Etiology-specific prognostic value of ultra-early diffusion-weighted MRI after out-of-hospital cardiac arrest: a multicenter cohort study

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) within 0–6 h after return of spontaneous circulation can detect hypoxic-ischemic brain injury following out-of-hospital cardiac arrest (OHCA). Whether ultra-early findings differ by arrest etiology and how they should guide prognostication remains uncertain. METHODS: We conducted a multicenter retrospective cohort study of OHCA survivors who underwent ultra-early DW-MRI (0–6 h); a subset had follow-up scans (72–96 h). Etiology was classified as cardiac or respiratory. We assessed the prognostic performance of qualitative ultra-early high-signal-intensity (HSI) and quantitative ADC-R(650) (% brain voxels with ADC ≤ 650 × 10⁻⁶ mm²/s) using receiver operating characteristic analysis to estimate the area under the curve (AUC) and sensitivity at 100% specificity. Qualitative HSI was based on routine clinical readings, with readers blinded to clinical outcomes and other clinical information. The primary outcome was poor neurological outcome at 6 months (CPC 3–5). RESULTS: Among 176 patients (77 cardiac, 99 respiratory), 94 (53.4%) had poor outcomes. Ultra-early HSI occurred exclusively in patients with poor outcomes, yielding 100% specificity in both etiologies. At 100% specificity, sensitivity was significantly lower for respiratory etiology (52% vs. 86%; P = 0.006). Ultra-early HSI predicted poor outcome (AUC 0.80), with higher discrimination in the cardiac etiology subgroup (0.93 vs. 0.76; P < 0.001). In contrast, ultra-early ADC-R(650) showed modest prognostic value (AUC 0.77), but with similar discrimination between cardiac and respiratory etiology subgroups (0.80 vs. 0.77; P = 0.71). In the follow-up subset (n = 150), HSI demonstrated high discrimination for poor outcome (AUC 0.93) with no difference in AUC between cardiac and respiratory etiologies (0.96 vs. 0.95; P = 0.57). At this later time point, ADC-R(650) demonstrated high prognostic performance (AUC 0.91), with comparable results across etiologies (0.89 vs. 0.93; P = 0.47). CONCLUSIONS: HSI on ultra-early DW-MRI is specific for poor outcome after OHCA, but sensitivity is lower in respiratory etiology. DW-MRI at 72–96 h provides prognostic performance independent of etiology. Following OHCA, ultra-early HSI may help phenotype patients, particularly those with cardiac etiology, supporting an etiology-aware staged approach to DW-MRI–based prognostication. Further validation is warranted to explain delayed diffusion restriction in respiratory etiology.