TY - JOUR
T1 - Diffusion tensor imaging reveals regional differences in the cervical spinal cord in amyotrophic lateral sclerosis
AU - Nair, Govind
AU - Carew, John D.
AU - Usher, Sharon
AU - Lu, Debbie
AU - Hu, Xiaoping P.
AU - Benatar, Michael
N1 - Funding Information:
The authors wish to thank Dr. Longchuan Li of BITC for his technical help with susceptibility correction algorithms. This work was supported by the Amyotrophic Lateral Sclerosis Association [grant number 1712 ]; Muscular Dystrophy Association [grant number 132866 ]; and National Institute of Health [grant number PO1AG026423 and RO1EB002009 ].
PY - 2010/11
Y1 - 2010/11
N2 - Therapeutic development in amyotrophic lateral sclerosis (ALS) is hampered by the lack of suitable biomarkers that might be sensitive to spatial and temporal patterns of neurodegeneration. Diffusion tensor imaging is a useful non-invasive tool that permits detection of microstructural tissue changes due, for example, to neurodegeneration. Even though the spinal cord bears the brunt of the disease process, diffusion tensor imaging has mainly been used to study white matter changes in the brain. The aim of this study was to examine the diffusion tensor imaging parameters of the cervical spinal cord (C1 through C6 segments) and brainstem (corticospinal tracts in the pyramids and pons) among ALS patients, to compare these to findings in age-matched healthy controls, and to correlate these differences with clinical measures of disease severity. Fractional anisotropy in the white matter of the cervical cord was 12% lower (p< 0.01) in ALS patients (n= 14) compared to age-matched healthy control subjects (n= 15), and showed significant positive correlation with the average finger and foot tapping speed (r= 0.61, p< 0.05) in ALS patients. Radial diffusivity in the cervical cord was 15% higher (p< 0.05) in ALS patients compared to healthy control subjects. Radial diffusivity in the white matter of the cervical cord was significantly correlated with clinical measures of disease severity such as forced vital capacity (FVC % predicted, r= -0.69, p< 0.01), average finger and foot tapping speed from all four limbs (r= -0.59, p< 0.05), and ALSFRS-R (r= -0.55, p< 0.05) in ALS patients. There were no significant differences in mean diffusivity or axial diffusivity in the cervical spinal cord, or in any diffusion tensor imaging parameters measured in the brainstem. Analysis of diffusion tensor imaging parameters from individual cervical segments as well as profile plots along the length of the cervical cord showed larger differences in fractional anisotropy and radial diffusivity at more distal cervical segments, providing evidence that supports the "dying-back" hypothesis of neurodegeneration in ALS.
AB - Therapeutic development in amyotrophic lateral sclerosis (ALS) is hampered by the lack of suitable biomarkers that might be sensitive to spatial and temporal patterns of neurodegeneration. Diffusion tensor imaging is a useful non-invasive tool that permits detection of microstructural tissue changes due, for example, to neurodegeneration. Even though the spinal cord bears the brunt of the disease process, diffusion tensor imaging has mainly been used to study white matter changes in the brain. The aim of this study was to examine the diffusion tensor imaging parameters of the cervical spinal cord (C1 through C6 segments) and brainstem (corticospinal tracts in the pyramids and pons) among ALS patients, to compare these to findings in age-matched healthy controls, and to correlate these differences with clinical measures of disease severity. Fractional anisotropy in the white matter of the cervical cord was 12% lower (p< 0.01) in ALS patients (n= 14) compared to age-matched healthy control subjects (n= 15), and showed significant positive correlation with the average finger and foot tapping speed (r= 0.61, p< 0.05) in ALS patients. Radial diffusivity in the cervical cord was 15% higher (p< 0.05) in ALS patients compared to healthy control subjects. Radial diffusivity in the white matter of the cervical cord was significantly correlated with clinical measures of disease severity such as forced vital capacity (FVC % predicted, r= -0.69, p< 0.01), average finger and foot tapping speed from all four limbs (r= -0.59, p< 0.05), and ALSFRS-R (r= -0.55, p< 0.05) in ALS patients. There were no significant differences in mean diffusivity or axial diffusivity in the cervical spinal cord, or in any diffusion tensor imaging parameters measured in the brainstem. Analysis of diffusion tensor imaging parameters from individual cervical segments as well as profile plots along the length of the cervical cord showed larger differences in fractional anisotropy and radial diffusivity at more distal cervical segments, providing evidence that supports the "dying-back" hypothesis of neurodegeneration in ALS.
KW - Amyotrophic lateral sclerosis
KW - Cervical spinal cord
KW - Diffusion tensor imaging
KW - Dying-back hypothesis
KW - Imaging biomarker of disease severity
KW - Neurodegeneration
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U2 - 10.1016/j.neuroimage.2010.06.060
DO - 10.1016/j.neuroimage.2010.06.060
M3 - Article
C2 - 20600964
AN - SCOPUS:77956056987
VL - 53
SP - 576
EP - 583
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
IS - 2
ER -