Faculty Bibliography

PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were 'stable,' exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed 'moderate' decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced 'rapid' decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION: Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status

BACKGROUND AND PURPOSE: The T2-weighted MR imaging total lesion volume and Expanded Disability Status Scale (EDSS) score are two common measures of relapsing-remitting multiple sclerosis disability and pathologic abnormality. Because the whole-brain N-acetylaspartate concentration is considered to be a new marker of the disease burden, the purpose of this study was to evaluate the relationship among these three measures. METHODS: The whole-brain N-acetylaspartate concentration and T2-weighted lesion volume were quantified by using MR imaging and proton MR spectroscopy in 49 patients with relapsing-remitting multiple sclerosis (36 female and 13 male patients; average age, 39 years; age range, 24-55 years; average EDSS score, 2; range of EDSS scores, 0-6). Correlations among whole-brain N-acetylaspartate concentrations, T2-weighted lesion volumes, and EDSS scores were obtained. RESULTS: No correlation was found between whole-brain N-acetylaspartate levels and either T2-weighted lesion volumes or EDSS scores. A weak correlation was found between the EDSS scores and T2-weighted lesion volumes (P =.043, r(s) = 0.292). CONCLUSION: Despite the lack of correlation between whole-brain N-acetylaspartate concentration and the clinical disability reflected in the EDSS score, only the former evaluates the global neuronal cell disease in the entire brain, including those lesions that are occult to conventional imaging techniques

The inter- and intrasubject reproducibility of the metabolite levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), obtained with three-dimensional (3D) multivoxel proton spectroscopy (1H-MRS), was analyzed in eight healthy volunteers. Serial, back-to-back measurements on a phantom showed the methodology and instrumentation to be highly reproducible, with a median coefficient of variation (CV) of 3.8%. In the human brain, the metabolite levels' variability was larger, with intrasubject median CVs for a total of 1876 signal voxels of 13.8%, 18.5%, and 20.1% for NAA, Cr, and Cho, respectively. These variations possibly arise from small, unavoidable, +/-1-2 mm volume-of-interest (VOI) repositioning uncertainties, which vary each 0.75-cm(3) voxel's partial fluid/gray/white-matter fractions. Comparing the CVs between eight subjects in a total of 324 selected voxels gave total interindividual CVs of 15.6%, 23.3%, and 24.4%, compared with intraindividual CVs in the same voxels of 14.4%, 14.8%, and 15.3%, for NAA, Cr, and Cho, respectively. Replacing the signal(s) from each voxel by the average of itself with its six canonical neighbors reduces the intrasubject median CVs to 8.3%, 9.5%, and 9.7%. The measurement uncertainties can be reduced at a cost of either spatial resolution (by using larger voxels) or time (by performing serial follow-ups)