Abstract TP75: Normal Appearing White Matter Integrity and Motor Impairment Severity 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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Diffusion Properties of Normal-Appearing White Matter Microstructure and Severity of Motor Impairment in Acute Ischemic Stroke

American Journal of Neuroradiology ◽

10.3174/ajnr.a6357 ◽

2019 ◽

Vol 41 (1) ◽

pp. 71-78 ◽

Cited By ~ 1

Author(s):

C. Ingo ◽

C. Lin ◽

J. Higgins ◽

Y.A. Arevalo ◽

S. Prabhakaran

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Motor Impairment ◽

Normal Appearing White Matter ◽

White Matter Microstructure ◽

Diffusion Properties

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Patients With Chronic Migraine Without History of Medication Overuse Are Characterized by a Peculiar White Matter Fiber Bundle Profile

10.21203/rs.3.rs-33717/v1 ◽

2020 ◽

Author(s):

Gianluca Coppola ◽

Antonio Di Renzo ◽

Emanuele Tinelli ◽

Barbara Petolicchio ◽

Cherubino Di Lorenzo ◽

...

Keyword(s):

White Matter ◽

Chronic Migraine ◽

Diffusion Tensor ◽

Internal Capsule ◽

Posterior Limb ◽

History Of ◽

The Right ◽

Normal White Matter ◽

Microstructural Integrity ◽

The Brain

Abstract Background: We investigated intracerebral fiber bundles using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) datato investigate microstructural integrity in patients with episodic (MO) and chronic migraine (CM).Methods: We performed DTI in 19 patients with MO within interictal periods, 18 patients with CM without any history of drug abuse, and 18 healthy controls (HCs) using a 3T magnetic resonance imaging scanner. We calculated diffusion metrics, including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD), and mean diffusion (MD).Results: TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups. In comparison to the HC group, theCM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC). In comparison to theMO group, theCM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC). Conclusion: Our results suggest that chronic migraine can be associated withthe widespread disruption of normal white matter integrity in the brain.

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Global white matter structural integrity mediates the effect of age on ischemic stroke outcomes

International Journal of Stroke ◽

10.1177/17474930211055906 ◽

2021 ◽

pp. 174749302110559

Author(s):

Mark R Etherton ◽

Markus D Schirmer ◽

Maria Clara Zanon Zotin ◽

Pamela M Rist ◽

Gregoire Boulouis ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Mean Diffusivity ◽

Stroke Outcomes ◽

Excellent Functional Outcome ◽

Microstructural Integrity ◽

Relationship Of ◽

Effect Of Age

Background The relationship of global white matter microstructural integrity and ischemic stroke outcomes is not well understood. Aims To investigate the relationship of global white matter microstructural integrity with clinical variables and functional outcomes after acute ischemic stroke. Methods A retrospective analysis of neuroimaging data from 300 acute ischemic stroke patients with magnetic resonance imaging brain obtained within 48 hours of stroke onset and long-term functional outcomes (modified Rankin, mRS) was performed. Peak width of skeletonized mean diffusivity (PSMD), as a measure of global white matter microstructural injury, was calculated in the hemisphere contralateral to the acute infarct. Multivariable linear and logistic regression analyses were performed to identify variables associated with PSMD and excellent functional outcome (mRS < 2) at 90 days, respectively. Mediation analysis was then pursued to characterize how PSMD mediates the effect of age on acute ischemic stroke functional outcomes. Results White matter hyperintensity volume, age, pre-stroke disability, and normal-appearing white matter mean diffusivity were independently associated with increased PSMD. In logistic regression analysis, increased infarct volume and PSMD were independent predictors of excellent functional outcome. Additionally, the effect of age on functional outcomes was indirectly mediated by PSMD ( P < 0.001). Conclusions As a marker of global white matter microstructural injury, increased PSMD mediates the effect of increased age to contribute to poor acute ischemic stroke functional outcomes. PSMD could serve as a putative radiographic marker of brain age for stroke outcomes prognostication.

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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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Patients with chronic migraine without history of medication overuse are characterized by a peculiar white matter fiber bundle profile

10.21203/rs.3.rs-33717/v2 ◽

2020 ◽

Author(s):

Gianluca Coppola ◽

Antonio Di Renzo ◽

Emanuele Tinelli ◽

Barbara Petolicchio ◽

Cherubino Di Lorenzo ◽

...

Keyword(s):

White Matter ◽

Chronic Migraine ◽

Diffusion Tensor ◽

Internal Capsule ◽

Posterior Limb ◽

History Of ◽

The Right ◽

Normal White Matter ◽

Microstructural Integrity ◽

The Brain

Abstract Background: We investigated intracerebral fiber bundles using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to investigate microstructural integrity in patients with episodic (MO) and chronic migraine (CM).Methods: We performed DTI in 19 patients with MO within interictal periods, 18 patients with CM without any history of drug abuse, and 18 healthy controls (HCs) using a 3T magnetic resonance imaging scanner. We calculated diffusion metrics, including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD), and mean diffusion (MD).Results: TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups. In comparison to the HC group, the CM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC). In comparison to the MO group, the CM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC). Conclusion: Our results suggest that chronic migraine can be associated with the widespread disruption of normal white matter integrity in the brain.

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Abstract TMP121: Gender Differences in Functional Outcomes After Acute Ischemic Stroke: The Role of White Matter Structural Integrity

Stroke ◽

10.1161/str.48.suppl_1.tmp121 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Mark Etherton ◽

Ona Wu ◽

Pedro Cougo ◽

Anne-Katrin Giese ◽

Lisa Cloonan ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Recovery ◽

Stroke Subtype ◽

Post Stroke ◽

Significant Difference ◽

Acute Infarct ◽

Underlying Mechanisms ◽

Microstructural Integrity

Background: Women are known to have worse post-stroke outcomes; however, the underlying mechanisms remain unclear. We evaluated sex-specific clinical and neuroimaging characteristics linked to cerebrovascular brain health in association with functional recovery after acute ischemic stroke (AIS). Methods: We reviewed 316 AIS patients with acute MRI (<48 hours from symptom onset) and modified Rankin scale score (mRS) assessed at 3-6 months post-stroke. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on FLAIR sequences were determined using a validated semi-automated method. Mean diffusivity (MD) and fractional anisotropy (FA) of normal appearing white matter (NAWM) were derived from the contralesional hemisphere. Wilcoxon rank sum, Spearman correlation, and Fisher’s exact tests were used at p-value <0.05, as appropriate. Results: Women comprised 41.1% of this AIS cohort, and as compared to men, they were older (68 vs. 62.8 years, p = 0.002), had higher prevalence of atrial fibrillation (21.5% vs. 12.4%, p = 0.04), and less tobacco use (21.1% vs. 36.3%, p = 0.03). There was no statistically significant difference between men and women in admission stroke severity, TOAST stroke subtype distribution, DWIv or WMHv. However, women were significantly less likely to have a favorable outcome (mRS <2), as compared to men (53.7% vs. 68.5%, p = 0.01). Both FA (ρ -0.18, p=0.04) and MD (ρ 0.28, p=0.002) values in NAWM correlated with follow-up mRS in women, but only MD (ρ 0.26, p=0.0004) in men. Conclusion: Despite no differences in admission NIHSS, acute infarct size, WMH burden or stroke subtype, women with AIS had significantly worse post-stroke outcomes in our cohort. Our findings suggest that microstructural integrity, as assessed by NAWM diffusivity anisotropy measurements, may represent a neuroimaging correlate of worse outcomes in women. The correlation between markers of white matter microstructural integrity and long-term mRS provides insight into the underlying mechanisms of disease that may influence 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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