Background Methylmalonic acid (MMA) accumulates due to mitochondrial dysfunction or enzymatic deficiencies. Methylmalonic acidemia causes central nervous system damage. In vivo detection of MMA using conventional proton (1H) MR spectroscopy is hindered by overlap with lactate and lipids at 1.33 ppm. Purpose To evaluate the feasibility of an optimized J-editing 1H MR spectroscopy protocol to selectively detect MMA and lactate signals in both phantoms and individuals with methylmalonic acidemia. Materials and Methods In this prospective pediatric case-control study, individuals with genetically confirmed methylmalonic acidemia and age-matched control participants underwent brain J-editing 1H MR spectroscopy. The primary endpoint was the feasibility of selective in vivo detection of cerebral MMA using J-editing 1H MR spectroscopy. Phantoms were prepared with different MMA to lactate ratios. Correlations between cerebral MMA signals and biochemical markers (blood propionylcarnitine to acetylcarnitine C3/C2 ratio and urinary MMA levels) were assessed using Spearman correlation in individuals diagnosed with methylmalonic acidemia. The diagnostic performance of MR spectroscopy and urinary MMA measurement was evaluated against genetic confirmation with use of sensitivity, specificity, and receiver operating characteristic curves. Results A total of 42 participants were included: 24 with methylmalonic acidemia (mean age, 8.7 years ± 5.2 SD) and 18 control participants (mean age, 8.9 years ± 4.0 SD). The J-editing 1H MR spectroscopy protocol effectively separated MMA and lactate signals in the brains of individuals with methylmalonic acidemia, consistent with phantom results. No abnormal MMA peaks were observed in control participants. The intensity of cerebral MMA signals correlated with blood C3/C2 ratio (Spearman ρ = 0.53 95% CI: 0.15, 0.78; P = .008) and urinary MMA levels (ρ = 0.66 95% CI: 0.33, 0.84; P 1H MR spectroscopy reliably and noninvasively detected cerebral MMA in vivo, distinguishing it from overlapping lactate signals. © RSNA, 2026 Supplemental material is available for this article.
Zhuo et al. (Sun,) studied this question.