MR Imaging of Neurometabolic Disorders

Dr Madhuri Behari, Director & HOD – Neurosurgery, Fortis Flt Lt Rajan Dhall Hospital, Vasant Kunj, shares insights on the potential of MRI as a strong tool for diagnosis of neurometabolic disorders

Dr Madhuri Behari

The potential of magnetic resonance imaging (MRI), functional MRI (fMRI) and magnetic resonance spectroscopy (MRS) to detect changes in brain metabolism and activation of specific brain areas during activities and presence of altered metabolic products under both physiological and pathological conditions is used to study/detect diseased state and to understand brain functioning in disease and in health.

MRI studies are done using transverse plane (T1) and longitudinal plane (T2) relaxation modes in which the time taken for the protons or hydrogen molecules to return to longitudinal relaxation when radio frequency waves are applied to T1 or relaxation of spins from transverse plane towards T2. These are very technical terms and better left to the specialists. For most of us, it is important to understand that when a tissue or body is placed in a strong magnetic field, it causes movements of omnipresent hydrogen molecules inside the tissue of a very small magnitude. Once the magnetic field is stopped the hydrogen molecules return to the original position or what is known as relaxation. Time taken to return to relaxed position is different for different tissues and this property is utilised to form images of structures in brain and other organ systems.

Now that we have understood how MRI works, let’s attempt to understand its utility in detecting various metabolic disorders of brain.

Broadly brain disorders can be classified as given below:

  • Vascular
  • Neoplastic
  • Traumatic
  • Demyelinating
  • Metabolic/endocrinologic
  • Infective
  • Deficiency/nutritional
  • Neuro-degenerative
  • Neurotransmitter related (psychiatric)

Having said that, invariably all disorders have metabolic disturbance which is what MRI can detect easily. For e.g. when blood supply in a major artery is interrupted, the main problem is that the lack of blood supply causes infarction of that part of brain supplied by that artery. In addition, there is a cascade of reactions, followed by generation of inflammatory molecules leading to accumulation of acidic byproducts due to an aerobic metabolism. An MRI can detect these changes. In case there is partial blockage of an artery, death of tissue does not ensue. Ischemic changes which result can also be detected. In addition, when there is haemorrhage in the brain due to rupture of a weak blood vessel, blood extravasates into brain and can be visualised easily. However, this accumulated blood undergoes changes over time and can be observed several years thereafter due to presence of heme products. Indeed these can be detected throughout one’s life.

Metabolic disorders

When we speak of metabolic disorders, characteristically we are talking about disorders of metabolism, which are usually genetic and are usually seen in children. These are disorders of carbohydrate metabolism, lipid and amino acid metabolism and some rare disorders in which handling of copper (Wilson’s disease) or iron is impaired (neuro-degeneration with brain iron accumulation – NBIA). Due to accumulation of copper/iron in brain in these disorders, there is neuro degeneration, atrophy, loss of choline (present in neurons) and accumulation of lipids (due to neuronal loss). In all these disorders, the proportional accumulation or loss and location of chemicals help to clinch the diagnosis.

In degenerative disorders/vascular diseases presence of glutamate,
N-acetylaspartate (NAA)/creatine (Cr) ratios were significantly lower in AD patients compared to both MCI and normal control. (MI)/Cr ratios measured from the posterior cingulate VOI were significantly higher in both MCI and AD patients than controls. The choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in AD patients compared to both MCI and control subjects. Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects.

In patients with chronic liver disease causing encephalopathy (encephalopathy is the state where brain is affected and patient may become drowsy/excessive sleepy/ unconscious/comatose), changes are seen in brain, which are different from normal as well as people with hepatic disease but without encephalopathy. The technique of water-suppressed stimulated-echo hydrogen-1 MR spectroscopy for detection of cerebral glutamate, glutamine, glucose, N-acetyl-aspartate, choline metabolites, (phospho) creatine, and myo-inositol shows elevation in cerebral glutamine levels, a 23 per cent reduction in choline metabolite levels, and more than 50 per cent reduction in cerebral myo-inositol levels. In some patients with liver disease but without clinical chronic hepatic encephalopathy, reduction in the myo-inositol level and elevation in the glutamine concentration can be observed. This may indicate that these patients may be on the threshold of developing encephalopathy.


Broadly brain disorders can be classified as given below:

  • Vascular
  • Neoplastic
  • Traumatic
  • Demyelinating
  • Metabolic/ Endocinologic
  • Infective
  • Deficiency/ nutritional
  • Neuro-degerative
  • Neurotransmitter related (psychiatric)

Biotin-responsive basal ganglia disease is an autosomal recessive, treatable underdiagnosed neurometabolic disorder, usually occurring in children and associated with basal ganglia involvement. It should be suspected in paediatric patients with unexplained encephalopathy whose brain MR present sub-acute encephalopathy that can cause death if left untreated. Neuroimaging features of this disorder are also characteristic. Brain MR imaging shows bilateral lesions in the caudate nuclei with complete or partial involvement of the putamen and sparing of the globus pallidus in all cases. 80 per cent cases also show discrete abnormal signals in the mesencephalon, cerebral cortical-subcortical regions, and thalami, whereas 53 per cent of advanced cases show patchy deep white matter involvement. The cerebellum is also affected in13.3 per cent of cases. Signal abnormalities of the mesencephalon, cortex, and white matter usually disappear after treatment whereas the caudate and putamen necrosis remains unchanged.

Depression

Depressive symptoms showed positive covariance with peri-genual, anterior cingulate cortex and amygdalar activity. In contrast,
anxiety was negatively associated with activities in all the regions, except for dorsal striatum. The findings identified brain substrates of affective dysregulation as potential targets for therapeutic intervention. Orbitofrontal rCMR glc abnormalities in MA abusers may also reflect a serotonergic deficit because of low levels of serotonin.

Drug abuse

A dopaminergic deficit in infragenual Anterior Cingulate Cortex, therefore may produce the local metabolic defect. Alternatively, defective Cerebral Metabolic Rate glucose (CMR glc) in the Orbito Frontal Cortex may reflect striatal dopaminergic deficiency as demonstrated by correlation between striatal dopamine D2 receptor availability with orbitofrontal regional Cerebral Metabolic Rate glucose (rCMRglu).

In conclusion, we find that several disorders which affect brain, be it due to metabolic or other non metabolic causes all lead to changes
in the brain. Depending on what is the cause, these changes are observed in different parts of brain. Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and functional MRI (fMRI) are strong tools and are emerging as promising tools in the diagnosis and study of metabolic brain disorders.

Fortis Flt Lt Rajan Dhall Hospital Vasant Kunj