White Matter Hyperintensities Subtypes in Cerebral Small Vessel Disease : 7 Tesla Ultra-high Resolution Imaging MRI (SV7)

Cerebral small vessel diseases (SVD) are a very frequent group of disorders all characterized by alterations of the structure and/or function of small arteries, veins and capillaries. In these disorders, brain tissue lesions accumulate years before the occurrence of clinical symptoms which can be devastating such as stroke, cognitive disturbances and gait disorders. So far, chronic hypoperfusion was considered to be responsible for the accumulation of such lesions. However, recent results have suggested that the lesions underlying white matter hyperintensities (WMH), the most common MRI marker of SVD visible on conventional MRI in quite every subject with SVD long before the occurrence of clinical events, may depend on the considered brain area and may correspond to various mechanisms. Some WMH may even be associated with less severe clinical manifestations.The aim of the present study is to identify different types of WMH by studying 100 patients with different forms of SVD with the most advanced MRI (including ultra-high-resolution imaging at 7 Tesla, new diffusion protocol, sodium MRI, contrast-enhanced angiography and relaxometry and post-processing techniques), and post-processing techniques (machine learning, deep learning, artificial intelligence).

Study Overview

• Status: Recruiting
• Conditions: Cerebral Small Vessel Diseases
• Intervention / Treatment: Other: Experimental Arm

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric Jouvent, Pr; Phone Number: 0149956529; Email: eric.jouvent@aphp.fr
• Study Contact Backup: Name: Matthieu RESCHE-RIGON, Pr; Phone Number: 0142499742 0142499742; Email: matthieu.resche-rigon@univ-paris-diderot.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Hopital Lariboisiere
    • Contact: Eric Jouvent, MD PhD; Phone Number: +33 149956529

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects or patients with MRI defined cerebral small vessel disease including different extents of white matter hyperintensities, presumably related to hypertension (30 patients), cerebral amyloid angiopathy (30 patients), CADASIL (30 patients) or any other monogenic form of cerebral small vessel disease (HTRA1 AD, COLIVA1… 10 patients)
• Age ≥ 18 years
• No dementia (MMSE > 24 and absence of dependence in daily activities)
• No disability (modified Rankin's scale < 2)
• No history of severe allergic reaction, in particular to gadolinium infusion
• No history of severe asthma
• No renal insufficiency (clearance < 60 ml/mn/1.73 m2)

Exclusion Criteria:

• Contraindications to MRI
• Standard MRI of bad quality due to movement artefacts
• Dementia or disability
• Patient without affiliation to the French social security

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Experimental arm	Other: Experimental Arm; 3T MRI, maximum 1H30 long duration, including diffusion tensor imaging, susceptibility weighted imaging, multiparametric acquisitions, without contrast perfusion acquisitions.; 7T MRI, maximum 1H30 long duration, including contrast enhanced acquisitions; Neuropsychological battery including chronometric measures obtained through a computer interface

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with a different form of white matter hyperintensities (WMH)	The different forms of white matter hyperintensities will be assessed and identified using MRI imaging.The pattern of co-variation of structural, functional, metabolic imaging modalities, estimated in each voxel of a reference space, both inside and outside the WMH, will be compared through massive statistical approaches, controlled, for multiple testing	at the time of specific imaging (between Day 1 to Day 60)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of different WMH subtypes in different types of small cerebral vessel disease	Distribution of white matter hyperintensities in different brain areas according to the small cerebral vessel disease	at the time of specific imaging (between Day 1 to Day 60)
Frequency of large tract involvement	Large tratreconstructed from diffusion imaging) by WMH depending on the the small cerebral vessel disease	at the time of specific imaging (between Day 1 to Day 60)
Global cognitive function	The global cognitive functions will be assessed using MOCA. The MoCA assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation to time and place	at inclusion
Language	Language assessment will be done using LAST and Boston Naming Test	at inclusion
Spatial exploration	The neglect and spatial exploration will be assessed with bells test from the BEN neglect battery	at inclusion
Spatial memory	Spatial memory will be assessed using the brief visual-spatial memory test (BVMT-R)	at inclusion
Visual memory	Visual memory will be assessed using the brief visual-spatial memory test (BVMT-R)	at inclusion
Episodic verbal memory	Episodic verbal memory test by the RL RI 16	at inclusion
Working memory	Working memory will be evaluated by the working memory index of the WAIS-IV	at inclusion
Executive function	Executive function will be assessed by the versions A and B of the Trail Making Test	at inclusion
Attentional Performances status	Attentional Performances will be assessed using a battery on a computer which tests different attentionnal and executive function	at inclusion
Depression and Anxiety status	Depression and anxiety will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire. The HAD scale is a self-assessment scale for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. HADS is a self-administered scale of 14 items which assessed levels of depression and anxiety, divided into 2 subscales of 7 items (Anxiety or HADS-A, Depression or HADS-D). Each item is scored on a scale of 0 to 3. A score is generated for each of the two sub-scales (sum of the 7 items, ranging from 0 to 21). Limit scores, for each of the scores, distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	at inclusion
Apathy status	Apathy status will be assessed using the Starkstein scale	at inclusion
Pulse wave Velocity count	Arterial stifness will be assessed by measuring the pulse wave velocity	at inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Anticipated): June 4, 2023
• Study Completion (Anticipated): June 4, 2023

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases
• Other Study ID Numbers: APHP180445

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No