IC-P-135: Baseline Normal Appearing White Matter Structural Integrity and Cerebral Blood Flow Can Predict White Matter Hyperintensity Expansion Over Time: A Voxel-Wise Analysis

ObjectiveWe aimed to describe and compare baseline cerebral blood flow (CBF) and microstructural characteristics of normal-appearing white matter (NAWM) within the vulnerable periventricular white matter hyperintensity (PVWMH) penumbra region in predicting white matter hyperintensity (WMH) growth over time.MethodsFifty-two patients, aged 82.8 years, underwent serial brain MRI, including pulsed arterial spin labeling and diffusion tensor imaging (DTI). New WMH and persistent NAWM voxels in relation to WMH penumbra at follow-up were identified. Mean baseline CBF and DTI variables of the new WMH and persistent NAWM voxels were computed. Univariate analyses with paired t tests were performed. Generalized estimating equation analyses were used to compare the relationships of baseline CBF, and structural penumbras with WMH growth, controlling for confounders.ResultsLow baseline CBF and fractional anisotropy, and high mean diffusivity (MD), were independently associated with new PVWMH voxels, with MD being the best predictor of WMH growth. A separate model demonstrated that radial diffusivity had the strongest relationship with WMH growth compared with CBF and axial diffusivity.ConclusionCBF and DTI measures independently predict WMH growth over time. DTI is a more sensitive predictor of WMH growth than CBF, with WMH progression likely due to demyelinating injury secondary to low perfusion. Findings support the use of MD as a sensitive marker of NAWM vulnerability in future trials aimed at preserving WM integrity.

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Comparison of cerebral blood flow and structural penumbras in relation to white matter hyperintensities: A multi-modal magnetic resonance imaging study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16651268 ◽

2016 ◽

Vol 36 (9) ◽

pp. 1528-1536 ◽

Cited By ~ 26

Author(s):

Nutta-on Promjunyakul ◽

David L Lahna ◽

Jeffrey A Kaye ◽

Hiroko H Dodge ◽

Deniz Erten-Lyons ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Structural Integrity ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Normal Appearing White Matter ◽

Increased Risk ◽

Fluid Attenuated Inversion Recovery

Normal-appearing white matter (NAWM) surrounding WMHs is associated with decreased structural integrity and perfusion, increased risk of WMH growth, and is referred to as the WMH penumbra. Studies comparing structural and cerebral blood flow (CBF) penumbras within the same individuals are lacking, however, and would facilitate our understanding of mechanisms resulting in WM damage. This study aimed to compare both CBF and structural WMH penumbras in non-demented aging. Eighty-two elderly volunteers underwent 3T-MRI including fluid attenuated inversion recovery (FLAIR), pulsed arterial spin labeling and diffusion tensor imaging (DTI). A NAWM layer mask was generated for periventricular and deep WMHs. Mean CBF, DTI-fractional anisotropy (DTI-FA), DTI-mean diffusivity (DTI-MD) and FLAIR intensity for WMHs and its corresponding NAWM layer masks were computed and compared against its mean within total brain NAWM using mixed effects models. For both periventricular and deep WMHs, DTI-FA, DTI-MD and FLAIR intensity changes extended 2-9 mm surrounding WMHs (p ≤ 0.05), while CBF changes extended 13-14 mm (p ≤ 0.05). The CBF penumbra is more extensive than structural penumbras in relation to WMHs and includes WM tissue both with and without microstructural changes. Findings implicate CBF as a potential target for the prevention of both micro and macro structural WM damage.

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Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽

10.1136/bmjopen-2020-040466 ◽

2020 ◽

Vol 10 (10) ◽

pp. e040466

Author(s):

Aravind Ganesh ◽

Philip Barber ◽

Sandra E Black ◽

Dale Corbett ◽

Thalia S Field ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Vascular Cognitive Impairment ◽

White Matter Injury ◽

White Matter Hyperintensity ◽

Limb Ischaemia ◽

Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

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Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures

NeuroImage Clinical ◽

10.1016/j.nicl.2015.04.012 ◽

2015 ◽

Vol 8 ◽

pp. 224-229 ◽

Cited By ~ 47

Author(s):

N. Promjunyakul ◽

D. Lahna ◽

J.A. Kaye ◽

H.H. Dodge ◽

D. Erten-Lyons ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

White Matter Hyperintensity

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IC-P-150: Characteristics of DTI-FA and flair intensity within white matter hyperintensity cerebral blood flow penumbra: A longitudinal study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.06.172 ◽

2015 ◽

Vol 11 (7S_Part_2) ◽

pp. P101-P101

Author(s):

Nutta-on Promjunyakul ◽

David Lahna ◽

Jeffrey Kaye ◽

Hiroko H. Dodge ◽

William D. Rooney ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Longitudinal Study ◽

White Matter ◽

White Matter Hyperintensity

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White Matter Hyperintensity Associations with Cerebral Blood Flow in Elderly Subjects Stratified by Cerebrovascular Risk

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2016.10.017 ◽

2017 ◽

Vol 26 (4) ◽

pp. 779-786 ◽

Cited By ~ 19

Author(s):

Ahmed A. Bahrani ◽

David K. Powell ◽

Guoqiang Yu ◽

Eleanor S. Johnson ◽

Gregory A. Jicha ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

White Matter Hyperintensity ◽

Elderly Subjects ◽

Cerebrovascular Risk

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Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-212285 ◽

2017 ◽

Vol 77 (3) ◽

pp. 441-448 ◽

Cited By ~ 19

Author(s):

Efrosini Papadaki ◽

Antonis Fanouriakis ◽

Eleftherios Kavroulakis ◽

Dimitra Karageorgou ◽

Prodromos Sidiropoulos ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Lupus Erythematosus ◽

Cerebral Perfusion ◽

Dynamic Susceptibility ◽

Neuropsychiatric Lupus ◽

Normal Appearing White Matter ◽

Conventional Mri ◽

Dsc Mri

ObjectivesCerebral perfusion abnormalities have been reported in systemic lupus erythematosus (SLE) but their value in distinguishing lupus from non-lupus-related neuropsychiatric events remains elusive. We examined whether dynamic susceptibility contrast-enhanced perfusion MRI (DSC-MRI), a minimally invasive and widely available method of cerebral perfusion assessment, may assist neuropsychiatric SLE (NPSLE) diagnosis.MethodsIn total, 76patients with SLE (37 primary NPSLE, 16 secondary NPSLE, 23 non-NPSLE) and 31 healthy controls underwent conventional MRI (cMRI) and DSC-MRI. Attribution of NPSLE to lupus or not was based on multidisciplinary assessment including cMRI results and response to treatment. Cerebral blood volume and flow were estimated in 18 normal-appearing white and deep grey matter areas.ResultsThe most common manifestations were mood disorder, cognitive disorder and headache. Patients with primary NPSLE had lower cerebral blood flow and volume in several normal-appearing white matter areas compared with controls (P<0.0001) and lower cerebral blood flow in the semioval centre bilaterally, compared with non-NPSLE and patients with secondary NPSLE (P<0.001). A cut-off for cerebral blood flow of 0.77 in the left semioval centre discriminated primary NPSLE from non-NPSLE/secondary NPSLE with 80% sensitivity and 67%–69% specificity. Blood flow values in the left semioval centre showed substantially higher sensitivity than cMRI (81% vs 19%–24%) for diagnosing primary NPSLE with the combination of the two modalities yielding 94%–100% specificity in discriminating primary from secondary NPSLE.ConclusionPrimary NPSLE is characterised by significant hypoperfusion in cerebral white matter that appears normal on cMRI. The combination of DSC-MRI-measured blood flow in the brain semioval centre with conventional MRI may improve NPSLE diagnosis.

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Cerebral blood flow in small vessel disease: A systematic review and meta-analysis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16662891 ◽

2016 ◽

Vol 36 (10) ◽

pp. 1653-1667 ◽

Cited By ~ 100

Author(s):

Yulu Shi ◽

Michael J Thrippleton ◽

Stephen D Makin ◽

Ian Marshall ◽

Mirjam I Geerlings ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Small Vessel Disease ◽

Meta Analysis ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Cross Sectional ◽

Vessel Disease ◽

Cross Sectional Studies

White matter hyperintensities are frequent on neuroimaging of older people and are a key feature of cerebral small vessel disease. They are commonly attributed to chronic hypoperfusion, although whether low cerebral blood flow is cause or effect is unclear. We systematically reviewed studies that assessed cerebral blood flow in small vessel disease patients, performed meta-analysis and sensitivity analysis of potential confounders. Thirty-eight studies ( n = 4006) met the inclusion criteria, including four longitudinal and 34 cross-sectional studies. Most cerebral blood flow data were from grey matter. Twenty-four cross-sectional studies ( n = 1161) were meta-analysed, showing that cerebral blood flow was lower in subjects with more white matter hyperintensity, globally and in most grey and white matter regions (e.g. mean global cerebral blood flow: standardised mean difference−0.71, 95% CI −1.12, −0.30). These cerebral blood flow differences were attenuated by excluding studies in dementia or that lacked age-matching. Four longitudinal studies ( n = 1079) gave differing results, e.g., more baseline white matter hyperintensity predated falling cerebral blood flow (3.9 years, n = 575); cerebral blood flow was low in regions that developed white matter hyperintensity (1.5 years, n = 40). Cerebral blood flow is lower in subjects with more white matter hyperintensity cross-sectionally, but evidence for falling cerebral blood flow predating increasing white matter hyperintensity is conflicting. Future studies should be longitudinal, obtain more white matter data, use better age-correction and stratify by clinical diagnosis.

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