Diffusion Properties of Normal-Appearing White Matter Microstructure and Severity of Motor Impairment in Acute Ischemic Stroke

Introduction: The effect of white matter hyperintensities (WMH) as measured by fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging on functional impairment and recovery after ischemic stroke has been investigated thoroughly. However, there has been growing interest to investigate normal-appearing white matter (NAWM) microstructural integrity following ischemic stroke onset with techniques such as diffusion tensor imaging (DTI). Methods: 52 patients with acute ischemic stroke and 36 without stroke were evaluated with a DTI and FLAIR imaging protocol and clinically assessed for severity of motor impairment using the Motricity Index within 72 hours of suspected symptom onset. Results: There were widespread decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) and radial diffusivity (RD) for the acute stroke group compared to the non-stroke group. As shown in the abstract figure with the blue voxels, there was a significant positive association between FA and motor function and a significant negative association between MD/RD and motor function. The NAWM regions of interest that were most sensitive to the Motricity Index were the anterior/posterior limb of the internal capsule in the infarcted hemisphere and the splenium of the corpus callosum, external capsule, posterior limb/retrolenticular part of the internal capsule, superior longitudinal fasciculus, and cingulum (hippocampus) of the intra-/contralateral hemisphere. Conclusion: The microstructural integrity of NAWM is a significant parameter to identify neural differences not only between those individuals with and without acute ischemic stroke, but also correlated with severity of acute motor impairment.

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Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke

Neurology ◽

10.1212/wnl.0000000000003890 ◽

2017 ◽

Vol 88 (18) ◽

pp. 1701-1708 ◽

Cited By ~ 28

Author(s):

Mark R. Etherton ◽

Ona Wu ◽

Pedro Cougo ◽

Anne-Katrin Giese ◽

Lisa Cloonan ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Stroke Severity ◽

Cerebral Tissue ◽

Nihss Score ◽

Normal Appearing White Matter ◽

Acute Infarct

Objective:To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS).Methods:Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses.Results:Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1–8), and median normalized WMHv was 6.19 cm3 (IQR 3.0–12.6 cm3). Admission stroke severity (β = 0.16, p < 0.0001) and small vessel stroke subtype (β = −1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (β = −9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv.Conclusions:FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.

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Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.117.019258 ◽

2017 ◽

Vol 48 (12) ◽

pp. 3387-3389 ◽

Cited By ~ 4

Author(s):

Mark R. Etherton ◽

Ona Wu ◽

Pedro Cougo ◽

Anne-Katrin Giese ◽

Lisa Cloonan ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Structural Integrity ◽

Normal Appearing White Matter

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Normal-appearing white matter microstructural injury is associated with white matter hyperintensity burden in acute ischemic stroke

International Journal of Stroke ◽

10.1177/1747493019895707 ◽

2019 ◽

pp. 174749301989570

Author(s):

Mark R Etherton ◽

Ona Wu ◽

Anne-Katrin Giese ◽

Natalia S Rost

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Linear Regression ◽

Acute Ischemic Stroke ◽

Diffusion Tensor ◽

Linear Regression Analysis ◽

White Matter Hyperintensity ◽

Radial Diffusivity ◽

Axial Diffusivity ◽

Normal Appearing White Matter

Background White matter hyperintensity of presumed vascular origin is a risk factor for poor stroke outcomes. In patients with acute ischemic stroke, however, the in vivo mechanisms of white matter microstructural injury are less clear. Aims To characterize the directional diffusivity components in normal-appearing white matter and white matter hyperintensity in acute ischemic stroke patients. Methods A retrospective analysis was performed on a cohort of patients with acute ischemic stroke and brain magnetic resonance imaging with diffusion tensor imaging sequences acquired within 48 h of admission. White matter hyperintensity volume was measured in a semi-automated manner. Median fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter and white matter hyperintensity in the hemisphere contralateral to the acute infarct. Linear regression analysis was performed to evaluate predictors of white matter hyperintensity volume and normal-appearing white matter diffusivity metrics. Results In 319 patients, mean age was 64.9 ± 15.9 years. White matter hyperintensity volume was 6.33 cm3 (interquartile range 3.0–12.6 cm3). Axial and radial diffusivity were significantly increased in white matter hyperintensity compared to normal-appearing white matter. In multivariable linear regression, age (β = 0.20, P = 0.003) and normal-appearing white matter axial diffusivity (β = 37.9, P < 0.001) were independently associated with white matter hyperintensity volume. Subsequent analysis demonstrated that increasing age (β = 0.004, P < 0.001) and admission diastolic blood pressure (β = 0.001, P = 0.02) were independent predictors of normal-appearing white matter axial diffusivity in multivariable linear regression. Conclusions Normal-appearing white matter axial diffusivity increases with age and is an independent predictor of white matter hyperintensity volume in acute ischemic stroke.

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Abstract TP476: White Matter Hyperintensity Burden is Associated With Poor Collateral Flow and Worse Outcomes in an Acute Ischemic Stroke Cohort

Stroke ◽

10.1161/str.51.suppl_1.tp476 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Rami-James Assadi ◽

Hongyu An ◽

Yasheng Chen ◽

Andria Ford ◽

Jin-Moo Lee

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Pearson Correlation ◽

Stroke Onset ◽

White Matter Hyperintensity ◽

Flow Index ◽

Acute Ischemia ◽

Collateral Flow ◽

Core Volume

Introduction: White matter hyperintensity volume (WMHv), a quantitative neuroimaging biomarker of cerebral small vessel disease (CSVD), is associated worse outcomes after ischemic stroke. In this study, we hypothesized that worse outcomes in CSVD patients were due to poor collateral flow during acute ischemia. Methods: 47 patients with acute ischemic stroke (AIS) were prospectively enrolled in this study. Serial MRIs were performed at 3 hours and 30 days after stroke onset. 3-hour FLAIR images were used to determine WMHv, after manually delineating lesions with MIPAV. An index of collateral flow (delayed perfusion to the penumbra) was determined by subtracting core volume (volume of tissue with ADC<600) from the volume of brain tissue with Tmax>2. Patient’s NIHSS was scored at 3 hours and 30 days after stroke onset and the difference was calculated (ΔNIHSS). Log-transformed WMHv was correlated to ΔNIHSS and the collateral flow index, using Pearson correlation. Results: Mean age = 63.9 years (SD 13.5); 37% female; median 3-hour NIHSS = 13 (IQR 6.5-20); median change in NIHSS between 3h and 30d = 4 (IQR: 0-7); median core volume = 13cm3 (IQR 4.3-35.6); median WMHv = 1.257cm3 (IQR 641-3595). WMHv was associated with reduced improvement in ΔNIHSS (R=-0.42, ρ=0.005). Furthermore, WMHv demonstrated a trend for association with poor collateral flow (R=-0.28, ρ=0.062). In this dataset, we will explore the relationship between WMHv and other tissue-based metrics of collateral flow, including the hypoperfusion intensity ratio (HIR) and the cerebral blood volume ratio (rCBV). Conclusions: Our study confirms that patients with CSVD have worse outcomes after AIS. The data also raise the possibility that these worse outcomes in CSVD patients may be mediated by compromised collateral flow in the setting of acute ischemia.

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Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.mp16 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Sungmin Hong ◽

Anne-katrin Giese ◽

Markus D Schirmer ◽

Adrian V Dalca ◽

Anna Bonkhoff ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Life Time ◽

Stroke Recovery ◽

White Matter Hyperintensity ◽

Brain Health ◽

Stroke Outcomes ◽

The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

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Abstract TP201: The Relationship Between Chronic Kidney Diseases and the Presence of Cerebral Small Vessel Disease in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.tp201 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Kana Ueki ◽

Asako Nakamura ◽

Masahiro Yasaka ◽

Takahiro Kuwashiro ◽

Seiji Gotoh ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

White Matter Lesion ◽

Kidney Diseases ◽

Univariate Analysis ◽

Small Vessel ◽

Chronic Kidney Diseases ◽

History Of ◽

The Relationship

Introduction: Cerebral small vessel diseases (SVDs) i.e. white matter lesion and cerebral microbleeds (CMBs) are related to the patients with stroke more deeply than those without. In general population, in addition to age, hypertension, diabetes chronic kidney diseases (CKD) is well known to be related to SVDs, but it remains unclear in patients with stroke. We investigated the relationship between CKD and the presence of SVDs in patients with acute ischemic stroke. Methods: We enrolled 493 patients with acute ischemic stroke patients or transient ischemic attack patients (mean age 71; 60% male) who had undergone 1.5T MR imaging within a week of the index events from April 2013 to march 2015. We evaluated kidney function by estimated glomerular filtration rate (eGFR) with the modification of diet in Renal Disease. CKD was defined as an eGFR less than 60mil/min/1.73m 2 . CMBs were defined as focal areas of very low signal intensity smaller than 10mm. White matter lesion as Periventricular hyper intensity (PVH)>grade 2 and Deep and Subcortical White Matter Hyper intensity (DSWMH)> grade 2 were defied as advanced PVH and advanced DSWMH, respectively. We investigated relationship between CKD and CMBs, advanced PVH and advanced DSWMH using a logistic regression analysis. Results: We noted CMBs in 173 patients (35%), PVH in 81 (16%), and DSWMH in 151 (31%). An univariate analysis revealed that the age, CKD, history of stroke, and antiplatelet agents were associated with presence of CMBs, advanced PVH and severe DSWMH . The multivariate analysis revealed that CMBs, advanced PVH and advanced DSWMH were associated with age (CMBs: odds ratio(OR) ; 1.32 ; 95% confidence interval(CI), 1.10-1.60, p=0.004, advanced PVH : OR ; 3.00 ; 95% CI, 2.17-4.26, p<0.01, advanced DSWMH: OR ; 1.94; 95% CI, 1.56-2.45, p<0.01 ), history of stroke(CMBs : OR ; 2.01 ; 95% CI, 1.21-3.34, p=0.007, advanced PVH : OR ; 2.25 ; 95% CI, 1.18-4.27, p=0.01, advanced DSWMH: OR ; 1.78 ; 95% CI, 1.03-3.06, p=0.038). CKD was associated with CMBs (OR ; 1.62 ; 95% CI, 1.04-2.52, p=0.03), but PVH and DSWMH were not. Conclusions: It seems that age and history of stroke are related to CMBs, advanced PVH and advanced DSWMH, and that CKD is associates with CMBs but not with either advanced PVH or advanced DSWMH.

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Neuroimaging risk factors for participation restriction after acute ischemic stroke: 1-year follow-up study

Journal of Investigative Medicine ◽

10.1136/jim-2020-001675 ◽

2021 ◽

pp. jim-2020-001675

Author(s):

Jian-Feng Qu ◽

Huo-Hua Zhong ◽

Wen-Cong Liang ◽

Yang-Kun Chen ◽

Yong-Lin Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Activities Of Daily Living ◽

Acute Ischemic Stroke ◽

Daily Living ◽

Male Gender ◽

Perivascular Spaces ◽

Participation Restriction ◽

Nihss Score

The aim of the present study was to determine the neuroimaging predictors of poor participation after acute ischemic stroke. A total of 443 patients who had acute ischemic stroke were assessed. At 1-year recovery, the Reintegration to Normal Living Index was used to assess participation restriction. We also assessed the Activities of Daily Living Scale and modified Rankin Scale (mRS) score. Brain MRI measurement included acute infarcts and pre-existing abnormalities such as enlarged perivascular spaces, white matter lesions, ventricular-brain ratio, and medial temporal lobe atrophy (MTLA). The study included 324 men (73.1%) and 119 women (26.9%). In the univariate analysis, patients with poor participation after 1 year were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, with more histories of hypertension and atrial fibrillation, larger infarct volume, more severely enlarged perivascular spaces and MTLA, and more severe periventricular hyperintensities and deep white matter hyperintensities. Patients with participation restriction also had poor activities of daily living (ADL) and mRS score. Multiple logistic regression showed that, in model 1, age, male gender, NIHSS score on admission, and ADL on follow-up were significant predictors of poor participation, accounting for 60.2% of the variance. In model 2, which included both clinical and MRI variables, male gender, NIHSS score on admission, ADL on follow-up, and MTLA were significant predictors of poor participation, accounting for 61.2% of the variance. Participation restriction was common after acute ischemic stroke despite good mRS score. Male gender, stroke severity, severity of ADL on follow-up, and MTLA may be predictors of poor participation.Trial registration number ChiCTR1800016665.

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