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

摘要 系统性硬化症（Ssc-硬皮病）是一种自身免疫性疾病，导致皮肤广泛纤维化， 内脏皮肤受累是这种疾病的痛苦和发病率的主要来源。修改后的 Rodnan皮肤评分（mRSS）作为目前评估皮肤增厚的金标准具有有限的准确性， 观察员之间的高度可变性，需要广泛的培训，这累积起来有助于实现以下事实 目前没有FDA批准的用于SSc皮肤受累的药物。因此，客观和 评估皮肤纤维化的准确工具可以改变临床试验设计和患者 通过提高我们跟踪治疗反应和疾病进展的能力来管理SSc。我们 初步数据表明，光学相干断层扫描（OCT）成像和弹性测量 通过光学相干弹性成像（OCE）可以提供安全，快速和准确的评估SSc皮肤 纤维化具体而言，OCT/OCE是第一个显示标准有效性的客观皮肤评估方法 并且在与前臂区域的组织学真皮厚度的相关性方面优于mRSS。作为OCE 主要评估组织硬度，但在其他一些身体区域（如手指）的性能较弱， 皮肤可以被束缚到下面的组织上。另一方面，改进的高分辨率OCT技术 伴随着可以对真皮深层成像的光密度测量， 皮肤纤维化的额外客观评估。这在SSc中尤其相关，因为纤维化主要发生在 真皮深层（网状真皮）。我们的假设是，一种改进的OCT结构成像 结合基于OCE的硬度评估，可以捕获更深的真皮层， 我们准确测量SSc皮肤纤维化的能力。本项目的主要目标是开发和验证 用于评估SSc皮肤厚度的深度OCT/OCT工具。为了实现这一目标， 在R61阶段将追求具体目标：目标1：提高信噪比（高达120 dB）， 目前可用的OCE/OCT系统的成像深度（最大2 mm），可更准确地评估SSc 皮肤目的2：确定OCE和深层皮肤OCT联合成像评估皮肤的准确性 用于在博来霉素诱导的皮肤纤维化小鼠模型中监测对治疗的反应。目标3： 表征深部OCT/OCE组合用于评估SSc皮肤纤维化的准确性和可靠性 患者基于上述研究，我们将描述OCE/OCT的纵向变化 评估皮肤纤维化并确定其对R33期SSc患者变化的敏感性。这 该项目可以导致开发一种用于客观评估皮肤纤维化的安全和定量工具， 可以通过促进SSc皮肤受累的新治疗方法的批准来改变范式。此外，委员会认为， 它可以帮助临床医生准确地跟踪疾病进展和对治疗的反应， 改善对这一潜在破坏性疾病的监测和治疗策略。

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.