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Multicenter Study
. 2025 Sep 1;82(9):932-940.
doi: 10.1001/jamaneurol.2025.2375.

Computed Tomography Perfusion and Angiography for Death by Neurologic Criteria

Michaël Chassé  1   2   3 , Jai Jai Shiva Shankar  4   5 , Dean A Fergusson  6   7 , Shane W English  8   9   10 , Sonny Dhanani  11 , François Lauzier  12   13   14 , Alexis F Turgeon  12   13 , Ian Ball  15   16 , Sultan Darvesh  17   18 , Joel Neves Briard  1   2   19 , Marco Essig  4   5 , David Boucher-Roy  2 , Polina Titova  2 , Martine Lebrasseur  2 , Philippe Couillard  20   21 , Andreas Kramer  20   21   22 , Frédérick D'Aragon  23   24 , Mathew Hannouche  25 , Donatella Tampieri  26 , Maureen O Meade  27 , Bijoy K Menon  21   28   29 , Robert Green  30   31   32   33 , Andrew J Baker  34 , Karen E A Burns  34 , Ryan Zarychanski  35   36   37 , Jason Shahin  38 , J Gordon Boyd  39   40 , Alexandra Binnie  41 , Andrew Gibson  41 , Han Ting Wang  1   2   42 , Sam Shemie  43 ; INDex InvestigatorsCanadian Critical Care Trials Group
Collaborators, Affiliations
Multicenter Study

Computed Tomography Perfusion and Angiography for Death by Neurologic Criteria

Michaël Chassé et al. JAMA Neurol. .

Abstract

Importance: 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.

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

Design, setting, and participants: 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.

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

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Chassé reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr Shankar reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study; and receiving grants from Medtronic Canada outside the submitted work. Dr English reported receiving grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study. Dr Dhanani reported receiving personal fees from Ontario Health and having a patent issued for the Donation Advisor decision support tool outside the submitted work. Dr Darvesh reported receiving grants from the Canadian Institutes of Health Research and the Nova Scotia Health Research Foundation during the conduct of the study; and receiving intellectual property costs and in-kind funding from Treventis Corporation for the Sultan Darvesh diagnostic patent estate, having European patent 2320891, US patent 8,795,630, Japanese patent 5734853, Canadian patent 2735118, and Israel patent 211347 issued, having a patent pending for butyrylcholinesterase compounds and methods of use in diseases of the nervous system (assigned to Treventis Corporation), having US utility patent application 17/592,942 filed, having a patent for The Behavioural Neurology Assessment issued, being a cofounder and shareholder of Treventis Corporation, and being an associate editor of Current Alzheimer Research outside the submitted work. Ms Titova reported receiving personal fees from the Centre de Recherche du Centre Hospitalier de l’Université de Montréal during the conduct of the study. Dr Boyd reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study; and receiving nonfinancial support from Edwards LifeSciences and a stipend from Ontario Health–Trillium Gift of Life Network outside the submitted work. Dr Shemie reported serving as a medical advisor for Canadian Blood Services outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
GCS indicates Glasgow Coma Scale; IV, intravenous. aThe reasons for these exclusions are not mutually exclusive.
Figure 2.
Figure 2.. Sensitivity and Specificity of Computed Tomography (CT) Perfusion and of CT Angiography for Death by Neurologic Criteria
See this image and copyright information in PMC

References

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