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ArticleJMIR research protocols2025

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.

Jasmin Annica Kuhn-Keller, Ingmar Eiling, Lydiane Hirschler, Lena Václavů, Marie-Noëlle Witjes-Ané, Marjolein Wijngaarden, Martijn Nagtegaal, Ece Ercan, Nathaly Rius Ottenheim, Marjan van der Elst and 5 more

Registry-linked trialAbstract readClinical Trial Protocol
In one paragraph

Article in JMIR research protocols, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06010511 (White Matter Hyperintensity Shape and Glymphatics), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06010511 recruitingnot on this map

White Matter Hyperintensity Shape and Glymphatics

TypeobservationalSponsorLeiden University Medical CenterRan2023 to 2027Enrolled50ConditionsCerebral Small Vessel Diseases, Dementia, Mixed, Dementia, Vascular, Mild Cognitive ImpairmentArms3T MRI scan, 7T MRI scan, Neuropsychological assessment, General baseline data
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Jasmin Annica Kuhn-KellerDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0001-7075-7525
Ingmar EilingDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0002-0229-663X
Lydiane HirschlerDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0003-2379-0861
Lena VáclavůDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0001-8617-7752
Marie-Noëlle Witjes-AnéDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0002-5904-3967
Marjolein WijngaardenDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0002-4697-0286
Martijn NagtegaalDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0002-6563-865X
Ece ErcanDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0002-8187-2075
Nathaly Rius OttenheimDepartment of Psychiatry, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0002-0721-7152
Marjan van der ElstDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0009-0004-6051-2590
Evelien SohlDepartment of Geriatrics, Alrijne Hospital Leiden, Leiden, South Holland, The Netherlands.ORCID 0009-0002-3149-3584
Mark A van BuchemDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0003-1881-1998
Simon MooijaartDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0003-3106-3568
Matthias Jp van OschDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0001-7034-8959
Jeroen de BresserDepartment of Radiology, Leiden University Medical Center, Leiden, South Holland, The Netherlands.ORCID 0000-0003-0759-8407

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSporadic cerebral small vessel disease (SVD) has a heterogeneous underlying pathology, and current SVD magnetic resonance imaging (MRI) markers do not accurately capture this heterogeneity. Novel ultrahigh-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 clearance system may be another early change or potential cause of SVD.

objectiveIn the White Matter Hyperintensity Shape and Brain Clearance (WHIMAS) study, we aim to assess the link between WMHs-their shape in particular-and brain clearance and other MRI markers on ultrahigh-field (7T) brain MRI and show whether these markers are associated with cognitive functioning in older adults with memory complaints.

methodsThis is a cross-sectional study conducted at the Leiden University Medical Center. A total of 50 outpatients from the memory or geriatric clinic aged ≥65 years will be recruited for a 3T and 7T MRI scan (including clinical structural scans, eg, 3D T1-weighted, 3D fluid-attenuated inversion recovery), and experimental scans such as cerebrospinal fluid (CSF)-selective T2-prepared readout with acceleration and mobility encoding (CSF-STREAM) and the relationship between blood oxygen level-dependent [BOLD] signals and CSF flow) and magnetic resonance fingerprinting, as well as a standardized 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 mobility and the relationship between blood oxygen level-dependent signals and CSF flow) and study their relationship to other MRI markers and cognitive functioning using multivariable regression analyses.

resultsPatient inclusion started in January 2023, and study enrollment of patients is expected to finish in the second quarter of 2027, whereas the main results are expected to be published in the first quarter of 2028.

conclusionsWe aim to understand variations in WMH shape and find their relationship to cerebral SVD and markers of brain clearance and cognitive functioning. WMH shape and brain clearance 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 the prevention of dementia.

trial registrationClinicalTrials.gov NCT06010511; https://clinicaltrials.gov/study/NCT06010511. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/77681.

Indexed as

BrainCerebral Small Vessel DiseasesMagnetic Resonance ImagingWhite MatterAgedBiomarkersCross-Sectional StudiesFemaleHumansMaleBiomarkersbrain clearancecerebral small vessel diseasecognitive impairmentdementiamagnetic resonance imaging

Identifiers

PMID41344663
PMCPMC12715474

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.