Patent Publication Number: US-2021169352-A1

Title: Devices and methods for determining blood flow around a body lumen

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     This patent application claims the benefit under 35 U.S.C. § 119 to U.S. Provisional Patent Application No. 62/522,168, filed on Jun. 20, 2017, the entirety of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     Implementations of the present disclosure relate to devices and methods for determining blood flow around a body lumen, and more specifically, an indicator for identifying inflamed regions of the gastrointestinal tract. 
     INTRODUCTION 
     Inflammatory Bowel Disease (IBD) is a disease that progresses from the mucosal lining of the small bowel or/and colon through the entire bowel/colon wall. Currently, the use of magnetic resonance imaging (MRI) slices as a non-invasive imaging technique for diagnosing IBD is limited by resolution, and does not provide real-time blood flow. Coherence tomography (CT) is another approach, but is not suitable for patients with certain gastrointestinal diseases because the requirement for multiple imaging sessions over time increases the risk of cancer for the patient. Other challenges include subjective severity in scoring from doctor to doctor, diagnosis through elimination, increased patient risk for cancer due to monitoring progression with repetitive CT-scans, and the unavailability of and lack of standardization associated with color enhanced ultrasound. 
     SUMMARY 
     In one implementation, the disclosure is directed to a system including an expandable member, and a plurality of sensors disposed on an outer surface of the expandable member and circumferentially spaced apart from one another, wherein each of the plurality of sensors includes a first emitter configured to emit light of a first wavelength, and a detector configured to detect light, and a controller communicatively coupled to the plurality of sensors. The controller may be configured to, from at least one detector, receive along a first short vector, a measurement of light intensity over time of light, reflected off of body tissue, at the first wavelength and originating from a first emitter from a same sensor; from at least one detector, receive along a first long vector, a measurement of light intensity over time of light, reflected off of body tissue, at the first wavelength and originating from a first emitter from a circumferentially adjacent sensor; calculate separate perfusion indexes corresponding to measured light intensity over time of each first short vector and each first long vector; and initiate the display of the separate perfusion indexes corresponding to measured light intensity over time of each first short vector and each first long vector. 
     Each of the plurality of sensors may include a second emitter configured to emit light of a second wavelength that is different than the first wavelength, wherein the controller is further configured to from each detector, receive along a second short vector, a measurement of light intensity over time of light, reflected off of body tissue, at the second wavelength and originating from a second emitter from a same sensor; from each detector, receive along a second long vector, a measurement of light intensity over time of light, reflected off of body tissue, at the second wavelength and originating from a second emitter from a circumferentially adjacent sensor; calculate separate perfusion indexes corresponding to each second short vector and each second long vector; and cause the display of the calculated separate perfusion indexes corresponding to each second short vector and each second long vector. The second emitter may be configured to emit light of a third wavelength different than the first wavelength and the second wavelength, wherein the controller is further configured to: from each detector, receive along a third short vector, a measurement of light intensity over time of light, reflected off of body tissue, at the third wavelength and originating from a second emitter from a same sensor; from each detector, receive along a third long vector, a measurement of light intensity over time of light, reflected off of body tissue, at the third wavelength and originating from a second emitter from a circumferentially adjacent sensor; calculate separate perfusion indexes corresponding to each third short vector and each third long vector; and cause the display of the calculated separate perfusion indexes corresponding to each third short vector and each third long vector. The controller may be further configured to, from each detector, receive along two third long vectors, measurements of light intensity over time of light, reflected off of body tissue, at the third wavelength and originating from second emitters of two different circumferentially adjacent sensors. The third wavelength may be infrared light. The controller may be further configured to, from each detector, receive along two second long vectors, measurements of light intensity over time of light, reflected off of body tissue, at the second wavelength and originating from second emitters of two different circumferentially adjacent sensors. The second wavelength may be visible red light. The controller may be further configured to, from each detector, receive along two first long vectors, measurements of light intensity over time of light, reflected off of body tissue, at the first wavelength and originating from first emitters of two different circumferentially adjacent sensors. The first wavelength may be visible green light. The system may include an ECG assembly coupled to the controller and configured to measure ECG signals. The controller may be further configured to: while calculating each perfusion index, synchronize in time, measured light intensity from each vector with a measurement from the ECG assembly to determine pulse transit time and perfusion intensity; and use the pulse transit time and the perfusion intensity to calculate a respective perfusion index corresponding to each vector. The controller may be configured to receive a measurement of light intensity over time along only one first short vector or first long vector at any given time. The plurality of sensors may include four circumferentially spaced apart sensors. Each detector may be longitudinally aligned with each other detector. Each first emitter may be longitudinally aligned with each other first emitter. 
     In another implementation, the disclosure is directed to a method for determining blood flow surrounding a body lumen, the method comprising: receiving, at separate times with a detector: a measurement of light intensity over time of light, reflected off of body tissue, at a first wavelength and originating from an emitter from a sensor circumferentially aligned with the detector; and a measurement of light intensity over time of light, reflected off of body tissue, at the first wavelength and originating from an emitter from a sensor circumferentially offset from the detector; calculating separate perfusion indexes corresponding to each measurement; and displaying the separate perfusion indexes. 
     In yet another implementation, the disclosure is directed to a method for determining blood flow surrounding a body lumen using a plurality of sensors, the method comprising: receiving, with a detector at each sensor, a measurement of light intensity over time of light, reflected off of body tissue, at a first wavelength and originating from a first emitter from a same sensor as the detector; receiving, with a detector at each sensor, a measurement of light intensity over time of light, reflected off of body tissue, at a first wavelength and originating from a first emitter from a sensor circumferentially adjacent to the detector; calculating separate perfusion indexes based on each measurement; and displaying the separate perfusion indexes. 
     The body lumen may be in a gastrointestinal tract. Only one measurement may be received at any given time. Each measurement may be taken while the plurality of sensors are in a same location within the body lumen. 
     In yet another implementation, the disclosure is directed to a medical device including a catheter; an optical sensor disposed at or adjacent to a distal end of the catheter, the optical sensor including a photodetector and one or more emitters, the photodetector and each of the one or more emitters of the optical sensor being disposed linearly along a longitudinal axis of the catheter; and a controller disposed within the catheter, the controller being configured to determine a thickness of tissue adjacent to the optical sensor based on input from the optical sensor. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various implementations and together with the description, serve to explain the principles of the disclosed implementations. 
         FIG. 1  is a schematic view of a perfusion measurement system, according to an implementation of the present disclosure. 
         FIG. 2  is a perspective view of an expandable member with a plurality of optical sensors. 
         FIG. 3  is a front view of an optical sensor. 
         FIG. 4  is a side view of the expandable member of  FIG. 2  with a plurality of optical sensors. 
         FIG. 5  is a flowchart of a method, according to an implementation of the disclosure. 
         FIG. 6A  is illustration of an electrocardiogram measured by the system of  FIG. 1 . 
         FIG. 6B  is an illustration of a photoplethysmogram measured by the system of  FIG. 1 . 
         FIG. 7  is a depiction of the electrocardiogram of  FIG. 6A  and the photoplethysmogram of  FIG. 6B  on common axes. 
         FIG. 8  is an illustration of a perfusion index created using optical data measured by the system of  FIG. 1 . 
         FIG. 9  is an illustration of tissue thickness created using optical data measured by the system of  FIG. 1 . 
         FIG. 10  is a perspective view of an expandable member and a plurality of sensors, according to another implementation of the present disclosure. 
         FIG. 11  is a perspective view of an expandable member and a plurality of sensors, according to yet another implementation of the present disclosure. 
         FIGS. 12 and 13  show un-deployed and deployed configurations, respectively, of an expandable member and a plurality of sensors, according to yet another implementation of the present disclosure. 
         FIG. 14  is a perspective view of an optical sensor according to another implementation of the present disclosure. 
         FIG. 15  is a side view of the optical sensor of  FIG. 14 . 
         FIG. 16  is a top view of a portion of the optical sensor of  FIG. 14 . 
         FIG. 17  is an illustration of a timing sequence of a photodetector and a plurality of emitters from the optical sensor of  FIG. 14 . 
         FIG. 18  is a fitted line plot regression of an experiment using an optical sensor. 
     
    
    
     DETAILED DESCRIPTION 
     Reference will now be made in detail to implementations of the present disclosure, which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts or components. The term “distal” refers to the direction that is away from the user or operator and into the patient&#39;s body. By contrast, the term “proximal” refers to the direction that is closer to the user or operator and away from the patient&#39;s body. In the discussion that follows, relative terms such as “about,” “substantially,” “approximately,” etc. are used to indicate a possible variation of ±10% in a stated numeric value. 
     Implementations of the present disclosure may provide a low-cost imaging solution for determining the severity of various gastrointestinal diseases. In some implementations, the data collected and displayed to a physician or clinician may be robust enough to enable differentiation of ulcerative colitis from Chrohn&#39;s disease. 
     Referring to  FIG. 1 , a system  100  may include a catheter  102 , an electrocardiogram (ECG) lead assembly  104 , controller  106 , and a fluid delivery device  108 . 
     Catheter  102  may extend from a proximal end  110  toward a distal end  112 , and may include an expandable member  114  at or adjacent distal end  112 . Expandable member  114  may be a compliant or semi-compliant balloon configured to inflate and deflate via a fluid conveyed by fluid delivery device  108 . In other implementations, expandable member  114  could be an expandable mesh or an expandable basket with a plurality of radially expandable basket legs. As explained in further detail below, one or more sensors may be coupled to expandable member  114  for measuring blood flow, pressure (e.g., pressure sensor  118 ), and/or impedance within a gastrointestinal tract of a patient. Pressure sensor  118  may be configured to measure pressure within expandable member  114 , and to measure intra-abdominal pressure (IAP) within the body lumen when expandable member  114  is deflated. In embodiments where expandable member  114  is a balloon, pressure sensor  118  may be integral or otherwise coupled to an inflating pump. In embodiments where expandable member  114  is a mesh, a miniature integrated MEMS sensor may be used to measure pressure, and could be placed in the same plane as one or more optical sensors. Controller  106  may evaluate signals from pressure sensor  118  to control inflation and deflation of expandable member  114 , so as not to cause any vascular restriction or accidental occlusion. Pressure sensor  118  also could be used to determine safe placement of stents. Increasing expansion while reading perfusion intensity may result in a temporary and substantial decrease in perfusion. Thus, pressure readings from sensor  118  can be used to reduce expansion in these instances to ensure safe delivery by determining whether expansion of the stent causes a temporary restriction of blood flow. 
     ECG lead assembly  104  may be coupled to controller  106 , and may be configured to sense an ECG signal based on electrical activity of the patient&#39;s heart sensed by one or more electrodes  120 . While ECG lead assembly  104  is shown in  FIG. 1  with four electrodes  120 , any other suitable number of electrodes  120  may be utilized. 
     Controller  106  may include a processor that is generally configured to accept information from the system and system components, and process the information according to various algorithms. The processor may be a digital IC processor, analog processor or any other suitable logic or control system that carries out the control algorithms. In some implementations, controller  106  may record treatment parameters such as, e.g., sensor data, so that they may be accessed for concurrent or subsequent analysis. Controller  106  may include software that provides a user interface to components within the system. The software may enable a user (e.g., clinician) to configure, monitor, and control operation of catheter  102 , ECG lead assembly  104 , and control circuitry and pump components within fluid delivery device  108 . As described in further detail below, the software may be configured to process a signal indicative of blood flow within a gastrointestinal tract to calculate an area indicative of a blood flow rate within the gastrointestinal tract. 
     Fluid delivery device  108  may include a pump, and may be configured to deliver fluid to and convey fluid from expandable member  114  to inflate and deflate expandable member  114 . Fluid delivery device  108  may be controlled by controller  106 , or another suitable controller. The pump may be any suitable pump, such as, e.g., a peristaltic pump, piston pump, motorized pump, infusion pump, or the like. Fluid delivery device  108  may be powered by electrical power, mechanical power, chemical power, or another suitable mechanism. Fluid delivery device  108  may include a source (e.g., a reservoir of liquid or a canister of gas) used to inflate and deflate the expandable member  114 . 
     Referring to  FIGS. 1-4 , one or more sensors  116  may be disposed on an outer surface of expandable member  114 . In one implementation, four sensors  116  may be circumferentially spaced about expandable member  114  about 90 degrees from one another, although other numbers of sensors and/or different spacing arrangements also are contemplated. Sensor  116  may be configured to generate a signal that can be used by controller  106  to determine blood flow, e.g., perfusion, within a gastrointestinal tract of a patient. Sensor  116  may include a first emitter  135 , a second emitter  136 , and a detector  137 . First emitter  135  and second emitter  136  each may be configured to emit light, e.g., non-visible infrared light and/or visible light toward body tissue. For example, first emitter  135  and second emitter  136  each may include one or more light emitting diodes (LEDs). In some implementations, first emitter  135  and second emitter  136  may be configured to direct different wavelengths of light at tissue. For example, first emitter  135  may be configured to direct light of a first wavelength (e.g., red light with a wavelength from about 620 nm to about 750 nm) toward body tissue, while second emitter  136  may be configured to direct light of a second wavelength different than the first wavelength (e.g., green light from about 520 nm to about 540 nm, or at about 530 nm) toward body tissue. First emitter  135  and/or second emitter  136  may be configured to separately or simultaneously direct one or more wavelengths of light toward body tissue. For example, first emitter  135  may be configured to direct infrared light (at a wavelength from about 700 nm to about 1 mm) in addition to visible red light. Emitted light may be absorbed by the body based on the blood volume at the absorption location. Absorption occurs when elements in the blood absorb photons and diffuse light passing through the blood. Hemoglobin, for example, is an absorber of light but absorbs different light wavelengths at different rates. Backscatter is the amount of light that is reflected back to the detector and is not absorbed in the blood. Detector  137  may be a photodiode (e.g., a silicon photodiode) that is configured to receive backscattered light reflected from the body. 
     Each detector  137  may be longitudinally aligned (e.g., disposed at the same longitudinal location) as each other detector  137 . Similarly, each first emitter  135  may be longitudinally aligned with each other first emitter  135 , and each second emitter  136  may be longitudinally aligned with each other second emitter  136 . 
     Referring to  FIG. 3 , detector  137  may be configured to measure reflected light that originates from an emitter (e.g., first emitter  135  and/or second emitter  136 ). For purposes of discussion herein, a short vector refers to reflected light detected by detector  137  that originated from an emitter on the same sensor  116  as the given detector  137 . Thus, depending on the configuration of emitters on a given sensor, each detector  137  may be configured to detect light along one or more short vectors. In one implementation, where first emitter  135  is configured to emit green light, and second emitter  136  is configured to emit red light and infrared light, each detector  137  may be configured to detect light along three short vectors (green, red, infrared). Different absorption rates in blood and tissue with known correlations can be used to determine various physiological parameters (photoplethysmography), such as, e.g., oxygen saturation, heart rate, perfusion intensity, surrogate blood pressure, and tissue thickness. 
     Referring to  FIG. 4 , a long vector refers to reflected light detected by detector  137  that originated from an emitter on a circumferentially adjacent emitter. Thus, when a given sensor  116  is disposed circumferentially between two other sensors  116 , the detector  137  of the given sensor  116  may be configured to detect light from one or more long vectors from each of the two adjacent sensors (emitters). In the implementation where first emitter  135  is configured to emit green light, and second emitter  136  is configured to emit red light and infrared light, each detector  137  may be configured to detect light along six long vectors (three long vectors originating from each of the two circumferentially adjacent sensors  116 ). 
     In one implementation of the disclosure where four sensors  116  are disposed around the circumference of expandable member  114 , system  100  may record measurements along a total of 36 vectors (12 short vectors and 24 long vectors). Each of the four sensors  116  includes three short vectors, totalling 12 short vectors. Additionally, each of the four sensors  116  includes six long vectors as set forth above, totalling 24 long vectors. Devices with only one optical sensor may have a single vector, which would not enable mapping of the blood vessels around the lumen, the determination of tissue thickness, or the data necessary to size a stent during deployment. 
     Referring now to  FIG. 5 , an exemplary method  500  is shown. Method  500  may begin at step  502 , where sensors  116  and ECG assembly  104  may be deployed. For example, catheter  102  may be orally inserted into a patient through the nose or mouth and into the gastrointestinal tract through the esophagus and stomach. Using fluoroscopic, ultrasonic, anatomic, or CT guidance, an endoscope (or expandable member  114  alone) may be positioned at a location (region of interest) within the gastrointestinal tract such as the duodenum. The region of interest then may be visualized using an imaging device (e.g., an endoscopic camera), and expandable member  114  may be extended to the region of interest via a working port of the endoscope. Once expandable member  114  is positioned at the location (region of interest), it may be expanded via fluid from fluid delivery device  108 . Before, during, or after insertion of catheter  102  into the body, electrodes  120  of ECG lead assembly  104  may be placed on a suitable site of a patient, such as the patient&#39;s chest, to monitor electrical activity of the heart. With expandable member  114  and sensors  116  in position, all other light emitting sources in the body lumen, such as, e.g., a guiding light of an endoscope, may be turned off to avoid interfering with measurements detected by sensor  116 . 
     Method  500  may proceed to step  504 , where the system  100  may calibrate sensors  116 . At step  504 , the required gains for detectors  137  and drive currents for the emitters  135  and  136  may be determined. In one implementation, calibration may be accomplished sequentially for each sensor  116 . Calibration for the short vector reflections of each wavelength (e.g., red, infrared, and green) may take place for each sensor  116 . Each of the sensors  116  will be calibrated for each of its short vectors, and the values for the detector gain and current setting for the emitters  135  and  136  may be stored. Then, each sensor  116  may be calibrated for its associated long vectors for each wavelength (e.g., red, infrared, and green) for each circumferentially adjacent sensor. 
     The primary purpose of the calibration is to optimize the signal to noise ratio received by detector  137 . The secondary purpose is to obtain the values of the gain and current settings for each vector, which are then used as scoring factors in mapping out the tissue perfusion around the body lumen. 
     After calibration, method  500  may proceed to step  506 , where light intensity measurements over time may be made continuously and sequentially for each of the 36 vectors. In some implementations, each detector  137  may be configured to perform more than one measurement at a given time (e.g., pulse, blood oxygen, surrogate blood pressure, mean arterial pressure, perfusion intensity, tissue thickness). Controller  106  may associate a time stamp to each measurement performed, or may otherwise associate the time of day with each waveform collected by each detector  137 . ECG lead assembly  104  may collect ECG data at all times that any detector  137  is collecting optical data. 
     After collecting data at step  506 , method  500  may proceed to step  508 , where the collected data may be analysed to generate a perfusion index corresponding to each vector at one or more wavelengths. Perfusion index may be the ratio of the pulsatile blood flow to the non-pulsatile static blood flow. Perfusion index is an indication of pulse strength at the measurement site, and may be indicative of tissue inflammation around the measurement site. The perfusion index may be calculated based on a determined perfusion intensity, which is a measure of blood velocity and its peak amplitude. The perfusion intensity may be determined using a pulse transit time (PTT) and a height of an associated P wave. PTT is the time it takes a pulse pressure (PP) waveform to propagate through a length of an arterial tree. The pulse pressure waveform results from the ejection of blood from the left ventricle and moves with a velocity much greater than the forward movement of the blood itself. The P wave represents atrial depolarization, which may result in atrial contraction. 
     The data collected for each vector will be weighed against the calibration values (gain and current), and used to create a perfusion intensity map. Higher gain settings and currents may be flagged as suspected low perfusion regions when looking at P wave heights. The perfusion intensity map then may be manipulated to create a perfusion index map. 
     The measured data from sensors  116  may be filtered using a suitable filter, such as a High-Pass Finite Impulse Response (FIR) filter, to remove noise in the data, such as noise caused by distortion created by mechanical ventilation or intestinal peristalsis. For each vector, a PPG signal  515  ( FIG. 6A ) and an ECG signal  516  ( FIG. 6B ) may synchronized relative to time at a suitable frequency, e.g., 100 Hz. This synchronization is illustrated in  FIGS. 6A and 6B , which shows the PPG signal  515  over time ( FIG. 6A ) for a given vector, and the corresponding ECG signal  516  obtained at the same time. 
     The data based on the ECG signal  516  is used to determine an R wave signal. Controller  106  may determine the R wave signal using a derivative based algorithm. Referring to  FIG. 6B , a graph is illustrated depicting ECG signal  516  having determined R waves marked with the letter R. R waves may be used as a trigger to identify PTT. The PTT may be calculated as the time of flight from the R wave of the ECG signal  516  to an associated P wave of PPG signal  515  (see  FIGS. 6A, 6B, and 7 ). 
     Referring back to  FIG. 6A , an area  600  under PPG signal  515  may be calculated. This area may represent the volume of pulse as a part of the intensity calculation. The PPG signal  515  is searched between two consecutive R waves, which are used to determine a time window in which to search for a minimum value (shown as “A” in  FIG. 6A ) of a segment of the PPG signal  515 . The minimum point A on the PPG signal  515  within the time window after the R wave is used as the starting point of a PPG segment. The ending point of the PPG segment is where the next minimum point of the PPG signal is detected (shown as A′ in  FIG. 6A ), which is also a starting point for the next PPG segment. To calculate AC area  600 , a boundary line  602  is drawn between minimum points A and A′ on the PPG curve. AC area  600  may be the area below PPG signal  515 , above boundary line  602 , and between minimum points A and A′. 
     Once area  600  is determined for each vector, a perfusion intensity I Perf  may be calculated by dividing the AC area  600  (pulse area) for each vector by the PTT of the same vector. To create the perfusion index, perfusion intensity I Perf  may be normalized for all 36 vectors as each may have different gain and current settings. Additionally, it is expected that the  24  long vectors will require higher current and gain settings than the short vectors. Short vector perfusion intensities may be calculated and compared separately from perfusion intensities of the longer vectors. A short vector perfusion index (SV_Index n ) for each of the  12  short vectors may be calculated using the following equation: 
     
       
         
           
             
               SV_Index 
               n 
             
             = 
             
               
                 I 
                 
                   Perf 
                   n 
                 
               
               
                 
                   GAIN 
                   n 
                 
                  
                 
                   xI 
                   
                     LED 
                     n 
                   
                 
               
             
           
         
       
     
     I LEDn  represents a current associated with a respective LED. A normalization (k) will be made between short and long vectors to create a normalized scoring index. Longer vectors require more current to get a reading that is at an acceptable level above a signal to noise ratio (SNR), and possibly require more gain. k may act as a scaling factor to compensate the larger gain and current settings. Determination of k may require empirical testing in some examples, and may include a balance between the short vector I_Perfn settings with the long vector I_Perf_n settings, for example, where SV_I_PERF=LV_I_PERF. If the resulting intensity measurements are kept the same, k may be the ratio of gain and current setting of long vectors over that of the short vectors. 
     The following equation may be used to calculate a long vector index (LV_Index m ), where k is used to scale the result so it is normalized with the short vectors. 
     
       
         
           
             
               LV_Index 
               m 
             
             = 
             
               
                 
                   I 
                   
                     Perf 
                     m 
                   
                 
                 
                   
                     GAIN 
                     m 
                   
                    
                   
                     xI 
                     
                       LED 
                       m 
                     
                   
                 
               
                
               k 
             
           
         
       
     
     The indexing score values may be represented as a radial map (see  FIG. 8 ), which when viewed (method step  510 ), gives a visual representation of perfusion index around the body lumen where the measurements were taken with sensors  116 . For illustration, a low perfusion is shown around the SV_2 portion and adjacent long vectors. 
     For two wavelengths (e.g., green and red wavelengths), a variation of the Green&#39;s function of a diffusion into a substance can be used with a slope-ratio method to determine tissue wall thickness. The spectral ratio of slopes shown in  FIG. 9  represent the difference between short vector perfusion to long vector perfusion of the green wavelength over the difference of the short vector perfusion to long vector perfusion of the red wavelength. 
     
       
         
           
             Ratio 
              
             
               = 
               
                 
                   
                     SV_Index 
                     green 
                   
                   - 
                   
                     L 
                      
                     
                       V 
                       
                         Index 
                         green 
                       
                     
                   
                 
                 
                   
                     SV_Index 
                     red 
                   
                   - 
                   
                     LV_Index 
                     red 
                   
                 
               
             
           
         
       
     
     This may be evaluated for each position around the sensor array. This ratio may approximate tissue thickness surrounding a body lumen and sensor array. In the example having four optical modules around a circumference of an expandable member, there are two long vectors for each short vector, and thus eight regional ratios. In some examples, slope tomography may be used to determine tissue wall thickness. 
     While the slopes used in some examples herein utilize multiple wavelengths of visible light (e.g., green and red), it other examples, combinations of visible and non-visible light may be used to determine tissue wall thickness, such as, e.g., green and IR, or red and IR. 
     After step  510 , method  500  may return to step  502  for repositioning of expandable member  114  for additional measurements at different locations in the body. 
     More complicated cases of Crohn&#39;s Disease, where a stricture may prevent the advancement of a scope/sensor array, may require extra steps of deploying a dilating device to open a passageway, and re-deploying the sensor array.  FIGS. 10-13  show various “over-the-scope” devices with sensors  116  that can be used in these more complicated cases. In particular,  FIG. 10  shows a system  1000  including an endoscopic device  1002  extending from a proximal end (not shown) to a distal end  1003 . Endoscopic device  1002  may be any suitable endoscopic member, such as, e.g., an endoscope, a ureteroscope, a nephroscope, a colonoscope, a hysteroscope, a uteroscope, a bronchoscope, a cystoscope, a sheath, or a catheter. Endoscopic device  1002  may include one or more additional lumens configured for the passage of a variety of tools and devices, including, but not limited to, imaging devices and tools for irrigation, vacuum suctioning, biopsies, and drug delivery. Endoscopic device  1002  also may include an imaging device, e.g., a camera, at distal end  1003 . 
     System  1000  may include a sensor assembly  1004  having an expandable member  1006  disposed between a proximal cuff  1007  and a distal cuff  1008 . Proximal cuff  1007  and distal cuff  1008  each may extend around an exterior surface of endoscopic device  1002 , and may be secured to endoscopic device  1002  by an interference fit or other suitable mechanism. Additionally, in system  1000 , a distalmost end of distal cuff  1008  may be positioned distal to a distalmost end of endoscopic device  1002 . 
     One or more sensors  116  may be disposed on an outer surface of expandable member  1006  in a substantially similar manner as described above with respect to sensors  116  and expandable member  114 . In system  1000 , each sensor  116  may be coupled to a control member (e.g., control wire)  1010  that is extended through a working channel of endoscopic device  1002  and connected at its proximal end to controller  106  (shown in  FIG. 1 ). For example, control members  1010  may be bundled into a sheath  1012 , and sheath  1012  may be extended through the working channel of endoscopic device  1002 . Distal portions of each control member  1010  also may be positioned on an exterior surface of expandable member  1006  and ultimately coupled with a given sensor  116 . Similar to expandable member  114 , expandable member  1006  may be a compliant or semi-compliant balloon configured to inflate and deflate via a fluid conveyed by fluid delivery device  108  (shown only in  FIG. 1 ). Sheath  1012  also may include a lumen coupled to fluid delivery device  108  to convey fluid to and from expandable member  1006  for inflation and deflation. Alternatively, expandable member  1006  may be coupled to fluid delivery device  108  by another mechanism. 
     A system  1100  is shown in  FIG. 11 , including a sensor assembly  1104  positioned over endoscopic device  1002  (e.g., the same endoscopic device described with reference to  FIG. 10 ). Sensor assembly  1104  may include an expandable member  1106  disposed between a proximal cuff  1107  and a distal cuff  1108 . Proximal cuff  1107  and distal cuff  1108  each may extend around an exterior surface of endoscopic device  1002 , and may be secured to endoscopic device  1002  by an interference fit or other suitable mechanism. Additionally, a distalmost end of distal cuff  1108  may be positioned proximal to a distalmost end of endoscopic device  1002 . 
     One or more sensors  116  may be disposed on an outer surface of expandable member  1106 . The arrangement of the sensors  116  on expandable member  1106  may be similar to the arrangement of sensors  116  on expandable member  1006  set forth above, except that control members  1010  may be positioned entirely external to endoscopic device  1002 . For example, control members  1010  may be bundled into a sheath  1112 , and sheath  1112  may extend along the exterior of endoscopic device  1002 . Similar to sheath  1012 , sheath  1112  also may include a lumen coupled to fluid delivery device  108  (shown in  FIG. 1 ) to convey fluid to and from expandable member  1106  for inflation and deflation. 
     A sensor assembly  1201  is shown in  FIGS. 12 and 13  in un-deployed and deployed configurations, respectively. Sensor assembly  1201  may be coupled to distal end  1003  of endoscopic device  1002 , and may be configured to position one or more sensors  116  in contact with an inner surface  1222  of a body lumen  1220  (referring to  FIG. 13 ). Sensor assembly  1201  may include a cuff  1202  having a proximal end  1203  and a distal end  1204 . Cuff  1202  may slide onto distal end  1003  of endoscopic device  1002 . Cuff  1202  may include one or more flexible arms  1208  that are circumferentially spaced apart from one another. Each arm  1208  may include a set curvature. For example, each arm  1208  may have a preset shape in a deployed configuration. As shown in  FIGS. 12 and 13 , each arm  1208  may include a concave curvature when viewed from a perspective distal to the arm  1208 , and may include a convex curvature when viewed from a perspective proximal to the arm  1208 . Arms  1208  may be biased into either the un-deployed or deployed configuration. 
     Each of the one or more arms  1208  may include a mounted end  1209  and a free end  1210 . Each of the one or more arms  1208  may be at least partially disposed in a corresponding recess  1211  in cuff  1202 . Thus, each recess  1211  may be circumferentially offset from each other recess  1211  of cuff  1202 . Mounted end  1209  of each arm  1208  may form a hinge  1212  with cuff  1202 . Arms  1208  may move from a first, un-deployed position, where free end  1210  is disposed proximally of mounted end  1209 , to a second, deployed position, where free end  1210  is disposed distally of mounted end  1209 . Arms  1208  may be moved between the first and second positions by manipulating endoscopic device  1002  to cause free ends  1210  to engage with tissue. For example, distal movement of endoscopic device  1002  may cause tissue of a body lumen to push proximally against free ends  1210 , moving arms  1208  into the configuration shown in  FIG. 12 . On the contrary, proximal movement of endoscopic device  1002  causes tissue of the body lumen to push distally against free ends  1210 , moving arms  1208  into the configuration shown in  FIG. 13 . Thus, arms  1208  may be moved between un-deployed and deployed positions by only passive mechanisms without any powered and/or automated components. Alternatively, arms  1208  may be actively moved between the un-deployed and deployed configurations by an active mechanism, such as, e.g., a combination of motors, gears, and actuators. For example, a user may activate an actuator that causes a combination of motors and gears to move arms  1208  between the un-deployed and deployed positions. Furthermore, in one embodiment, each arm  1208  may lie flat/flush within a corresponding recess  1211 , and an actuator may release each arm  1208  when arms  1208  are positioned at a desired tissue site. 
     A sensor  116  may be coupled to free end  1210  of each arm  1208 . When arms  1208  are in the first, un-deployed position shown in  FIG. 12 , the optical components of sensors  116  may face radially inward toward a central longitudinal axis  1230  of sensor assembly  1201 , and may not be operable. In the second, deployed position shown in  FIG. 13 , the optical components of sensors  116  may face radially outward away from central longitudinal axis  1230  and toward surface tissue  1222 . Similar to the device shown in  FIG. 11 , control members  1010  may be positioned entirely external to endoscopic device  1002 . For example, control members  1010  may be bundled into a sheath  1212 , and sheath  1212  may extend along the exterior of endoscopic device  1002 . 
     The systems shown in  FIGS. 10 and 11  may be configured to operate in a similar manner as set forth in step  502  of method  500  ( FIG. 5 ). For example, the region of interest may be observed using an imaging device (e.g., endoscopic camera). Then, instead of deploying catheter  102  to the region of interest, distal end  1003  of endoscopic device  1002  may be advanced to the region of interest, where a respective expandable member ( 1006  or  1106 ) is expanded to position sensors  116  in contact with tissue. The system shown in  FIGS. 12 and 13  also may operate in a similar manner. For example, after visualization of the region of interest using the system of  FIGS. 12 and 13 , distal end  1003  of endoscopic device  1002  may be extended distally of the region of interest, and then pulled proximally to the region of interest to cause arms  1208  to move from the first, un-deployed configuration to the second, deployed configuration. 
     The systems shown in  FIGS. 10-13  also may stabilize the endoscopic devices on which they are deployed, and centralize the field of view within the lumen being observed. These devices also may be used to stretch out folds within the observed lumen to improve visibility in areas that are difficult to see (e.g., around or within folds in the colon and/or intestinal walls). These effects may improve diagnostic outcomes. Yet another advantage of at least certain embodiments of these devices may be to free up the working port of the endoscopic device, enabling an operator to deploy other medical devices (for, e.g., irrigation, hemostasis stabilization, suturing, tissue sampling, or the like). Devices and methods of the present disclosure may help quantify the severity of tissue damage or healing following treatment, improving diagnostic outcomes by making them less speculative. This may be particularly relevant for inflammatory bowel diseases and ulcerative colitis. Furthermore, at least certain embodiments of devices and methods of the disclosure help improve diagnostic techniques by enabling the measurement of perfusion and thickness in regions of interest. These measurements also help enable physicians to follow the progression of treatment. Furthermore, it is contemplated that any of the inflatable members (e.g., balloons) described herein may be shaped such that, in one or more inflated configurations (including a fully inflated configuration), the outer surface of the balloon contacts less than an entirety of a body lumen (e.g., 270 degrees or less, 180 degrees or less, 90 degrees or less around the lumen). 
     A medical device  1400  is shown in  FIGS. 14-16 . Medical device  1400  extends from a proximal end (not shown) toward a distal end  1402 . Medical device  1400  may have a relatively slim profile, and may be used to measure tissue thickness in areas of the body that are not accessible by larger devices. Medical device  1400  may include a diagnostic catheter with at least a two-way steering mechanism. Such a catheter could be made for deployment in a 3.7 mm working port of an endoscope so that it can be visually placed at the region of interest, allowing for tangential tissue measurements. 
     Medical device  1400  includes a catheter  1403  and an optical sensor  1404  disposed at or adjacent to distal end  1402 . Catheter  1403  may be a hollow catheter having an open distal portion  1406  in which optical sensor  1404  rests. A majority of catheter  1403  may have a circular cross-section. However, open distal portion  1406  may have a different cross-section, such as, e.g., a half-moon shaped cross-section or another suitable design that enables components of optical sensor  1404  to be placed flush against tissue. Thus, optical components of optical sensor  1404  may face radially outward from a side-facing surface of catheter  1403  (a surface that faces a direction perpendicular to a longitudinal axis of catheter  1403 ). Open distal portion  1406  may include a distal and side facing opening of catheter  1403 . The side-facing portion of the opening may extend distally of the distal facing opening. 
     Catheter  1403  also may include an articulating joint  1412 . Control cables (not shown) may be connected to a set of control knobs at the proximal end of medical device  1400 , and to articulating joint  1412  to control articulation of articulating joint  1412 . By manipulating the control knobs, an operator may be able to actuate, or bend, articulating joint  1412  during insertion and direct it to a region of interest. Catheter  1403  also may include an atraumatic tip  1414 . For example, tip  1414  may include a soft or flexible material to allow catheter  1403  to navigate and traverse the tortuous pathways of a body in a generally atraumatic manner. 
     A substrate  1435   a  may be disposed at open distal portion  1406  of catheter  1403 . Substrate  1435   a  may include a flexible printed circuit board (PCB) that is semi-rigid and that includes a stiffener. Components of optical sensor  1404  may be mounted on to substrate  1435   a . One or more control wires  1435   c  may extend proximally from optical sensor  1404  to couple optical sensor  1404  to, e.g., power sources, computing devices, and the like. 
     Optical sensor  1404  may include a photodetector  1437 , and emitters  1436   a ,  1436   b , and  1436   c . Photodetector  1437  and emitters  1436  may be substantially similar to detector  137  and emitters  136  set forth above. Each emitter  1436   a - c  may be configured to radiate infrared light, or another suitable wavelength. For example, some applications may benefit from infrared light, while other applications may benefit from other wavelengths of light. For example, infrared light wavelengths may penetrate deeper into tissue while visible light provides more information regarding surface characteristics. Different wavelengths reflect back de-oxygenated/oxygenated blood differently, and there are known ratios that related to levels of oxygen, carbon dioxide and other characteristics in the tissue. While three emitters are shown in the embodiment of  FIGS. 14-16 , any other suitable number may be utilized. Photodetector  1437  and each of emitters  1436   a - c  may be disposed linearly along a same axis, such as, e.g., a longitudinal axis of catheter  1403 . Exemplary dimensions of optical sensor  1404  are shown in  FIG. 16 . While certain values for each dimension are discussed below, it is contemplated that alternative dimensions also may be used. Substrate  1435  may have a length  1602  (e.g., 15 mm), and a width  1604  (e.g., 3 mm). A distalmost portion of photodetector  1437  may be disposed a distance  1606  (e.g., 1 mm) from a distalmost end of substrate  1435 . A proximalmost portion of photodetector  1437  may be disposed distances  1608  (2 mm),  1610  (6 mm), and  1612  (10 mm) from distalmost portions of emitters  1436   a ,  1436   b , and  1436   c , respectively. It is contemplated that other suitable dimensions also may be utilized. 
     A lens  1438  may be disposed over optical sensor  1404  (including photodetector  1437  and each emitter  1436   a - c ). Lens  1438  may isolate optical sensor  1404  from tangential back scatter light between emitters  1436  and photodetector  1437  from substrate  1435   a . Lens  1438  also may provide a barrier between tissue and the optical elements of optical sensor  1404 . The configuration of lens  1438  and optical sensor  1404  may help enable medical device  1400  to determine tissue thickness in the body with a relatively small profile and package. Lens  1438  may be formed from plastic, glass, or another suitable material. 
     Photodetector  1437  may be a square-shaped photodetector having sides with a length of 2 mm, although other suitable shapes and dimensions are contemplated. Each emitter  1436  may be a square-shaped emitter having sides with a length of 1 mm, although other suitable shapes and dimensions are contemplated. In some implementations, a length of the flexible substrate is no more than 15 mm. In another embodiment, a length of the flexible substrate is no more than 11 mm. 
     Optical sensor  1404  may be coupled to a controller  1450  attached to a substrate  1435   b  that is substantially similar to substrate  1435   a  described above. Controller  1450  may be disposed entirely within a volume contained within catheter  1403 . When controller  1450  is disposed within catheter  1403 , it may have a width less than 3 mm. Alternatively, controller  1450  may be disposed external to medical device  1400 , in which case, the control wires from controller  1450  to optical sensor  1404  may be attached to a flexible extension of the device. 
     Controller  1450  may be configured to direct and source constant current for each emitter  1436   a - c  separately, but not simultaneously, as the data acquisition may be time multiplexed during a sampling cycle. In other words, at any given time, only one of emitters  1436   a - c  may emit light. The current setting for each emitter  1436   a - c  may change due to the spatial diversity from photodetector  1437 , and may be adjusted during a calibration process. Photodetector  1437  may require control of an amplification device. Since photodetector  1437  may be mostly capacitive, a trans-impedance amplifier may be used for the analog interface. 
     The spatially diverse optical sensor  1404  may be driven through three time division slots to activate each emitter  1436   a - c  separately, with a fourth time slot allowing for data acquisition when none of the emitters  1436   a - c  is activated. This fourth time slot enables the sampling of ambient light. If an operator is confident that the area being measured has no ambient light, then the fourth time slot may be skipped to reduce procedure time. This sequence is shown in  FIG. 17 . The acquisition of samples may be timed sequentially to enable each emitter  1436  a small period of on-ramp to allow for wavelength and temperature stabilization before a measurement is obtained by photodetector  1437 . Suggested sample times could be from 50 microseconds to 200 microseconds per data acquisition. A sample period may include the complete cycle of all four periods, and may impact the overall sample rate of the signal data acquisition. 
     For tissue thickness measurements, 50 samples per second may be adequate, allowing for a total sample period of 20 milliseconds. This would allow for 200 microsecond emitter (LED) sampling. In order to increase data fidelity, the sample period may be increased to, e.g., up to 200 samples. In this case, the total sampling period for all four channels is 500 microseconds, allowing for emitter sampling of about 100 microseconds. A longer emitter sampling period allows for a more refined dynamic range of the analog sampling through photodetector  1437  with lower emitter current being supplied (similar to more exposure time in photography for a lower light setting). 
     The analog data provided by the amplifier after sampling each emitter may be converted to digital format for further processing. This disclosure contemplates any suitable type of analog to digital converter (ADC). The accuracy of the ADC may be at least comparable to an 8-bit or greater ADC to meet the measurement requirements of the applications contemplated by this disclosure. 
     The medical devices described with respect to  FIGS. 14-17  can enable the use of emitters using a centroid wavelength of approximately 940 nm (e.g., 930-950 nm) arranged linearly apart from one another to collect a diffusion gradient of reflected and absorbed light in tissue. Evaluation of the gradient makes use of a slopes-ratio method to correlate measurements made by photodetector  1437  with tissue thickness. The ratio comprises three different vectors coming from three LED emitters (e.g., emitters  1436   a - c ) relative to a fixed photodiode (e.g., photodetector  1437 ). Considering the distance of the emitters  1436   a - c  from photodetector  1437 , emitter  1436   a  is the closest to photodetector  1437  at a distance of two mm, emitter  1436   b  is mid-range relative to photodetector  1437  at a distance of six mm, and the furthest is emitter  1436   c  at a distance of ten mm relative to photodetector  1437 . 
     Tissue thickness may be determined based on data collected by photodetector  1437 . For example, a ratio of slopes method can be used for evaluating the short, mid and long reflective distances as shown in the formula below: 
     
       
         
           
             
               T 
               ratio 
             
             = 
             
               
                 
                   1 
                    
                   4 
                    
                   3 
                    
                   6 
                    
                   a 
                 
                 - 
                 
                   1 
                    
                   4 
                    
                   3 
                    
                   6 
                    
                   b 
                 
               
               
                 
                   1 
                    
                   4 
                    
                   3 
                    
                   6 
                    
                   a 
                 
                 - 
                 
                   1 
                    
                   4 
                    
                   3 
                    
                   6 
                    
                   c 
                 
               
             
           
         
       
     
     In the above equation,  1436   a ,  1436   b , and  1436   c  represent values measured by photodetector  1437  in response to emissions from emitters  1436   a ,  1436   b , and  1436   c , respectively. This equation is used further in the linear model described below. 
     The use of different wavelengths may provide an ability to measure different skin depths. Infrared light, for example, may provide better skin depth penetration than some of the wavelengths in the visible spectrum. Other wavelengths offer different optical properties in live tissue, and may be used for other characteristics and still provide thickness measurements. Empirical results from a study show slight variations in early results using simulated tissue phantoms. The basis of certain results are from fabricated models. In a lab setup, different wavelengths were evaluated to determine different absorption and reflection patterns. 
     A fitted line for linear model statistical regression from data collected with an exemplary device similar to the device described by  FIGS. 14-16  is shown below. 
     Coefficients: 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Statistical Curve for Collected Data 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Estimate 
                 Standard Error 
                 t value 
                 Pr(&gt;|t|) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Intercept 
                 0.891731 
                 0.011087 
                 80.434 
                 1.43E−07 
               
               
                 Thickness 
                 −0.017409 
                 0.002181 
                 −7.982 
                 0.00134 
               
               
                   
               
            
           
         
       
     
     Table 1 illustrates how well the regression fits in the data. Intercept (b) and thickness (m) estimates are the coefficients for scaling according to the collected data. The significance codes are a function of the R utility to give a approximation of how valid the probability of the null hypothesis tested is. The smaller the Pr value, the higher the significance. When significance is higher, the mathematical outcome being evaluated is higher. 
     The residual standard error was 0.0128 on four degrees of freedom. The multiple R-squared was 0.9409, and the adjusted R-squared was 0.9262. The F-statistic was 63.71 on one and four degrees of freedom, and the p-value was 0.001335. The correlation value was −0.9700123, which measures the linear relationship between two variables. In this case, there is a negative correlation between the IR slope value and tissue thickness. As the thickness increases, IR slope value decreases (i.e., they are inversely related to each other). Both of the p-values were below 0.05 thresholds, and thus, this model was statistically significant. 
     Model Fitted Values 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 shows the delta between the real values collected for each 
               
               
                 thickness measurement and the related curve fit plot. 
               
            
           
           
               
               
               
            
               
                   
                 Actual IR 
                   
               
               
                 Thickness 
                 Values 
                 Fitted IR Values 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1.6 
                 0.869627 
                 0.8638776 
               
               
                 2.5 
                 0.858604 
                 0.8482098 
               
               
                 3.0 
                 0.834698 
                 0.8395055 
               
               
                 4.9 
                 0.789127 
                 0.8064291 
               
               
                 6.4 
                 0.773979 
                 0.7803161 
               
               
                 8.5 
                 0.756061 
                 0.743758 
               
               
                   
               
            
           
         
       
     
     Linear Model 
         Y= 0.891731 −0.017409 X  
 
     The R-squared value was 0.9409. 94 percent represents the proportion of variation in the response variable. Thus, as tissue thickness increases, the IR slope value decreases. 
     The linear model is shown in  FIG. 18 , which is a fitted line plot regression analysis of this experiment in an SIG lab with phantom optical equivalent tissue models using slopes ratios methods. 
     One example translation with this dataset is: 
     
       
         
           
             
               Thickness 
                
               
                   
               
                
               
                 ( 
                 mm 
                 ) 
               
             
             = 
             
               
                 R 
                 - 
                 
                   T 
                   ratio 
                 
               
               k 
             
           
         
       
     
     Where R is the intercept (0.8917 in this example) and k (0.01741 in this example) is the slope (negative) derived from experimental data. 
     The relatively slim profile of medical device  1400  also may enable internal placement of medical device  1400  though a scope using direct visualization methods. Medical device  1400  may be used to access many regions of interest in the intestinal tract (e.g., esophagus, stomach, large intestines, duodenum, and parts of the small intestines). In other examples, medical device  1400  may be used to measure thickness in a region of interest, which can then be used as a datapoint to help quantify the severity of healing or inflammation. The data can be part of an index if used with other measurements, such as, e.g., changes in perfusion, temperature, microvascular changes for severity scoring and healing of the tissue of interest. Furthermore, because optical sensor  1404  is flat, it may be used to determine tissue thickness when placed external to a patient, such as, for example, against the skin of a patient. 
     Those skilled in the art will understand that the medical devices set out above can be implemented in any suitable body lumen (e.g., blood vessels, the biliary tract, urological tract, gastrointestinal lumens, and the like) without departing from the scope of the disclosure as defined by the claims. In particular, constructional details, including manufacturing techniques and materials, are well within the understanding of those of skill in the art and have not been set out in any detail here. These and other modifications and variations are well within the scope of the present disclosure and can be envisioned and implemented by those of skill in the art. 
     Other implementations of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the implementations disclosed herein. It is intended that the specification and implementations be considered as examples only, and departures in form and detail may be made without departing from the scope and spirit of the present disclosure as defined by the following claims.