Combined Optical Coherence Elastography and Tomography for Assessing Skin Involvement in Systemic Sclerosis

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Abstract Systemic sclerosis (SSc-scleroderma) is an autoimmune disease leading to widespread fibrosis in skin and internal organs. Skin involvement is a prominent source of distress and morbidity in this disease. The modified Rodnan skin score (mRSS) as the current gold standard for assessment of skin thickening has limited accuracy, high inter-observer variability, requires extensive training which have cumulatively contributed to the fact there are currently no FDA approved medications for skin involvement in SSc. Therefore, an objective and accurate tool for assessment of skin fibrosis can be paradigm shifting for clinical trial design and patient management in SSc by improving our ability to track treatment response and disease progression. Our preliminary data indicate that the imaging by optical coherence tomography (OCT) and elasticity measurement by optical coherence elastography (OCE) can provide a safe, rapid, and accurate assessment of SSc skin fibrosis. Specifically, OCT/OCE is the first objective dermal assessment method showing criterion validity and outperforming mRSS for correlation with the histological dermal thickness in the forearm area. As the OCE primarily assesses tissue stiffness, its performance is weaker in some other body areas such as fingers, where the skin can be tethered to the underlying tissue. On the other hand, an improved high-resolution OCT technology with accompanying optical density measurement that can image deeper layers of dermis would provide an additional objective assessment of dermal fibrosis. This is especially relevant in SSc as fibrosis primarily occurs in deeper layers of dermis (reticular dermis). Our hypothesis is that an improved OCT based structural imaging that can capture the deeper dermal layers in combination with the OCE based stiffness assessment will improve our ability to accurately measure dermal fibrosis in SSc. The primary goal of this project to develop and validate a deep OCT/OCT based tool for assessment of SSc skin thickness. To accomplish this goal, the following Specific Aims will be pursued during the R61 phase: Aim 1: To enhance signal-to-noise ratio (up to 120 dB) and imaging depth (up to 2 mm) of the currently available OCE/OCT system for more accurate assessment of SSc skin. Aim 2: To determine the accuracy of combined OCE and deep dermal OCT imaging for assessment of skin fibrosis and for monitoring response to treatment in bleomycin induced dermal fibrosis mouse model. Aim 3: To characterize the accuracy and reliability of a combination of deep OCT/OCE for assessing skin fibrosis in SSc patients. Building on the above studies, we will characterize the longitudinal changes in the OCE/OCT assessment of skin fibrosis and determine its sensitivity to change in SSc patients during the R33 phase. This project can lead to development of a safe and quantitative tool for objective assessment of dermal fibrosis which can be paradigm shifting by facilitating approval of novel treatments for SSc skin involvement. Moreover, it can aid clinicians to accurately track disease progression and response to treatment and ultimately lead to improved monitoring and treatment strategies in this potentially devastating disease.