Reduction in Cerebrospinal Fluid Volume as an Early Quantitative Biomarker of Cerebral Edema After Ischemic Stroke

Abstract

Background and Purpose— Cerebral edema (CED) develops in the hours to days after stroke; the resulting increase in brain volume may lead to midline shift (MLS) and neurological deterioration. The time course and implications of edema formation are not well characterized across the spectrum of stroke. We analyzed displacement of cerebrospinal fluid (ΔCSF) as a dynamic quantitative imaging biomarker of edema formation. Methods— We selected subjects enrolled in a stroke cohort study who presented within 6 hours of onset and had baseline and ≥1 follow-up brain computed tomography scans available. We applied a neural network-based algorithm to quantify hemispheric CSF volume at each imaging time point and modeled CSF trajectory over time (using a piecewise linear mixed-effects model). We evaluated ΔCSF within the first 24 hours as an early biomarker of CED (defined as developing MLS on computed tomography beyond 24 hours) and poor outcome (modified Rankin Scale score, 3–6). Results— We had serial imaging in 738 subjects with stroke, of whom 91 (13%) developed CED with MLS. Age did not differ (69 versus 70 years), but baseline National Institutes of Health Stroke Scale was higher (16 versus 7) and baseline CSF volume lower (132 versus 161 mL, both P <0.001) in those with CED. ΔCSF was faster in those developing MLS, with the majority seen by 24 hours (36% versus 11% or 2.4 versus 0.8 mL/h; P <0.0001). Risk of CED almost doubled for every 10% ΔCSF within 24 hours (odds ratio, 1.76 [95% CI, 1.46–2.14]), adjusting for age, glucose, and National Institutes of Health Stroke Scale. Risk of neurological deterioration (1.6-point increase in National Institutes of Health Stroke Scale at 24 hours) and poor outcome (adjusted odds ratio, 1.34 [95% CI, 1.15–1.56]) was also greater for every 10% increase in ΔCSF. Conclusions— CSF volumetrics provides quantitative evaluation of early edema formation. ΔCSF from baseline to 24-hour computed tomography is a promising early biomarker for the development of MLS and worse neurological outcome.

Quantitative Serial CT Imaging-Derived Features Improve Prediction of Malignant Cerebral Edema after Ischemic Stroke

“…Our prior study suggested that measuring reduction in CSF volume from baseline to follow-up CT at 24-h may provide a useful biomarker of edema severity [15]. We chose to evaluate CSF volume rather than brain volume primarily because it is easier to accurately segment on CT images of variable quality and represents a proxy that reciprocates brain volume increases.…”

“…For example, measuring baseline intracranial reserve (i.e., CSF volume as a proportion of cranial volume) may be more informative than patient age in predicting which patients are more likely to develop MLS and deterioration [13,14]. We have recently demonstrated that serial measurements of CSF volume (i.e., applying reduction in CSF volume as a surrogate of the brain volume increase from edema) can provide quantitative data on edema severity [15]. Additionally, we demonstrated that incorporating follow-up imaging data within 24-h significantly improves prediction of potentially lethal cerebral edema (death or need for DHC) [16].…”

The Stroke Neuro-Imaging Phenotype Repository: An Open Data Science Platform for Stroke Research

“…As an example, a containerized stroke edema pipeline was developed to automate image segmentation and measurement of CSF volume in serial CT scans in stroke patients ( Figure 4 ). The pipeline includes five containerized modules, including neural network-based labeling of image acquisition type ( Szegedy et al, 2015 ; Mohammadian Foroushani et al, 2020a ), DICOM to NIfTI conversion ( Li, 2016 ), FSL-based preregistration for skull stripping ( Jenkinson, 2011 ), ANTS-based registration of longitudinal brain masks ( Avants et al, 2009 ), U-Net-based segmentation of CSF ( Chen et al, 2016 ), and its volumetric calculation ( Dhar et al, 2020 ). This parallels the recent recommendations for processing head CT data ( Muschelli, 2019 ).…”

Hemispheric CSF volume ratio quantifies progression and severity of cerebral edema after acute hemispheric stroke

“…5 Once this reserve of CSF in the sulci, cisterns, and ventricles is exhausted, cerebral herniation with neurologic deterioration will rapidly ensue. 6 Volumetric assessment of CSF displacement provides a quantitative surrogate for edema severity that is measurable from routine CT scans within the first 24-hours after stroke, often before infarct-related hypodensity and midline shift are apparent on CT. 7,8 However, quantifying ΔCSF requires comparison of baseline and follow-up imaging and only captures global edema, obscuring prominent early compartmental shifts. We propose that the ratio of CSF volume in the lesional hemispheric to the contralateral unaffected hemisphere may provide a powerful dynamic biomarker of edema that can be measured from routine post-stroke CTs.…”