Two Pools of ATP Detected in the Brains of Pediatric Patients with Myelin Oligodendrocyte Glycoprotein Antibody Disorders (MOGAD) by 3D 31P MR Spectroscopic Imaging (MRSI) at 7T

Over the past four decades, ATP, the obligatory energy molecule for keeping all cells alive and functioning, was thought to contribute only one set of 31P MR signals in the human brain. Here we report for the first time the simultaneous detection of two pools of ATP in the human brain by high-resolution 3D 31P MRSI at ultrahigh field 7T. These two ATP pools differ in cytosolic Mg2+ concentration (1:0.5 ratio), with a resonance separation of 0.5 ppm at {beta}-ATP, a well-established imaging marker of intracellular Mg2+ concentration. Mg2+ is a cofactor of ATPase and its deficiency is associated with immune dysfunction, free radical damage, perturbations in Ca2+ homeostasis, and development of atherosclerosis, dyslipidemia and a number of neurological disorders, such as cerebral vasospasm, stroke, migraine, Alzheimers disease, and Parkinsons disease. Our study documents reduced Mg levels in the brain of patients with myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), which is an idiopathic, inflammatory, demyelinating condition of the central nervous system (CNS) more common in pediatric patients. Low-Mg2+ ATP signals were detected mostly in the white matter regions in MOGAD, suggesting an association between Mg2+ deficiency and compromised functions of oligodendrocytes in maintenance and generation of the axonal myelin sheath. This preliminary study demonstrates the utility of the 7T 3D 31P MSRI for probing altered energy metabolism at reduced availability of Mg2+ rather than ATP itself. The potential correlation between [Mg2+] and disease progression over time should be assessed in larger cohorts. Author ApprovalYes