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

Abstract

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, development of atherosclerosis and 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-Mg2+ ATP signals in MOGAD were detected mostly in the white matter regions, which may suggest Mg2+ deficiency in oligodendrocytes, which are primarily responsible for maintenance and generation of the axonal myelin sheath. This preliminary study demonstrates the utility of the 7T 3D 31P MSRI for revealing altered energy metabolism with reduced Mg availability at a normal ATP level. The potential correlation between [Mg2+] and disease progression over time should be assessed in larger cohorts.