Abstract
Diffusion tensor imaging (DTI) has become a useful tool for investigating early white matter (WM) abnormalities in motor neuron disease. Furthermore, fiber tracking packages that apply multi-tensorial algorithms, such as q-ball imaging (QBI), have been proposed as alternative approaches to overcome DTI limitations in depicting fiber tracts with different orientations within the same voxel. We explored motor and extra-motor WM tract abnormalities in phenotypically heterogeneous amyotrophic lateral sclerosis (ALS) cases aiming to establish a consistent QBI-based WM signature of disease. We performed a whole-brain, QBI tract-based spatial statistics analysis with deterministic tractography of genu, body and splenium of corpus callosum (CC) and corticospinal tracts (CST) in 20 ALS patients (12 classical and 8 lower motor neuron variants) compared to 20 healthy controls. Mean tract length, fiber volume and density, and generalized fractional anisotropy were extracted and related to clinical indices of pyramidal impairment (upper motor neuron score), disease disability (ALS functional rating scale-revised) and progression. ALS patients showed significantly decreased fiber density and volume, and increased tract length in all regions of CC and left CST (p < 0.05, corrected). In CC body, pyramidal impairment was inversely correlated to fiber density (p = 0.01), while in CC splenium, clinical disability (p = 0.01) and progression (p = 0.02) were inversely correlated to tract length. Our findings further suggest that QBI tractography might represent a promising approach for investigating structural alterations in neurodegenerative diseases and confirm that callosal involvement is a consistent feature of most ALS variants, significantly related to both pyramidal dysfunction and disease disability.
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Abbreviations
- ACE-R:
-
Addenbrooke’s cognitive examination revised
- ALS:
-
Amyotrophic lateral sclerosis
- ALSFRS-R:
-
ALS functional rating scale-revised
- BDNF:
-
Brain-derived neurotrophic factor
- CC:
-
Corpus callosum
- CST:
-
Corticospinal tract
- DTI:
-
Diffusion tensor imaging
- DW-MRI:
-
Diffusion-weighted-magnetic resonance imaging
- FMRIB:
-
Functional magnetic resonance imaging of the brain
- FDT:
-
FMRIB’s diffusion toolbox
- FLIRT:
-
FMRIB’s linear image registration tool
- FrSBe:
-
Frontal systems behavior
- FSL:
-
FMRIB software library
- FUS/TLS:
-
Fused in sarcoma/translocated in liposarcoma
- GFA:
-
Generalized fractional anisotropy
- HARDI:
-
High-angular-resolution diffusion imaging
- IGF 1:
-
Insulin-like growth factor 1
- LMN:
-
Lower motor neuron
- MND:
-
Motor neuron disease
- MNI:
-
Montreal Neurological Institute
- ODF:
-
Orientation distribution function
- PMA:
-
Progressive muscular atrophy
- PLS:
-
Primary lateral sclerosis
- QBI:
-
Q-ball imaging
- SMN1:
-
Survival motor neuron 1
- SOD1:
-
Superoxide dismutase 1
- TARDBP:
-
Transactive response DNA-binding protein
- TBSS:
-
Tract-based spatial statistics
- TCFE:
-
Threshold-free cluster enhancement
- TDP-43:
-
Transactivating DNA binding protein-43
- UMN:
-
Upper motor neuron
- VOI:
-
Volume of interest
- WM:
-
White matter
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We thank Dr. Antonella Paccone for her expert technical support.
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G. Caiazzo and D. Corbo have equally contributed to the manuscript.
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Caiazzo, G., Corbo, D., Trojsi, F. et al. Distributed corpus callosum involvement in amyotrophic lateral sclerosis: a deterministic tractography study using q-ball imaging. J Neurol 261, 27–36 (2014). https://doi.org/10.1007/s00415-013-7144-3
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DOI: https://doi.org/10.1007/s00415-013-7144-3