MR imaging of venous transit time in vascular cognitive impairment and dementia

/Abstract: Small-vessel-disease related vascular cognitive impairment and dementia (VCID) represent the second leading cause of cognitive dysfunction in older individuals. Small artery abnormalities have been assessed using surrogate markers such as cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and arterial transit time (ATT). However, post-mortemly it has been shown that VCID hallmarks such as white matter hyperintensities (WMH) are more associated with small vein pathologies such as stenotic or tortuous veins. However, few studies have examined in vivo venous hemodynamics in small vessel disease, due to a scarcity of available tools. Importantly, venous transit time (VTT) provides unique information about venous vessel function and represents an important candidate biomarker in small vessel disease. VTT denotes the time it takes for the water molecules to travel from the exchange site, typically the capillary bed, to draining cerebral veins, e.g., superior sagittal sinus (SSS). The central goal of this application is to develop and validate a novel non-contrast MRI technique, dubbed Venous transit time Imaging by Changes in T1 Relaxation (VICTR), to measure VTT in the brain and to conduct the first clinical application of VTT in VCID. This technique is based on the notion that, when water molecules are exchanged from the tissue into the veins, they will experience a transition in T1 relaxation time. Therefore, by measuring the T1 recovery curve of MR signals in the vein, one can estimate the time at which the transition took place. Our preliminary studies revealed excellent feasibility and sensitivity of the proposed technique. Our new preliminary data collected during the resubmission period also demonstrated the associations of VTT with vascular risk factors and white matter hyperintensities (WMH). This project has three Aims. Aim 1 will develop a non-contrast technique, VICTR MRI, to quantitatively evaluate VTT. We will conduct VTT measurements in several clinically important veins, including superior sagittal sinus (SSS), straight sinus (SS), internal cerebral veins (ICV), the vein of Galen (GV), basal veins of Rosenthal (BV), and internal jugular veins (IJV). VTT measurements in these veins will provide a comprehensive assessment of venous hemodynamics in different brain regions, based on their respective draining territories. Aim 2 will conduct validation, verification, and multi-vendor harmonization of VICTR MRI for VTT assessment. We will test the sensitivity of VICTR MRI to VTT increase (using caffeine ingestion) and VTT decrease (using CO2-inhalation). We will validate VICTR MRI with contrast-agent-based bolus-tracking MRI. We will also harmonize VICTR MRI across major vendors of MRI (General Electric, Philips, and Siemens), making VICTR MRI a scalable technique. Aim 3 will conduct clinical application of VICTR MRI in small-vessel- disease related VCID. We will compare VTT between cognitively normal controls and impaired patients, and examine the associations among VTT, cognitive function, WMH, and Alzheimer’s biomarkers. Project Number: 1R01AG091312-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Hanzhang Lu | Institution: JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD | Award Amount: $465,035 | Activity Code: R01 | Study Section: Imaging Technology for Neuroscience Study Section[ITN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11229280