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 the same time, maximizing the amount of information
used for model parameter estimation, in order to quantify the levels of these compounds.
Fitting also allows estimation of the levels of total choline (tCho), myo-inositol
(Ins), glutamate (Glu), and glutamine (Gln). Quantitative HERCULES results were compared
between two grey- and white-matter-rich brain regions (11 min acquisition time each)
in 10 healthy volunteers. Coefficients of variation (CV) of quantified measurements
from the HERCULES fitting approach were compared against those from a single-spectrum
fitting approach, and against estimates from short-TE PRESS data. HERCULES successfully
segregates overlapping resonances into separate Hadamard combinations, allowing for
the estimation of levels of seven coupled metabolites that would usually require a
single 11-min editing experiment each. Metabolite levels and CVs agree well with published
values. CVs of quantified measurements from the multiplexed HERCULES fitting approach
outperform single-spectrum fitting and short-TE PRESS for most of the edited metabolites,
performing only slightly to moderately worse than the fitting method that gives the
lowest CVs for tCho, NAA, NAAG, and Asp. HERCULES is a new experimental approach with
the potential for simultaneous editing and multiplexed fitting of up to seven coupled
low-concentration and six high- concentration metabolites within a single 11-min acquisition
at 3T.