PROJECT SUMMARY/ABSTRACT Pelvic radiotherapy is the standard of care for numerous gynecological and anorectal cancers affecting women. Post-operative intravaginal brachytherapy (IVRT) is used to prevent cancer recurrence at the vaginal cuff for high-intermediate risk endometrial cancer patients. IVRT delivers conformal radiation dose to the vagina cuff and canal. This results in high rates of acute and late vaginal toxicities, such as vaginal stenosis, which is defined as the abnormal tightening and shortening of the vagina due to fibrosis. These effects can lead to debilitating pain, sexual dysfunction, and poor quality of life. Current clinical assessments of vaginal toxicity are subjective and based on clinician and patient reported grading scales that leads to variability. There is a clinical need for objective measurements of vaginal tissue health, and we propose a multiparametric ultrasound imaging approach for vaginal tissue characterization before and after IVRT. In this study, we will develop a system and methodology for three-dimensional (3D) multiparametric imaging of the vaginal wall using B-mode, ultrasensitive microvessel imaging (UMI), shear-wave elastography (SWE), and tissue microstructure characterization with quantitative ultrasound (QUS). As a secondary objective, we will test the system in a clinical study with fifteen endometrial cancer patients receiving IVRT to identify associations between multiparametric ultrasound metrics and current clinical assessments of vaginal toxicity. This will be the first study using a multimodal ultrasound approach for characterization of vaginal tissue. We hypothesize that multiparametric ultrasound will be produce metrics that are sensitive to anatomical changes (B-mode), microvascular damage (UMI), fibrosis stage (SWE), and tissue microstructure and cellular death (QUS). There is increasing awareness of radiation-induced toxicities and considerable effort has gone into strategies to reduce toxicities and improve overall quality of life and sexual functioning. Multiparametric ultrasound imaging offers a non-subjective, quantitative approach for detecting and characterizing vaginal health, which is typically overlooked with current medical imaging. Ultimately, this approach will lead to predictive imaging biomarkers that clinicians can use as outcome metrics of novel treatment strategies and interventions aimed at preventing and treating radiotherapy-induced vaginal toxicities. If successful, the research will introduce a safe, cost- effective imaging platform to improve the health of women suffering from this chronic gynecological condition.

PROJECT NARRATIVE Radiation-induced vaginal toxicity is a common side effect of pelvic radiotherapy, and no clinical tools exist for objective, quantitative evaluation of vagina health. The goal of this research project is to develop a system and methodology for multiparametric ultrasound-based assessment of vaginal toxicity in the acute and late stages following radiotherapy.