculating 4139, for each segment, and RMS value of the samples to generate an RMS envelope 4141 of spiking activity. The RMS envelope 4141 may be used for evaluating spike rhythmicity 4143, which may include splitting 4145 the RMS envelopes 4141 into 2-minutes segments. Evaluating spike rhythmicity 4143 may further include detrending 4147 each segment, applying 4149 a window function, e.g., a Hanning window function, and calculating 4151 short-time Fourier transforms of each segment to generate individual spectrum and variance of spiking activity 4153 for each channel. The individual spectrum and variance of spiking activity 4153 may be used with benchmark 4155 spectrum and variance of spiking activity from a normal population to compare 4157 spectral power values across frequencies and locations (channels) and latencies to find statistical anomalies.The preprocessed data 4115 may further be used to evaluate spike synchronicity 4159 to generate individual spike synchronization 4161 of spiking activity across each channel. The individual spike synchronization 4161 may be used with benchmark 4163 synchronization of spiking activity from a normal population to compare 4165 synchronization of spiking activity across locations (channels) and latencies to find statistical anomalies.

[0302] While example embodiments have been particularly shown and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the embodiments encompassed by the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A multi-modal endoscopic system, comprising: an electrical module comprising an electrical probe configured for functional assessment of tissue of a gastrointestinal (GI) tract; an optical module comprising an optical probe configured for optical assessment of the tissue of the GI tract; and optionally, a delivery module configured to deliver the electrical and optical probes to the GI tract.

2. The multi-modal endoscopic system of claim 1, wherein the optical probe is configured for micro-anatomical assessment, for functional or for physiological assessment of the tissue of the GI tract.

3. The multi-modal endoscopic system of claim 2, wherein the optical module is configured to acquire optical coherence tomography (OCT) measurements or to deliver energy in the form of light to the tissue.

4. The multi-modal endoscopic system of claim 3, wherein the optical probe comprises an optical coherence tomography sensor.

5. The multi-modal endoscopic system of any one of claims 1-4, wherein the optical probe includes one or more optical fibers optically coupled to a light source or to a detector of the optical module, the one or more optical fibers configured to transmit at least one of light from the light source or light reflected from the tissue.

6. The multi-modal endoscopic system of claim 5, wherein the one or more optical fibers include a double clad fiber, a first portion of the double clad fiber being configured to transmit light from a first light source, and a second portion of the double clad fiber being configured to transmit light from a second light source.

7. The multi-modal endoscopic system of claim 5, wherein a given fiber of the one or more optical fibers is optically coupled to an optical element configured to change a direction of light transmitted through the given fiber.

8. The multi-modal endoscopic system of any one of claims 1-7, wherein the optical probe is configured to move with respect to the delivery module.

9. The multi-modal endoscopic system of claim 8, wherein movement of the optical probe with respect to the delivery module includes at least one of translational movement along a longitudinal axis of the delivery module or rotational movement around the longitudinal axis.

10. The multi-modal endoscopic system of claim 9, wherein the optical module is configured to acquire measurements while the optical probe undergoes the translational movement or the rotational movement.

11. The multi-modal endoscopic system of any one of claims 1-10, wherein the optical assessment includes at least one of a volumetric OCT scans, radial OCT scan, longitudinal OCT scan, an en-face OCT image, a circumferential OCT scan, or timeseries OCT imaging of a single point acquisition or multipoint acquisition.

12. The multi-modal endoscopic system of any one of claims 1-11, wherein at least one of the electrical module or the optical module is configured to deliver energy to the tissue.

13. The multi-modal endoscopic system of claim 12, wherein the electrical module is configured for stimulation of the tissue to elicit, inhibit or alter function of the tissue and the optical module is configured for activation of the tissue to elicit, inhibit or alter the function of the tissue.

14. The multi-modal endoscopic system of claim 12, wherein the electrical module is configured to deliver at least one of a time-varying electrical signal or a spatially- varying electrical signal.

15. The multi-modal endoscopic system of claim 12, wherein the optical module is configured for activation of the tissue to elicit, inhibit or alter its function by activating an optogenetic sensor.

16. The multi-modal endoscopic system of any one of claims 1-15, wherein the electrical probe comprises a plurality of electrodes on a carrier.

17. The multi-modal endoscopic system of claim 16, wherein the plurality of electrodes is configured to acquire electrical measurements of the tissue of the GI tract, to deliver electrical signals to the tissue, or a combination thereof.

18. The multi-modal endoscopic system of claim 17, wherein the plurality of electrodes is configured to acquire the electrical measurements and to deliver the electrical signals at a plurality of positions of the GI tract, the plurality of positions including at least a circumferential portion of the tissue or a longitudinal portion of the tissue.

19. The multi-modal endoscopic system of claim 18, wherein a given electrical signal of the electrical signals delivered by a given electrode of the plurality of electrodes is determined by a corresponding position of the given electrode.

20. The multi-modal endoscopic system of claim 16, wherein the carrier comprises a flexible, non-conductive substrate and wherein respective leads of the plurality of electrodes are configured to extend through the non-conductive substrate or along a surface of the non-conductive substrate.

21. The multi-modal endoscopic system of claim 16, wherein the delivery module is in coupled arrangement with the carrier.

22. The multi-modal endoscopic system of claim 16, wherein at least a portion of the carrier is configured to cause the plurality of electrodes to contact the tissue.

23. The multi-modal endoscopic system of claim 22, wherein the carrier includes a plurality of members configured to project radially relative to a longitudinal axis of the carrier, the plurality of members in coupled arrangement with the electrodes and further configured to cause the plurality of electrodes to contact the tissue.

24. The multi-modal endoscopic system of claim 23, wherein the plurality of members comprise a flexible substrate configured to form a plurality of repeating arches projecting radially outward relative to the longitudinal axis of the carrier.

25. The multi-modal endoscopic system of claim 24, wherein the carrier defines one or more apertures below the one or more arches and wherein the optical probe is configured to extend through the one or more apertures.

26. The multi-modal endoscopic system of claim 23, wherein a member of the plurality of members is configured to be a flexible protrusion and wherein at least one electrode of the plurality of electrodes is positioned along the flexible protrusion.

27. The multi-modal endoscopic system of claim 22, wherein the carrier includes a flexible substrate configured to be attached to the tissue.

28. The multi-modal endoscopic system of claim 22, wherein the carrier includes at least one inflatable balloon and wherein inflating the at least one inflatable balloon causes the plurality of electrodes to extend radially from the longitudinal axis of the carrier.

29. The multi-modal endoscopic system of claim 28, wherein the carrier further comprises a semi-rigid cage configured to surround the at least one inflatable balloon and to define one or more apertures, further wherein inflating the at least one inflatable balloon causes the at least one inflatable balloon to extend through the one or more apertures.

30. The multi-modal endoscopic system of claim 22, wherein the carrier includes a sleeve, wherein the sleeve in an inverted collapsed state is configured to be contained in a channel of the carrier and wherein filling the sleeve causes the sleeve to evert beyond a distal tip of the carrier.

31. The multi-modal endoscopic system of claim 22, wherein the carrier includes one or more clips, a clip of the one or more clips in coupled arrangement with at least one electrode of the plurality of electrodes.

32. The multi-modal endoscopic system of any one of claims 21-31, wherein the carrier is configured to be removable from the delivery module.

33. The multi-modal endoscopic system of any one of claims 1-32, wherein at least a portion of the delivery module is configured to be substantially transparent to light.

34. The multi-modal endoscopic system of any one of claims 1-33, wherein the delivery module includes a hollow channel, and the optical module is configured to pass through the hollow channel.

35. The multi-modal endoscopic system of any one of claims 1-34, further comprising a processing module communicatively coupled to the electrical module and the optical module, the processing module further configured to acquire electrical measurements of the tissue using the electrical module and to acquire optical measurements of the tissue using the optical module.

36. The multi-modal endoscopic system of claim 35, wherein the processing module is configured to cause at least one of an electrical stimulation to elicit, inhibit, or alter function of the tissue and an optical activation of the tissue to elicit, inhibit or alter the function of the tissue in response to at least one of the electrical measurements and the optical measurements acquired.

37. The multi-modal endoscopic system of claim 35, wherein the processing module is further configured to co-register the electrical measurements and the optical measurements using features of the electrical measurements or the optical measurements.

38. A multi-modal endoscopic device, comprising: a plurality of electrodes on a carrier, the plurality of electrodes configured to record electrical activity of tissue of a GI tract, an optical fiber configured to deliver light into the tissue and to collect light reflected from the tissue; and optionally, a conduit configured to enclose the optical fiber, the conduit further configured to deliver and to deploy the electrode carrier.

39. The multi-modal endoscopic device of claim 38, wherein the plurality of electrodes is further configured to deliver an electrical stimulus to the tissue.

40. The multi-modal endoscopic device of claim 39, wherein the plurality of electrodes is configured to acquire the electrical measurements and to deliver the electrical signals at a plurality of positions on the tissue of the GI tract, the plurality of positions including at least a circumferential portion of the tissue and a longitudinal portion of the tissue41. The multi-modal endoscopic device of any one of claims 38-40, wherein the carrier comprises a flexible, non-conductive substrate and wherein respective leads of the plurality of electrodes are configured to extend through the non-conductive substrate or along a surface of the non-conductive substrate.

42. The multi-modal endoscopic device of any one of claims 38-41, wherein at least a portion of the carrier is configured to cause the plurality of electrodes to contact the tissue.

43. The multi-modal endoscopic device of claim 42, wherein the carrier includes a plurality of members configured to project radially relative to a longitudinal axis the carrier, the plurality of members in coupled arrangement with the electrodes and further configured to cause the plurality of electrodes to contact the tissue.

44. The multi-modal endoscopic system of claim 43, wherein the plurality of members comprise a flexible substrate configured to form a plurality of repeating arches projecting radially outward relative to the longitudinal axis of the carrier.

45. The multi-modal endoscopic device of claim 44, wherein the carrier is configured to define one or more apertures between or below the one or more arches and wherein the optical probe is configured to extend through the one or more apertures.

46. The multi-modal endoscopic device of claim 43, wherein a member of the plurality of members is configured to be a flexible protrusion and wherein at least one electrode of the plurality of electrodes is positioned along the flexible protrusion.

47. The multi-modal endoscopic device of claim 42, wherein the carrier includes at least one inflatable balloon and wherein inflating the at least one inflatable balloon causes the plurality of electrodes to extend radially from the longitudinal axis of the carrier.

48. The multi-modal endoscopic device of claim 47, wherein the carrier further comprises a semi-rigid cage configured to surround the at least one inflatable balloon and to define one or more apertures, further wherein inflating the at least one inflatable balloon causes the at least one inflatable balloon to extend through the one or more apertures.

49. The multi-modal endoscopic device of claim 42, wherein the carrier includes at least one sleeve, and wherein the at least one sleeve in an inverted collapsed state is configured to be contained in a channel of the carrier and wherein filling the at least one sleeve causes the at least one sleeve to evert beyond a distal tip of the delivery module.

50. The multi-modal endoscopic device of claim 42, wherein the carrier includes one or more clips, a clip of the one or more clips in coupled arrangement with at least one electrode of the plurality of electrodes.

51. The multi-modal endoscopic device of any one of claims 38-50, wherein the multimodal endoscopic device is configured for imaging tissue structures in the intestinal wall using optical coherence tomography or another optical modality with endogenous and / or exogenous contrast to achieve penetration depth of at least 2 mm, spatial resolution of less than 100 microns, and axial resolution of less than 10 microns for analysis of morphology of the tissue structures.

52. The multi-modal endoscopic device of any one of claims 38-51, wherein the optical fiber is: a single mode optical fiber; a multi-mode optical fiber; or a double-clad optical fiber, a first portion of the double clad fiber configured to transmit light from a first light source and a second portion of the double clad fiber configured to transmit light from a second light source.

53. The multi-modal endoscopic device of any one of claims 38-52, wherein the optical fiber is a first optical fiber and the multi-modal endoscopic device includes at least one additional optical fiber configured to deliver light into the tissue or to collect light reflected from the tissue.

54. The multi-modal endoscopic device of any one of claims 38-53, wherein a given fiber of the one or more optical fibers is optically coupled to an optical element, the optical element configured to change a direction of light transmitted through the given fiber.

55. The multi-modal endoscopic device of any one of claims 38-54, wherein the optical fiber is configured to move with respect to the conduit.

56. The multi-modal endoscopic device of claim 55, wherein movement of the optical fiber with respect to the conduit includes at least one of translational movement or rotational movement.

57. The multi-modal endoscopic device of any one of claims 38-56, wherein at least a portion of the conduit is configured to be substantially transparent to light.

58. The multi-modal endoscopic device of claim 57, wherein the conduit is constructed at least in part using a transparent polymer, glass, or transparent nylon material.

59. A method for multi-modal evaluation of a tubular structure, the method comprising: inserting a measurement device into a lumen of the tubular structure; acquiring a first measurement of the tubular structure along a first length of the measurement device using a first measurement modality, the first measurement including data representative of electrical activity of the tubular structure; acquiring a second measurement of the tubular structure along a second length of the measurement device using a second measurement modality, the second measurement occurring with the first measurement; co-registering the first measurement and the second measurement to generate multi-modal measurement data; and analyzing the multi-modal measurement data generated to characterize one or more properties of the tubular structure.

60. The method of claim 59, wherein the one or more properties characterized include structural integrity, architecture, physiology, patency, responsivity, or function of the tubular structure.

61. The method of claim 59 or 60, wherein co-registering the first measurement and the second measurement includes aligning the first measurement and the second measurement temporally, spatially, or spectrally.

62. The method of any one of claims 59-61, wherein analyzing the multi-modal measurement data includes, for the first measurement, identifying and characterizingspike patterns of the electrical activity, further wherein characterizing the spike patterns includes determining spike morphology, intensity, rhythmicity or spatiotemporal synchronicity of spiking activity.

63. The method of any one of claims 59-62, further comprising introducing a stimulus to the tubular structure, the stimulus being temporally correlated with the first measurement or the second measurement.

64. The method of claim 63, wherein analyzing the multi-modal measurement data includes characterizing a response of the tubular structure to the stimulus introduced.

65. The method of claim 63, wherein the stimulus introduced includes an optical stimulus , an electrical stimulus, a magnetic stimulus, mechanical stimulus, acoustic stimulus, or a chemical stimulus.

66. The method of claim 63, wherein the stimulus is delivered after the first measurement and the second measurement, the method further comprising determining a type of the stimulus based on the first measurement or the second measurement.

67. The method of claim 66, further comprising acquiring additional measurements of the tubular structure after delivering the stimulus and delivering a subsequent stimulus based on the additional measurements acquired.

68. The method of any one of claims 59-67, further comprising co-registering the multimodal measurement data with data acquired from an additional measurement modality.

69. The method of claim 68, wherein the additional measurement modality includes magnetic resonance imaging.

70. The method of any one of claims 59-69, further comprising acquiring at least one additional measurement using the first measurement modality or the second measurement modality.

71. The method of any one of claims 59-70, wherein the second measurement includes data representative of a functional parameter or an architecture of the tubular structure.

72. The method of any one of claims 59-71, wherein the second measurement is acquired using an optical, acoustic, opto-acoustic, mechanical, electrical, or magnetic measurement modality.

73. The method of any one of claims 59-72, wherein aligning the first measurement acquired and the second measurement acquired includes aligning within the measurement device a first instrument configured to acquire the first measurement and a second instrument configured to acquire the second measurement.

74. The method of any one of claims 59-73, wherein aligning the first measurement acquired and the second measurement acquired occurs after acquiring the first measurement and acquiring the second measurement.

75. The method of any one of claims 59-74, wherein analyzing the multi-modal measurement data includes applying a correction for one of the first measurement or the second measurement based on the other of the first measurement or the second measurement.

76. The method of any one of claims 59-75, wherein the first measurement and the second measurement overlap at least in part in space or in time.

77. The method of any one of claims 59-76, wherein the tubular structure is tissue of a gastrointestinal (GI) tract.

78. The method of claim 77, wherein the measurement device is an endoscopic device comprising: an electrical module for acquiring the first measurement, the electrical module comprising an electrical probe configured for functional assessment and stimulation of the tissue to elicit, inhibit or alter function of the GI tract; and an optical module for acquiring the second measurement, the optical module comprising an optical probe configured for micro-anatomical assessment and activation of the tissue to elicit, inhibit or alter the function of the GI tract.

79. The method of claim 78, wherein the optical probe comprises an optical coherence tomography (OCT) sensor, and wherein the electrical probe comprises a plurality of electrodes on a carrier.

80. The multi-modal endoscopic system of claim 22, wherein the carrier includes an ellipsoid structure configured to adhere to the tissue of the GI tract and wherein the electrodes are in coupled arrangement with a surface of the ellipsoid structure.

81. The multi-modal endoscopic device of claim 42, wherein the carrier includes an ellipsoid structure configured to adhere to the tissue of the GI tract and wherein the electrodes are in coupled arrangement with a surface of the ellipsoid structure.

82. The multi-modal endoscopic system or device of any one of claims 1-58 and 80-81, further comprising a sensor in coupled arrangement with the carrier, the sensor configured to acquire data representative of at least one of a position, motion, or orientation of the carrier.

83. A device for measuring properties of a gastrointestinal tract of a human or animal, the device comprising: a plurality of electrodes configured to acquire electrical measurements of a tissue of the gastrointestinal tract; and a carrier including one or more flexible members configured to extend with respect to a longitudinal axis of the carrier, an electrode of the plurality of electrodes being in coupled arrangement with a member of the one or more members and the one or more members being further configured to cause the electrode to contact the tissue.

84. A device for measuring properties of a gastrointestinal tract of a human or animal, the device comprising: a plurality of electrodes configured to acquire electrical measurements of a tissue of the gastrointestinal tract; and one or more carriers, a carrier of the one or more carriers including a substrate in coupled arrangement with at least one electrode of the one or more electrodes, the substrate or the at least one electrode configured to attach the electrode to a surface of the tissue.

85. A device for measuring properties of a gastrointestinal tract of a human or animal, the device comprising: a plurality of electrodes configured to acquire electrical measurements of a tissue of the gastrointestinal tract; anda carrier including one or more inflatable balloons in coupled arrangement with the plurality of electrodes, the one or more inflatable balloons configured to expand radially from a longitudinal axis of the carrier and the one or more inflatable balloons expanding causing the plurality of electrodes to contact the tissue of the gastrointestinal tract of the human or animal.

86. A device for measuring properties of a gastrointestinal tract of a human or animal, the device comprising: a plurality of electrodes configured to acquire electrical measurements of a tissue of the gastrointestinal tract; and a carrier including an ellipsoid structure in coupled arrangement with the plurality of electrodes, the plurality of electrodes disposed on a surface of the ellipsoid structure.

87. The device of any one of claims 83-86, further comprising: an optical module configured to acquire optical measurements of the tissue of the gastrointestinal tract, the optical module including an optical fiber configured to transmit light to the tissue or to transmit light collected from the tissue.

88. The device of any one of claims 83-87, further comprising: a sensor in coupled arrangement with the carrier, the sensor configured to acquire data representative of at least one of a position, motion, or orientation of the carrier.

89. The device of any one of claims 83-88, wherein the device is configured to be delivered to the gastrointestinal (GI) tract via an endoscopic procedure, and wherein at least the electrodes and the carrier are configured to reside in the GI tract for a period of time beyond a duration of the endoscopic procedure.

90. The device of claim 89, wherein the electrodes are communicatively coupled to a monitoring device positioned external to the human or the animal.

91. The device of any one of claims 83-90, wherein the carrier is configured to be moved along a length of the GI tract by natural processes of the GI tract.

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