Imaging biomarkers of cerebral edema automatically extracted from routine CT scans of large vessel occlusion strokes

Abstract

Background and purpose: Volumetric and densitometric biomarkers have been proposed to better quantify cerebral edema after stroke, but their relative performance has not been rigorously evaluated.

Methods: Patients with large vessel occlusion stroke from three institutions were analyzed. An automated pipeline extracted brain, cerebrospinal fluid (CSF), and infarct volumes from serial CTs. Several biomarkers were measured: change in global CSF volume from baseline (ΔCSF); ratio of CSF volumes between hemispheres (CSF ratio); and relative density of infarct region compared with mirrored contralateral region (net water uptake [NWU]). These were compared to radiographic standards, midline shift and relative hemispheric volume (RHV) and malignant edema, defined as deterioration resulting in need for osmotic therapy, decompressive surgery, or death.

Results: We analyzed 255 patients with 210 baseline CTs, 255 24-hour CTs, and 81 72-hour CTs. Of these, 35 (14%) developed malignant edema and 63 (27%) midline shift. CSF metrics could be calculated for 310 (92%), while NWU could only be obtained from 193 (57%). Peak midline shift was correlated with baseline CSF ratio (ρ = -.22) and with CSF ratio and ΔCSF at 24 hours (ρ = -.55/.63) and 72 hours (ρ = -.66/.69), but not with NWU (ρ = .15/.25). Similarly, CSF ratio was correlated with RHV (ρ = -.69/-.78), while NWU was not. Adjusting for age, National Institutes of Health Stroke Scale, tissue plasminogen activator treatment, and Alberta Stroke Program Early CT Score, CSF ratio (odds ratio [OR]: 1.95 per 0.1, 95% confidence interval [CI]: 1.52-2.59) and ΔCSF at 24 hours (OR: 1.87 per 10%, 95% CI: 1.47-2.49) were associated with malignant edema.

Conclusion: CSF volumetric biomarkers can be automatically measured from almost all routine CTs and correlate better with standard edema endpoints than net water uptake.

Keywords: biomarkers; brain water; cerebral edema; cerebrospinal fluid; computed tomography; midline shift; stroke.

Figure 1:

Output of image analysis for a follow-up CT at 72 hours after stroke for a patient with large right hemispheric infarction. The first column shows three axial slices from the non-contrast head CT (note: there are several regions of petechial hemorrhagic transformation and there was 3-mm of midline shift measured). The second column shows the extracted brain mask with automated delineation of the midline, separating the brain into right (ipsilateral) and left (contralateral) hemispheres. This allows calculation of the relative hemispheric volume (1.165). The third column shows the automated cerebrospinal fluid (CSF) segmentation, with hemispheric CSF separated using the same midline. The ratio of hemispheric CSF volumes is 0.07. In the final column, the orange region highlights the automated infarct segmentation. White regions within this represent areas thresholded out (i.e. Hounsfield units above 40). The purple region is the mirror of the infarct region within the contralateral hemisphere. The white regions within this represent areas of CSF not included in the mean density calculation. The ratio of infarct to mirror region densities is the net water uptake. Abbreviations: CSF = cerebrospinal fluid, ml = milliliters, HU = Hounsfield units, NWU = Net Water Uptake

Figure 2:

Flow of Subjects within this Study. FU, follow-up; ICA, internal carotid artery; LVO, large vessel occlusion; MCA, middle cerebral artery; N, number

Figure 3:

A) Correlation of hemispheric CSF ratio and relative hemispheric brain volume on 24-hour CT scans (line represents linear regression with 95% confidence interval); B) Plot of hemispheric CSF ratio and midline shift on 24-hour CT (line represents quadratic regression with 95% confidence interval)

Figure 3:

A) Correlation of hemispheric CSF ratio and relative hemispheric brain volume on 24-hour CT scans (line represents linear regression with 95% confidence interval); B) Plot of hemispheric CSF ratio and midline shift on 24-hour CT (line represents quadratic regression with 95% confidence interval)

Figure 4:

Correlation matrix showing relationships between all edema biomarkers. Blue indicates positive correlations and red negative correlations. Darker colors indicate stronger correlations. Significance of correlations represented by stars: one star indicates p<0.05, two stars p<0.001, and three stars p<0.0001. CSF, cerebrospinal fluid; hr = hour; NWU, net water uptake; RHV, relative hemispheric volume; ΔCSF, change in CSF volume (from baseline).

Figure 5:

Spaghetti plots showing the trajectories of each edema biomarker (A, CSF Ratio; B, Total CSF Volume; C, Midline Shift; D, Net Water Uptake, NWU) over time, plotted for each subject at each available time point, with linear group averages plotted with 95% confidence intervals (grey regions), separated between those without malignant edema (left panel, red) and in those with malignant edema (right panel, blue).

Figure 5:

Spaghetti plots showing the trajectories of each edema biomarker (A, CSF Ratio; B, Total CSF Volume; C, Midline Shift; D, Net Water Uptake, NWU) over time, plotted for each subject at each available time point, with linear group averages plotted with 95% confidence intervals (grey regions), separated between those without malignant edema (left panel, red) and in those with malignant edema (right panel, blue).

Figure 5:

Spaghetti plots showing the trajectories of each edema biomarker (A, CSF Ratio; B, Total CSF Volume; C, Midline Shift; D, Net Water Uptake, NWU) over time, plotted for each subject at each available time point, with linear group averages plotted with 95% confidence intervals (grey regions), separated between those without malignant edema (left panel, red) and in those with malignant edema (right panel, blue).

Figure 5:

Spaghetti plots showing the trajectories of each edema biomarker (A, CSF Ratio; B, Total CSF Volume; C, Midline Shift; D, Net Water Uptake, NWU) over time, plotted for each subject at each available time point, with linear group averages plotted with 95% confidence intervals (grey regions), separated between those without malignant edema (left panel, red) and in those with malignant edema (right panel, blue).