In Vivo Characterization of White Matter Hyperintensity Using Individualized Analysis of Multimodal Imaging

White matter hyperintensities (WMHs) are common findings in older adults, appearing as high-signal areas on T2-weighted MRI scans. While often linked to cerebral small vessel disease, they reflect non-specific changes in white matter composition and have been linked to a wide range of conditions, including neurodegenerative diseases. This non-specificity makes it difficult to determine the underlying cause of WMHs based solely on their size or location on an MRI scan. The challenge becomes even more pronounced in dementia clinics, where distinguishing between the different causes of WMHs is crucial but complicated by the interplay of Alzheimer’s disease (AD) and aging, vascular cognitive impairment and dementia (VCID). These conditions often coexist, contributing to white matter damage, making it harder to isolate their individual contributions. Without a clear understanding of WMH pathologies, the relationship between AD and VCID will remain unsolved, and tailored interventions will remain challenging. To address this gap, we propose an innovative multimodal-neuroimaging approach that integrates modern advanced techniques. The proposed project aims to identify distinct imaging features that characterize the mechanistic, cellular, and hemodynamic aspects of diffuse white matter disease in AD vs. VCID. By employing advanced neuroimaging techniques, including diffusion MRI for cellular microstructure, perfusion MRI for blood flow, and quantitative susceptibility mapping for microbleed and myelination, we will develop an individualized analysis approach to characterize WMHs. This comprehensive approach will differentiate the pathophysiology of periventricular versus deep-brain WMH in relation to AD and vascular risk factors. The goal is to distinguish WMH related to AD from those linked to cardiovascular issues, ultimately improving diagnoses and enabling more personalized and effective intervention for patients facing cognitive decline. Project Number: 1RF1NS146659-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Yu-Chien Wu | Institution: INDIANA UNIVERSITY INDIANAPOLIS, INDIANAPOLIS, IN | Award Amount: $1,870,941 | Activity Code: RF1 | Study Section: Special Emphasis Panel[ZRG1 AN-E (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11391734