[P2-420]: A COMPARISON OF BRAIN WHITE MATTER HYPERINTENSITY BURDEN ASSESSED IN VIVO AND EX VIVO

ABSTRACTWe 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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Abstract TMP56: Differential Effect of Left versus Right White Matter Hyperintensity Burden on Functional Decline: The Northern Manhattan Study

Stroke ◽

10.1161/str.48.suppl_1.tmp56 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Mandip S Dhamoon ◽

Ying-Kuen Cheung ◽

Ahmet M Bagci ◽

Dalila Varela ◽

Noam Alperin ◽

...

Keyword(s):

White Matter ◽

Large Population ◽

Functional Decline ◽

Frontal Lobes ◽

White Matter Hyperintensity ◽

Periventricular White Matter ◽

Parietal Lobes ◽

Brain White Matter ◽

The Right

Background: We previously showed that overall brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right WMHV asymmetry was associated with functional trajectories. Methods: In the Northern Manhattan MRI study, participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter) was determined separately by combining bimodal image intensity distribution and atlas based methods.. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years. Generalized estimating equations models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up. Results: Among 1195 participants, mean age was 71 (SD 9) years, 39% were male, 67% had hypertension and 19% diabetes. Greater WMHV asymmetry in the frontal lobes (-3.53 BI points per unit greater WMHV on the right compared to left, 95% CI -0.18, -6.88) and whole brain (-7.23 BI points, 95% CI 0.07, -14.54) was associated with lower overall function. Greater WMHV asymmetry in the frontal lobes (-0.74 additional BI points per year per unit greater WMHV on the right compared to left, 95% CI 0.05, -1.54) and parietal lobes (1.11 additional BI points per year, 95% CI 0.30, 1.93) was independently associated with accelerated functional decline. Periventricular WMHV asymmetry was not associated with function. Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline, especially with greater WMHV on the right. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional decline.

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Real-Time Ex-Vivo Magnetic Resonance Image—Guided Dissection of Human Brain White Matter: A Proof-of-Principle Study

World Neurosurgery ◽

10.1016/j.wneu.2019.01.196 ◽

2019 ◽

Vol 125 ◽

pp. 198-206 ◽

Cited By ~ 1

Author(s):

Giacomo Bertolini ◽

Emanuele La Corte ◽

Domenico Aquino ◽

Elena Greco ◽

Zefferino Rossini ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Human Brain ◽

Real Time ◽

Magnetic Resonance Image ◽

Ex Vivo ◽

Image Guided ◽

Brain White Matter ◽

Proof Of Principle

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Acute ex vivo changes in brain white matter diffusion tensor metrics

PLoS ONE ◽

10.1371/journal.pone.0223211 ◽

2019 ◽

Vol 14 (9) ◽

pp. e0223211

Author(s):

Matthew R. Walker ◽

Jidan Zhong ◽

Adam C. Waspe ◽

Thomas Looi ◽

Karolina Piorkowska ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Ex Vivo ◽

Brain White Matter

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Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa134 ◽

2020 ◽

Author(s):

Maria A Di Biase ◽

Andrew Zalesky ◽

Suheyla Cetin-Karayumak ◽

Yogesh Rathi ◽

Jinglei Lv ◽

...

Keyword(s):

White Matter ◽

Large Scale ◽

Interleukin 2 ◽

Free Water ◽

Markers Of Inflammation ◽

Brain White Matter ◽

Inflammatory Processes ◽

Weighted Magnetic Resonance Imaging

Abstract Introduction Clarifying the role of neuroinflammation in schizophrenia is subject to its detection in the living brain. Free-water (FW) imaging is an in vivo diffusion-weighted magnetic resonance imaging (dMRI) technique that measures water molecules freely diffusing in the brain and is hypothesized to detect inflammatory processes. Here, we aimed to establish a link between peripheral markers of inflammation and FW in brain white matter. Methods All data were obtained from the Australian Schizophrenia Research Bank (ASRB) across 5 Australian states and territories. We first tested for the presence of peripheral cytokine deregulation in schizophrenia, using a large sample (N = 1143) comprising the ASRB. We next determined the extent to which individual variation in 8 circulating pro-/anti-inflammatory cytokines related to FW in brain white matter, imaged in a subset (n = 308) of patients and controls. Results Patients with schizophrenia showed reduced interleukin-2 (IL-2) (t = −3.56, P = .0004) and IL-12(p70) (t = −2.84, P = .005) and increased IL-6 (t = 3.56, P = .0004), IL-8 (t = 3.8, P = .0002), and TNFα (t = 4.30, P < .0001). Higher proinflammatory signaling of IL-6 (t = 3.4, P = .0007) and TNFα (t = 2.7, P = .0007) was associated with higher FW levels in white matter. The reciprocal increases in serum cytokines and FW were spatially widespread in patients encompassing most major fibers; conversely, in controls, the relationship was confined to the anterior corpus callosum and thalamic radiations. No relationships were observed with alternative dMRI measures, including the fractional anisotropy and tissue-related FA. Conclusions We report widespread deregulation of cytokines in schizophrenia and identify inflammation as a putative mechanism underlying increases in brain FW levels.

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P4-184: Elevated arterial stiffness and deep-brain white matter hyperintensity in patients with mild cognitive impairment

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1888 ◽

2012 ◽

Vol 8 (4S_Part_19) ◽

pp. P700-P701

Author(s):

Benjamin Tseng ◽

Muhammad Ayaz ◽

Estee Brunk ◽

Kyle Armstrong ◽

Kristin Martin-Cook ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Arterial Stiffness ◽

White Matter Hyperintensity ◽

Brain White Matter ◽

Deep Brain

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Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19893600 ◽

2019 ◽

Vol 40 (12) ◽

pp. 2454-2463 ◽

Cited By ~ 2

Author(s):

Weiyi Zeng ◽

Yaojing Chen ◽

Zhibao Zhu ◽

Shudan Gao ◽

Jianan Xia ◽

...

Keyword(s):

White Matter ◽

Episodic Memory ◽

Specific Pattern ◽

White Matter Hyperintensity ◽

Common Finding ◽

Superior Cerebellar Peduncle ◽

Brain White Matter ◽

Brain Microstructure ◽

Cerebellar Peduncle ◽

Fazekas Scale

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

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