PROJECT SUMMARY Myofascial Pelvic Pain (MPP) is a frequently overlooked musculoskeletal cause of chronic pelvic pain affecting 10-20% of all adult women. Pelvic floor muscle tightening in MPP results in acidosis and accumulation of neuroinflammatory mediators, leading to self-reinforcing pelvic pain and bowel, bladder, and sexual dysfunction. A challenge in the management of MPP has been a lack of quantitative measures of pelvic floor physiology capable of quantifying functional alterations in the pelvic floor musculature in 3- dimensional space. This deficiency has in turn hampered both a greater understanding of the mechanisms of MPP and the development of novel therapeutics. Our research group has developed an innovative approach to identify pelvic floor muscle dysfunction using a near infra-red spectroscopy (NIRS) optical, vaginal interface designed to image and quantify in real-time oxygenation and hemodynamics regionally throughout the pelvic floor in response to contraction and relaxation of the muscle. During the R61 phase, we plan to validate this technology as an effective, non-invasive, and scalable method to assess pelvic floor muscle fitness. We will seek to establish parameters to describe the severity and spatial patterns of myofascial dysfunction and how these parameters correlate with individual muscular assessment, the spectrum of pelvic pain manifestations, and bowel, bladder, and sexual complaints. We will also correlate these findings with current subjective methods of pelvic floor assessment in control subjects and MPP subjects, specifically focusing on the ability of NIRS to provide repeatable measurements independent of user expertise and training. In the R33 phase, we will utilize this technology to examine prospective changes in pelvic floor fitness in MPP patients following a range of myofascially-directed therapies, including pharmacologic muscle relaxation, onabotulinumA toxin pelvic floor injection, and myofascial release physical therapy. We will correlate NIRS outcomes and symptomatic measures with systemic inflammatory markers pre- and post-treatment to understand better the role of neuroinflammation in the clinical syndrome of MPP. We will also employ machine learning models to examine if this technology can be utilized to predict responses to individual treatments. Demonstration that objective measures of muscle fitness recover as symptoms improve following myofascially-directed therapies will provide the first direct evidence of the underlying nature of MPP, evidence needed to evolve current therapeutic approaches. Through interdisciplinary collaboration of specialists in urology, gynecology, integrative medicine, and computational medicine, this novel imaging technique providing both spatial and functional evaluation of the pelvic floor will assist in the diagnosis and management of chronic pelvic pain and promote additional research into novel approaches to address the poorly recognized epidemic of myofascial pelvic pain in women.

PROJECT NARRATIVE This proposal lays out a new approach to use optical technology to provide novel imaging and physiologic measures relevant to the pelvic floor muscle as a method to quantify and spatially distinguish the muscular dysfunction underlying female myofascial pelvic pain. Once validated, this approach may serve as an effective, non-invasive, and scalable method to assess pelvic floor muscle fitness and allow for the prospective study of changes in pelvic floor fitness following myofascially-directed therapies. The development of machine learning models will also attempt to predict individual responses to different treatments for myofascial pelvic pain using the spatial NIRS assessment of the pelvic floor, both improving the clinical care of the condition and providing novel insight into the disease pathophysiology.