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To demonstrate the framework of a novel Hadamard-encoded spectral editing approach for simultaneously detecting multiple low-concentration brain metabolites in vivo at 3T.

HERCULES (Hadamard Editing Resolves Chemicals Using Linear-combination Estimation of Spectra) is a four-step Hadamard-encoded editing scheme. 20-ms editing pulses are applied at: (A) 4.58 and 1.9 ppm; (B) 4.18 and 1.9 ppm; (C) 4.58 ppm; and (D) 4.18 ppm. Edited signals from γ-aminobutyric acid (GABA), glutathione (GSH), ascorbate (Asc), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), aspartate (Asp), lactate (Lac), and likely 2-hydroxyglutarate (2-HG) are separated with reduced signal overlap into distinct Hadamard combinations: (A+B+C+D); (A+B–C–D); and (A–B+C–D). HERCULES uses a novel multiplexed linear-combination modeling approach, fitting all three Hadamard combinations at …