NCT05902039

MRI Study of Blood-brain Barrier Function in CADASIL

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: Peking University First Hospital · Academic / Other
• Sex: All
• Age: 20 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Diffusion prepared pseudo-continuous ASL (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of blood-brain barrier (BBB). The investigators aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with CADASIL, and to analyze the association between BBB water exchange rate and MRI/clinical features in these patients.

Detailed description

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by NOTCH3 gene mutations, is the most frequent monogenic type of hereditary cerebral small vessel disease (CSVD). The unique pathophysiological mechanisms that small vessel disorders in CADASIL are caused by genetic mutations and that the majority of patients do not combine cerebrovascular disease risk factors make CADASIL an ideal model for studying CSVD, and the imaging findings on CADASIL can be used to diagnose and investigate the etiology of CSVD. While abnormalities in the cerebrovascular structure and hemodynamics have been well demonstrated in CADASIL, the abnormality of the BBB remains controversial. One DCE-MRI study suggested an increase in BBB permeability to gadolinium contrast in CADASIL, whereas no abnormality of BBB was found in subsequent studies in mouse models and patients. The aim of this study was to assess whether BBB function is abnormal in patients with CADASIL using DP-pCASL, which is more sensitive to subtle changes in the BBB compared to DCE-MRI. The investigators hypothesized that the BBB water exchange rate (kw) is reduced in patients with CADASIL compared to controls as assessed by DP-pCASL and that the degree of reduction in BBB water exchange rate correlates with the severity of disease in patients with CADASIL.

Conditions

• Cadasil
• Blood Brain Barrier Defect

Interventions

Type	Name	Description
OTHER	MRI	All participants underwent an MR examination on a 3T whole-body Prisma MRI system (Siemens, Erlangen, Germany) with a 64-channel head coil, and a 7T whole-body MAGNETOM MR system (Siemens, Erlangen, Germany) using a 32-channel receive/birdcage transmit head coil (NOVA medical). DP-pCASL, Multi-delay pCASL (MD-pCASL) was acquired to evaluate BBB function and cerebral perfusion. T1-weighted magnetization-prepared rapid gradient echo (T1w-MPRAGE) was scanned at both 3T and 7T for registration in the post-processing workflow. T2-weighted fluid-attenuated inversion recovery (T2w-FLAIR) and T2\*-weighted gradient echo (T2\*w-GRE) were acquired at 7T for high-resolution structural images and evaluation of lesions.

Timeline

• Start date: 2021-04-01
• Primary completion: 2025-04-01
• Completion: 2026-04-01
• First posted: 2023-06-13
• Last updated: 2023-06-13

Locations

1 site across 1 country: China