Imaging neurovascular, endothelial and structural integrity in preparation to treat small vessel diseases. The INVESTIGATE-SVDs study protocol. Part of the SVDs@Target project

Blair, Gordon W.; Stringer, Michael; Thrippleton, Michael J.; Chappell, Francesca M; Shuler, Kirsten; Hamilton, I.; García, Daniela Jaime; Doubal, Fergus; Kopczak, Anna; Duering, Marco; Ingrisch, Michael; Kerkhofs, Danielle; Staals, Julie; Brink, Hilde van den; Arts, Tine; Backes, Walter H.; Oostenbrugge, Robert J. van; Biessels, Geert Jan; Dichgans, Martin; Wardlaw, Joanna M.

doi:10.1016/j.cccb.2021.100020

Cited by 12 publications

(36 citation statements)

References 33 publications

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“…This was a secondary cross-sectional analysis from a prospective multicenter observational study (Imaging NeuroVascular, Endothelial and STructural Integrity in prepAration to TrEat Small Vessel Diseases, INVESTIGATE-SVD, ISRCTN 10514229). 9 The study was approved by the local ethics committee in each participating institution, and informed consent was obtained from all participants. The full protocol of the study is available elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…The INVESTIGATE-SVD study cohort included patients with symptomatic sporadic (a lacunar ischemic stroke in the past 5 years or vascular cognitive impairment with SVD) or genetic SVD (diagnosis of CADASIL). 9 Patients with other causes of stroke such as ≥50% luminal stenosis, major-risk cardioembolic source of embolism (i.e., atrial fibrillation), and other specific causes of stroke identified (i.e., hemorrhage and arteritis) were not enrolled in the study. 9 The patients with sporadic SVD were recruited from centers in Edinburgh (UK) and Maastricht (the Netherlands), and patients with CADASIL from Munich (Germany).…”

Section: Methodsmentioning

confidence: 99%

“… 9 Patients with other causes of stroke such as ≥50% luminal stenosis, major-risk cardioembolic source of embolism (i.e., atrial fibrillation), and other specific causes of stroke identified (i.e., hemorrhage and arteritis) were not enrolled in the study. 9 The patients with sporadic SVD were recruited from centers in Edinburgh (UK) and Maastricht (the Netherlands), and patients with CADASIL from Munich (Germany). We excluded patients with unusable SWI acquisition.…”

Section: Methodsmentioning

confidence: 99%

“…11 All image analysis was centralized and conducted by an analyst not involved in the clinical assessments and masked to patient characteristics and CVR results and performed before the assessment of this study. 9 We defined as "vessel-clusters" the presence on SWI of grouped low-signal small tubular-like structures (seen as dots or lines depending on the orientation in reference to the axial plane) in white matter (Figure 1) that appear like small vessels but present a disorganized distribution compared with the large deep medullary veins with normal appearance on SWI (eFigure 1, links.lww.com/WNL/C29). 12 Hence, the definition of "vessel-cluster" is based on its radiologic appearance, although the nature of such finding may need further confirmation in pathology studies.…”

Section: Image Acquisitionmentioning

confidence: 99%

“…Cerebrovascular reactivity (CVR) was assessed using an established validated blood-oxygen-level-dependent (BOLD) MRI with CO 2 challenge. 9 Image Qualitative Analysis Radiologic markers of SVD, that is, lacunes, PVS, microbleeds, and WMH, on structural MRI sequences were identified according to STRIVE criteria 2 and graded using validated qualitative scales for WMH (Fazekas scale) 10 and PVS load scale in basal ganglia and centrum semiovale. 11 All image analysis was centralized and conducted by an analyst not involved in the clinical assessments and masked to patient characteristics and CVR results and performed before the assessment of this study.…”

Section: Image Acquisitionmentioning

confidence: 99%

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Prevalence and Significance of the Vessel-Cluster Sign on Susceptibility-Weighted Imaging in Patients With Severe Small Vessel Disease

Rudilosso¹,

Chui²,

Stringer³

et al. 2022

Neurology

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Background:Magnetic resonance susceptibility-weighted imaging (SWI) can identify small brain blood vessels that contain deoxygenated blood due to its induced magnetic field disturbance. We observed focal clusters of possible dilated small vessels on SWI in white matter in severe small vessel disease (SVD). We assessed their prevalence, associations with SVD lesions and vascular reactivity in patients with sporadic SVD and in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL).Methods:Secondary cross-sectional analysis of a prospective multicentre observational study of patients with either sporadic SVD or CADASIL (INVESTIGATE-SVD) studied with 3 Tesla MRI including blood-oxygen-level-dependent-MRI cerebrovascular reactivity (CVR). Two independent raters evaluated SWI sequences to identify “vessel-clusters” in white matter as focal low-signal dots/lines with small vessel appearance (interrater agreement, kappa statistic= 0.66). We assessed per-patient and per-cluster associations with SVD lesions type and severity on structural MRI sequences. We also assessed CVR within and at 2-voxel concentric intervals around the vessel-clusters using contralateral volumes as reference.Results:Amongst the 77 patients enrolled, 76 had usable SWI sequences, 45 with sporadic SVD [mean age 64 years (SD 11), 26 males (58%)] and 31 with CADASIL [53 years (11), 15 males (48%)]. We identified 94 vessel-clusters in 36/76 patients (15/45 sporadic SVD, 21/31 CADASIL). In covariate-adjusted analysis, patients with vessel-clusters had more lacunes (OR, 95%CI) (1.30, 1.05-1.62), higher white matter hyperintensity (WMH) volume (per-log10 increase, 1.92, 1.04-3.56), lower CVR in normal appearing white matter (per %/mmHg, 0.77 (0.60-0.99), compared with patients without vessel-clusters. Fifty-seven of 94 vessel-clusters (61%) corresponded to non-cavitated or partially-cavitated WMH on Fluid Attenuated Inversion Recovery, and 37/94 (39%) to complete cavities. CVR magnitude was lower than in corresponding contralateral volumes [mean difference (SD), t, p] within vessel-cluster volumes [-0.00046 (0.00088), -3.021, 0.005) and in surrounding volume expansion shells up to 4 voxels [-0.00011 (0.00031), -2.140, 0.039; and -0.00010 (0.00027), -2.295, 0.028] in vessel-clusters with complete cavities, but not in vessel-clusters without complete cavitation.Conclusions:Vessel-clusters might correspond to maximally dilated vessels in white matter that are approaching complete tissue injury and cavitation. The pathophysiological significance of this new feature warrants further longitudinal investigation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%