Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Li, Yue; Li, Man; Zuo, Long; Shi, Qinglei; Qin, Wei; Yang, Lei; Jiang, Tao; Hu, Wenli

doi:10.3389/fneur.2018.00221

Cited by 46 publications

(41 citation statements)

References 32 publications

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“…This matter of fact most likely depends on the severity of the SVD (2, 9-11) and the exact disease stage (9,10,12,(40)(41)(42). WMH may present with impaired blood brain barrier, loss of oligodendrocytes and reduced density of glia, vacuolation and axonal damage and impaired white matter integrity as reported on diffusion tensor imaging (2,9,10,12,(43)(44)(45). However, as in MSL, conventional MRI does not allow for a differentiation of histologically different WMH (4,5).…”

Section: Discussionmentioning

confidence: 99%

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

Sartoretti

Wyss

et al. 2019

Front. Neurol.

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Objectives: To assess the ability of 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis to discriminate between multiple sclerosis lesions (MSL) and white matter hyperintensities of presumed vascular origin (WMH) and to compare APTw signal intensity of healthy white matter (healthy WM) with APTw signal intensity of MSL and WHM. Materials and Methods: A total of 27 patients (16 female, 11 males, mean age 39.6 years) with multiple sclerosis, 35 patients (17 females, 18 males, mean age 66.6 years) with small vessel disease (SVD) and 20 healthy young volunteers (9 females, 11 males, mean age 29 years) were included in the MSL, the WMH, and the healthy WM group. MSL and WMH were segmented on fluid attenuated inversion recovery (FLAIR) images underlaid onto APTw images. Histogram parameters (mean, median, 10th, 25th, 75th, 90th percentile) were calculated. Mean APTw signal intensity values in healthy WM were defined by "Region of interest" (ROI) measurements. Wilcoxon rank sum tests and receiver operating characteristics (ROC) curve analyses of clustered data were applied. Results: All histogram parameters except the 75 and 90th percentile were significantly different between MSL and WMH (p = 0.018-p = 0.034). MSL presented with higher median values in all parameters. The histogram parameters offered only low diagnostic performance in discriminating between MSL and WMH. The 10th percentile yielded the highest diagnostic performance with an AUC of 0.6245 (95% CI: [0.532, 0.717]). Mean APTw signal intensity values of MSL were significantly higher than mean values of healthy WM (p = 0.005). The mean values of WMH did not differ significantly from the values of healthy WM (p = 0.345). Sartoretti et al. APTw of White Matter Lesions Conclusions: We found significant differences in APTw signal intensity, based on straightforward magnetization transfer analysis, between MSL and WMH and between MSL and healthy WM. Low AUC values from ROC analyses, however, suggest that it may be challenging to determine type of lesion with APTw imaging. More advanced analysis of the APT CEST signal may be helpful for further differentiation of MSL and WMH.

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Section: Discussionmentioning

confidence: 99%

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

Sartoretti

Wyss

et al. 2019

Front. Neurol.

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“…The total CSVD score and most of the individual imaging markers of CSVD were associated with the aortic pulse wave velocity (PWV) (Del Brutto et al, 2019). A study revealed that BBB permeability in the brain measured by dynamic contrast enhancement (DCE)-MRI was positively correlated with total CSVD burden (Li et al, 2018). Higher total CSVD burden in the brain was associated with lower plasma volume fraction (Li et al, 2018), and blood plasma volume was related to the cerebral blood flow (CBF) (Arba et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…A study revealed that BBB permeability in the brain measured by dynamic contrast enhancement (DCE)-MRI was positively correlated with total CSVD burden (Li et al, 2018). Higher total CSVD burden in the brain was associated with lower plasma volume fraction (Li et al, 2018), and blood plasma volume was related to the cerebral blood flow (CBF) (Arba et al, 2017). However, the relationship between global CBF and total CSVD score is uncertain until now.…”

Section: Introductionmentioning

confidence: 99%

Alterations of the Whole Cerebral Blood Flow in Patients With Different Total Cerebral Small Vessel Disease Burden

Qiu

et al. 2020

Front. Aging Neurosci.

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Background: Cerebral small vessel disease (CSVD) is a common age-related vascular disease of the brain associated with slowly accumulating tissue damage. At present, total CSVD burden score is a commonly used method to evaluate the severity of the disease. Purpose: To observe whether global and regional cerebral perfusion is related to total CSVD score and to explore global and regional cerebral blood flow (CBF) changes in patients with different degrees of CSVD. Methods: We collected 130 subjects with different total burden score of CSVD (0 point: 33 subjects, 1 point: 39 subjects, 2 points: 24 subjects, 3 points: 24 subjects, 4 points: 10 subjects). Total CSVD burden score was evaluated by clinically routine sequences (T2WI, T2-FLAIR, T1WI, DWI, and SWAN sequence). Global and regional CBF were calculated and correlation analysis was used to investigate the relationship between total CSVD score and CBF of the whole brain and several brain regions. Results: The analysis results showed that there was a negative correlation between total CSVD burden score and global CBF (r = −0.33, p = 0.001). Total CSVD burden score also had moderately negative correlations with CBF of almost all the brain regions. Conclusion: CSVD is a disease that affects the whole brain. With the increase of total CSVD burden score, the global and regional CBF decreased. The CSVD total burden score could be used to evaluate the overall condition of brain perfusion.

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“…In addition, higher load of WMH is associated with adverse age-associated cognitive outcomes, such as slowed processing speed and increased risk of AD dementia 40,41 . In the absence of frank neurodegenerative phenotypes, age-associated WMH is frequently presumed secondary to cerebral vascular endotheliopathies resulting in increased BBB leakage and activation of CNS immune system, leading to reactive gliosis 40,[42][43][44][45] . In this model, endothelial cells play a central role.…”

Section: Discussionmentioning

confidence: 99%

Endothelial-derived exosomes demonstrate a link between endothelial innate inflammation and brain dysfunction and injury in aging

Elahi

Harvey

Altendahl

et al. 2019

Preprint

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We test the hypothesis that endothelial cells take on an inflammatory phenotype in functionally intact human subjects with radiographic evidence of white matter injury. Markers within all three complement effector pathways and regulatory proteins were quantified from endothelial-derived exosomes (EDE) of subjects (age 70-82) with (n=11) and without (n=16) evidence of white matter hyperintensity on MRI. Group differences and associations with systemic markers of immune activation (IL6, ICAM1), cognition and neuroimaging were calculated via regression modelling.EDE complement factors within the alternative and classical pathways were found to be higher and regulatory proteins lower in subjects with WMH. EDE levels of several factors demonstrated significant associations with cognitive slowing and systolic blood pressure. The inhibitor of the membrane attack complex, CD46, showed a significant positive association with cerebral grey matter volume. Systemic inflammatory markers, IL6 and ICAM1, were positively associated with EDE levels of several factors.These findings provide the first in vivo evidence of the association of endothelial cell inflammation with white matter injury, cognition, and brain degeneration in functionally normal older individuals, and form the basis for future biomarker development in early or preclinical stages of vascular cognitive impairment and dementia.

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Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Cited by 46 publications

References 32 publications

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

Alterations of the Whole Cerebral Blood Flow in Patients With Different Total Cerebral Small Vessel Disease Burden

Endothelial-derived exosomes demonstrate a link between endothelial innate inflammation and brain dysfunction and injury in aging

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