Anjan Bhattarai1,2, Zhaolin Chen2, Phillip G D Ward2, Paul Talman3, Susan Mathers4,5, Thanh G Phan5, Caron Chapman4, James Howe4, Sarah Lee4, Yennie Lie4, Gary F Egan2, Phyllis Chua1,4. 1. Department of Psychiatry, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia. 2. Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia. 3. Department of Neuroscience, Barwon Health, Geelong, Victoria, Australia. 4. Statewide Progressive Neurological Services, Calvary Health Care Bethlehem, South Caulfield, Victoria, Australia. 5. Department of Neurology, Monash Health, and School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Abstract
BACKGROUND: Dysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with amyotrophic lateral sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based quantitative susceptibility mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a 6-month period. METHODS: Iron concentration was investigated using magnetic resonance based QSM in the primary motor cortex and the pre-motor area in 13 limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and 11 age- and sex-matched control subjects. Nine ALS patients underwent follow-up scans at 6 months. RESULTS: Significantly increased QSM values were observed in the left posterior primary motor area (P=0.02, Cohen's d =0.9) and right anterior primary motor area (P=0.02, Cohen's d =0.92) in the group of limb-onset ALS patients compared to that of control subjects. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to control subjects. No significant change in QSM was observed at the 6-month follow-up scans in the ALS patients. CONCLUSIONS: The findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a quantitative radiological indicator in early disease diagnosis in limb-onset ALS and its subtypes. Our serial scans results suggest a longer period than 6 months is needed to detect significant quantitative changes in the motor cortex. 2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.
BACKGROUND: Dysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with amyotrophic lateral sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based quantitative susceptibility mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a 6-month period. METHODS: Iron concentration was investigated using magnetic resonance based QSM in the primary motor cortex and the pre-motor area in 13 limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and 11 age- and sex-matched control subjects. Nine ALS patients underwent follow-up scans at 6 months. RESULTS: Significantly increased QSM values were observed in the left posterior primary motor area (P=0.02, Cohen's d =0.9) and right anterior primary motor area (P=0.02, Cohen's d =0.92) in the group of limb-onset ALS patients compared to that of control subjects. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to control subjects. No significant change in QSM was observed at the 6-month follow-up scans in the ALS patients. CONCLUSIONS: The findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a quantitative radiological indicator in early disease diagnosis in limb-onset ALS and its subtypes. Our serial scans results suggest a longer period than 6 months is needed to detect significant quantitative changes in the motor cortex. 2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.
Entities:
Keywords:
Amyotrophic lateral sclerosis (ALS); iron; magnetic resonance imaging (MRI); motor cortex; quantitative susceptibility mapping (QSM)
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