Multimodal MR Imaging Reveals the Mechanisms of Post-Cardiac-Arrest Brain edema: Ferroptosis-Mediated BBB Disruption and AQP4 Dysfunction.

BACKGROUND: The role of ferroptosis in Cardiac arrest (CA)-induced cerebral edema remains unclear. PURPOSE: To investigate whether ferroptosis contributes to blood-brain barrier (BBB) disruption and aquaporin-4 (AQP4) dysfunction following CA. STUDY TYPE: Prospective. ANIMAL MODEL: Asphyxia-induced CA rat model. Forty two rats were used and assigned to the CA (24) and the sham (18) group. FIELD STRENGTH/SEQUENCE: T2-weighted anatomical imaging with 2D turbo spin-echo sequence, QSM with 3D GRE sequence, IVIM with 2D RESOLVE EPI sequence, ASSESSMENT: Multiparametric MRI was performed 24 h after return of spontaneous circulation (ROSC). Imaging findings were validated using histology, immunohistochemistry, Western blot, and transmission electron microscopy. STATISTICAL TESTS: Unpaired two-tailed Student's T-test was used. A p value less than 0.05 was considered statistically significant. RESULTS: CA led to marked neurological deficits, although no obvious abnormalities were observed on T DATA CONCLUSION: This study provides evidence for a sequential cascade after CA and ROSC in which iron overload is associated with ferroptosis, which is linked to disruption of the blood-brain barrier. This barrier disruption coincides with AQP4 depolarization, inducing cytotoxic and vasogenic edema, which, along with depolarization, is accompanied by neuronal death. Multimodal MRI noninvasively captures this process, offering an early detection and monitoring platform for ferroptosis-related brain injury and underscoring its potential as a translational tool for neuroprotective interventions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 1. Cardiac arrest often causes brain damage due to fluid accumulation and cell death, but early changes are hard to detect with standard imaging. This study used advanced MRI techniques to examine rat brains 24 h after circulation recovery. The researchers found that iron buildup is associated with a specific type of cell death that correlates with blood–brain barrier damage and altered water channel proteins, causing brain cells to swell. These changes were invisible on routine scans but detectable using specialized imaging. The findings suggest doctors could use these MRI methods to spot brain injury early and develop treatments to protect the brain.