Assessing neuronal metabolism in vivo by modeling imaging measures

Abstract

Mitochondrial dysfunction contributes to the pathogenesis of many neurological diseases, including multiple sclerosis (MS), but is not directly measurable in vivo. We modeled N-acetyl-aspartate (NAA), which reflects axonal structural integrity and mitochondrial metabolism, with imaging measures of axonal structural integrity (axial diffusivity and cord cross-sectional area) to extract its mitochondrial metabolic contribution. Lower residual variance in NAA, reflecting reduced mitochondrial metabolism, was associated with greater clinical disability in MS, independent of structural damage.

Figure 1.

Imaging neuronal metabolism in vivo. a, Sagittal T2 image of a patient 6 months after an acute spinal cord relapse due to the two lesions between C1 and C3 (yellow circles). b, Spectroscopic volume of interest between C1 and C3 on the coronal image. c, Regions of interest located in the white matter columns on the axial diffusivity maps. d, FSPGR image at C2–C3 with the regions of interest contoured around the cord. e, Spectrum obtained by the LCModel analysis of the volume of interest shown in b. The NAA concentration was 3.94 mm/L (percentage SD = 11).

Figure 2.

Relationship between the residual variance in NAA concentration after taking into account structural imaging measures and clinical scores. a, Scatter plot of ResNAA versus EDSS (R² = 0.5) with a fitted line. b, Scatter plot of ResNAA versus TWT (R² = 0.42). c, Scatter plot of ResNAA versus MSWS12 (R² = 0.4).