MRI Study of Blood-brain Barrier Function in CADASIL

NCT05902039 | Recruiting DMC

• 1 other identifier: 2022-715
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cadasil; Blood Brain Barrier Defect

Outcome Measures

Primary Outcomes (1)

• kw

  Post-processing of DP-pCASL data was performed offline using LOFT BBB Toolbox. Head motion was corrected using SPM12 and the temporal fluctuations were minimized by using principal component analysis. DP-pCASL data with the b value of 50 s/mm2 were used to obtain the ASL signal from the tissue and capillary compartments respectively, and kw was quantified by using a single-pass approximation model with total generalized variation regularization.

  30 Minutes

Secondary Outcomes (3)

• CBF

  30 Minutes

• ATT

  30 Minutes

• QSM

  30 Minutes

Study Arms (2)

CADASIL patients

Inclusion Criteria: 1. Patients with CADASIL confirmed by gene or/and skin biopsy. 2. The age range is 20-70 years old. 3. There is no contraindication to MRI examination, and the informed consent is signed. exclusion criteria： 1. Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases. 2. CADASIL is not confirmed. 3. There are contraindications to examination or refusal to sign the informed consent.

Other: MRI

Healthy controls

Inclusion Criteria: 1. The age range is 20-70 years old. 2. There is no contraindication to MRI examination, and the informed consent is signed. exclusion criteria： 1. Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases. 2. There are contraindications to examination or refusal to sign the informed consent.

Interventions

MRI OTHER

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.

Also known as: Cognitive Scale and Clinical Scale Evaluation

CADASIL patients

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All CADASIL patients and controls who met the criteria described below and who agreed to participate in this study were enrolled. All CADASIL patients included in this study have been visited at Peking University First Hospital, and the included controls were recruited from the community.

You may qualify if:

• Patients with CADASIL confirmed by gene or/and skin biopsy.
• The age range is 20-70 years old.
• There is no contraindication to MRI examination, and the informed consent is signed.

You may not qualify if:

• Combined with definite cerebrovascular disease, or combined with brain tumor, brain trauma and other causes of brain diseases.
• CADASIL is not confirmed.
• There are contraindications to examination or refusal to sign the informed consent.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Chinese Academy of Sciences: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, China

RECRUITING

Related Publications (7)

• St Lawrence KS, Owen D, Wang DJ. A two-stage approach for measuring vascular water exchange and arterial transit time by diffusion-weighted perfusion MRI. Magn Reson Med. 2012 May;67(5):1275-84. doi: 10.1002/mrm.23104. Epub 2011 Aug 19.

  PMID: 21858870 BACKGROUND

• Shao X, Ma SJ, Casey M, D'Orazio L, Ringman JM, Wang DJJ. Mapping water exchange across the blood-brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI. Magn Reson Med. 2019 May;81(5):3065-3079. doi: 10.1002/mrm.27632. Epub 2018 Dec 18.

  PMID: 30561821 BACKGROUND

• Uchida Y, Kan H, Sakurai K, Arai N, Inui S, Kobayashi S, Kato D, Ueki Y, Matsukawa N. Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL. Neurology. 2020 Sep 1;95(9):e1188-e1198. doi: 10.1212/WNL.0000000000010148. Epub 2020 Jun 25.

  PMID: 32586899 BACKGROUND

• Walsh J, Tozer DJ, Sari H, Hong YT, Drazyk A, Williams G, Shah NJ, O'Brien JT, Aigbirhio FI, Rosenberg G, Fryer TD, Markus HS. Microglial activation and blood-brain barrier permeability in cerebral small vessel disease. Brain. 2021 Jun 22;144(5):1361-1371. doi: 10.1093/brain/awab003.

  PMID: 34000009 BACKGROUND

• Sun C, Wu Y, Ling C, Xie Z, Sun Y, Xie Z, Li Z, Fang X, Kong Q, An J, Wang B, Zhuo Y, Zhang W, Wang Z, Yuan Y, Zhang Z. Reduced blood flow velocity in lenticulostriate arteries of patients with CADASIL assessed by PC-MRA at 7T. J Neurol Neurosurg Psychiatry. 2022 Apr;93(4):451-452. doi: 10.1136/jnnp-2021-326258. Epub 2021 Sep 28. No abstract available.

  PMID: 34583945 BACKGROUND

• Li Y, Ying Y, Yao T, Jia X, Liang H, Tang W, Jia X, Song H, Shao X, Wang DJJ, Wang C, Cheng X, Yang Q. Decreased water exchange rate across blood-brain barrier in hereditary cerebral small vessel disease. Brain. 2023 Jul 3;146(7):3079-3087. doi: 10.1093/brain/awac500.

  PMID: 36625892 BACKGROUND

• Li Z, Sun D, Ling C, Bai L, Zhang J, Wu Y, Yuan Y, Wang Z, Wang Z, Zhuo Y, Xue R, Zhang Z. Quantitative modeling of lenticulostriate arteries on 7-T TOF-MRA for cerebral small vessel disease. Eur Radiol Exp. 2024 Nov 5;8(1):126. doi: 10.1186/s41747-024-00512-7.

  PMID: 39499373 DERIVED

MeSH Terms

Conditions

CADASIL

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Central Study Contacts

Chen Ling, PhD

CONTACT

+86 18101358135; lnyy.chen@foxmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2023
• First Posted: June 13, 2023
• Study Start: April 1, 2021
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2026
• Last Updated: June 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)