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 Superficial white matter microstructure affects processing speed in cerebral small vessel disease

2022 ◽  
Author(s):  
Shuyue Wang ◽  
Fan Zhang ◽  
Peiyu Huang ◽  
Hui Hong ◽  
Yeerfan Jiaerken ◽  
...  
Keyword(s):  
White Matter ◽  
Processing Speed ◽  
Diffusion Mri ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Large Contribution ◽  
Vessel Disease ◽  
White Matter Microstructure ◽  
Patient Subgroups

White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD). This condition contributes to about 50% of dementias worldwide, a massive health burden in aging. Microstructural alterations in the deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in the superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In this paper, 141 patients with CSVD were studied. Processing speed was assessed by the completion time of the Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (lesion volume on T2-FLAIR) and diffusion MRI, including DTI and free-water (FW) imaging microstructure measures. The results of our study indicate that the superficial white matter may play a particularly important role in cognitive decline in CSVD. SWM imaging measures resulted in a large contribution to processing speed, despite a relatively small WMH burden in the SWM. SWM FW had the strongest association with processing speed among all imaging markers and, unlike the other diffusion MRI measures, significantly increased between two patient subgroups with the lowest WMH burdens (possibly representing early stages of disease). When comparing two patient subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Given significant effects of WMH volume and regional FW on processing speed, we performed a mediation analysis. SWM FW was found to fully mediate the association between WMH volume and processing speed, while no mediation effect of DWM FW was observed. Overall, our findings identify SWM abnormalities in CSVD and suggest that the SWM has an important contribution to processing speed. Results indicate that FW in the SWM is a sensitive marker of microstructural changes associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes in future research.

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 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.

Multi-shell diffusion MRI models for white matter characterization in cerebral small vessel disease

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011213
Author(s):  
Marek J. Konieczny ◽  
Anna Dewenter ◽  
Annemieke ter Telgte ◽  
Benno Gesierich ◽  
Kim Wiegertjes ◽  
...  
Keyword(s):  
White Matter ◽  
Processing Speed ◽  
Diffusion Mri ◽  
Small Vessel Disease ◽  
Diffusion Imaging ◽  
Cerebral Small Vessel Disease ◽  
3T Mri ◽  
Vessel Disease ◽  
Speed Performance

ObjectiveTo test the hypothesis that multi-shell diffusion models improve the characterization of microstructural alterations in cerebral small vessel disease (SVD), we assessed associations with processing speed performance, longitudinal change and reproducibility of diffusion metrics.MethodsWe included 50 sporadic and 59 genetically defined SVD patients (CADASIL) with cognitive testing and standardized 3T MRI, including multi-shell diffusion imaging. We applied the simple diffusion tensor imaging (DTI) model and 2 advanced models: diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI). Linear regression and multivariable random forest regression (including conventional SVD markers) were used to determine associations between diffusion metrics and processing speed performance. The detection of short-term disease progression was assessed by linear mixed models in 49 sporadic SVD patients with longitudinal high-frequency imaging (in total 459 MRIs). Inter-site reproducibility was determined in 10 CADASIL patients scanned back-to-back on 2 different 3T MRI scanners.ResultsMetrics from DKI showed the strongest associations with processing speed performance (R2 up to 21%) and the largest added benefit on top of conventional SVD imaging markers in sporadic SVD and CADASIL patients with lower SVD burden. Several metrics from DTI and DKI performed similarly in detecting disease progression. Reproducibility was excellent (intraclass correlation coefficient >0.93) for DTI and DKI metrics. NODDI metrics were less reproducible.ConclusionMulti-shell diffusion imaging and DKI improve the detection and characterization of cognitively relevant microstructural white matter alterations in SVD. Excellent reproducibility of diffusion metrics endorses their use as SVD markers in research and clinical care. Our publicly available inter-site dataset facilitates future studies.Classification of evidenceThis study provides Class I evidence that in patients with SVD, diffusion MRI metrics are associated with processing speed performance.

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

Characterizing Extracellular White Matter Pathologies Using Free Water Imaging Across the Schizophrenia Illness Course: A Multi-Site Harmonized Diffusion MRI Study

2021 ◽  
Vol 89 (9) ◽  
pp. S85
Author(s):  
Suheyla Cetin-Karayumak ◽  
Ofer Pasternak ◽  
Fan Zhang ◽  
Johanna Seitz ◽  
Doron Elad ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Mri ◽  
Free Water ◽  
Mri Study

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.

Sign in / Sign up

Export Citation Format

Share Document