Dilated perivascular space is related to reduced free-water in surrounding white matter among healthy adults and elderlies but not in patients with severe cerebral small vessel disease

2021 ◽  
pp. 0271678X2110058
Author(s):  
Yeerfan Jiaerken ◽  
Chunfeng Lian ◽  
Peiyu Huang ◽  
Xinfeng Yu ◽  
Ruiting Zhang ◽  
...  
Keyword(s):  
White Matter ◽  
Water Content ◽  
Interstitial Water ◽  
Small Vessel Disease ◽  
Free Water ◽  
Perivascular Space ◽  
Elderly Subjects ◽  
Vessel Disease ◽  
Normal Appearing White Matter ◽  
Free Water Content

Perivascular space facilitates cerebral interstitial water clearance. However, it is unclear how dilated perivascular space (dPVS) affects the interstitial water of surrounding white matter. We aimed to determine the presence and extent of changes in normal-appearing white matter water components around dPVS in different populations. Twenty healthy elderly subjects and 15 elderly subjects with severe cerebral small vessel disease (CSVD, with lacunar infarction 6 months before the scan) were included in our study. And other 28 healthy adult subjects were enrolled under a different scanning parameter to see if the results are comparable. The normal-appearing white matter around dPVS was categorized into 10 layers (1 mm thickness each) based on their distance to dPVS. We evaluated the mean isotropic-diffusing water volume fraction in each layer. We discovered a significantly reduced free-water content in the layers closely adjacent to the dPVS in the healthy elderlies. however, this reduction around dPVS was weaker in the CSVD subjects. We also discovered an elevated free-water content within dPVS. DPVS played different roles in healthy subjects or CSVD subjects. The reduced water content around dPVS in healthy subjects suggests these MR-visible PVSs are not always related to the stagnation of fluid.

scholarly journals Lower Aβ-PET signal in white matter lesions relates to higher extracellular free water in mixed small vessel disease and Alzheimer's pathology

2021 ◽  
Author(s):  
Julie Ottoy ◽  
Miracle Ozzoude ◽  
Katherine Zukotynski ◽  
Min Su Kang ◽  
Sabrina Adamo ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Small Vessel Disease ◽  
Free Water ◽  
Partial Least Square ◽  
Least Square ◽  
Amyloid Pet ◽  
Tissue Specific ◽  
Vessel Disease ◽  
Partial Least Square Analysis

Background and Objectives: Positron emission tomography (PET) with amyloid-ligands recently gained interest for evaluating white matter (WM) pathology. Here, we investigated the neurobiological underpinnings of the amyloid-PET signal in the WM using free water (FW) diffusion MRI in a mixed cohort of small vessel disease (SVD) and Alzheimer's disease (AD) pathology. Methods: We included data from two large cohort imaging studies, including MITNEC-C6 with moderate-to-severe white matter hyperintensity (WMH) burden and ADNI-2 with mild-to-moderate WMH burden, covering the spectrum of cognitively normal to dementia. Subjects underwent diffusion MRI, 18F-AV45 amyloid-PET, and cognitive testing. We calculated WM diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD). In addition, we applied a bi-tensor diffusion MRI model that differentiates between extracellular (FW fraction) and tissue-specific (FW-adjusted FA) compartments of the WM. We tested associations of all diffusion metrics with 18F-AV45 SUVR in regions of WMH vs. normal-appearing WM (NAWM), and with cognition. We further performed partial-least-square analysis to investigate how the diffusion metrics as well as age, sex, education, WMH volume, and cortical 18F-AV45 SUVR covary with WM 18F-AV45 SUVR. Results: 18F-AV45 SUVR was significantly lower in regions of WMH compared to NAWM (t=25.08, P<0.0001, n=115 subjects). Within WMH, lower 18F-AV45 SUVR was associated with higher FW (β=-0.36±0.13, P=0.005) and lower FA (β=+0.24±0.12, P=0.046), but not with the tissue-specific metric FW-adjusted FA. Partial-least-square analysis further confirmed that FW had the most influence on 18F-AV45 SUVR in regions of WMH. In contrast, FW-adjusted FA had more influence on 18F-AV45 SUVR in NAWM. Last, correlation with cognitive impairment was higher for FW than FW-adjusted FA, both in regions of WMH (MMSE: βFW=-0.40±0.13, P=0.003; βFW-adjustedFA=0.14±0.09, P=0.11) and NAWM (MMSE: βFW=-0.30±0.11, P=0.01; βFW-adjustedFA=0.21±0.09, P=0.02. Conclusion: In a cohort representative of the more common AD population, reduced amyloid-PET uptake in WM lesions may largely reflect the appearance of extracellular FW, while changes in NAWM may associate with tissue-specific damage. Ultimately, our findings may support FW and amyloid-PET as markers of WM abnormalities in SVD and AD.

scholarly journals Oxygenation differs among white matter hyperintensities, intersected fiber tracts and unaffected white matter†

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Rikke B Dalby ◽  
Simon F Eskildsen ◽  
Poul Videbech ◽  
Jesper Frandsen ◽  
Kim Mouridsen ◽  
...  
Keyword(s):  
Blood Flow ◽  
White Matter ◽  
Metabolic Rate ◽  
Blood Volume ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Late Onset ◽  
Vessel Disease ◽  
Fiber Tracts ◽  
Normal Appearing White Matter

Abstract White matter hyperintensities of presumed vascular origin are frequently observed on magnetic resonance imaging in normal aging. They are typically found in cerebral small vessel disease and suspected culprits in the etiology of complex age- and small vessel disease-related conditions, such as late-onset depression. White matter hyperintensities may interfere with surrounding white matter metabolic demands by disrupting fiber tract integrity. Meanwhile, risk factors for small vessel disease are thought to reduce tissue oxygenation, not only by reducing regional blood supply, but also by impairing capillary function. To address white matter oxygen supply–demand balance, we estimated voxel-wise capillary density as an index of resting white matter metabolism, and combined estimates of blood supply and capillary function to calculate white matter oxygen availability. We conducted a cross-sectional study with structural, perfusion- and diffusion-weighted magnetic resonance imaging in 21 patients with late-onset depression and 21 controls. We outlined white matter hyperintensities and used tractography to identify the tracts they intersect. Perfusion data comprised cerebral blood flow, blood volume, mean transit time and relative transit time heterogeneity—the latter a marker of capillary dysfunction. Based on these, white matter oxygenation was calculated as the steady state cerebral metabolic rate of oxygen under the assumption of normal tissue oxygen tension and vice versa. The number, volume and perfusion characteristics of white matter hyperintensities did not differ significantly between groups. Hemodynamic data showed white matter hyperintensities to have lower blood flow and blood volume, but higher relative transit time heterogeneity, than normal-appearing white matter, resulting in either reduced capillary metabolic rate of oxygen or oxygen tension. Intersected tracts showed significantly lower blood flow, blood volume and capillary metabolic rate of oxygen than normal-appearing white matter. Across groups, lower lesion oxygen tension was associated with higher lesion number and volume. Compared with normal-appearing white matter, tissue oxygenation is significantly reduced in white matter hyperintensities as well as the fiber tracts they intersect, independent of parallel late-onset depression. In white matter hyperintensities, reduced microvascular blood volume and concomitant capillary dysfunction indicate a severe oxygen supply–demand imbalance with hypoxic tissue injury. In intersected fiber tracts, parallel reductions in oxygenation and microvascular blood volume are consistent with adaptations to reduced metabolic demands. We speculate, that aging and vascular risk factors impair white matter hyperintensity perfusion and capillary function to create hypoxic tissue injury, which in turn affect the function and metabolic demands of the white matter tracts they disrupt.

scholarly journals T2 relaxation time of the normal-appearing white matter is related to the cognitive status in cerebral small vessel disease

2020 ◽  
pp. 0271678X2097251
Author(s):  
Annemarie Brandhofe ◽  
Christoph Stratmann ◽  
Jan-Rüdiger Schüre ◽  
Ulrich Pilatus ◽  
Elke Hattingen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cognitive Status ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Imaging Biomarker ◽  
Vessel Disease ◽  
Normal Appearing White Matter

Previous diffusion tensor imaging (DTI) studies indicate that impaired microstructural integrity of the normal-appearing white matter (NAWM) is related to cognitive impairment in cerebral small vessel disease (SVD). This study aimed to investigate whether quantitative T2 relaxometry is a suitable imaging biomarker for the assessment of tissue changes related to cognitive abnormalities in patients with SVD. 39 patients and 18 age-matched healthy control subjects underwent 3 T magnetic resonance imaging (MRI) with T2-weighted multiple spin echo sequences for T2 relaxometry and DTI sequences, as well as comprehensive cognitive assessment. Averaged quantitative T2, fractional anisotropy (FA) and mean diffusivity (MD) were determined in the NAWM and related to cognitive parameters controlling for age, normalized brain volume, white matter hyperintensity volume and other conventional SVD markers. In SVD patients, quantitative T2 values were significantly increased compared to controls (p = 0.002) and significantly negatively correlated with the global cognitive performance (r= –0.410, p = 0.014) and executive function (r= –0.399, p = 0.016). DTI parameters did not correlate with cognitive function. T2 relaxometry of the NAWM seems to be sensitive to microstructural tissue damage associated with cognitive impairment in SVD and might be a promising imaging biomarker for evaluation of disease progression and possible effects of therapeutic interventions.

Deep white matter hyperintensity is associated with the dilation of perivascular space

2021 ◽  
pp. 0271678X2110022
Author(s):  
Peiyu Huang ◽  
Ruiting Zhang ◽  
Yeerfan Jiaerken ◽  
Shuyue Wang ◽  
Wenke Yu ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Interstitial Fluid ◽  
Diffusion Tensor ◽  
Free Water ◽  
Perivascular Space ◽  
White Matter Hyperintensity ◽  
Deep White Matter ◽  
Free Water Content ◽  
Tight Association

Understanding the pathophysiology of white matter hyperintensity (WMH) is necessary to reduce its harmfulness. Dilated perivascular space (PVS) had been found related to WMH. In the present study, we aimed to examine the topological connections between WMH and PVS, and to investigate whether increased interstitial fluid mediates the correlation between PVS and WMH volumes. One hundred and thirty-six healthy elder subjects were retrospectively included from a prospectively collected community cohort. Sub-millimeter T2 weighted and FLAIR images were acquired for assessing the association between PVS and WMH. Diffusion tensor imaging and free-water (FW) analytical methods were used to quantify white matter free water content, and to explore whether it mediates the PVS-WMH association. We found that most (89%) of the deep WMH lesions were spatially connected with PVS, exhibiting several interesting topological types. PVS and WMH volumes were also significantly correlated (r = 0.222, p < 0.001). FW mediated this association in the whole sample (β = 0.069, p = 0.037) and in subjects with relatively high WMH load (β = 0.118, p = 0.006). These findings suggest a tight association between PVS dilation and WMH formation, which might be linked by the impaired glymphatic drainage function and accumulated local interstitial fluid.

scholarly journals Venous disruption affects white matter integrity through increased interstitial fluid in cerebral small vessel disease

2020 ◽  
Vol 41 (1) ◽  
pp. 157-165
Author(s):  
Ruiting Zhang ◽  
Peiyu Huang ◽  
Yeerfan Jiaerken ◽  
Shuyue Wang ◽  
Hui Hong ◽  
...  
Keyword(s):  
White Matter ◽  
Interstitial Fluid ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Free Water ◽  
Cerebral Small Vessel Disease ◽  
White Matter Integrity ◽  
Small Vessel ◽  
White Matter Damage ◽  
Vessel Disease

Deep medullary veins (DMVs) participate in the drainage of surrounding white matter. In cerebral small vessel disease (CSVD), disrupted DMVs were often observed together with damaged white matter, but the phenomenon lacked validation and explanation. We hypothesized that venous disruption might cause white matter damage through increased interstitial fluid resulting from hemodynamic alteration, and we designed a comprehensive multi-modality MRI study to testify our hypothesis. Susceptibility-weighted imaging was used to investigate the characteristics of DMVs and derive DMVs scores. Free water elimination diffusion tensor imaging model was used to analyze interstitial fluid fraction (fraction of free water, fFW) and white matter integrity (tissue fractional anisotropy, FAt). Totally, 104 CSVD patients were included. Total DMVs score was associated with FAt of DMVs drainage area. The effect of total DMVs score on FAt was mediated by fFW, after controlling for age, sex, hypertension, regional cerebral blood flow and lacune numbers. The relationships between DMVs score, fFW and FAt were also significant in most DMVs drainage subregions. Therefore, we discovered the DMVs disruption – increased interstitial fluid – white matter damage link in CSVD patients, which was independent of arterial perfusion variations.

Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts

2021 ◽  
Vol 30 (7) ◽  
pp. 105824
Author(s):  
Salvatore Rudilosso ◽  
Luis Mena ◽  
Diana Esteller ◽  
Marta Olivera ◽  
Juan José Mengual ◽  
...  
Keyword(s):  
White Matter ◽  
Disease Burden ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease

scholarly journals Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinfeng Yu ◽  
Xinzhen Yin ◽  
Hui Hong ◽  
Shuyue Wang ◽  
Yeerfan Jiaerken ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Extracellular Fluid ◽  
Free Water ◽  
Inverse Correlation ◽  
Brain Regions ◽  
Fiber Density ◽  
Four Levels

Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.

Abstract P499: The Effect of Small Vessel Disease Burden on Core/Penumbra Mismatch and Outcomes in Extended Window Thrombectomy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Destiny Hooper ◽  
Tariq Nisar ◽  
Meryim Poursheykhi ◽  
Andy Lin ◽  
C. David McCane ◽  
...  
Keyword(s):  
White Matter ◽  
Perfusion Imaging ◽  
Functional Outcomes ◽  
Time Window ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Collateral Flow ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Vessel Disease

Objective: Recent studies have shown the benefit of revascularization in select patients with extended window large vessel occlusion (EWLVO). We sought to assess the effect of cerebral small vessel disease (CSVD) burden on eligibility for intervention with mechanical thrombectomy (MT) and functional outcomes in patients with EWLVO. Methods: We conducted a retrospective single-center study of 135 patients with anterior circulation LVO who presented in the extended time window, 6 to 24 hours from LKW, between August 2018 and March 2020. All patients underwent perfusion imaging at initial presentation and those with target ischemic core to penumbra mismatch profiles, as defined by DAWN/DEFUSE3 criteria, were treated with MT. Included patients were evaluated for CSVD burden using T2-FLAIR MRI. The Fazekas scale (0-3) was used to quantify the amount of white matter T2 hyperintense lesions in both the periventricular (PVWM) and deep white matter (DWM). Patients’ functional outcomes were assessed at 90 days using the mRS. Multivariate ordinal logistic regression models were used and adjusted for age, gender, thrombus location and LKW to perfusion imaging time. Patient information was collected from the Houston Methodist Hospital Outcomes Based Prospective Endpoints in Stroke (HOPES) registry. Results: Of the 135 patients, 111 met imaging inclusion criteria for revascularization with MT for EWLVO. MT was deferred in 44 of these patients due to other clinical exclusions or patient refusal. Patients ineligible for MT were approximately 13 times more likely to have a higher PVWM Fazekas grade (OR =13.53, 95% CI. [2.94 - 62.39], p=0.001) and 17 times more likely to have a higher DWM Fazekas grade (OR =17.54, 95% CI. [4.20 - 73.17], p<0.001), when compared to patients who were eligible for MT. Patients who did not meet criteria for MT were nearly 7 times more likely to have poor functional outcomes at 90 days (OR =6.85, 95% CI. [2.09 - 22.44], p=0.001). Conclusion: Based on our analytical cohort of EWLVO patients, those with severe CSVD burden were more likely to be excluded from MT and had worse functional outcomes. Poor cerebrovascular reserve and diminished collateral flow leading to rapid infarct progression in patients with greater CSVD burden may be a potential explanation.

scholarly journals Cognitive heterogeneity among community-dwelling older adults with Cerebral Small Vessel Disease

2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  
Keyword(s):  
White Matter ◽  
Subjective Experience ◽  
Small Vessel Disease ◽  
Neuropsychological Testing ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Vessel Disease ◽  
Age Related ◽  
Subjective Complaints

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.

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