Project Grant R01CA280972

COLORECTAL CANCER SCREENING WITH OPTICAL COHERENCE TOMOGRAPHY - THE OVERALL INCIDENCE RATE OF COLORECTAL CANCER (CRC) HAS DECLINED OVER THE PAST TWO DECADES LARGELY DUE TO POPULATION-BASED COLONOSCOPIC SCREENING FOR AND REMOVAL OF PRECURSOR ADENOMAS. EVEN THOUGH COLONOSCOPY HAS BEEN BENEFICIAL FOR CANCER INTERCEPTION, IT HAS LIMITATIONS THAT HAVE SUBSTANTIAL FINANCIAL AND HEALTH CONSEQUENCES. NEARLY ALL COLONOSCOPY PATIENTS IN THE US UNDERGO CONSCIOUS SEDATION/ANESTHESIA WHICH IS RESPONSIBLE FOR ~$15B IN HEALTH CARE COSTS ANNUALLY. RESECTION OF POLYPS, MANY OF WHICH DO NOT HAVE NEOPLASTIC POTENTIAL, IS ALSO EXPENSIVE, RAISING COLONOSCOPY COSTS BY ~50%. COLONOSCOPY MISSES MANY ADENOMAS, LEADING TO A HIGH RATE OF INTERVAL CANCERS, ACCOUNTING FOR ABOUT 7,000 NEW CRC CASES EACH YEAR. KEY FACTORS LEADING TO THIS HIGH MISS RATE INCLUDE THE FORWARD-VIEWING ENDOSCOPE THAT MISSES POLYPS BEHIND COLONIC FOLDS, SUBTLE SERRATED PRECURSOR LESIONS, AND DISPARITIES IN ENDOSCOPIST PROFICIENCY. THESE ISSUES UNDERLIE UNMET NEEDS FOR IMPROVED ADENOMA SCREENING TECHNOLOGIES THAT 1) ENABLE THE ENTIRE COLON TO BE VISUALIZED, INCLUDING BEHIND MUCOSAL FOLDS, 2) ARE MORE SENSITIVE AND OBJECTIVE FOR POLYP IDENTIFICATION, 3) PROVIDE REAL-TIME POLYP DIAGNOSIS, AND 4) CAN DETECT AND TREAT ADENOMAS BY AT THE POINT OF CARE WITHOUT REQUIRING SEDATION. OPTICAL COHERENCE TOMOGRAPHY (OCT) IS A CROSS-SECTIONAL IN VIVO MICROSCOPY IMAGING TECHNOLOGY THAT WITH FURTHER DEVELOPMENT CAN ADDRESS MANY OF THESE ADENOMA SCREENING NEEDS. HERE, WE WILL CREATE AND CLINICALLY VALIDATE A NEW OCT SYSTEM AND TWO DISTINCT OCT PROBES THAT ARE OPTIMIZED FOR ADENOMA SCREENING. THE OCT SYSTEM WILL UTILIZE INNOVATIVE TECHNOLOGY TO OBTAIN THREE-DIMENSIONAL MICROSCOPIC IMAGES OF THE ENTIRE COLON IN 5 MINUTES (AIM 1.3). ONE OF THE PROPOSED OCT IMAGING PROBES WILL OPERATE THROUGH THE ACCESSORY PORT OF A COLONOSCOPE, ACCELERATING CLINICAL TRANSLATION THROUGH ITS COMPATIBILITY WITH STANDARD OF CARE COLONOSCOPY (AIM 1.1). THIS PROBE WILL UTILIZE NOVEL EXTENDED DEPTH OF FOCUS (EDOF) OPTICS, ALLOWING IT TO BE CENTERED IN THE COLON'S LUMEN AND CAPTURE HIGH-RESOLUTION, CROSS-SECTIONAL OCT IMAGES THAT RETAIN 3D TOPOLOGY. WE WILL USE THIS COLONOSCOPE- COMPATIBLE PROBE IN A CLINICAL STUDY OF 200 PATIENTS TO DEVELOP AND TEST AN AUTOMATED MACHINE LEARNING ALGORITHM FOR POLYP CLASSIFICATION IN VIVO (AIM 2). THE SECOND OCT PROBE, TERMED A RETROGRADE TETHERED CAPSULE ENDOMICROSCOPE (R-TCE), WILL BE DESIGNED TO SCREEN FOR ADENOMAS IN UNSEDATED PATIENTS AT THE POINT OF CARE (AIM 1.2). THE R-TCE DEVICE WILL BE A TETHERED EDOF OCT IMAGING CAPSULE THAT IS INSERTED INTO THE ANUS AND ADVANCED TO THE CECUM VIA A ROTATING SCREW-LIKE MOTION. ONCE THERE, THE CAPSULE WILL BE CENTERED IN THE LUMEN BY A BALLOON AND PULLED BACK THROUGH THE COLON WHILE IMAGING. AFTER THE CAPSULE IS DEVELOPED, WE WILL CONDUCT A CLINICAL STUDY TO ESTABLISH THE R-TCE CLINICAL PROCEDURE AND THEN TEST SAFETY AND FEASIBILITY OF WHOLE-COLON R-TCE IMAGING IN 45 PATIENTS (AIM 3). FINALLY, TO ENABLE FUTURE TREATMENT OF SMALL ADENOMAS IDENTIFIED BY R-TCE, AN R-TCE DEVICE THAT ABLATES DIMINUTIVE ADENOMAS WILL BE DEVELOPED/TESTED IN A SWINE POLYPOSIS MODEL (AIM 1.4).