Dynamic Tracer Kinetic Model to Detect Preclinical Diabetic Retinopathy (DR)

用于检测临床前糖尿病视网膜病变 (DR) 的动态示踪动力学模型

• 批准号: 10708172
• 负责人: JENNIFER J Kang-Mieler
• 金额: $ 45.23万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708172
• 关键词: Acceleration; Address; Angiography; Angiotensin II Receptor; Angiotensin-Converting Enzyme Inhibitors; Area; Biochemical; Biological Markers; Blindness; Blood Vessels; Blood flow; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical; Clinical Sensitivity; Data; Detection; Diabetes Mellitus; Diabetic Retinopathy; Dose; Early Diagnosis; Early treatment; Ensure; Evans blue stain; Fluorescein; Fluorescein Angiography; Genetic; Goals; Growth Factor Inhibition; Hyperglycemia; Imaging Device; Imaging technology; Intervention; Measurement; Measures; Methods; Microspheres; Modeling; Morphologic artifacts; Motion; Nature; Optical Coherence Tomography; Patients; Perfusion; Pericytes; Permeability; Phase; Production; Protein Kinase C; Receiver Operating Characteristics; Reporting; Retina; Retinal Diseases; Rodent Model; Scanning; Sensitivity and Specificity; Severities; Surrogate Endpoint; Techniques; Technology; Tracer; Translating; Vascular Endothelial Growth Factors; Vascular Permeabilities; Vascular remodeling; Vision; Visual impairment; Visualization; X-Ray Computed Tomography; adaptive optics scanning laser ophthalmoscopy; blood flow measurement; clinical examination; clinical practice; data acquisition; detection sensitivity; diabetic; diabetic patient; high risk; imaging modality; kinetic model; novel; novel therapeutics; polyol; pre-clinical; prevent; retina blood vessel structure; retinal damage; retinal imaging; statistics; structural determinants; success; tool; uptake

Project Summary Diabetic retinopathy (DR) is one of the most common complications associated with diabetes. Detection of clinical DR signs can take several years from the onset of diabetes; hence, the long preclinical phase should provide a window to apply interventions that can slow or prevent progression to clinical endpoint (mild to severe visual impairment). In fact, early detection and treatment of DR can prevent more than 90% of vision loss. However, the current unmet clinical challenge is finding an appropriate tool or technology to detect preclinical signs (biomarkers) of DR. Since the retinal vessels are early and prevalent targets of diabetic damage, sensitive identifiers of structural and functional blood vessel changes hold great potential as biomarkers. Recent advances in retinal imaging technology have allowed a better visualization of vessel characteristics. Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) and OCT angiography (OCTA) studies recently suggested that there may be a transitional vascular remodeling during the preclinical phase in diabetic patients. Though the main benefit of these technologies is the non-invasive nature of data acquisition, there are limitations (e.g., long scan times, limited field-of-view, motion artifacts and need for an expert operator) that prevent these technologies to be effective preclinical detection tools to be used in a clinical setting. Therefore, there is a great need for enhanced detection sensitivity and quantitative means to analyze the early preclinical vasculature changes that can be readily translated into clinical practice. To address this critical unmet clinical need, we have developed a novel dynamic tracer kinetic model to measure quantitatively vascular permeability and blood flow changes based on fluorescein video-angiography (FVA). The approach is immediately translatable to FVA data collected in patients as demonstrated by our preliminary data. In this proposal, we will demonstrate that our dynamic tracer kinetic model can detect preclinical DR with a higher sensitivity and specificity than other retinal imaging modalities such as OCTA and AOSLO. Specific Aim 1 will optimize/validate the retinal vascular permeability and blood flow measurements against gold standard techniques of permeability (Evans-blue) and blood flow (microspheres). Specific Aim 2 will demonstrate that longitudinal preclinical changes in the retinal vascular permeability and blood flow detected by our model will occur before clinical retinopathy in diabetic rodent model. Specific Aim 3 will characterize longitudinal changes in retinal vascular permeability and blood flow in both normal subjects and diabetic patients. Specific Aim 4 will demonstrate higher sensitivity of preclinical DR detection by the dynamic tracer kinetic model over optical coherence tomography angiography (OCTA) and adaptive optics scanning laser ophthalmoscopy (AOSLO) in diabetic patients without clinical retinopathy (DMnoDR).

项目总结

项目成果

Optimizing the protocol for retinal vascular permeability mapping from fluorescein videoangiography data.

根据荧光素视频血管造影数据优化视网膜血管通透性映射的协议。

• DOI: 10.1117/12.2610279
• 发表时间: 2022
• 期刊: Proceedings of SPIE--the International Society for Optical Engineering
• 作者: Nalbant,ElifKayaalp;Annepureddy,Laasya;Hu,Shaoxian;Liu,Wenqiang;Tang,Fangyao;Sun,Zihan;Cheung,CarolY;Mieler,WilliamF;Kang-Mieler,JenniferJ;Tichauer,KennethM
• 通讯作者: Tichauer,KennethM

Fluorescein videoangiography data analysis protocol for mapping retinal vascular permeability in humans.

用于绘制人类视网膜血管通透性的荧光素视频血管造影数据分析协议。

• DOI: 10.1117/12.2650304
• 发表时间: 2023
• 期刊: Proceedings of SPIE--the International Society for Optical Engineering
• 作者: Vavrek,Sarah;Kayaalp-Nalbant,Elif;Konopek,Nicholas;Bou-Ghanem,Ghazi;Fawzi,AmaniA;Mieler,WilliamF;Kang-Mieler,JenniferJ;Tichauer,KennethM
• 通讯作者: Tichauer,KennethM