Background: Methylmalonic acidemia (MMAemia) is a genetic metabolic disorder characterized by an accumulation of methylmalonic acid (MMA) and impaired energy metabolism leading to increased lactate (Lac). The signals of MMA (1.23 ppm) and Lac (1.33 ppm) overlap, making their separation using conventional MRS challenging. An MRS method to differentiate the two metabolites could enhance pathophysiological understanding and improve treatment monitoring - Hadamard-edited MRS has the potential to achieve this. Purpose: To develop a Hadamard-encoded J-difference editing approach for independent detection of MMA and Lac at 3T. Methods: A novel Hadamard-encoded editing scheme was implemented and evaluated with density-matrix simulations, phantom and in vivo experiments. The new four-step scheme uses frequency-selective editing pulses, applied at 3.2 ppm and 4.1 ppm to modulate the J-coupled methyl resonances of MMA and Lac, respectively. Hadamard combinations of the four sub-experiments yield the separate difference-edited spectra for each target metabolite. Results: Simulations and phantom experiments clearly illustrate the separated signals of MMA and Lac. In vivo validation experiments show a Lac signal (but no MMA) in a healthy infant, and both Lac and MMA (separated into their respective Hadamard-combination spectra) in a patient with MMAemia. Conclusion: Hadamard-encoded editing at 3T can separate MMA and Lac signals and shows promise for studying altered metabolism in patients with MMAemia.
Song, y., Gong, T., Shams, Z., Sun, X., Davies-Jenkins, C. W., Wang, S., Simegn, G. L., Murali-Manohar, S., Gad, A., Oeltzschner, G., Wang, G., Edden, R. A. E.
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