Assessment of Structural Brain Changes Related to Anoxic Coma Using High-field (3T) and Very Low-field (0.064T) Mobile MRI - CUBE

About two-thirds of patients who are in coma after resuscitation from cardiac arrest (CA) die before hospital discharge, of whom two-thirds die from neurological injury. However, only a minority of these deaths occur as a direct consequence of major brain injury. Actually, most of the deaths caused by CA-related hypoxic-ischemic brain injury result from withdrawal of life-sustaining treatments (WLST) following prognostication of a poor neurological outcome. Indeed, a timely, robust and generalizable neuroprognostication after CA appears to be essential to provide patient's family and caregivers with critical information to avoid both inappropriate WLST or prolonged treatment of patients with no chance of neurologically meaningful survival.

Many studies have investigated clinical examination, serum biomarkers, electrophysiological investigations, and neuroimaging test to predict neurological outcome after CA. Most of these tests have substantial limitation in terms of reliability, because many of them are based on low-certainty evidence due to their retrospective design, low power, potential bias (self-fulfilling prophecy) and confounders (sedation). For these reasons, to reduce prediction uncertainty, current guidelines recommend using a combination of predictors. Moreover, the optimal multimodal predictive strategy has yet to be defined and be prospectively validated and growing evidence suggest that these strategies can be applied only to a minority of patients.

In anoxic coma, prognostication is crucial in informing patient's relatives and to help clinicians to target treatments based on the patient's chances of achieving neurologically meaningful recovery. Currently, there is an urgent need for early, accurate and generalizable outcome predictors for these patients.

Although the exact brain neuronal structures subtending arousal and awareness are not yet perfectly delineated, some key subcortical and cortical regions have now been identified within an anterior forebrain 'meso-circuit' (comprising the reticular activating system, the striato-pallidal structures, the thalamus and associative cortical areas) and the 'frontoparietal' network. Accumulating evidence suggests that the common pathophysiological mechanism underlying coma is a broad withdrawal of excitatory synaptic activity within both these networks. Accordingly, the structural integrity of anterior forebrain 'mesocircuit' and the 'frontoparietal' networks have been consistently related to severity of chronic disorders of consciousness (vegetative state/unresponsive wakefulness syndrome - VS/UWS - and minimally conscious state/cortically mediated syndrome - MCS/CMS) and the potential of recovery from coma.

Overall, neurological recovery from coma is now conceptualized as being contingent upon the re-emergence of dynamic interaction between anterior forebrain 'mesocircuit' and 'frontoparietal' networks. Theoretically, assessing the structural integrity within these critical networks, hold the promise of providing innovative, powerful and mechanistic predictors of consciousness recovery after CA.