Optical imaging platform for staging vascular impairment in Alzheimer's disease

用于对阿尔茨海默病血管损伤进行分期的光学成像平台

• 批准号: 8203542
• 负责人: Alexander Justin Lin
• 金额: $ 3.41万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8203542
• 关键词: Actins; Address; Age; Alzheimer' s Disease; Amyloid beta-Protein; Animal Experiments; Animals; Basic Science; Biochemistry; Biological Assay; Biological Markers; Biology; Blood Vessels; Brain; Cell Death; Clinic; Clinical; Clinical Management; Collaborations; Coupling; Data; Dementia; Development; Disease; Disease Progression; Early Diagnosis; Engineering; Exhibits; Fellowship; Fibrosis; Foundations; Frequencies; Functional disorder; Goals; Histology; Human; Image; Impairment; Influentials; Institutes; Knowledge; Lasers; Learning; Lesion; Letters; Light; Maps; Measurement; Medical; Memory Loss; Memory impairment; Metabolic; Metabolism; Mitochondria; Modeling; Monitor; Mus; Muscular Atrophy; Neuronal Dysfunction; Neurosciences; Optics; Pathogenesis; Pathology; Patients; Physiology; Prevention; Proteins; Research; Risk Factors; Senile Plaques; Severities; Signal Transduction; Smooth Muscle; Smooth Muscle Actin Staining Method; Spectrum Analysis; Staging; Structure; Techniques; Technology; Testing; Therapeutic; Thick; Time; TimeLine; Tissues; Transgenic Mice; Transgenic Organisms; Translating; United States National Institutes of Health; Vascular Smooth Muscle; Work; absorption; abstracting; age group; brain tissue; cerebrovascular; clinical care; cost; cost effective; experience; extracellular; hyperphosphorylated tau; imaging modality; improved; in vivo; instrument; interest; mouse model; muscle hypertrophy; nervous system disorder; new technology; novel; optical imaging; outcome forecast; pre-clinical; tool

DESCRIPTION (provided by applicant): Novel translatable optical imaging platform for staging vascular impairment in Alzheimer's disease Project summary/abstract A challenge in studying and treating Alzheimer's disease (AD) is cost-effective quantitative imaging. Current imaging strategies focus on identifying amyloid-beta (A2) plaques, the defining lesion in AD, and are expensive and hard to use. Even so, plaques alone have been shown to not be specific for clinical dementia, and evidence is building for cerebrovascular risk factors and impairments downstream of A2 pathology. The critical question is whether a set progression of vascular impairments are caused by and likely exacerbate A2 pathology leading ultimately to cell death and memory loss. If so, an alternate strategy of imaging for specific vascular impairments and cellular hypometabolism may supplement current imaging modalities in the study and management of AD. The objective for this fellowship proposal is to apply and develop a novel in vivo non- contact spectroscopy mapping technique called spatial frequency domain imaging (SFDI) with these aims: 1) To use SFDI to sequence specific vascular impairments in triple transgenic AD mice in vivo. 2) To correlate cellular hypometabolism to levels of vascular impairment. This project will exploit SFDI's unique ability to intrinsically resolve both neurovascular physiology as well as brain structural alterations. The results could increase basic science understanding of AD, suggest therapies, and translate to prognosis and monitoring of AD in the clinic, directly addressing the goals of the NIA at the NIH. Several features render this project particularly suitable for the F30 mechanism. SFDI, capable of assaying metabolism, microvascular function, and tissue composition changes in the brain was developed by the trainee's sponsor Dr. Bruce Tromberg, who also directs the Beckman Laser Institute and Medical Clinic, a state-of-the-art biomedical optics imaging facility with new translational instruments constantly being developed. Several of these technologies will be used and further developed by the trainee under Dr. Tromberg's guidance. The proposed animal experiments are done in collaboration with the UCI Institute for Memory Impairment and Neurological Disorders led by Dr. Frank LaFerla, famous for developing the first mouse model expressing AD-specific pathology, namely extracellular amyloid plaques and intracellular hyper- phosphorylated tau. Learning and communicating the concepts/techniques from engineering and animal work will lay the foundation for incorporating similar interdisciplinary components in the trainee's future research endeavors. Thus, the development of SFDI for alternative, non-invasive testing strategies for AD is likely to equip the trainee with technical imaging and neuroscience experience, in addition to greatly improving knowledge of early vascular impairment in AD. PUBLIC HEALTH RELEVANCE: More than 35 million people world-wide have Alzheimer's disease (AD) 33, but prevention, early detection, and quantitative monitoring of disease progression is limited. Understanding the progression of vascular impairment in the pathogenesis of AD will suggest treatment, prognosis and monitoring strategies for AD. Furthermore, analogous tissue spectroscopy techniques and optical biomarkers advanced by this project can directly translate into human trials and, eventually, the clinic relatively easily and cost-effectively.

描述（由申请人提供）：用于对阿尔茨海默病血管损伤进行分期的新型可翻译光学成像平台 项目摘要/摘要 研究和治疗阿尔茨海默病 (AD) 的一个挑战是具有成本效益的定量成像。目前的成像策略侧重于识别淀粉样蛋白 (A2) 斑块（AD 的定义性病变），并且价格昂贵且难以使用。即便如此，单独的斑块已被证明对临床痴呆并不具有特异性，并且正在建立关于脑血管危险因素和 A2 病理下游损伤的证据。关键问题是一系列血管损伤是否由 A2 病理引起并可能加剧，最终导致细胞死亡和记忆丧失。如果是这样，针对特定血管损伤和细胞代谢低下的成像替代策略可能会补充当前 AD 研究和治疗中的成像方式。该奖学金提案的目标是应用和开发一种称为空间频域成像 (SFDI) 的新型体内非接触光谱测绘技术，其目标如下： 1) 使用 SFDI 对三重转基因 AD 小鼠体内的特定血管损伤进行测序。 2) 将细胞代谢低下与血管损伤水平相关联。该项目将利用 SFDI 的独特能力从本质上解决神经血管生理学和大脑结构改变。研究结果可以增加对 AD 的基础科学理解，提出治疗建议，并转化为 AD 的临床预后和监测，直接实现 NIH 的 NIA 目标。多项功能使该项目特别适合 F30 机构。 SFDI 能够分析大脑中的新陈代谢、微血管功能和组织成分变化，由学员的资助者 Bruce Tromberg 博士开发，他同时也是贝克曼激光研究所和医疗诊所的负责人，这是一家最先进的生物医学光学成像机构不断开发新翻译工具的设施。其中一些技术将由受训者在 Tromberg 博士的指导下使用和进一步开发。拟议的动物实验是与 Frank LaFerla 博士领导的 UCI 记忆障碍和神经疾病研究所合作完成的，Frank LaFerla 博士因开发第一个表达 AD 特异性病理学（即细胞外淀粉样蛋白斑和细胞内过度磷酸化 tau）的小鼠模型而闻名。学习和交流工程和动物工作中的概念/技术将为受训者未来的研究工作中纳入类似的跨学科组成部分奠定基础。因此，开发 SFDI 用于 AD 的替代性非侵入性测试策略，除了大大提高对 AD 早期血管损伤的了解之外，还可能为学员提供技术成像和神经科学经验。 公共卫生相关性：全世界有超过 3500 万人患有阿尔茨海默病 (AD) 33，但疾病进展的预防、早期检测和定量监测有限。了解 AD 发病机制中血管损伤的进展将为 AD 的治疗、预后和监测策略提供建议。此外，该项目先进的类似组织光谱技术和光学生物标记可以直接转化为人体试验，并最终相对容易且经济高效地转化为临床。