Non-invasive, quantitative microscopic biomarkers for chemotherapy-induced peripheral neuropathy - Project Summary/Abstract A large proportion (40-90%) of cancer patients receiving chemotherapy suffer from chemotherapy-induced peripheral neuropathy (CIPN). During treatment, CIPN causes acute sensory dysfunction (e.g. numbness, tingling) and pain, which is the second most common reason for limiting chemotherapy dose and negatively impacts prognosis. After treatment, CIPN can result in chronic symptoms (e.g., debilitating pain, functional impairment). Currently, there is no standardized, reliable tool for assessing CIPN. Our overarching goal is to provide non-invasive, quantitative microscopic biomarkers for CIPN using an imaging technology termed portable confocal microscopy (PCM). Reflectance confocal microscopy is a non-invasive imaging method that could visualize CIPN-associated changes in nerve ending. Meissner’s corpuscles (MCs) are mechanoreceptors in glabrous skin (e.g. fingers, toes) composed of peripheral nerve ending. In confocal images, MCs are readily visualized as bright, round structures with a diameter of 40-75 µm. Dr. Ramnarine (Co-investigator, Guy’s and St. Thomas’ Hospital) carried out the first ever prospective study imaging MCs in cancer patients receiving chemotherapy with reflectance confocal microscopy. This preliminary study showed that MC density measured by confocal microscopy was i) reduced significantly in CIPN patients compared to the controls prior to chemotherapy, and ii) highly correlated with other validated but time-consuming sensory measures during and after chemotherapy. While this study showed the potential of confocal microscopy for assessing CIPN, the standard device (Vivascope 1500) has several limitations: slow imaging speed, unstable device-to-tissue connection, and high device cost (~$100,000). Dr. Kang (PI, University of Arizona) has been leading development of portable confocal microscopy (PCM) devices. PCM reduced the device material cost to $4-5,000, visualized characteristic cellular morphologic features of skin cancers and benign conditions, and visualized MCs from human fingers in vivo with similar image quality to the high-cost, standard confocal microscope (Preliminary data). In this R01 project, we will develop a new portable confocal microscope that enables rapid, repeatable imaging of MCs and evaluate its clinical utility for assessing CIPN. The new PCM will provide quantitative imaging biomarkers for CIPN and completely change how we 1) conduct clinical trials for prevention and treatment of CIPN, 2) identify patients at risk, and 3) assess, treat, and monitor individual patients with CIPN. The low device cost and portability of PCM will make the technology readily integrated into routine care of cancer patients. We will achieve this goal through following aims: Aim 1) Develop a new portable confocal microscope for rapid MC imaging in cancer patients, Aim 2) Evaluate the clinical utility of PCM for assessing CIPN, and Aim 3) Develop deep learning-based algorithms for automatically counting MCs.
