Real-time In Vivo Visualization of the Molecular Processes in Choroidal Neovascularization

脉络膜新生血管形成分子过程的实时体内可视化

基本信息

批准号：
10237996
负责人：
Yannis Mantas Paulus
金额：
$ 22.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10237996
关键词：
Age related macular degeneration Anatomy Angiography Animals Biological Markers Biological Models Biology Blindness Blood Vessels Burn injury Cell Death Choroidal Neovascularization Cicatrix Complex Contrast Media Deformity Detection Development Diagnosis Discipline Drusen Early Diagnosis Edema Electron Microscopy Electroretinography Endoglin Endothelial Cells Evaluation Fluorescein Fluorescein Angiography Fluorescence Fluorescence Microscopy Functional disorder Fundus photography Future Goals Grant Hemorrhage Histopathology Home Image Imaging Device Immunohistochemistry Individual Indocyanine Green Inflammation Integrin alphaVbeta3 KDR gene Knowledge Lasers Lateral Light Macular degeneration Maps Measures Mentors Methods Michigan Microscopy Modeling Molecular Molecular Biology Monitor Mus Ophthalmic examination and evaluation Ophthalmologist Optical Coherence Tomography Oryctolagus cuniculus Outcome Patient Care Patients Play Process Research Research Personnel Resolution Retina Retinal Diseases Role Rupture Safety Scientist Sensitivity and Specificity Signal Transduction System Testing Time Tissues Training Universities Vision Visual Visual Acuity Visualization Work career development cell injury contrast enhanced imaging modality imaging system improved in vivo individualized medicine intravenous administration molecular imaging multimodality nanoGold nanoparticle neovascularization novel polyacrylamide precision medicine research and development skills sound targeted treatment temporal measurement tool translational impact

项目摘要

ABSTRACT Neovascularization plays a pivotal role in the leading causes of blindness in the developed world, including wet age-related macular degeneration (AMD). At its early stage, wet AMD is characterized by molecular changes. Later, choroidal neovascularization (CNV) develops, leading to subretinal hemorrhage, scarring, and irreversible vision loss. Thus, detection of wet AMD at an earlier stage, before the hemorrhage develops, can improve vision. This K08 research will develop and investigate a novel multimodal molecular imaging system using photoacoustic microscopy (PAM), optical coherence tomography (OCT), and fluorescence microscopy to detect wet AMD at an earlier stage than currently possible using molecular contrast agents to visualize αvβ3 integrin in neovascularization. CNV will be localized and quantified to sub-10 micron resolution. This real-time, in vivo molecular information will allow for targeted treatment and precision medicine tailored to each patient’s unique molecular expression. The central hypothesis is molecular imaging of αvβ3 integrin will be sensitive and specific in early choroidal neovascularization and can thus be used as a biomarker in early detection of neovascularization in macular degeneration. The objectives are to: 1) demonstrate the safety of photoacoustic microscopy; 2) perform multimodal molecular imaging of αvβ3 integrin using PAM, OCT, and fluorescence microscopy; and 3) demonstrate that molecular imaging of αvβ3 integrin allows for earlier detection of CNV in rabbit models. The two specific aims of this study are 1) Test the prediction that photoacoustic microscopy (PAM) can safely visualize the chorioretinal microvasculature, and 2) Quantify the extent that molecular imaging using gold nanoparticles targeting αvβ3 integrin localize to CNV and enable earlier visualization of CNV. The long-term goals of this career development research plan is for the investigator to develop the skills and expertise in high resolution, multimodal molecular ophthalmic imaging to understand the molecular mechanisms leading to choroidal neovascularization. This will improve the care of patients through early detection diagnosis, precision medicine, and improved understanding of fundamental biology. The world- renowned mentors and advisors from the University of Michigan are leaders of their respective fields and are fully commited to guiding the candidate's development into an independent investigator clinician scientist.

抽象的新血管形成在发达世界的失明主要原因中起关键作用，包括与年龄相关的黄斑变性（AMD）。在早期阶段，湿AMD的特征是分子变化。后来，脉络膜新生血管形成（CNV）的发展，导致超级出血，疤痕和不可逆转的视力丧失。在出血之前，在早期阶段检测到湿AMD 发展，可以改善视力。这项K08研究将开发和研究一种新型的多峰分子使用光声显微镜（PAM），光学相干断层扫描（OCT）和荧光显微镜在更早的阶段检测湿AMD，而不是当前使用分子对比剂在新血管形成中可视化αVβ3整联蛋白。 CNV将被定位并量化为10 微分分辨率。实时的体内分子信息将允许有针对性的治疗和精度为每个患者独特的分子表达量身定制的药物。中心假设是αVβ3整合素的分子成像将是敏感的，并且在早期会很特异脉络膜新生血管形成，因此可以用作生物标志物在早期发现新生血管中的生物标志物黄斑变性。目标是：1）证明光声显微镜的安全性； 2）使用PAM，OCT和荧光显微镜对αVβ3整合素进行多模式分子成像； 3）证明αVβ3整合素的分子成像允许在兔模型中早期检测CNV。这这项研究的两个具体目的是1）测试光声显微镜（PAM）可以安全的预测可视化平民微脉管系统，2）量化使用金的分子成像的程度靶向αVβ3整联蛋白的纳米颗粒本地化为CNV并实现了CNV的早期可视化。该职业发展研究计划的长期目标是研究人员发展技能以及高分辨率，多模式分子眼观成像的专业知识，以了解分子导致脉络膜新生血管形成的机制。这将通过早期改善患者的护理检测诊断，精确医学以及对基本生物学的了解。世界 - 密歇根大学的著名导师和顾问是各自领域的领导者，是完全致力于将候选人的发展引入独立研究者临床科学家。