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

光学相干弹性成像和断层扫描相结合用于评估系统性硬化症的皮肤受累情况

基本信息

批准号：
10247808
负责人：
Shervin Assassi
金额：
$ 38.09万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10247808
关键词：
Area Assessment tool Autoimmune Diseases Clinical Clinical Research Clinical Trials Clinical Trials Design Cutaneous sclerosis Data Dermal Dermis Development Devices Disease Disease Progression Distress Elasticity FDA approved Fatty acid glycerol esters Fibrosis Fingers Forearm Functional Imaging Funding Goals Gold Histologic Human Image Interobserver Variability Lead Longitudinal cohort Measurement Measures Methods Monitor Morbidity - disease rate Noise Optical Coherence Tomography Optics Organ Palpation Pathology Patients Performance Pharmaceutical Preparations Phase Principal Investigator Resolution Rheumatism Scleroderma Signal Transduction Skin Source Staging Standardization Structure System Systemic Scleroderma Technology Texas Thick Time Tissues Training Universities base clinical care clinical development clinical practice cohort density effective therapy elastography experience improved indium-bleomycin mortality mouse model new technology novel optical imaging skills skin fibrosis subcutaneous tomography tool translational study treatment response treatment strategy ultrasound

项目摘要

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.

抽象的系统性硬化症（SSc-硬皮病）是一种自身免疫性疾病，会导致皮肤和皮肤广泛纤维化内脏器官。皮肤受累是这种疾病的痛苦和发病的主要原因。修改后的 Rodnan 皮肤评分（mRSS）作为当前评估皮肤增厚的金标准，其准确性有限，观察者之间的高变异性，需要大量的培训，这些培训不断积累，导致了这一事实目前尚无 FDA 批准用于治疗 SSc 皮肤受累的药物。因此，客观而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的范式通过提高我们跟踪治疗反应和疾病进展的能力来管理 SSc。我们的初步数据表明，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) 可以安全、快速、准确地评估 SSc 皮肤纤维化。具体来说，OCT/OCE 是第一个显示标准有效性的客观皮肤评估方法与前臂区域组织学真皮厚度的相关性优于 mRSS。作为OCE 主要评估组织硬度，其在其他身体部位（例如手指）的性能较弱，其中皮肤可以拴在下面的组织上。另一方面，改进的高分辨率OCT技术附带的光密度测量可以对真皮更深层进行成像，这将提供真皮纤维化的额外客观评估。这在 SSc 中尤其重要，因为纤维化主要发生在真皮深层（网状真皮）。我们的假设是基于 OCT 的改进结构成像可以捕获更深的真皮层，结合基于 OCE 的硬度评估将改善我们能够准确测量 SSc 中的真皮纤维化。该项目的主要目标是开发和验证一种基于 OCT/OCT 的深度工具，用于评估 SSc 皮肤厚度。为了实现这一目标，需要采取以下措施 R61 阶段将追求的具体目标：目标 1：提高信噪比（高达 120 dB）和当前可用的 OCE/OCT 系统的成像深度（高达 2 毫米），可更准确地评估 SSc 皮肤。目标 2：确定 OCE 和深层真皮 OCT 成像组合用于皮肤评估的准确性纤维化并用于监测博来霉素诱导的真皮纤维化小鼠模型的治疗反应。目标 3：表征深度 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 阶段 SSc 患者变化的敏感性。这该项目可以开发出一种安全、定量的工具来客观评估真皮纤维化，可以通过促进 SSc 皮肤受累新疗法的批准来实现范式转变。而且，它可以帮助临床医生准确跟踪疾病进展和对治疗的反应，并最终导致改善这种潜在破坏性疾病的监测和治疗策略。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Methods for objective assessment of skin involvement in systemic sclerosis.

客观评估系统性硬化症皮肤受累的方法。

DOI：
发表时间：
2023-11-01
期刊：
影响因子：
5.1
作者：
Desai, Ruhani;Chawla, Harshdeep;Larin, Kirill;Assassi, Shervin
通讯作者：
Assassi, Shervin

Updates on translational and clinical research in systemic sclerosis.

系统性硬化症转化和临床研究的最新进展。

DOI：
发表时间：
2023-11-01
期刊：
影响因子：
5.1
作者：
Assassi; Shervin
通讯作者：
Shervin

Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalisation over time.

对系统性硬化症中纵向皮肤基因表达的大规模分析揭示了免疫细胞和成纤维细胞活性与皮肤厚度的关系以及随着时间的推移趋于正常化的趋势。

DOI：
发表时间：
2022-04
期刊：
影响因子：
27.4
作者：
Skaug, Brian;Lyons, Marka A;Swindell, William R;Salazar, Gloria A;Wu, Minghua;Tran, Tuan M;Charles, Julio;Vershel, Connor P;Mayes, Maureen D;Assassi, Shervin
通讯作者：
Assassi, Shervin

Longitudinal global transcriptomic profiling of preclinical systemic sclerosis reveals molecular changes associated with disease progression.

临床前系统性硬化症的纵向整体转录组学分析揭示了与疾病进展相关的分子变化。

DOI：
发表时间：
2023-04-03
期刊：
影响因子：
0
作者：
Bellocchi, Chiara;Beretta, Lorenzo;Wang, Xuan;Lyons, Marka A;Marchini, Maurizio;Lorini, Maurizio;Carbonelli, Vincenzo;Montano, Nicola;Assassi, Shervin
通讯作者：
Assassi, Shervin

Repetitive optical coherence elastography measurements with blinking nanobombs.

使用闪烁纳米炸弹进行重复光学相干弹性成像测量。

DOI：
10.1364/boe.401734
发表时间：
2020-10-22
期刊：
Biomedical optics express
影响因子：
3.4
作者：
P. Boerner;Dmitry Nevozhay;M. Hatamimoslehabadi;H. Chawla;Fern;o Zvietcovich;o;S. Aglyamov;K. Larin;K. Sokolov
通讯作者：
K. Sokolov