Proton MR spectroscopy of mitochondrial diseases: analysis of brain metabolic abnormalities and their possible diagnostic relevance

Abstract

Background and purpose: Proton (hydrogen-1 [(1)H]) MR spectroscopy is a useful diagnostic tool in many metabolic diseases, but only scattered and inconclusive data are available on mitochondrial diseases. We performed MR imaging and (1)H MR spectroscopy of the brain in patients with different types of primary mitochondrial diseases to investigate the role of (1)H MR spectroscopy in the clinical evaluation of these disorders.

Methods: In 15 patients (11 adults, four children) with mitochondrial diseases, localized MR spectra were obtained at short TEs in cerebellar white matter, paratrigonal white matter, and parieto-occipital cortex that appeared normal on MR images. Additional spectra of basal ganglia and cortical gray matter structural lesions were obtained in three patients.

Results: A significant choline reduction and N-acetylaspartate reduction were found in areas that appeared normal on MR images. Lactate was never found in areas that appeared normal on MR images, except in two children in whom MR studies were performed during episodes of symptom exacerbation and revealed elevated lactate both in areas that appeared damaged on MR images and in normal-appearing areas. An additional abnormal signal at 0.9 ppm was found in a consistent number of studies.

Conclusion: (1)H MR spectroscopy proved to be a useful investigational tool for mitochondrial diseases, as it enabled detection of metabolic abnormalities even in areas of brain that appeared normal on MR images, especially when it was performed during episodes of clinical relapses or clinical exacerbation.

Fig 1.

Patient 14 with Leigh syndrome. A and B, Axial FLAIR images show bilateral and symmetrical hyperintensity of corpora striata. The VOIs used for spectroscopy are also shown. C, Spectrum from the VOI containing the right affected putamen demonstrates resonances at 1.33 and 0.9 ppm coming respectively from lactate (Lac) and lipids or branched amino-acids (Lip/aa). D, Abnormally high brain lactate (Lac) is also revealed in the spectrum from the VOI located in paraventricular white matter that appeared normal on the MR image. Cho indicates choline; Cr, creatine.

Fig 2.

Patient 15 with MELAS. A and B, Axial FLAIR images demonstrate multiple cortical strokelike lesions, the largest of which was located along the parieto-occipital cortex (not shown). Tiny frontal and parietal cortical hyperintensities and the VOIs used for spectroscopy are visible. C and D, Spectra reveal high lactate (Lac) and the 0.9 ppm signal (Lip/aa) not only into the damaged cortex (C) but also into the normal-appearing parietal cortex (D). A significant decrease of NAA may also be appreciated in the spectrum in C. Cho indicates choline; Cr, creatine.

Fig 3.

A–C, Single-voxel proton spectra from a normal-appearing cerebellar volume (A, patient 12), a normal-appearing parieto-occipital white matter volume (B, patient 3), and a normal-appearing parieto-occipital cortex (C, patient 1). Spectra reveal a significant decrease of choline (Cho) and the presence of a low amplitude signal at 0.9 ppm (Lip/aa) in each anatomic location. NAA is decreased in cerebellar (A) and parieto-occipital cortex (C) locations. Cr indicates creatine.

Fig 4.

A–C, Plots of the metabolite ratios reported in Table 3 for cerebellum (A), white matter (B), and parieto-occipital cortex (C). Vertical bars are the range of each ratio in 15 control subjects. mI indicates myo-inositol; Cho, choline; Lac, lactate