Oxidative stress measured in vivo without an exogenous contrast agent using QUEST MRI

Decades of experimental studies have implicated excessive generation of reactive oxygen species (ROS) in the decline of tissue function during normal aging, and as a pathogenic factor in a vast array of fatal or debilitating morbidities. This massive body of work has important clinical implications since many antioxidants are FDA approved, readily cross blood-tissue barriers, and are effective at improving disease outcomes. Yet, the potential benefits of antioxidants have remained largely unrealized in patients because conventional methods cannot determine the dose, timing, and drug combinations to be used in clinical trials to localize and decrease oxidative stress. To address this major problem and improve translational success, new methods are urgently needed that non-invasively measure the same ROS biomarker both in animal models and patients with high spatial resolution. Here, we summarize a transformative solution based on a novel method: QUEnch-assiSTed MRI (QUEST MRI). The QUEST MRI index is a significant antioxidant-induced improvement in pathophysiology, or a reduction in 1/T1 (i.e., R1). The latter form of QUEST MRI provides a unique measure of uncontrolled production of endogenous, paramagnetic reactive oxygen species (ROS). QUEST MRI results to-date have been validated by gold standard oxidative stress assays. QUEST MRI has high translational potential because it does not use an exogenous contrast agent and requires only standard MRI equipment. Summarizing, QUEST MRI is a powerful non-invasive approach with unprecedented potential for (i) bridging antioxidant treatment in animal models and patients, (ii) identifying tissue subregions exhibiting oxidative stress, and (iii) coupling oxidative stress localization with behavioral dysfunction, disease pathology, and genetic vulnerabilities to serve as a marker of susceptibility.