Impact of Encephalomalacia and White Matter Hyperintensities on ASPECTS in Patients With Acute Ischemic Stroke: Comparison of Automated- and Radiologist-Derived Scores

Introduction: Cerebral Small Vessel Disease (CSVD) is a major cause of acute ischemic stroke (AIS), intracerebral hemorrhage and cognitive impairment. Methods to quantify the disease burden have been largely limited to white matter hyperintensities (WMH) as the disease surrogate and focused mainly on MRI sequences acquired for research purposes. We develop here novel methods to quantify WMH and enlarged perivascular spaces (EPVs) based on clinically acquired MRI sequences in patients with transient ischemic attack (TIA) or AIS. Methods: Subjects presenting with TIA or AIS and had brain MRI within 24 hour of hospital admission were selected for this study. Preprocessing pipeline was developed locally that included bias correction, image rescaling, rigid body registration to the Montreal Neurological Institute (MNI) space, skull stripping and intensity normalization. WMH segmentation was performed using a combination of global thresholding of FLAIR sequences that was spatially restricted to the white matter regions which were defined using a population-based atlas of age matched controls. EPVs in the basal ganglia were segmented on T2 sequences using adaptive thresholding of basal ganglia mask that was created from the ICBM template image and age-matched population average atlas. Segmented objects less than 3 mm in diameter were labelled as EPVs. Validation of the accuracy of EPVs segmentation was performed by expert counting of EPVs and WMH was validated using volume similarity against expert manual segmentation of WMH. Results: 41 patients (age 61.2±16.1, 65% males, 19.5% had TIAs, and 79.5% had AIS) were included. WMH volume was (manual: 21.34±20.48 mls vs automated: 15.74±14.56 mls) achieving a volume similarity of 0.92±0.01. EPVs in the basal ganglia counts were 16.32±5.4 using the automated method. Validation through comparison with manual segmentation of the axial slice with the highest EPVs (Doubal Method) showed significant correlation (Spearman’s rho=0.53, P = 0.0004). Conclusions: We describe successful segmentation of WMH and EPVs on clinically acquired MRI sequences in patients with TIA or AIS. This method will have applications to quantify CSVD burden in large clinical trials and clinical practice.

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Thyroid-Stimulating Hormone, White Matter Hyperintensities, and Functional Outcome in Acute Ischemic Stroke Patients

Cerebrovascular Diseases Extra ◽

10.1159/000360217 ◽

2014 ◽

Vol 4 (1) ◽

pp. 61-68 ◽

Cited By ~ 8

Author(s):

Christopher O. Leonards ◽

Harald J. Schneider ◽

Thomas G. Liman ◽

Jochen B. Fiebach ◽

Matthias Endres ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

White Matter Hyperintensities ◽

Thyroid Stimulating Hormone ◽

Stroke Patients ◽

Stimulating Hormone

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Gut-Derived Metabolite Phenylacetylglutamine and White Matter Hyperintensities in Patients With Acute Ischemic Stroke

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.675158 ◽

2021 ◽

Vol 13 ◽

Author(s):

Fang Yu ◽

Xianjing Feng ◽

Xi Li ◽

Yunfang Luo ◽

Minping Wei ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

White Matter Hyperintensities ◽

White Matter Hyperintensity ◽

Liquid Chromatography Mass Spectrometry ◽

Recovery Sequence ◽

Fluid Attenuated Inversion Recovery ◽

Fazekas Scale ◽

The Relationship

Background: White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. Phenylacetylglutamine (PAGln) is a gut microbiota-derived metabolite that may induce cardiovascular events by activating platelets and increasing the risk of thrombosis. The relationship between plasma PAGln and WMH burden in patients with ischemic stroke is unknown. This study was designed to investigate the association between plasma PAGln and WMH burden in patients with acute ischemic stroke.Methods: A total of 595 patients with acute ischemic stroke were enrolled in this study within 14 days of symptom onset. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none–mild WMH (total Fazekas score 0–2) or moderate–severe WMH (total Fazekas score 3–6). Based on the severity of periventricular WMH (P-WMH) and deep WMH (D-WMH), patients were categorized into either a none–mild (Fazekas score 0–1) group or a moderate–severe (Fazekas score 2–3) group. Plasma PAGln levels were quantified using liquid chromatography–mass spectrometry.Results: We found that patients with moderate–severe overall WMH showed higher plasma PAGln levels than patients with none–mild overall WMH, and similar results were found in the analyses according to P-WMH and D-WMH. The logistic regression analysis showed that the fourth PAGln quartile was independently associated with moderate–severe overall WMH (adjusted 95% CI 1.134–4.018) and P-WMH (adjusted 95% CI 1.174–4.226).Conclusion: These findings suggest that higher plasma PAGln levels are associated with moderate–severe overall WMH and P-WMH in patients with acute ischemic stroke.

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Abstract TP563: White Matter Hyperintensities are Associated With Intracranial Internal Carotid Artery Calcifications in a Cohort of Patients With Acute Ischemic Stroke or Transient Ischemic Attack

Stroke ◽

10.1161/str.50.suppl_1.tp563 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Nikitaa Nath ◽

Monica Sarkar ◽

Melissa Le Roux ◽

Kimerly A Powell ◽

Michel T Torbey ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Carotid Artery ◽

Internal Carotid Artery ◽

Acute Ischemic Stroke ◽

Transient Ischemic Attack ◽

White Matter Hyperintensities ◽

Internal Carotid ◽

Ischemic Attack

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Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

Brain Sciences ◽

10.3390/brainsci9010016 ◽

2019 ◽

Vol 9 (1) ◽

pp. 16 ◽

Cited By ~ 2

Author(s):

Imama Naqvi ◽

Emi Hitomi ◽

Richard Leigh

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Stroke ◽

Blood Brain Barrier ◽

White Matter Hyperintensities ◽

Brain Barrier ◽

Common Finding ◽

Blood Brain ◽

History Of ◽

Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

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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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