Neuroimaging in mitochondrial disorders

Essays Biochem. 2018 Jul 20;62(3):409-421. doi: 10.1042/EBC20170109. Print 2018 Jul 20.

Abstract

MRI and 1H magnetic resonance spectroscopy (1HMRS) are the main neuroimaging methods to study mitochondrial diseases. MRI can demonstrate seven 'elementary' central nervous system (CNS) abnormalities in these disorders, including diffuse cerebellar atrophy, cerebral atrophy, symmetric signal changes in subcortical structures (basal ganglia, brainstem, cerebellum), asymmetric signal changes in the cerebral cortex and subcortical white matter, leukoencephalopathy, and symmetric signal changes in the optic nerve and the spinal cord. These elementary MRI abnormalities can be variably combined in the single patient, often beyond what can be expected based on the classically known clinical-pathological patterns. However, a normal brain MRI is also possible. 1HMRS has a diagnostic role in patients with suspected mitochondrial encephalopathy, especially in the acute phase, as it can detect within the lesions, but also in normal appearing nervous tissue or in the ventricular cerebrospinal fluid (CSF), an abnormally prominent lactate peak, reflecting failure of the respiratory chain with a shift from the Krebs cycle to anaerobic glycolysis. So far, studies correlating MRI findings with genotype in mitochondrial disease have been possible only in small samples and would greatly benefit from data pooling. MRI and 1HMRS have provided important information on the pathophysiology of CNS damage in mitochondrial diseases by enabling in vivo non-invasive assessment of tissue abnormalities, the associated changes of blood perfusion and cellular metabolic derangement. MRI and 1HMRS are expected to serve as surrogate biomarkers in trials investigating therapeutic options in mitochondrial disease.

Keywords: NMR spectroscopy; mitochondrial dysfunction; neuroimaging.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / diagnostic imaging
  • Brain / pathology
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Spectroscopy / methods*
  • Mitochondrial Diseases / cerebrospinal fluid
  • Mitochondrial Diseases / diagnostic imaging*
  • Mitochondrial Diseases / pathology
  • Neuroimaging / methods*
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / pathology