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 14 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%

Section: Methodsmentioning

confidence: 99%

Section: Image Acquisitionmentioning

confidence: 99%

Section: Image Acquisitionmentioning

confidence: 99%

See 3 more Smart Citations

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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Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease

Stringer,

Blair,

Kopczak

et al. 2024

Annals of Neurology

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ObjectiveCerebral small vessel diseases (SVDs) are associated with cerebrovascular dysfunction, such as increased blood–brain barrier leakage (permeability surface area product), vascular pulsatility, and decreased cerebrovascular reactivity (CVR). No studies assessed all 3 functions concurrently. We assessed 3 key vascular functions in sporadic and genetic SVD to determine associations with SVD severity, subtype, and interrelations.MethodsIn this prospective, cross‐sectional, multicenter INVESTIGATE‐SVDs study, we acquired brain magnetic resonance imaging in patients with sporadic SVD/cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), including structural, quantitative microstructural, permeability surface area product, blood plasma volume fraction, vascular pulsatility, and CVR (in response to CO2) scans. We determined vascular function and white matter hyperintensity (WMH) associations, using covariate‐adjusted linear regression; normal‐appearing white matter and WMH differences, interrelationships between vascular functions, using linear mixed models; and major sources of variance using principal component analyses.ResultsWe recruited 77 patients (45 sporadic/32 CADASIL) at 3 sites. In adjusted analyses, patients with worse WMH had lower CVR (B = −1.78, 95% CI −3.30, −0.27) and blood plasma volume fraction (B = −0.594, 95% CI −0.987, −0.202). CVR was worse in WMH than normal‐appearing white matter (eg, CVR: B = −0.048, 95% CI −0.079, −0.017). Adjusting for WMH severity, SVD subtype had minimal influence on vascular function (eg, CVR in CADASIL vs sporadic: B = 0.0169, 95% CI −0.0247, 0.0584). Different vascular function mechanisms were not generally interrelated (eg, permeability surface area product~CVR: B = −0.85, 95% CI −4.72, 3.02). Principal component analyses identified WMH volume/quantitative microstructural metrics explained most variance in CADASIL and arterial pulsatility in sporadic SVD, but similar main variance sources.InterpretationVascular function was worse with higher WMH, and in WMH than normal‐appearing white matter. Sporadic SVD‐CADASIL differences largely reflect disease severity. Limited vascular function interrelations may suggest disease stage‐specific differences. ANN NEUROL 2024

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Imaging subtle leaks in the blood–brain barrier in the aging human brain: potential pitfalls, challenges, and possible solutions

et al. 2022

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

Cited by 14 publications

References 33 publications

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

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

Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease

Imaging subtle leaks in the blood–brain barrier in the aging human brain: potential pitfalls, challenges, and possible solutions

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