Two Pools of ATP Detected in the Brains of Pediatric Patients with Myelin Oligodendrocyte Glycoprotein Antibody Disorders (MOGAD) by 3D31P 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 31 P 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 31 P MRSI at ultrahigh field 7T. These two ATP pools differ in cytosolic Mg 2+ concentration (1:0.5 ratio), with a resonance separation of 0.5 ppm at β-ATP, a well-established imaging marker of intracellular Mg 2+ concentration. Mg 2+ is a cofactor of ATPase and its deficiency is associated with immune dysfunction, free radical damage, perturbations in Ca 2+ homeostasis, and development of atherosclerosis, dyslipidemia and a number of neurological disorders, such as cerebral vasospasm, stroke, migraine, Alzheimer’s disease, and Parkinson’s 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-Mg 2+ ATP signals were detected mostly in the white matter regions in MOGAD, suggesting an association between Mg 2+ 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 31 P MSRI for probing altered energy metabolism at reduced availability of Mg 2+ rather than ATP itself. The potential correlation between [Mg 2+ ] and disease progression over time should be assessed in larger cohorts. Author Approval Yes