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Accepted for/Published in: JMIR Research Protocols

Date Submitted: May 18, 2025
Open Peer Review Period: May 17, 2025 - Jul 12, 2025
Date Accepted: Nov 7, 2025
(closed for review but you can still tweet)

The final, peer-reviewed published version of this preprint can be found here:

The White Matter Hyperintensity Shape and Brain Clearance (WHIMAS) Study for Identification of Novel 7T Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease: Protocol for a Cross-Sectional Study

Kuhn-Keller JA, Eiling I, Hirschler L, Hirschler L, Václavů L, Witjes-Ané MN, Wijngaarden M, Nagtegaal M, Ercan E, Rius Ottenheim N, van der Elst M, Sohl E, van Buchem MA, Mooijaart S, van Osch MJ, de Bresser J

The White Matter Hyperintensity Shape and Brain Clearance (WHIMAS) Study for Identification of Novel 7T Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease: Protocol for a Cross-Sectional Study

JMIR Res Protoc 2025;14:e77681

DOI: 10.2196/77681

PMID: 41344663

PMCID: 12715474

The WHIte MAtter hyperintensity Shape and brain clearance (WHIMAS) study for identification of novel 7T MRI markers of cerebral small vessel disease: a research protocol of a cross-sectional study

  • Jasmin Annica Kuhn-Keller; 
  • Ingmar Eiling; 
  • Lydiane Hirschler; 
  • Lydiane Hirschler; 
  • Lena Václavů; 
  • Marie-Noëlle Witjes-Ané; 
  • Marjolein Wijngaarden; 
  • Martijn Nagtegaal; 
  • Ece Ercan; 
  • Nathaly Rius Ottenheim; 
  • Marjan van der Elst; 
  • Evelien Sohl; 
  • Mark A. van Buchem; 
  • Simon Mooijaart; 
  • Matthias J.P. van Osch; 
  • Jeroen de Bresser

ABSTRACT

Introduction: Sporadic cerebral small vessel disease (SVD) has heterogeneous underlying pathology and current SVD MRI markers do not accurately capture this heterogeneity. Novel ultra-high field (7T) brain MRI markers provide a window of opportunity to study early changes and potential determinants of SVD. White matter hyperintensity (WMH) shape is a relatively novel MRI marker of SVD and has shown prognostic potential. However, the exact microstructural changes within or surrounding WMHs or potential causes related to WMH shape variations are unknown. Furthermore, impaired brain clearance via the recently discovered brain glymphatic system may be another early change or potential cause of SVD. In the WHIMAS (white matter hyperintensity shape and glymphatics study) we aim to study the link between WMH and especially their shape with brain clearance and other MRI markers on ultra-high field (7T) brain MRI and show if these markers are associated with cognitive functioning in older adults with memory complaints. Methods and analysis: The WHIMAS is a cross-sectional study that will be conducted at the Leiden University Medical Center (LUMC). Fifty outpatients from the memory/geriatric clinic, aged 65 years or older will be recruited for a 3T and a 7T MRI scan, as well as a standardised neuropsychological test battery (domains: memory, executive function, visuoconstruction, and processing speed). We will assess WMH shape markers (solidity, convexity, concavity index, fractal dimension, and eccentricity) and brain clearance markers (CSF-BOLD-coupling, CSF-mobility) and study their relation to other MRI markers and cognitive functioning. Discussion: We aim to understand variations in WMH shape and find their relation to cerebral SVD and markers of brain clearance and cognitive functioning. These markers early in the disease process of SVD are extremely important as they may represent a basis for future patient selection for lifestyle interventions or for treatment trials aimed at prevention of dementia.


 Citation

Please cite as:

Kuhn-Keller JA, Eiling I, Hirschler L, Hirschler L, Václavů L, Witjes-Ané MN, Wijngaarden M, Nagtegaal M, Ercan E, Rius Ottenheim N, van der Elst M, Sohl E, van Buchem MA, Mooijaart S, van Osch MJ, de Bresser J

The White Matter Hyperintensity Shape and Brain Clearance (WHIMAS) Study for Identification of Novel 7T Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease: Protocol for a Cross-Sectional Study

JMIR Res Protoc 2025;14:e77681

DOI: 10.2196/77681

PMID: 41344663

PMCID: 12715474

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