Brain volume is a better biomarker of outcomes in ischemic stroke compared to brain atrophy

Absolute stupidity to measure this, nothing in this measurement gets survivors recovered!

 Brain volume is a better biomarker of outcomes in ischemic strokecompared to brain atrophy

Kenda Alhadid1, Robert W. Regenhardt1, Natalia S. Rost1, Markus D. Schirmer1*1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA,USA.* Correspondence:Markus D. Schirmer mschirmer1@mgh.harvard.edu>Keywords: arterial ischemic stroke, brain volume, brain parenchymal fraction, BPF, modified Rankin Scale, mRS

Abstract

Objective: 

To assess if brain volume at the time of ischemic stroke injury is a better biomarker offunctional outcome than brain atrophy.

 

Background:

 

Brain parenchymal fraction (BPF) has been used as a surrogate measure of global brain atrophy, and as a neuroimaging biomarker of brain reserve in studies evaluating clinical outcomes afterbrain injury. Brain volume itself is affected by natural aging, cardiovascular risk factors, and biologicalsex, amongst other factors. Recent works have shown that brain volume at the time of injury caninfluence functional outcomes, where larger brain volumes are associated with better outcomes.

 

Methods: 

 

Acute ischemic stroke cases at a single center between 2003 and 2011, with MRneuroimaging obtained within 48 hours from presentation were eligible. Functional outcomes favorable outcome) were obtained via patient interview or per chart review. Deep learning enabledautomated segmentation pipelines were used to calculate brain volume, intracranial volume (ICV), and BPF on the acute neuroimaging data. Patient outcomes were modeled through logistic regressions, and model comparison was conducted using the Bayes Information Criterion (BIC).

 

Results:

467 patients with arterial ischemic stroke were included in the analysis. Median age was 65.8(interquartile range: 55.3-76.3) years, and 65.3% were male. In both models, age and a larger stroke lesion volume were associated with worse functional outcomes. Higher BPF and a larger brain volume were both associated with favorable functional outcomes, however, comparison of both models suggested that the brain volume model (BIC=501) explains the data better compared to the BPF model(BIC=511).

 

Conclusions: 

 

The extent of global brain atrophy (and its surrogate biomarker BPF) has been regardedas an important biomarker of post-stroke functional outcomes and resilience to acute injury. Here, we demonstrate that a higher global brain volume at the time of injury better explains favorable functional outcomes, which can be directly clinically assessed.2 1 Introduction With aging populations in the US and worldwide, and the increased incidence of stroke in younger patient populations, the prevalence of arterial ischemic stroke is increasing.(1) Understanding the determinants of post-stroke outcomes is of great clinical, societal, and economic importance. Determining the most relevant clinical and imaging biomarkers of functional outcomes is essential for developing targeted preventative and therapeutic approaches. Phenotypic information, such as age and lesion volume,(2±4) have been utilized to model post-stroke outcome, however, current models are insufficient to adequately explain clinically observed variations in outcomes.Recently, neuroimaging studies revealed other important factors pertaining to clinical outcomes, such as white matter hyperintensity volume (WMHv).(5±7) Additionally, studies have demonstrated that brain volume, specifically cortical volume, is related to an individual∂s cognitive abilities and intelligence, even when corrected for age, sex and other collinearities.(8±12) Importantly, brain volume of stroke patients at the time of admission has been identified as an independent biomarker for functional post-stroke outcome.(13±15) Volumetric brain studies often normalize each patient∂s brain volume by their intracranial volume, also known as brain parenchymal fraction (BPF), which can serve as a surrogate measure of global brain atrophy in cross-sectional studies.(16) However, no consensus on the utility of non-normalized and normalized brain volume exists. In this work, we utilize advances in deep-learning enabled segmentation algorithms to estimate brain volume and BPF in a cohort of 476 acute ischemic stroke patients based on their acute clinical neuroimaging data acquired in the emergency department or during hospital admission. Using multivariable logistic regression models of functional outcome, measured by the 90-day modified Rankin Scale (mRS) score, we compare the models including either BPF as a surrogate measure of brain atrophy or a volumetric measure of brain volume We demonstrate that an individual's brain volume at the time of acute injury rather than a measure of brain atrophy, is a better marker for modeling functional outcome.