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Comparing brain structural MRI and metabolic FDG-PET changes in patients with ALS-FTD: 'the chicken or the egg?'
Venkateswaran Rajagopalan1, Erik P Pioro2
1Department of Electrical and Electronics Engineering, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad, India Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Objective:
Our previous voxel based morphometry (VBM) studies in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (ALS-FTD) showed reduced motor and extramotor grey matter (GM) volume when compared to neurological controls. However, erroneously high GM values can result because VBM analysis includes both cortical gyri and sulci as a single GM region. In addition, the relationship between structural and functional changes is unknown. Therefore, we determined whether GM volumetric changes seen in patients with ALS-FTD were due to changes in cortical thickness, area or both, and compared these structural changes with metabolic changes as revealed by positron emission tomography (PET).
Methods:
T1-weighted MRIs were obtained in unaffected neurological controls and in patients with ALS-FTD; the latter also underwent PET imaging. We assessed brain GM structural changes using VBM and cortical thickness, and metabolic changes using PET images. Significant (p<0.05) reductions in GM volume and cortical thickness were observed in motor and extramotor regions in patients with ALS-FTD compared to controls. No significant difference in cortical surface area was observed in any of the brain regions. Results Significant (p<0.05) reductions in cerebral glucose metabolism rate were observed in brain regions where structural changes were also observed. Significant reductions primarily in cortical thickness were the likely reason for decreased GM volume in ALS-FTD.
Conclusions:
Metabolic changes corresponded well with structural changes in motor and extramotor areas, and sometimes occurred even in the absence of GM volume reduction. Coincident structural and functional GM changes suggest that neurodegeneration may occur as "neuronopathy" in patients with ALS-FTD.
Insights
Structural and metabolic brain changes in amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) are linked to decreased cortical thickness, not surface area. These findings suggest neurodegeneration may manifest as "neuronopathy" in ALS-FTD patients.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Previous voxel-based morphometry (VBM) studies indicated reduced grey matter (GM) volume in amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD).
- VBM analysis may overestimate GM volume by including both gyri and sulci.
- The relationship between structural and functional brain changes in ALS-FTD remains unclear.
Purpose of the Study:
- To investigate whether GM volume changes in ALS-FTD are attributable to alterations in cortical thickness, surface area, or both.
- To compare structural brain changes with metabolic changes assessed via positron emission tomography (PET).
Main Methods:
- T1-weighted magnetic resonance imaging (MRI) and PET scans were acquired from patients with ALS-FTD and healthy neurological controls.
- Brain GM structural changes were analyzed using VBM and cortical thickness measurements.
- Metabolic changes were assessed using PET imaging.
Main Results:
- Patients with ALS-FTD exhibited significant reductions in GM volume and cortical thickness in motor and extramotor regions compared to controls.
- No significant differences in cortical surface area were found between groups.
- Cerebral glucose metabolism reductions correlated with structural changes in affected brain regions.
Conclusions:
- Significant reductions in cortical thickness are the primary drivers of decreased GM volume in ALS-FTD.
- Metabolic and structural changes in ALS-FTD often co-occur, particularly in motor and extramotor areas.
- Coincident structural and functional changes suggest neurodegeneration in ALS-FTD may be characterized as 'neuronopathy'.
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