QUANTITATIVE MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY STUDIES OF RESTLESS LEGS SYNDROME: CEREBRAL IRON, MORPHOLOGY AND METABOLISM

Open Access
Author:
Lee, Byeong-Yeul
Graduate Program:
Bioengineering
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
September 29, 2010
Committee Members:
  • Qing X Yang, Dissertation Advisor
  • James Robert Connor, Committee Member
  • Christopher Collins, Committee Member
  • Paul Joseph Eslinger, Committee Member
  • Qing X Yang, Committee Chair
Keywords:
  • voxel-based morphometry
  • iron deficiency
  • RLS
  • restless legs syndrome
  • magnetic resonance imaging
  • magnetic resonance spectroscopy
Abstract:
Restless legs syndrome (RLS) is a neurological disorder that has 5-10% prevalence in Western countries. Its clinical symptoms are characterized by sensorimotor dysfunction, such as uncontrollable urges to move the legs and uncomfortable sensations, causing sleep disturbances at night. Although a number of studies have suggested that brain iron deficiency is strongly coupled with RLS pathophysiology, the exact mechanism of how iron deficiency affects brain function in RLS subjects remains unclear due to inconsistent findings from single imaging data sets. For this reason, in this study multimodal neuroimaging techniques were applied using magnetic resonance imaging (MRI) and spectroscopy (MRS), respectively, in order to investigate the impact of iron deficiency on brain structural changes and neurochemical metabolism in RLS. Twenty-four RLS patients and 24 age-matched controls were studied for the acquisition of multimodal data sets. Multi spin-echo T2 images, high resolution T1 images, and proton MR spectra were acquired in order to quantify iron levels, brain morphology, and neurometabolite levels, respectively. MRI analysis revealed that iron deficit was significantly involved in the sensorimotor regions in RLS subjects. Additionally, brain morphological structure and callosal thickness in RLS patients were significantly reduced in these regions as compared to control subjects. The proton MRS data showed significantly increased concentrations of various metabolites in RLS subjects. Based on the roles of iron in myelin synthesis in the brain, the reduced brain volume could be caused by a myelin deficit (hypomyelination) due to iron deficiency. This could also result in a decrease in the thickness of the corpus callosum, which requires high myelination of its fibers. The MRS results are particularly notable in that they show increased levels of the neurometabolites N-acetylaspartate and myo-inositol. Since these compounds are used in myelin production, higher levels of these metabolites may suggest that glial cells increase the production of NAA and myo-inositol in an attempt to rescue myelin deficits. Therefore, the fusion of multi-modal imaging data provides a realistic approach to understanding the mechanism underlying RLS, and is clinically useful for its early diagnosis and interpretation of the pathological basis of RLS.