TY - JOUR
T1 - Blood-brain barrier leakage hotspots collocating with brain lesions due to sporadic and monogenic small vessel disease
AU - Rudilosso, S.
AU - Stringer, M.S.
AU - Thrippleton, M.
AU - Chappell, F.
AU - Blair, G.W.
AU - Garcia, D.J.
AU - Doubal, F.
AU - Hamilton, I.
AU - Janssen, E.
AU - Kopczak, A.
AU - Ingrisch, M.
AU - Kerkhofs, D.
AU - Backes, W.H.
AU - Staals, J.
AU - Duering, M.
AU - Dichgans, M.
AU - Wardlaw, J.M.
AU - SVDs@Target Investigators
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: SR receives funding from Instituto de Salud Carlos III, with a grant for health research and a mobility grant (CM18/00116; RH041992; JR21/00011). INVESTIGATE@SVDs is funded by the European Union Horizon 2020, PHC-03-15, Project No. 666881, “SVDs@target’. This study was also supported by the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, Ref. No. 16 CVD 05: The Row Fogo Charitable Trust; The Row Fogo Centre for Research into Ageing and the Brain, Ref. No.: AD.ROW4.35. BRO-D.FID3668413; the Stroke Association Princess Margaret Research Development Fellowship scheme (GWB); the Stroke Association Garfield Weston Foundation Senior Clinical Lectureship and NHS Research Scotland (FND); the NHS Lothian Research and Development Office (MJT); the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK (JMW, DJG); and the Edinburgh 3T MRI scanner is funded by the Wellcome Trust (104916/Z/14/Z), Dunhill Trust (R380R/1114), the Edinburgh and Lothians Health Foundation (2012/17), the Muir Maxwell Research Fund, and the University of Edinburgh. The procurement of the MRI scanner in Munich was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grant for major research instrumentation (DFG, INST 409/193-1 FUGG). For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Acknowledgements
Publisher Copyright:
© The Author(s) 2023.
PY - 2023/9
Y1 - 2023/9
N2 - Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.
AB - Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.
KW - Blood-brain barrier
KW - cerebral small vessel disease
KW - dynamic-contrast enhanced imaging
KW - lacunar
KW - white matter hyperintensities
KW - WHITE-MATTER LESIONS
KW - ABNORMALITIES
KW - STROKE
U2 - 10.1177/0271678X231173444
DO - 10.1177/0271678X231173444
M3 - Article
C2 - 37132279
SN - 0271-678X
VL - 43
SP - 1490
EP - 1502
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 9
ER -