Abstract
Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1 weighted spoiled gradient recalled sequence with and without MT saturation pulse. A voxel-based analysis (VBA) was adopted in order to automatically compute the regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By using a multimodal image analysis MTr was adjusted for local gray matter (GM) atrophy to investigate if MTr changes can be independent of atrophy of the cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr decrease in motor-related areas and extra-motor frontotemporal cortex. The multimodal image analysis identified areas of isolated MTr decrease in premotor and extra-motor frontotemporal areas. VBM and MTr are capable to detect the distribution of neurodegenerative alterations in the cortical GM of ALS patients, supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging changes exist beyond volume loss in frontotemporal cortices.
Highlights
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder characterized by upper motor neuron (UMN) and lower motor neuron (LMN) degeneration [1]
Voxel-based morphometry (VBM) Results of the between group VBM analysis revealed several clusters of reduced cortical gray matter (GM) in ALS patients compared to healthy controls (p,0.05 Family-wise Error (FWE) corrected for multiple comparisons)
Results of the between group regional Magnetization Transfer Imaging (MTI) analysis corrected for atrophy revealed that the MT ratio (MTr) values were significantly lower in ALS patients than in the healthy controls in the superior, middle and inferior frontal gyri
Summary
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder characterized by upper motor neuron (UMN) and lower motor neuron (LMN) degeneration [1]. Conventional MR studies subjectively evaluated the cortical morphology and signal changes in ALS patients [3,5,6,7,14,15], but were limited by low specificity since similar findings are age related and can be detected in subjects without ALS [16]. Further VBM studies [18,19,21,22] revealed that the cortical atrophy in ALS is not confined to the primary motor cortex but extends to premotor and parietal areas [18,21] and to extramotor cortices such as temporal and prefrontal cortex [18,19,22]. Atrophy in prefrontal and temporal cortex of ALS patients was described by pathological studies [26,27,28,29], both in demented and non-demented ALS patients
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