Abstract P64: Longitudinal Brain Structural Changes After Stroke

Background: Stroke causes focal and diffuse structural brain changes that may contribute to subsequent cognitive decline and dementia. We hypothesize that MRI structural measures can detect continued cerebral degeneration over the first year after stroke. We identify predictors for progression of brain atrophy, leukoaraiosis and diffusion tensor imaging (DTI) metrics. Methods: Patients with ischemic stroke were enrolled prospectively in an observational study that included serial brain MRI. Patients underwent MRI FLAIR and DTI at the time of acute stroke and were followed for at least 9 months with multiple MRIs between 30 days and 15 months post-stroke. We used FLAIR to measure brain atrophy as the percent brain parenchymal fraction (BPF) of the total intracranial volume (TICV) and white matter hyperintensity volume (WMHV) as a percentage of TICV. DTI was used to calculate Peak Skeletonized Mean Diffusivity (PSMD), a global measure of white matter integrity previously validated in cerebral small vessel disease. Longitudinal changes in BPF, WMHV or PSMD were measured from 30 days post-stroke onward using linear regression models that included age, stroke volume, baseline BPF and WMHV as predictors. Results: Twenty-six patients had a median of 4 follow-ups over 9-15 months. Median age was 74 years (range 51-84) and 38% were women. Mean stroke volume was 4.5cc (0 - 30cc). Mean BPF was 78% (72 - 86%) and mean baseline WMHV was 1.1% (0.1 - 3.9%). BPF was associated with age and declined by 0.7% per year (t(111) = 2.7, p = 0.007). Progression was associated with baseline BPF (t(111) = -3.4, p < 0.001). WMHV in the non-stroke hemisphere was associated with age and increased by 0.10% per year (t(87) = -5.8, p < 0.001). Accumulation was associated with age (t(87) = 5.8, p < 0.001). PSMD was associated with baseline WMHV and had a relative increase of 1.9% per year in the non-stroke hemisphere and 4.5% in the stroke hemisphere (t(174) = -2.1, p = 0.03). Progression was associated with age (t(174) = 2.3, p = 0.03) and stroke volume (t(174) = 2.4, p = 0.02). Conclusions: During the months after ischemic stroke, BPF, WMHV and PSMD can detect persistent structural changes that may reflect later phases of stroke injury or ongoing contributions of aging, silent ischemia, or neurodegeneration.

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Abstract WMP18: Global White Matter Microstructural Injury Predicts Poor Outcomes After Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wmp18 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Mark R Etherton ◽

Ona Wu ◽

Natalia Rost

Keyword(s):

Logistic Regression ◽

Ischemic Stroke ◽

White Matter ◽

Functional Outcomes ◽

Brain Mri ◽

Mean Diffusivity ◽

Stepwise Logistic Regression ◽

Excellent Outcome ◽

Post Stroke ◽

Female Sex

Background: Early outcome prediction after acute ischemic stroke (AIS) is critical to guide care and rehabilitation strategies. Pre-existing chronic structural injury to cerebral white matter (WM), including ischemic WM hyperintensity (WMH) and microstructural changes within the normal-appearing WM (NAWM), is known to impede post-stroke recovery. Quantitative assessment of total pre-existing WM injury may therefore improve prognostication of functional stroke outcomes. Peak width of skeletonized mean diffusivity (PSMD) is an automated marker of cerebral small vessel disease and global WM injury. In a cohort of AIS patients, we measured PSMD in the hemisphere contralateral to the acute infarct and characterized its association with 90-day functional outcomes. Methods: Brain MRI with diffusion tensor imaging sequences was acquired within 48 hours of AIS admission. WMH volume (WMHv) was measured in a semi-automated manner. NAWM masks were constructed by subtracting the WMH and chronic infarct masks from a probabilistic WM atlas. NAWM mean diffusivity (MD) was then measured in the NAWM mask. PSMD was extracted by skeletonizing the WM tracts in the MD image using the Fractional Anisotropy image and the FSL Tract-Based Spatial Statistics pipeline with a mask for the contralesional hemisphere. Excellent outcome was defined as a modified Rankin scale score < 2 at 3-6 months post-stroke. Logistic regression analysis was performed to evaluate predictors of excellent outcome. Results: In 292 AIS patients, increasing PSMD and NAWM MD, but not WMHv, were associated with decreased likelihood of excellent outcome in univariable analysis. Increasing age, admission NIHSS score, DWI volume, and female sex were also negatively associated with excellent outcome. In backward stepwise logistic regression, including all significant variables from the univariable step, increasing age (β = -0.03; P = 0.01), NIHSS (β = -0.1; P = 0.0005), DWI volume (β = -0.02; P = 0.0004), PSMD (β = -0.08; P = 0.03), and female sex (β = -0.7; P = 0.01) were associated with decreased likelihood of excellent outcome. Conclusion: In AIS patients, automated determination of contralesional PSMD, as a marker of chronic, global white matter injury, is an independent predictor of functional outcomes.

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18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy

10.1101/19000596 ◽

2019 ◽

Author(s):

Nicolas Nicastro ◽

Patricia Vazquez Rodriguez ◽

Maura Malpetti ◽

William Richard Bevan-Jones ◽

P. Simon Jones ◽

...

Keyword(s):

White Matter ◽

Progressive Supranuclear Palsy ◽

Pet Imaging ◽

Diffusion Tensor ◽

Brain Mri ◽

Mean Diffusivity ◽

White Matter Integrity ◽

Tau Pathology ◽

Cross Sectional ◽

White Matter Changes

ABSTRACTIntroductionProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.ResultsWidespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.

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Age-Related Variations in Regional White Matter Volumetry and Microstructure During the Post-adolescence Period: A Cross-Sectional Study of a Cohort of 1,713 University Students

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2021.692152 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ami Tsuchida ◽

Alexandre Laurent ◽

Fabrice Crivello ◽

Laurent Petit ◽

Antonietta Pepe ◽

...

Keyword(s):

White Matter ◽

University Students ◽

Diffusion Tensor ◽

Brain Mri ◽

Mean Diffusivity ◽

High Angular Resolution ◽

White Matter Volume ◽

Matter Volume ◽

Brain White Matter ◽

Age Related

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

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White Matter Microstructural Integrity and Executive Function in Parkinson's Disease

Journal of the International Neuropsychological Society ◽

10.1017/s1355617712001373 ◽

2013 ◽

Vol 19 (3) ◽

pp. 349-354 ◽

Cited By ~ 22

Author(s):

Catherine Gallagher ◽

Brian Bell ◽

Barbara Bendlin ◽

Matthew Palotti ◽

Ozioma Okonkwo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Executive Function ◽

White Matter ◽

Diffusion Tensor ◽

A Priori ◽

Mean Diffusivity ◽

Pathological Process ◽

Intracranial Volume ◽

Mean Values

AbstractRecent studies suggest that white matter abnormalities contribute to both motor and non-motor symptoms of Parkinson's disease. The present study was designed to investigate the degree to which diffusion tensor magnetic resonance imaging (DTI) indices are related to executive function in Parkinson's patients. We used tract-based spatial statistics to compare DTI data from 15 patients to 15 healthy, age- and education-matched controls. We then extracted mean values of fractional anisotropy (FA) and mean diffusivity (MD) within an a priori frontal mask. Executive function composite Z scores were regressed against these DTI indices, age, and total intracranial volume. In Parkinson's patients, FA was related to executive composite scores, and both indices were related to Stroop interference scores. We conclude that white matter microstructural abnormalities contribute to cognitive deficits in Parkinson's disease. Further work is needed to determine whether these white matter changes reflect the pathological process or a clinically important comorbidity. (JINS, 2013, 19, 1–6)

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Plasma P-tau181 levels reflects white matter microstructural changes across Alzheimer’s disease progression

10.21203/rs.3.rs-115316/v3 ◽

2021 ◽

Author(s):

Fardin Nabizadeh ◽

Seyed Behnamedin Jameie ◽

Saghar Khani ◽

Aida Rezaei ◽

Fatemeh Ranjbaran ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Behavioral Problems ◽

Structural Changes ◽

Diffusion Tensor ◽

Cognitive Impairments ◽

Mean Diffusivity ◽

Diagnostic Procedures ◽

Microstructural Changes

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties that hinder daily activities and lead to personal and behavioral problems. Plasma hyperphosphorylated tau protein at threonine 181 (p-tau181), a blood-based biomarker, has recently emerged as a new tool with sufficient sensitivity for distinguishing AD patients from healthy people. We herein investigated the association of plasma P-tau181 and white matter (WM) microstructural changes in AD. We examined data from a large prospective cohort of elderly individuals participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) which covers a wide clinical spectrum from normal cognition to AD dementia with measurements of plasma P-tau181 and imaging findings at baseline. A subset of 41 patients with AD, 119 patients with mild cognitive impairments (MCI), and 43 healthy controls (HC) were included in the study, all of whom had baseline blood P-tau181 levels and had also undergone Diffusion Tensor Imaging (DTI). The analysis revealed that the plasma level of P-tau181 have positive correlation with changes in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AxD), but a negative with Fractional Anisotropy (FA) parameters in WM regions of all participants. There is also a significant association between WM microstructural changes in different regions and P-tau181 plasma measurements within each MCI, HC and AD group. In conclusion, our findings clarified that plasma P-tau181 levels are associated with changes in WM integrity in AD. P-tau181 could improve the accuracy of diagnostic procedures and support the application of blood-based biomarkers to diagnose WM neurodegeneration. Longitudinal clinical studies are also needed to demonstrate the efficacy of the P-tau181 biomarker and predict its role in structural changes.

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Patterns of white matter degeneration in remote brain areas from the basal ganglion lesion of ischemic stroke patients with motor impairment

10.21203/rs.3.rs-36124/v3 ◽

2020 ◽

Author(s):

xuejin cao ◽

Zan Wang ◽

Xiaohui Chen ◽

Yanli Liu ◽

Wei Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Basal Ganglia ◽

Structural Changes ◽

Diffusion Tensor ◽

Brain Magnetic Resonance Imaging ◽

Stroke Patients ◽

Brain Areas ◽

Ischemic Lesion ◽

The Brain

Abstract Background: Diffusion tensor imaging (DTI) studies have revealed distinct white matter characteristics of the brain following diseases. Beyond the lesion-symptom mapping, recent studies have demonstrated extensive structural and functional alterations of remote areas to local lesions caused by stroke in the brain. Here, we further investigated the structural changes from a global level using DTI data through multivariate pattern analysis (MVPA) and network-based statistic (NBS). Methods: Ten ischemic stroke patients with basal ganglia lesions and motor dysfunctions and eleven demographically matched adults as controls underwent brain Magnetic Resonance Imaging scans. DTI data were processed to obtain fractional anisotropy (FA) maps and MVPA was used to explore brain regions that play an important role in classification based on FA maps. The white matter (WM) structural network was constructed by the deterministic fiber tracking approach according to the Automated Anatomical Labeling (AAL) atlas. NBS was used to explore differences in structural networks between groups. Results: MVPA applied to FA images correctly identified stroke patients with a statistically significant accuracy of 100% (P≤0.001). Compared with the controls, the study patients showed FA reductions in the perilesional basal ganglia and brainstem, with a few showing reductions in bilateral frontal lobes. Using NBS, we found a significant decrease in FA-weighted WM subnetwork in stroke patients. Conclusions: We identified some patterns of WM degeneration affecting brain areas remote to the ischemic lesion, revealing the abnormal organization of WM network in stroke patients, which may be helpful for the understanding of the neural mechanisms of stroke sequela.

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Abstract TP154: Arcuate Fasciculus Integrity and Outcome of Post-stroke Aphasia: A 6-month Follow-up DTI Study

Stroke ◽

10.1161/str.51.suppl_1.tp154 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Chorong Bae ◽

Yoonhye Na ◽

Minjae Cho ◽

Yu Mi Hwang ◽

Woo-Suk Tae ◽

...

Keyword(s):

Structural Changes ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Type I ◽

Type Ii ◽

Arcuate Fasciculus ◽

Type Iii ◽

Post Stroke ◽

Fiber Number

Objectives: We evaluated the changes of arcuate fasciculus (AF), an important connecting pathway for language function, using DTI at 1-month and 6-month after stroke and investigated the relationship between structural changes of AF and improvement of post-stroke aphasia. Methods: We collected data from the STroke Outcome Prediction (STOP) database that is prospective data collecting system for functional recovery prediction after stroke based on neuroimaging study. Twenty-six patients with aphasia (PWA) who had first-ever stroke, presence of aphasia evaluated by Western Aphasia Battery (WAB) and no previous neurological or psychiatric diagnosis. The WAB and DTI data within 1 month (initial) and 6 months after (follow-up) stroke onset were used for analysis. And fractional anisotropy (FA), mean diffusivity (MD), fiber number (FN) and differences (Δ) at two time points of these parameters were obtained in bilateral AF in diffusion tensor tractography (DTT). Three types (I: not reconstructed, II: disrupted, discontinued or shallow, III: preserved) of classification according to integrity of AF was also included. Results: DTT parameters of bilateral AF showed statistically significant decrease in FA and increase in MD. Types of AF were changed in 6 patients (23%): 3 patients from type III to type II, 2 patients from type II to type I, and 1 patient from type II to type III. In Pearson’s correlation analysis, significant correlation was observed between 6-mon aphasia quotient (AQ) and parameters of left AF; positive correlation with FA (r=0.707, p<0.001), and negative correlation with MD (r=-.540, p<0.001). However, there was no correlation between 6-mon AQ score and FN of left AF, and all parameters of right AF. In addition, ΔDTT parameters were not correlated with either 6-mon AQ or ΔAQ. Conclusions: The AF changes over time not only in dominant but also in nondominant hemispheres in patients with aphasia after stroke. But amount of changes (Δ) in AF parameters were not associated with language recovery. Acknowledgement: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2019R1A2C2003020).

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White Matter Changes in Bipolar Disorder, Alzheimer Disease, and Mild Cognitive Impairment: New Insights from DTI

Journal of Aging Research ◽

10.4061/2011/286564 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Aikaterini Xekardaki ◽

Panteleimon Giannakopoulos ◽

Sven Haller

Keyword(s):

Bipolar Disorder ◽

White Matter ◽

Alzheimer Disease ◽

Structural Changes ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Basic Principles ◽

Diffusion In Brain ◽

Diffusion Tensor Imaging Dti

Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI), a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasivein vivotechnique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease.

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Deep medullary veins are associated with widespread brain structural abnormalities

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211065210 ◽

2021 ◽

pp. 0271678X2110652

Author(s):

Zi-Yue Liu ◽

Fei-Fei Zhai ◽

Dong-Hui Ao ◽

Fei Han ◽

Ming-Li Li ◽

...

Keyword(s):

White Matter ◽

Gray Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Cortical Atrophy ◽

Intracranial Volume ◽

Brain Parenchymal ◽

Occipital Lobes ◽

Microstructural Integrity ◽

Deep Medullary Veins

Our aim is to investigate the association of cerebral deep medullary veins (DMVs) with white matter microstructural integrity and regional brain atrophy in MRI. In a community-based cohort of 979 participants (mean age 55.4 years), DMVs were identified on susceptibility-weighted imaging. Brain structural measurements including gray matter and hippocampus volumes, as well as diffusion tensor metrics, were evaluated. The mean (SD)number of DMVs was 19.0 (1.7). A fewer number of DMVs was related to lower fractional anisotropy and higher mean diffusivity in multiple voxels on the white matter skeleton (threshold-free cluster enhancement corrected p < 0.05, adjusted for age and sex). Also, fewer DMVs were significantly related to a lower gray matter fraction and a hippocampal fraction (0.10 and 0.11 per DMV, respectively; SE, 0.03 for both; p < 0.001 for both). A significant correlation between DMVs’ reduction and cortical atrophy was observed in the bilateral occipital lobes, temporal lobes, hippocampus, and frontal lobes (p < 0.001, adjusted for age, sex, and total intracranial volume). Our results provided evidence that cerebral small venules disease play a role in brain parenchymal lesions and neurodegenerative processes.

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Patterns of white matter degeneration in remote brain areas from the basal ganglion lesion of ischemic stroke patients with motor impairment

10.21203/rs.3.rs-36124/v2 ◽

2020 ◽

Author(s):

Xuejin Cao ◽

Zan Wang ◽

Xiaohui Chen ◽

Yanli Liu ◽

Wei Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Basal Ganglia ◽

Structural Changes ◽

Diffusion Tensor ◽

Brain Magnetic Resonance Imaging ◽

Stroke Patients ◽

Brain Areas ◽

Ischemic Lesion ◽

The Brain

Abstract Background: Diffusion tensor imaging (DTI) studies have revealed distinct white matter characteristics of the brain following diseases. Beyond the lesion-symptom mapping, recent studies have demonstrated extensive structural and functional alterations of remote areas to local lesions caused by stroke in the brain. Here, we further investigated the structural changes from a global level using DTI data through multivariate pattern analysis (MVPA) and network-based statistic (NBS). Methods: Ten ischemic stroke patients with basal ganglia lesions and motor dysfunctions and eleven demographically matched adults as controls underwent brain Magnetic Resonance Imaging scans. DTI data were processed to obtain fractional anisotropy (FA) maps and MVPA was used to explore brain regions that play an important role in classification based on FA maps. The white matter (WM) structural network was constructed by the deterministic fiber tracking approach according to the Automated Anatomical Labeling (AAL) atlas. NBS was used to explore differences in structural networks between groups.Results: MVPA applied to FA images correctly identified stroke patients with a statistically significant accuracy of 100% (P≤0.001). Compared with the controls, the study patients showed FA reductions in the perilesional basal ganglia and brainstem, with a few showing reductions in bilateral frontal lobes. Using NBS, we found a significant decrease in FA-weighted WM subnetwork in stroke patients. Conclusions: We identified some patterns of WM degeneration affecting brain areas remote to the ischemic lesion, revealing the abnormal organization of WM network in stroke patients, which may be helpful for the understanding of the neural mechanisms of stroke sequela.

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