Detection Accuracy of Ischemia and Neuroinflammation in Traumatic Brain Injury in Rats Using Amide Proton Transfer‐Weighted MRI

ABSTRACT Ischemia and neuroinflammation are two key secondary injury events following traumatic brain injuries (TBIs), but they are difficult to assess in vivo. Early detection of these secondary injuries post‐TBI allows for precise severity assessment and enables timely, targeted interventions to reduce adverse outcomes. This study aimed to quantify the diagnostic accuracy of amide proton transfer‐weighted (APTw) imaging to detect these two post‐TBI endophenotypes. Controlled cortical impact (CCI) at depths of 1 mm (mild), 3 mm (moderate), and 5 mm (severe) was induced in 55 adult rats (28 males, 27 females), followed by 4.7 T MRI scanning (at 1 h, 1, 3, 7, 14, and 28 days). T 2 , T 1 , apparent diffusion coefficient, cerebral blood flow, APTw, and magnetization transfer ratio values in the perilesional cortex were analyzed. The area under the receiver operating curve (AUC) was calculated to assess the ability of these MRI signals to identify ischemia and neuroinflammation. At 1 h post‐injury, perilesional cortical APTw signals decreased due to ischemia. APTw hypointensities used to identify ischemia had medium to large effect sizes of −0.620, −0.931, and −0.516 for mild, moderate, and severe TBI, respectively. At 3 days post‐injury, perilesional cortical APTw signals increased due to neuroinflammation. APTw hyperintensities used to identify neuroinflammation had effect sizes of 0.247, 2.099, and 2.830 for mild, moderate, and severe TBI, respectively, superior to all other MRI parameters (APTw AUC = 0.950). APTw imaging shows promise for the detection of ischemia and neuroinflammation at an early stage post‐CCI.