Impaired Cerebrovascular Reactivity With Steal Phenomenon Is Associated With Increased Diffusion in White Matter of Patients With Moyamoya Disease

Conklin, John; Fierstra, Jorn; Crawley, Adrian; Han, Jay; Poublanc, Julien; Mandell, Daniel M.; Silver, Frank L.; Tymianski, Michael; Fisher, Joseph A.; Mikulis, David J.

doi:10.1161/strokeaha.110.579540

Cited by 89 publications

(76 citation statements)

References 29 publications

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“…29 We therefore suggest that negative CVR is capable of detecting areas in the NAWM with subtle pathologic features indicating structural damage to white matter that resulted in increased water diffusivity. Other studies in humans have shown that steal physiology is associated with elevated white matter diffusivity in patients with intracranial 30 and extracranial 31 large artery stenoocclusive disease. After accounting for the confound of spatial location, there was no significant difference in T2 values between NAWM with negative and positive CVR.…”

Section: Methods Participant Recruitment and Assessmentmentioning

confidence: 89%

Cerebrovascular reactivity and white matter integrity

et al. 2016

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Objective: To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR).Methods: Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons.Results: Areas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p , 0.01), compared to areas with positive CVR.Conclusions: Impaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease. Changes in the periventricular and subcortical white matter are observed on both CT and MRI scans of elderly individuals.1 The affected areas appear hyperintense on T2-weighted MRI, and are labeled as white matter hyperintensities (WMHs) if they are of presumed vascular origin. 2They are associated with an increased risk of dementia, 3 stroke, 4 and cognitive disability, 5 and correlated with age; as many as 95% of individuals over age 50 have WMHs.6,7 Therefore, preventing or slowing the progression of WMHs has the potential to lower the disease burden. Although several modifiable risk factors have been associated with WMH progression, such as smoking and high blood pressure, 8 the detailed pathogenesis of WMHs remains controversial. Nevertheless, the prevailing view is that a chronic low-grade ischemic injury is the final common pathway for these lesions, 9,10 and this view was the motivation for our study. Accordingly, this study characterized vascular pathophysiology in normal-appearing white matter (NAWM) before progression to overt leukoaraiosis by measuring cerebrovascular reactivity (CVR); the change in cerebral blood flow in response to a vasodilatory stimulus. Negative CVR values represent steal physiology, in which blood flow is redistributed from regions of exhausted cerebral vasodilatory reserve to areas with preserved vasodilatory capacity. 11 WeFrom the Department of Physiology

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Section: Methods Participant Recruitment and Assessmentmentioning

confidence: 89%

Cerebrovascular reactivity and white matter integrity

et al. 2016

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“…Mandell et al 28 have demonstrated that in young, healthy subjects (age range, 22 to 42 years), the presence of steal physiology in the deep white matter precisely matches with frequency maps of leukoaraiosis. 29 Furthermore, Conklin et al 30 have shown an increase in apparent diffusion coefficient in normal-appearing white matter underlying the cortex with steal physiology. Like cortical thinning, leukoaraiosis and elevated apparent diffusion coefficient values in white matter tissue have been associated with vascular cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Surgical Revascularization Reverses Cerebral Cortical Thinning in Patients With Severe Cerebrovascular Steno-Occlusive Disease

Fierstra

MacLean

Fisher

et al. 2011

Stroke

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Background and Purpose-Chronic deficiencies in regional blood flow lead to cerebral cortical thinning without evidence of gross tissue loss at the same time as potentially negatively impacting on neurological and cognitive performance. This is most pronounced in patients with severe occlusive cerebrovascular disease in whom affected brain areas exhibit "steal physiology," a paradoxical reduction of cerebral blood flow in response to a global vasodilatory stimulus intended to increase blood flow. We tested whether surgical brain revascularization that eliminates steal physiology can reverse cortical thinning. Methods-We identified 29 patients from our database who had undergone brain revascularization with pre-and postoperative studies of cerebrovascular reactivity using blood oxygen(ation) level-dependent MRI and whose preoperative study exhibited steal physiology without MRI-evident structural abnormalities. Cortical thickness in regions corresponding to steal physiology, and where applicable corresponding areas in the normal hemisphere, were measured using Freesurfer software. Results-At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere (nϭ30). Mean cortical thickness in the revascularized regions increased by 5.1% (from 2.40Ϯ0.03 to 2.53Ϯ0.03; PϽ0.0001). Conclusions-Successful regional revascularization and reversal of steal physiology is followed by restoration of cortical thickness.

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“…We therefore assume that in our study the localized regional analysis for centrum semiovale revealed significant differences in diffusion characteristics, suggesting microstructural damage in the NAWM of patients with MMD without infarction. Recently, Conklin et al 30 revealed that regions of steal phenomenon are spatially correlated with elevated ADC in NAWM of patients with MMD, suggesting that even if there is no overt infarction in MMD, microstructural damage of NAWM can develop from low-grade ischemia. Our finding of increased ADC in NAWM of patients with MMD without infarction is consistent with the findings of Conklin et al 30 We found a significantly lower mean FA CS value and a higher mean ADC CS value in patients with MMD, probably reflecting cumulative white matter damage from chronic hypoperfusion and recurrent ischemic attacks.…”

Section: Discussionmentioning

confidence: 99%