Evolution of Perihematomal Edema Mean Hounsfield Unit and Its Association with Clinical Outcome in Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial

TL;DR

This study examines how the density of brain swelling around a hemorrhage changes over time and finds it does not predict long-term outcomes in patients.

Contribution

The study challenges the use of CT hypodensity as a predictive marker for clinical outcomes in intracerebral hemorrhage.

Findings

Perihematomal edema becomes more hypodense on CT scans within 3–4 days after hemorrhage.

The degree of hypodensity was not linked to worse outcomes at 90 or 180 days.

Findings question the utility of this imaging marker in ICH research.

Abstract

Lower mean Hounsfield unit (mHU) values, indicating greater computed tomography (CT) hypodensity of perihematomal edema (PHE), have been proposed as a novel quantitative imaging marker in intracerebral hemorrhage (ICH). We explored its evolution and prognostic importance in a post hoc analysis of the Intracerebral Hemorrhage-Deferoxamine trial (NCT02175225).

We included participants with primary supratentorial ICH who had available CT scans at baseline and follow-up after 72–96 h and 90-days and/or 180-days outcome data. The primary exposure variable was the mHU of PHE measured on the follow-up CT scan. We investigated (1) its change from baseline and (2) its association with unfavorable outcome (modified Rankin Scale score 3–6) in adjusted mixed-effects models, accounting for between-center and between-participant variability.

Among 273 of 293 Intracerebral Hemorrhage-Deferoxamine trial participants eligible for analysis (median age 61 years, 39% female), the median (interquartile range) mHU of PHE was 30.3 (28.3–32.7) at baseline and 26.9 (24.6–29.2) at follow-up. Τhe mHU of PHE decreased from baseline to follow-up scan by an average of 3.6 (95% confidence interval [CI] 3.2–4.0, p < 0.001). There was no association between the mHU of follow-up PHE with unfavorable outcome at 90 days (n = 273; odds ratio 1.05, 95% CI 0.95–1.17, p = 0.32), or at 180 days (n = 261; odds ratio 1.01, 95% CI 0.92–1.11, p = 0.81).

Perihematomal edema after ICH tends to grow more hypodense on CT by day 3–4 compared with baseline. The degree of PHE hypodensity was not associated with long-term clinical outcomes in the setting of a multicenter randomized trial, challenging its utility as a radiological marker in ICH research.

ClinicalTrials.gov: NCT02175225.

The online version contains supplementary material available at 10.1007/s12028-025-02337-7.

Figures