Development of perivascular space mapping toolset as a diagnostic aid for Alzheimer's disease

开发血管周围空间测绘工具集作为阿尔茨海默病的诊断辅助工具

• 批准号: 10255954
• 负责人: Jeiran Choupan
• 金额: $ 46.1万
• 依托单位: NEUROSCOPE INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255954
• 关键词: Abeta clearance; Adopted; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; American; Amyloid; Amyloid beta-Protein; Animal Experimentation; Axon; Blood - brain barrier anatomy; Brain; California; Cerebrospinal Fluid; Clinic; Clinical; Clinical Data; Clinical Research; Clinical assessments; Cognitive; Collaborations; Computational Technique; Computer software; Consumption; Data; Data Set; Demyelinations; Development; Diagnosis; Diagnostic; Disease; Economic Burden; Ensure; Feedback; Goals; Hippocampus (Brain); Human; Image; Impaired cognition; Individual; Industry; Infrastructure; Intercellular Fluid; Intervention; Liquid substance; Lymphatic; Lymphatic System; Machine Learning; Magnetic Resonance Imaging; Manuals; Maps; Measures; Medical Imaging; Metabolic; Monitor; Morphology; Neurofibrillary Tangles; Neuroglia; Neurologist; Operating System; Outcome; Participant; Pathologic; Pathology; Pathway interactions; Patient Monitoring; Phase; Play; Positron-Emission Tomography; Protocols documentation; Public Health; Research; Resolution; Role; Scanning; Senile Plaques; Sensitivity and Specificity; Sex Distribution; Small Business Technology Transfer Research; Standardization; Structure; Techniques; Technology; Testing; Time; Translating; Translations; Treatment Efficacy; United States National Aeronautics and Space Administration; Universities; Validation; Visual; amnestic mild cognitive impairment; base; brain health; clinical Diagnosis; clinical predictors; clinically significant; cohort; connectome; cost estimate; efficacy evaluation; human data; hyperphosphorylated tau; imaging biomarker; imaging study; in vivo; in vivo imaging; insight; interest; magnetic field; medical schools; neuroimaging; neurovascular; predictive modeling; prevent; protein aggregation; radiological imaging; radiologist; socioeconomics; success; tau Proteins; technology validation; tool; uptake; vascular cognitive impairment and dementia; wasting

Project Summary Alzheimer’s disease (AD) is a devastating disease that affects millions of Americans and imposes a huge socio- economic burden. AD-related cognitive decline is associated with the accumulation of Aβ (Amyloid beta) plaques and neurofibrillary tangles of hyperphosphorylated tau protein, which are insufficiently cleared and degraded by mechanisms such as the glia-lymphatic system or by transport across the blood-brain barrier (BBB). Animal research has shown that the glia-lymphatic pathway plays a substantial role in the net clearance of Aβ. In addition, reduction of interstitial fluid efflux to the cerebrospinal fluid, or reduction of transport across the BBB, could lessen the Aβ clearance. Human magnetic resonance imaging (MRI) studies have also shown that the integrity of the perivascular space (PVS), the pathway of glia-lymphatic system, is a marker of glia-lymphatic brain health and its alteration is an important feature of AD pathology. PVS alteration in AD has been shown to be independent of Amyloid uptake, implicating astroglial involvement specific to AD. Information about PVS integrity could assist clinicians with making specific diagnosis about patients AD status and mechanism. Therefore, a tool that allows non-invasive in-vivo mapping of PVS from clinical MRI is of high significance to aid AD diagnosis and disease monitoring but does not yet exist. Current clinical routine to investigate PVS is a relatively crude approach based on counting total number of observed PVS in MRI by neuro-radiologists, which is non-specific, rater-dependent, and does not capture the distribution, whole extent of PVS change nor volumetric features of the PVS. From a practical point of view, this technique is time consuming and laborious. These limitations in part have prevented neurologists from adopting PVS quantification into their clinical routine. We have developed computational techniques for mapping and quantifying PVS morphology from MRI, which enables automated and accurate quantification of PVS across the brain without the need for time consuming manual intervention. These techniques were developed on research data, which had slightly higher resolution than clinical MRI. The goal of this proposal is to validate and optimize this technology on clinical MRI data, which can be variable in quality and resolution. We also aim to develop a scanner- and hardware-agnostic deployable analytical solution for automated PVS quantification, so that PVS mapping can be performed independent of the radiology/imaging IT infrastructure. If successful, we will have a fully developed and validated backend software that enables automated assessment of PVS and aids specific AD diagnosis and disease monitoring. Upon the completion of this goal, our Phase II will focus on translation of the technology via implementation and testing of the technology in collaboration with our strategic partners in clinic (Neuroradiology division of Keck School of Medicine), industry (BioGen Inc.) and research (MarkVCID and NASA). Our ultimate goal will be to integrate PVS measures into clinical diagnosis, disease monitoring and intervention efficacy assessment, as a specific non-invasive and in-vivo imaging marker of AD pathology that can be automatically and reliably measured.

项目概要 阿尔茨海默病（AD）是一种毁灭性的疾病，影响着数百万美国人，并给社会带来了巨大的影响。 经济负担。 AD 相关的认知能力下降与 Aβ（β 淀粉样蛋白）斑块的积累有关 和过度磷酸化的 tau 蛋白的神经原纤维缠结，这些缠结未被充分清除和降解 神经胶质淋巴系统等机制或通过血脑屏障（BBB）运输。动物 研究表明，神经胶质细胞-淋巴通路在 Aβ 的净清除中起着重要作用。在 此外，减少间质液流向脑脊液，或减少穿过血脑屏障的运输， 可以减少 Aβ 清除率。人体磁共振成像（MRI）研究还表明， 血管周围空间（PVS）的完整性，即神经胶质-淋巴系统的通路，是神经胶质-淋巴系统的标志物 大脑健康及其改变是 AD 病理学的一个重要特征。 AD 中的 PVS 改变已被证明 独立于淀粉样蛋白的摄取，暗示 AD 特有的星形胶质细胞受累。关于PVS的信息 完整性可以帮助临床医生对患者的 AD 状态和机制做出具体诊断。 因此，一种能够通过临床 MRI 对 PVS 进行非侵入性体内映射的工具对于帮助 但AD诊断和疾病监测尚不存在。目前研究 PVS 的临床常规是 相对粗略的方法基于计算神经放射科医生在 MRI 中观察到的 PVS 总数， 是非特定的、依赖于评估者的，并且不捕获 PVS 变化的分布、整体范围，也不捕获 PVS 的体积特征。从实用角度来看，这种技术既费时又费力。 这些限制在一定程度上阻碍了神经科医生将 PVS 量化纳入他们的临床常规。 我们开发了用于从 MRI 中绘制和量化 PVS 形态的计算技术，该技术 无需耗时即可自动准确地量化整个大脑的 PVS 手动干预。这些技术是根据研究数据开发的，其分辨率稍高 与临床 MRI 相比。该提案的目标是在临床 MRI 数据上验证和优化该技术， 质量和分辨率可能会有所不同。我们还致力于开发一种与扫描仪和硬件无关的可部署 用于自动 PVS 定量的分析解决方案，以便 PVS 映射可以独立于 放射学/成像 IT 基础设施。如果成功，我们将拥有一个完全开发和验证的后端软件 它能够自动评估 PVS 并帮助特定的 AD 诊断和疾病监测。于 为了完成这一目标，我们的第二阶段将重点通过实施和测试来转化技术 该技术与我们的临床战略合作伙伴（凯克医学院神经放射学部门）合作 医学）、工业（BioGen Inc.）和研究（MarkVCID 和 NASA）。我们的最终目标是整合 PVS衡量临床诊断、疾病监测和干预效果评估，作为具体的措施 可以自动、可靠地测量 AD 病理的非侵入性体内成像标记。