Accurate and timely confirmation of death by neurologic criteria (DNC) is essential for clinical decision-making and organ-donation processes, yet currently available ancillary tests have suboptimal diagnostic performance or limited validation.

To determine the diagnostic accuracy, interrater reliability, and safety of brain computed tomography (CT) perfusion and CT angiography as ancillary investigations for DNC.

Between April 25, 2017, and March 10, 2021, a prospective, multicenter, blinded diagnostic accuracy cohort study was conducted in 15 adult intensive care units across Canada. Consecutive, critically ill adults (aged ≥18 years) with a Glasgow Coma Scale score of 3 and no confounding factors who were at high risk of DNC were included. Data collection and analysis were performed from April 2021 to July 2024.

Contrast-enhanced brain CT perfusion with CT angiography reconstructions performed within 2 hours of a blinded, standardized clinical DNC examination.

The primary outcomes were the sensitivity and specificity of qualitative and quantitative brainstem CT perfusion for DNC determination, assessed by 2 independent neuroradiologists blinded to clinical findings; the prespecified validation threshold was greater than 98%. Secondary outcomes were the diagnostic accuracy of whole-brain CT perfusion and CT angiography, interrater reliability (Cohen κ), and adverse events associated with imaging.

A total of 282 patients (mean [SD] age, 57.8 [15.4] years; 133 [47%] female) completed the study protocol and were included in the primary analysis; 204 (72%) of these were ultimately declared deceased by standardized clinical criteria. Qualitative brainstem CT perfusion showed a sensitivity of 98.5% (95% CI, 95.8%-99.7%) and a specificity of 74.4% (95% CI, 63.2%-83.6%); quantitative brainstem CT perfusion was not diagnostically accurate. Qualitative whole-brain CT perfusion yielded a sensitivity of 93.6% (95% CI, 89.3%-96.6%) and a specificity of 92.3% (95% CI, 84.0%-97.1%). CT angiography sensitivity ranged from 75.5% (95% CI, 69.0%-81.2%) to 87.3% (95% CI, 81.9%-91.5%), and its specificity ranged from 89.7% (95% CI, 80.8%-95.5%) to 91.0% (95% CI, 82.4%-96.3%). Interrater reliability was excellent for all ancillary tests (κ ranged from 0.81 [95% CI, 0.73-0.89] to 0.84 [95% CI, 0.78-0.91]). Fourteen patients (5%) experienced minor, self-limited adverse events; no serious adverse events occurred.

The observed sensitivity and specificity measures for CT perfusion and CT angiography as an ancillary test for DNC did not meet the prespecified validation threshold of greater than 98%. Clinical examination remains the cornerstone of DNC, and ancillary imaging should be interpreted cautiously within a comprehensive clinical assessment.