PROJECT SUMMARY Genitourinary Syndrome of Menopause (GSM) affects up to 50% of women and negatively affects their quality of life with regard to general health and sexual function. Hormone therapy is the most commonly performed procedure to supplement the natural estrogen, but health risk associated with long-term therapy exists. Recently, an alternative therapy has been proposed using fractional CO2 micro- ablation that may benefit patients that cannot receive hormone therapies. Although laser micro- ablation showed a clear benefit in dermatology, it remains controversial in female pelvic medicine. The main problem is that, without a clear indication to routinely perform an invasive biopsy for benign genitourinary changes, the pathophysiology of tissue response and factors leading to refractory symptoms remain poorly understood. Thus, this is an area of research that would greatly benefit from non-invasive imaging technologies such as Optical Coherence Tomography (OCT). Our long-term goal is to provide individualized patient management by screening patients who will benefit the most from laser therapy, optimize the laser duration and dose, and assess the need for follow-up care. To achieve this goal, we will develop a point-of-care endoscopic imaging system that combines OCT and OCT angiogram (OCTA) to obtain simultaneous information on structural and functional changes during the vaginal laser treatment. We further proposed to use 1.7 μm center wavelength swept-source laser to image 500 μm deeper than the traditional 1.3 μm laser. We will achieve our objectives by pursuing the following specific aims. Aim 1: Design and develop a 1.7 μm OCT/OCTA system and a multifunctional endoscope imaging probe. Aim 2: Establish the reproducibility of the integrated endoscope in human subjects by assessing vaginal tissue integrity in different demographic groups. Aim 3: Investigate the effects of laser ablation over a time course of several laser therapies and understand the tissue response. The endoscopic OCT/OCTA system will serve as a noninvasive biopsy tool in the gynecological practice and it can, non- invasively, provides structural and functional information about the tissue. This will provide clinicians and scientists with an important tool to screening the patients that will benefit from the laser, monitor the progression of laser therapy, and evaluate the tissue response from the laser treatment and further individualize treatment strategies. The proposed research is expected to have a significant impact on image-guided laser therapy and the management of GSM.

PROJECT NARRATIVE Despite the emerging market in energy-based devices to treat Genitourinary Syndrome of Menopause (GSM) in menopausal women, the exact effect of the laser on vaginal tissue remains poorly understood. We propose to develop a point-of-care, multifunctional intravaginal endoscope that can obtain simultaneous information on structural, vascular, and biomechanical changes before and during the vaginal laser procedure. The proposed research is expected to have a significant impact on the patient screening and monitoring of laser tissue interaction.