Automated whole-brain N-acetylaspartate proton MRS quantification

Concentration of the neuronal marker, N-acetylaspartate (NAA), a quantitative metric for the health and density of neurons, is currently obtained by integration of the manually defined peak in whole-head proton (¹H)-MRS. Our goal was to develop a full spectral modeling approach for the automatic estimation of the whole-brain NAA concentration (WBNAA) and to compare the performance of this approach with a manual frequency-range peak integration approach previously employed. MRI and whole-head ¹H-MRS from 18 healthy young adults were examined. Non-localized, whole-head ¹H-MRS obtained at 3T yielded the NAA peak area through both manually defined frequency-range integration and the new, full spectral simulation. The NAA peak area was converted into an absolute amount with phantom replacement and normalized for brain volume (segmented from T₁-weighted MRI) to yield WBNAA. A paired-sample t test was used to compare the means of the WBNAA paradigms and a likelihood ratio test used to compare their coefficients of variation. While the between-subject WBNAA means were nearly identical (12.8±2.5mm for integration, 12.8±1.4mm for spectral modeling), the latter's standard deviation was significantly smaller (by ~50%, p=0.026). The within-subject variability was 11.7% (±1.3mm) for integration versus 7.0% (±0.8mm) for spectral modeling, i.e., a 40% improvement. The (quantifiable) quality of the modeling approach was high, as reflected by Cramer-Rao lower bounds below 0.1% and vanishingly small (experimental - fitted) residuals. Modeling of the whole-head ¹H-MRS increases WBNAA quantification reliability by reducing its variability, its susceptibility to operator bias and baseline roll, and by providing quality-control feedback. Together, these enhance the usefulness of the technique for monitoring the diffuse progression and treatment response of neurological disorders.