A Call for Pediatric Magnetic Resonance Spectroscopy Harmonization in Neurometabolic Disorders with a Simple Approach for Diagnosis, Treatment Monitoring and Data Aggregation for Clinical Trials.

Abstract

There is a pressing demand to implement a standard acquisition and post-processing approach for proton magnetic resonance spectroscopy performed in children within the clinical setting. Clinical magnetic resonance spectroscopy data is needed to characterize and understand phenotypes and track treatment response, especially in rare genetic disorders with distinct metabolite signatures. For instance, infants and children with cerebral creatine deficiency syndromes are too often misdiagnosed, which leads to delay in life-changing supplementation especially for those with synthesis deficiencies. Quantitative information about brain creatine concentrations is useful in characterizing these syndromes, potentially tracking relevant biomarkers in relation to treatment response, and guiding future clinical trial designs for patients. Spectroscopists began discussions about the usage of magnetic resonance spectroscopy in late 2024 with the leadership of the Association for Creatine Deficiencies (ACD). The ACD is a charitable organization established by parents of children with creatine deficiencies to provide patient, family, and public education, to advocate for early intervention through newborn screening, and to promote and fund medical research for treatments and cures for Cerebral Creatine Deficiency Syndromes. The ACD hosts a patient registry where families complete surveys and upload medical reports. Upon review of radiologist reports, the group noted the variability in acquisition, post-processing and interpretation across patient studies and clinical imaging sites. A team of spectroscopists reviewed the literature, identified common parameters across vendors and developed a harmonized approach that can serve as a starting point for imaging sites adopting magnetic resonance spectroscopy or a supplement to those already using it. This paper is a call for the usage and provides a recommendation of a minimum standard single voxel proton magnetic resonance spectroscopy approach that can be implemented for rapidly evaluating pediatric patients with neurodevelopmental delays consistent with genetic etiologies.