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Novel Biomarkers of Small Vessel Contributions to Vascular Cognitive Impairment and Dementia (VCID)

小血管对血管认知障碍和痴呆 (VCID) 贡献的新型生物标志物

基本信息

批准号：
10201780
负责人：
JOHN A DETRE
金额：
$ 73.53万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201780
关键词：
Adult Aging Angiography Arteries Biological Biological Markers Blood Vessels Blood capillaries Brain Caliber Central Nervous System Diseases Cerebral small vessel disease Cerebrovascular Circulation Cerebrovascular Disorders Cerebrum Clinical Clinical Research Clinical Trials Cognitive Data Dementia Development Disease Disease Progression Functional disorder Goals Human Impaired cognition Individual Investigation Ischemic Brain Injury Lesion Magnetic Resonance Imaging Measurement Measures Metabolic Microvascular Dysfunction Monitor Optical Coherence Tomography Optical Methods Organ Patients Perfusion Persons Physiology Predictive Value Research Research Personnel Resolution Retina Role Site Spin Labels Structure Syndrome Technology Testing Therapeutic Effect Therapeutic Intervention Vascular Cognitive Impairment Vascular Diseases Vascular blood supply White Matter Hyperintensity Work arteriole base cohort density gray matter imaging modality improved in vivo instrumentation interest middle age millimeter multidisciplinary neuroimaging non-invasive imaging novel novel marker predictive marker recruit retinal imaging specific biomarkers vascular cognitive impairment and dementia white matter

项目摘要

Small vessel disease (SVD) is thought to be among the most prevalent disorders of the central nervous system and contributes a key mechanistic role in the syndrome of vascular cognitive impairment and dementia (VCID). A major challenge in the investigation of cerebral SVD is that small vessel integrity cannot be visualized in vivo. Instead, MRI lesions, most notably white matter hyperintensities, currently provide the most widely accepted biomarker of SVD. However, MRI white matter lesions represent downstream effects of SVD and further are not specific to ischemic brain injury. Noninvasive imaging strategies capable of detecting mechanistically- specific changes in small vessel structure or function would improve the identification and quantification of small vessel contributions to cognitive impairment and dementia and serve as biomarkers for monitoring the effects of therapeutic interventions in clinical trials. As we show in preliminary data, recent developments in the spatial resolution and sensitivity of arterial spin labeled (ASL) perfusion MRI now allow noninvasive quantification of cerebral blood flow (CBF) from the periventricular white matter (PVWM), which is supplied by the terminal distributions of long arterioles much less than 100 microns in diameter. PVWM-CBF accordingly represents a promising biomarker of small vessel perfusion, allowing quantification of small vessel functional integrity without spatially resolving individual arteries. Concomitantly, emerging optical methods such as optical coherence tomographic angiography (OCTA) also allow small vessels and even capillaries to be rapidly noninvasively imaged in the human retina using relatively inexpensive and increasingly widely available instrumentation. Both biomarkers hold the potential to detect mechanistically specific changes in small vessel structural or functional integrity prior to the development of brain lesions been formally established. However, while retina has been described as a “window” to the brain, the relationship between OCTA measures of retina and brain structure and function has yet to be adequately tested. The overall goal of this proposal is to validate PVWM CBF and OCTA-derived microvascular density as bona fide biomarkers of human small vessel structure for use in clinical research. We will investigate the biological and technical determinants of PVWM CBF and OCTA-derived microvascular density, associate changes in retinal microvasculature with brain WML and perfusion, and preliminarily show their predictive value in SVD by correlating baseline measures with longitudinal changes in healthy and clinical cohorts. A multidisciplinary team of investigators with expertise in neuroimaging, retinal imaging, cerebral blood flow physiology, cerebrovascular disorders, aging, and dementia will collaborate to carry out this work.

小血管疾病（SVD）被认为是最普遍的中枢神经系统疾病之一