Methylmalonic acid: a new target for Hadamard-edited MRS

Area of Science:

• Biomedical Engineering
• Metabolic Disorders
• Magnetic Resonance Imaging

Background:

• Methylmalonic acidemia (MMAemia) is a genetic disorder causing methylmalonic acid (MMA) buildup and impaired energy metabolism, leading to increased lactate (Lac).
• Conventional magnetic resonance spectroscopy (MRS) struggles to differentiate overlapping MMA and Lac signals, hindering accurate diagnosis and treatment monitoring.
• Developing an MRS method to distinguish MMA and Lac is crucial for understanding MMAemia pathophysiology.

Purpose of the Study:

• To develop a Hadamard-encoded J-difference editing MRS approach for independent detection of MMA and Lac at 3 Tesla.
• To overcome the spectral overlap challenge between MMA and Lac signals in MRS.

Main Methods:

• A novel four-step Hadamard-encoded editing scheme was implemented and validated using density-matrix simulations, phantom studies, and in vivo experiments.
• Frequency-selective editing pulses at 3.2 ppm and 4.1 ppm were used to modulate the J-coupled methyl resonances of MMA and Lac.
• Hadamard combinations of sub-experiments generated separate difference-edited spectra for MMA and Lac.

Main Results:

• Simulations and phantom experiments successfully demonstrated the separated signals of MMA and Lac.
• In vivo studies showed a Lac signal in a healthy infant, but no MMA signal.
• In a patient with MMAemia, both Lac and MMA signals were detected and separated into their respective Hadamard-combination spectra.

Conclusions:

• Hadamard-encoded MRS at 3T can effectively separate MMA and Lac signals.
• This technique shows significant promise for studying altered metabolism in patients with MMAemia.
• The developed MRS method could improve diagnostic accuracy and treatment monitoring for MMAemia.