The California Medical Innovations Institute Inc

DEFECATION MECHANISMS AND SUBTYPING OF CONSTIPATION PATIENTS WITH FECOBIONICS - ABSTRACT CHRONIC CONSTIPATION (CC) IS A COMMON CONDITION THAT AFFECTS UP TO 25% OF THE POPULATION IN NORTH AMERICA WITH RISING INCIDENCE THAT POSES A MAJOR BURDEN ON THE HEALTHCARE COST. THE PATHOPHYSIOLOGY OF THIS CONDITION IS POORLY UNDERSTOOD AND CONSEQUENTLY THERE ARE INADEQUATE TREATMENTS. THE SIGNIFICANT PROBLEMS ARE, 1) INCOMPLETE UNDERSTANDING OF THE DEFECATION REFLEX AND 2) LACK OF PHYSIOLOGICALLY RELEVANT AND PRACTICAL DIAGNOSTIC TEST FOR IDENTIFYING THE UNDERLYING MECHANISM(S). CURRENT DIAGNOSTIC TESTS PROVIDE INCOMPLETE AND OFTEN CONFLICTING INFORMATION. NOT SURPRISINGLY, RESULTS OF THESE TESTS CORRELATE POORLY WITH SYMPTOMS AND TREATMENT OUTCOMES. OUR OBJECTIVE IS TO PROVIDE AN IMPROVED UNDERSTANDING OF THE CONTINENCE MECHANISMS AND DEFECATION PATTERNS IN HEALTHY SUBJECTS AND PATIENTS WITH CC USING A NOVEL FECOBIONICS DEVICE FOR MAPPING THE GEOMETRIC AND MANOMETRIC PROFILES DURING EVACUATION. FECOBIONICS IS AN ELECTRONIC SIMULATED STOOL THAT HAS THE CONSISTENCY AND SHAPE OF NORMAL STOOL. THE DEVICE RECORDS PRESSURES, CROSS-SECTIONAL AREA, ORIENTATION, BENDING, SHAPE, AND VISCOELASTIC PROPERTIES OF THE RECTUM AND ANAL CANAL SIMULTANEOUSLY. OUR CENTRAL HYPOTHESIS IS THAT RECTAL PERISTALSIS IS A KEY COMPONENT OF THE DEFECATORY REFLEX WHICH IS NOT ASSESSED IN THE CURRENT PARADIGM OF DIAGNOSTIC TESTING. THE NOVEL FECOBIONICS DEVICE WILL MIMIC THE NATURAL DEFECATION AND PROVIDE NEW MECHANISTIC INSIGHTS INTO THE ANORECTAL PHYSIOLOGY AND PATHOPHYSIOLOGY TO FACILITATE THE DEVELOPMENT OF NEW TREATMENTS FOR CC. FECOBIONICS CAN PROVIDE COMPLETE PICTURE OF THE NORMAL DEFECATION PATTERN (“SIGNATURES”) THAT INCLUDES RECTAL PERISTALTIC REFLEX, DEFORMABILITY OF THE DEVICE AND DISTENSIBILITY OF THE ANAL SPHINCTERS IN HEALTHY SUBJECTS AND PATIENTS WITH VARIOUS SUBTYPES OF CC. THE SPECIFIC AIMS ARE AS FOLLOWS: 1) STUDY THE DEFECATION DYNAMICS IN NORMAL CONTROL SUBJECTS USING FECOBIONICS. WE WILL ESTABLISH THE ROLE OF RECTAL CONTRACTION/PERISTALSIS IN THE NORMAL EVACUATION PROCESS. 2) DEFINE THE DEFECATORY PATTERNS IN PATIENTS WITH CC ASSOCIATED WITH DEFECATORY DISORDERS. WE WILL DETERMINE IF ABNORMALITIES OF RECTAL CONTRACTION CONTRIBUTE TO THE CC. 3) USE A MATHEMATICAL MODEL OF ANORECTAL PASSAGE OF FECOBIONICS FOR ENHANCED UNDERSTANDING OF THE NORMAL AND ABNORMAL DEFECATORY PATTERNS, INCLUDING THE LENGTH-TENSION PROPERTIES OF THE RECTUM AND ANAL SPHINCTER MUSCLES. OUR PROPOSAL SEEKS TO SHIFT CURRENT CC RESEARCH BY PROVIDING A STOOL SURROGATE FOR EXAMINING THE PHYSIOLOGIC PARAMETERS OF DEFECATION REFLEX USING A NOVEL DEVICE THAT WILL RECORD, PRESSURE, DEFORMABILITY, BIOMECHANICS, VECTORAL AND TOPOGRAPHIC CHANGES IN THE RECTUM AND ANAL CANAL. THE NOTED PARAMETERS WILL BE RECORDED USING A WIRELESS FECOBIONICS DEVICE THAT CAN EXAMINE IN DETAIL THE MECHANISTIC UNDERPINNINGS (STRESS AND DEFORMATION) OF DEFECATION REFLEX/PROCESS IN HEALTH AND DISEASE. THE IMPACT OF THIS PROJECT IS THAT IT ASSESSES A NOVEL, SAFE, LOW COST, LESS INVASIVE, LOW-RISK, RADIATION-FREE DEVICE IN ITS ABILITY TO PROVIDE BETTER UNDERSTANDING OF EVACUATION AND CONTINENCE MECHANISMS AND THEREBY FACILITATE FUTURE DEVELOPMENT OF INNOVATIVE THERAPIES. THE IMPROVEMENT CAN LEAD TO IMPROVEMENT IN DIAGNOSTIC AND THERAPEUTIC MODALITIES AND REDUCE HEALTHCARE COSTS ASSOCIATED WITH ANORECTAL DISORDERS.

MECHANISMS OF CORONARY FLOW HETEROGENEITY: IMPLICATIONS FOR CORONARY SINUS OCCLUSION THERAPY - ABSTRACT SIGNIFICANT SPATIAL HETEROGENEITY OF CORONARY BLOOD FLOW EXISTS IN THE NORMAL HEART AND IT IS EXAGGERATED IN CORONARY HEART DISEASE (CHD). DESPITE THE SIGNIFICANT CLINICAL RELEVANCE OF ISCHEMIA IN CHD, THE PHYSICAL AND BIOLOGICAL DETERMINANTS OF SPATIAL HETEROGENEITY OF CORONARY BLOOD FLOW IN HEALTH AND DISEASE REMAIN UNCERTAIN. AS A RESULT, THE MECHANISMS OF SOME TREATMENTS, SUCH AS CORONARY SINUS (CS) OCCLUSION, PULSATILE INTERMITTENT CORONARY SINUS (CS) OCCLUSION (PICSO) AND SELECTIVE AUTO-RETROPERFUSION (SARP), ARE ALSO NOT WELL UNDERSTOOD. ADVANCES IN HIGH-PERFORMANCE COMPUTING NOW MAKE IT POSSIBLE TO ATTEMPT ANATOMICALLY REALISTIC DISTRIBUTIVE MATHEMATICAL MODELS, WHERE MORPHOLOGICAL DETAILS OF THE CORONARY VASCULAR SYSTEM ARE CONSIDERED TO TRULY ELUCIDATE THE SPATIAL HETEROGENEITY OF FLOW. HENCE, OUR GENERAL OBJECTIVE IN THIS PROPOSAL IS TO DEVELOP A VALIDATED FULL MODEL OF AN AUTOREGULATED CORONARY CIRCULATION BASED ON ANATOMICALLY ACCURATE 3D DATA IN A DYNAMIC MODEL OF THE BEATING HEART; ONE THAT INTEGRATES MYOCARDIUM-VESSEL INTERACTION (MVI) AND VASOREACTIVITY, CAN EXPLAIN THE SPATIAL HETEROGENEITY OF CORONARY BLOOD FLOW IN ISCHEMIA, AND ELUCIDATE THE RATIONALE FOR THESE CS INTERVENTIONS. THE VALIDATED MODEL WILL ILLUMINATE CLINICALLY SIGNIFICANT MECHANISMS UNDERLYING THE REDISTRIBUTION OF CORONARY FLOW IN ISCHEMIA AND THE MECHANISMS OF CS INTERVENTIONS. OUR CENTRAL HYPOTHESIS IS THAT REGIONAL DIFFERENCES IN MYOCARDIAL OXYGEN (O2) DEMAND PRODUCE SPATIAL HETEROGENEITY IN CORONARY FLOW AND THAT ISCHEMIA INCREASES FLOW HETEROGENEITY BY COMPROMISING MVI AND AUTOREGULATION. DUE TO INHERENT DIFFICULTIES ASSOCIATED WITH SUBENDOCARDIAL MEASUREMENTS IN VIVO, THE ABSENCE OF A VALIDATED BIOPHYSICAL MODEL OF THE CORONARY CIRCULATION HAS BEEN A CRITICAL BARRIER TO PROGRESS. OUR PROPOSAL ADDRESSES THIS BARRIER AND HAS THE POTENTIAL TO ADVANCE SCIENTIFIC KNOWLEDGE IN MULTI-SCALE, MULTI-PHYSICS MODELING AND, ULTIMATELY, CLINICAL PRACTICE IN DIAGNOSIS AND TREATMENT OF CHD. ACCORDINGLY, THE THREE SPECIFIC AIMS ARE TO: 1) DEVELOP AN EXPERIMENTALLY VALIDATED, PHYSICS- BASED COMPUTATIONAL FRAMEWORK COUPLING AUTOREGULATED CORONARY CIRCULATION WITH CARDIAC MECHANICS. 2) ELUCIDATE THE MECHANICAL MECHANISMS OF SUBENDOCARDIAL VULNERABILITY TO ISCHEMIA. 3) DETERMINE THE MECHANICAL MECHANISM OF ACTION OF CSO, PICSO AND SARP AS WELL AS FACTORS AFFECTING THESE TREATMENTS. THIS PROPOSAL TAKES AN INTEGRATED APPROACH (THEORY, COMPUTATIONAL MODELS, AND EXPERIMENTS) TO ELUCIDATE THE RELATIONSHIP BETWEEN SPATIAL HETEROGENEITY OF PERFUSION AND CARDIAC MECHANICAL WORK, AUTOREGULATION, AND O2 CONSUMPTION UNDER PATHOLOGICAL AND TREATMENT CONDITIONS. THE PROPOSED WORK WILL PRODUCE A NOVEL COMPUTATIONAL FRAMEWORK THAT WILL BE USED TO ELUCIDATE THE KEY FACTORS CONTROLLING SUBENDOCARDIAL VULNERABILITY IN ISCHEMIA AND THE MECHANISM OF ACTIONS OF CSO, PICSO AND SARP. THE BIOPHYSICAL MODELING FRAMEWORK WILL ALSO SERVE AS A FOUNDATION FOR CONSTRUCTING PATIENT-SPECIFIC HEART MODEL BASED ON STANDARD MEDICAL IMAGING TO ASSIST IN DIAGNOSIS AND TREATMENT OF CHD

PATHOPHYSIOLOGY, DIAGNOSIS AND BIOFEEDBACK THERAPY IN FECAL INCONTINENCE USING FECOBIONICS - ABSTRACT FECAL INCONTINENCE (FI) AFFECTS 1 IN 7 AMERICANS WITH A RISING INCIDENCE THAT POSES A MAJOR HEALTHCARE BURDEN. ITS PATHOPHYSIOLOGY IS POORLY UNDERSTOOD AND CONSEQUENTLY THERE IS DEARTH OF EFFECTIVE TREATMENT(S). A CRITICAL BARRIER TO PROGRESS HAS BEEN THE LACK OF COMPREHENSIVE, PHYSIOLOGICALLY-RELEVANT AND PRACTICAL DIAGNOSTIC TEST FOR IDENTIFYING THE UNDERLYING MECHANISM(S). CURRENT TESTS PROVIDE EITHER INCOMPLETE OR CONFLICTING INFORMATION THAT DO NOT CORRELATE WITH SYMPTOMS AND TREATMENT OUTCOMES. OUR GOAL IS TO DETERMINE THE ROLE OF ANORECTAL MUSCLES IN MAINTAINING CONTINENCE AND FACILITATING DEFECATION, AND HOW ANORECTAL MALFUNCTIONS CAN CAUSE FI BY USING A NOVEL TECHNOLOGY CALLED FECOBIONICS (AN ELECTRONIC SIMULATED STOOL) TO EVALUATE ITS DIAGNOSTIC AND THERAPEUTIC UTILITY. FECOBIONICS HAS THE CONSISTENCY AND SHAPE OF NORMAL STOOL THAT CAN RECORD PRESSURES, CROSS- SECTIONAL AREA, ORIENTATION, AND VISCOELASTIC PROPERTIES OF THE ANORECTUM. WITH HEAVILY UPGRADED HARDWARE, SOFTWARE AND GRAPHICAL USER INTERFACE, THE NEW FECOBIONICS DEVICE MAP THE GEOMETRIC PROFILES DURING EVACUATION AND RELATE THEM TO SIMULTANEOUS CHANGES IN PRESSURES (FORCES) AND BENDING. OUR CENTRAL HYPOTHESIS IS THAT THE MOVEMENT OF THE FECOBIONICS DEVICE THROUGH THE ANORECTUM WILL PROVIDE UNKNOWN AND NEW MECHANISTIC INSIGHTS ON ANORECTAL PHYSIOLOGY INCLUDING INTRALUMINAL PRESSURE CHANGES, ANAL MUSCLE LENGTH-TENSION RELATIONS, RESISTANCE GENERATED DURING MOVEMENT OF THE SURROGATE STOOL AND ITS DEFORMABILITY, AS WELL AS DISTENSIBILITY OF THE ANAL SPHINCTERS IN NORMAL SUBJECTS AND FI PATIENTS. THIS MULTIDIMENSIONAL DATA COULD FACILITATE NEW TREATMENTS FOR FI. ACCORDINGLY, OUR SPECIFIC AIMS ARE TO: 1) DETERMINE THE LENGTH-TENSION PROPERTIES OF THE ANAL SPHINCTERS USING FECOBIONICS IN NORMAL SUBJECTS AND FI PATIENTS DURING ANAL DISTENSION AND DURING SIMULATED EVACUATION. 2) ELUCIDATE THE PATHOPHYSIOLOGICAL CHARACTERISTICS AND BIOMECHANICAL PROPERTIES OF INDIVIDUAL MUSCLE COMPONENTS, EXTERNAL, INTERNAL ANAL SPHINCTER AND PUBORECTALIS MUSCLE USING THE FECOBIONICS DEVICE AND COMPARING FI PATIENTS WITH NORMAL SUBJECT CONTROLS; AND 3) EVALUATE THE USE OF FECOBIONICS AS A BIOFEEDBACK TREATMENT (BT) AND MONITORING TOOL IN FI PATIENTS TO DETERMINE THE PREDICTORS FOR TREATMENT SUCCESS, BY PERFORMING A RANDOMIZED CONTROLLED TRIAL OF FECOBIONICS-ASSISTED BIOFEEDBACK THERAPY (FBT) VERSUS CONVENTIONAL OFFICE-BASED BIOFEEDBACK THERAPY (OBT). OUR PROPOSAL SEEKS TO SHIFT CURRENT FI RESEARCH BY TESTING A STOOL SURROGATE FOR PERFORMING BT AS OPPOSED TO A THIN MANOMETRY PROBE AND EXAMINE THE MULTI-DIMENSIONAL PHYSIOLOGIC CHANGES (I.E., PRESSURE, DEFORMABILITY, BIOMECHANICS, VECTORAL AND TOPOGRAPHIC CHANGES) AS WELL AS CLINICAL OUTCOME FOLLOWING BT. THE UNIQUE ASPECT OF OUR PROPOSAL IS TO SIMULATE STOOLING WITH A WIRELESS BIONICS DEVICE AND EXAMINE IN DETAIL THE MECHANISTIC UNDERPINNINGS IN HEALTH AND IN FI PATIENTS. THE IMPACT OF OUR PROJECT IS TO PROVIDE NEW MECHANISTIC UNDERSTANDING OF ANORECTAL FUNCTION AND PATHOPHYSIOLOGY IN FI AND VALIDATE THE CLINICAL UTILITY OF A NOVEL, HIGHLY INTEGRATED DEVICE FOR DIAGNOSTICS AND FACILITATION OF BIOFEEDBACK THERAPY WITH AN UNPRECEDENTED GRAPHICAL FEEDBACK TO THE PATIENT OF MECHANOSENSORY ACTIONS.

MICRO-MECHANICAL ROLE OF HYPERTENSION IN INTIMAL HYPERPLASIA

MATHEMATICAL MODEL-BASED OPTIMIZATION OF CRT RESPONSE IN ISCHEMIA - PROJECT SUMMARY/ABSTRACT APPLICATION OF MULTISCALE COMPUTER MODELING TO HELP GUIDE AND ELUCIDATE HEART DISEASE TREATMENTS IS EMERGING. COMPUTATIONAL MODELING, HOWEVER, HAS NOT BEEN EXPLOITED FOR OPTIMIZING CARDIAC RESYNCHRONIZATION THERAPY (CRT). WHILE CRT HAS EMERGED AS A POWERFUL TREATMENT FOR HEART FAILURE (HF) TO RESTORE NORMAL ACTIVATION PATTERN IN THE HEART, ABOUT 30% OF PATIENTS STILL DO NOT IMPROVE AFTER THERAPY (NON-RESPONDERS). IMPROVEMENT OF RESPONDER RATE THEREFORE REMAINS A CRUCIAL CLINICAL CHALLENGE AND THE HOLY GRAIL OF CRT. WE BELIEVE THAT COMPUTATIONAL MODELING CAN HELP OPTIMIZE CRT AND IMPROVE THE RESPONDER RATE. EQUALLY IMPORTANT, THE DEVELOPMENT OF A MULTISCALE COMPUTATIONAL FRAMEWORK THAT CONSIDERS THE KEY PHYSICS OF THE HEART CAN HELP UNDERSTAND SEVERAL NOVEL PACING THERAPIES (E.G., CONDUCTION SYSTEM PACING (CSP) INCLUDING HIS BUNDLE PACING AND LEFT BRANCH BUNDLE (LBB) PACING) THAT HAVE BEEN DEVELOPED RECENTLY TO IMPROVE THE RESPONDER RATE. SPECIFICALLY, COMPUTATIONAL MODELING CAN HELP ELUCIDATE THE KEY FACTORS AFFECTING THE LONG AND SHORT-TERM EFFECTIVENESS OF THESE PACING THERAPIES IN PATIENTS WITH DIFFERENT INTRAVENTRICULAR CONDUCTION DELAY AND/OR LV SCAR/ISCHEMIA. HERE, THE OVERALL GOAL HERE IS TO DEVELOP COMPUTATIONAL APPROACHES THAT COMBINE MACHINE LEARNING ALGORITHMS AND PHYSICS-BASED MODELING TO FUNDAMENTALLY UNDERSTAND THE SHORT AND LONG-TERM EFFECTS OF CRT THAT INCLUDES CSP, OPTIMIZE CRT, AND TO ELUCIDATE THE ADVANTAGES AND DISADVANTAGES OF CSP OVER STANDARD CRT. THE FOLLOWING SPECIFIC AIMS ARE CONSTRUCTED TO ACCOMPLISH THIS GOAL. FIRST, WE WILL DEVELOP AN EXPERIMENTALLY-VALIDATED MULTISCALE CARDIAC ELECTRO-MECHANICS-PERFUSION (EMP) COMPUTATIONAL FRAMEWORK TO SIMULATE THE CHRONIC EFFECTS OF CRT AND CSP IN TREATING MECHANICAL DYSSYNCHRONY IN LBBB + ISCHEMIA. SECOND, WE WILL INTEGRATE THE COMPUTATIONAL MODELING FRAMEWORK WITH EFFICIENT MACHINE LEARNING AND OPTIMIZATION ALGORITHMS TO OPTIMIZE CRT WITH LV EPICARDIAL AND ENDOCARDIAL PACING IN ISCHEMIA. THIRD, WE WILL USE THE VALIDATED MULTISCALE COMPUTATIONAL EMP FRAMEWORK TO ELUCIDATE THE EFFECTS AND FACTORS AFFECTING THE RESPONSE OF CSP IN ISCHEMIA. THE PROPOSED APPROACH AND METHODOLOGIES ARE INNOVATIVE. MORE IMPORTANTLY, SUCCESSFUL COMPLETION WILL DIRECTLY TRANSLATE THE FINDINGS TO THE CLINIC FOR OPTIMIZATION OF CRT THERAPY TO REDUCE NON-RESPONDER RATES AS WELL AS PATIENT IDENTIFICATION FOR DIFFERENT PACING THERAPIES. THIS WOULD HAVE SUBSTANTIAL IMPACT ON IMPROVING THE TREATMENT AND REDUCING THE COST OF HF EPIDEMIC.

FECOBIONICS MONITORING AND PREDICTION OF BIOFEEDBACK THERAPY OUTCOME IN PATIENTS WITH OBSTRUCTED DEFECATION. - ABSTRACT DEFECATORY DISORDERS AFFECT 25% OF THE POPULATION AND THEY ARE POORLY RECOGNIZED AND TREATED. THE INCIDENCE OF DEFECATORY DISORDERS INCLUDING CHRONIC CONSTIPATION IS RISING AND IT POSES A MAJOR HEALTHCARE BURDEN. THE UNDERLYING MECHANISMS FOR THESE DISORDERS ARE OFTEN NOT WELL UNDERSTOOD. OBSTRUCTED DEFECATION (DYSSYNERGIA) HAS SEVERAL CAUSES AND IS SUBDIVIDED IN FOUR SUBTYPES. DESPITE THE HIGH PREVALENCE AND INCIDENCE, DIAGNOSTICS AND TREATMENT OPTIONS ARE SPARSE. A SIGNIFICANT PROBLEM IN ANORECTAL PHYSIOLOGY TESTING IS A LACK OF PHYSIOLOGICALLY RELEVANT AND PRACTICAL DIAGNOSTIC TEST FOR IDENTIFYING THE UNDERLYING MECHANISMS TO IDENTIFY PROPER TREATMENT. CURRENT DIAGNOSTIC TESTS PROVIDE INCOMPLETE AND OFTEN CONFLICTING INFORMATION BECAUSE THEY DO NOT SIMULATE FECES OR THE DEFECATION PROCESS. NOT SURPRISINGLY, RESULTS OF THESE TESTS CORRELATE POORLY WITH SYMPTOMS AND TREATMENT OUTCOMES. BIOFEEDBACK THERAPY IS A WELL-ESTABLISHED THERAPY FOR OBSTRUCTED DEFECATION BUT DESPITE THE SUBSTANTIAL POTENTIAL AND PROMISING RESULTS, BIOFEEDBACK THERAPY IS ONLY DONE AT SPECIALIZED CENTERS AND SHOULD BE ADVANCED CLOSER TO THE POINT OF CARE. THE OBJECTIVE OF THIS SMALL R01 PROPOSAL IS TO MONITOR AND PREDICT THE OUTCOME OF BIOFEEDBACK THERAPY BASED ON UNPRECEDENTED INTEGRATED VISUAL FEEDBACK FROM THE NOVEL SIMULATED FECES DEVICE TERMED FECOBIONICS. THE DEVICE IS ELECTRONIC SIMULATED FECES THAT HAS THE CONSISTENCY AND SHAPE OF NORMAL STOOL. FECOBIONICS WILL PROVIDE MECHANISTIC UNDERSTANDING OF DEFECATION FOR THE EXAMINER BY VISUALIZING THE GEOMETRIC (CROSS-SECTIONAL AREA, BENDING AND SHAPE OF DEVICE) AND MANOMETRIC PROFILES OF THE SIMULATED FECES BEFORE AND DURING DEFECATION. THE CENTRAL HYPOTHESIS IS THAT THE FECOBIONICS DEVICE THAT MIMICS NATURAL DYNAMIC DEFECATION PROVIDES VALID DATA ON RECTAL EMPTYING ATTEMPTS FOR THE VARIOUS COMPONENTS OF THE DEFECATORY SYSTEM SUCH AS THE TONE OF ANAL SPHINCTERS AND PUBORECTALIS MUSCLE, AND ON MECHANOSENSORY PROPERTIES. THE OBJECTIVE IS TO MONITOR AND PREDICT BIOFEEDBACK THERAPY BASED ON MECHANISM-BASED AND HIGHLY INTEGRATED DATA THAT CAN BE VISUALIZED DURING ANORECTAL NEUROMUSCULAR EXERCISES. FOR THE PROPOSED STUDIES, WE WILL SELECT DYSSYNERGIA PATIENTS, WHO WILL BE MONITORED WITH FECOBIONICS BEFORE, DURING AND AFTER BIOFEEDBACK THERAPY. THE HYPOTHESIS IS FECOBIONICS DATA WILL CORRELATE BETTER TO SYMPTOMS BASED ON CONSTIPATION SCORES THAN CONVENTIONAL TECHNOLOGIES AND THAT SUCH DATA CAN BE USED TO PREDICT RESPONDERS AND NON-RESPONDERS TO THERAPY. OUR PROPOSAL SEEKS TO SHIFT CURRENT RESEARCH IN CONSTIPATION THERAPY BY USE OF A NOVEL DEVICE THAT PROVIDES MECHANISTIC INSIGHTS BY SIMULATING DEFECATION PATHOPHYSIOLOGICALLY AND EXAMINING THE MECHANISTIC CHANGES MULTI-DIMENSIONALLY: PRESSURE, DEFORMABILITY, BIOMECHANICS, AND TOPOGRAPHIC CHANGES TO MONITOR UNDERLYING DEFECTS IN PATIENTS WITH OBSTRUCTED DEFECATION, ESPECIALLY IN DYSSYNERGIA. THE UNIQUE ASPECTS OF OUR PROPOSAL ARE TO SIMULATE STOOL WITH A BIONICS DEVICE THAT INTEGRATES MULTIPLE VARIABLES THAT EXAMINE THE MECHANISTIC UNDERPINNINGS OF OBSTRUCTED DEFECATION. THE IMPACT OF THIS PROJECT IS TO SHED NEW UNDERSTANDING OF CONSTIPATION AND TO PREDICT RESPONDERS. THIS WILL FACILITATE DEVELOPMENT OF INNOVATIVE BOWEL MANAGEMENT PROGRAMS USING FECOBIONICS AS THE BIOFEEDBACK THERAPY TOOL.

MODELS OF THE LYMPHATIC SYSTEM FOR IMPROVED THERAPY