Lang et al. conducted an observational sub-study within the TTM2 trial assessing CT signs of hypoxic–ischaemic encephalopathy (HIE) after cardiac arrest. The sample included 140 comatose patients imaged 48 hrs- 7 days post cardiac arrest. All patients underwent non-contrast CT imaging independently assessed by five radiologists. The analysis focused on established radiological markers of hypoxic–ischaemic encephalopathy (HIE). Markers assessed included loss of grey–white matter distinction at three anatomical levels, sulcal effacement at four levels, as well as the pseudo-subarachnoid haemorrhage sign, the white cerebellum sign, and the reversal sign. The primary objective of the study was to evaluate the prognostic accuracy of these features in predicting poor 6-month neurological outcomes (mRS 4-6). All evaluated signs were highly specific for poor neurological function outcome, but showed variable sensitivity. Loss of grey–white matter distinction emerged as the most reliable marker, with 100% specificity, approximately 50% sensitivity, and the highest interrater agreement. On the other hand, the pseudo-subarachnoid hemorrhage sign, the reversal sign, and the white cerebellum sign, while highly specific, were limited by very low sensitivity and weaker reproducibility. Sulcal effacement had moderate sensitivity but had false-positives particularly in younger patients, and should be used cautiously as a prognostic tool. Overall, the study concludes that loss of grey–white matter distinction should constitute a key radiological feature in post–cardiac arrest CT evaluation, given its strong association with poor neurological outcomes. The study also highlights the need for improved standardization of CT assessment and suggests that advanced imaging technologies and repeat or comparative imaging may enhance sensitivity and prognostic accuracy in the future.