Gray matter perfusion correlates with disease severity in ALS

Abstract

Objective: The goal of this study is to determine if regional brain perfusion, as measured by arterial spin labeling (ASL) MRI, is correlated with clinical measures of amyotrophic lateral sclerosis (ALS) disease severity. The presence of such a relationship would indicate a possible role for ASL perfusion as a marker of disease severity and upper motor neuron involvement in ALS.

Methods: Disease severity was assessed in 16 subjects with ALS (age 54 +/- 11) using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and the pulmonary function measure, forced vital capacity (FVC). Upper motor neuron involvement was assessed by testing rapid tapping of the fingers and feet. Magnetic resonance perfusion images were coregistered with structural T1-weighted MRI, corrected for partial volume effects using the structural images and normalized to a study-specific atlas. Correlations between perfusion and ALS disease severity were analyzed, using statistical parametric mapping, and including age as a factor. Analyses were adjusted for multiple clusters.

Result: ALS severity, as measured by the ALSFRS and FVC, was correlated with gray matter perfusion. This correlation was predominantly observed in the hemisphere contralateral to the more affected limbs. ALSFRS scores correlated with perfusion in the contralateral frontal and parietal lobe (p < 0.001) and ipsilateral frontal lobe (p < 0.02). FVC scores correlated with gray matter perfusion in contralateral frontal lobe (p < 0.001). Upper motor neuron involvement, as measured by rapid finger tapping, correlated bilaterally with perfusion in the middle cingulate gyrus (p < 0.001).

Conclusion: Amyotrophic lateral sclerosis (ALS) severity is correlated with brain perfusion as measured by arterial spin labeling (ASL) perfusion. This correlation appears to be independent of brain atrophy. ASL perfusion may be a useful tool for monitoring disease progression and assessing treatment effects in ALS.

Figure 1 Finger tapping positive correlation with arterial spin labeling (ASL) perfusion (left = ipsilateral) Voxels exhibiting increased ASL perfusion with increased Amyotrophic Lateral Sclerosis Functional Rating Scale. Voxels were only included if they were in clusters of at least 100 voxels (p < 0.001). The images in A project these voxels onto a 3-dimensional rendering of the Montreal Neurological Institute atlas. The images in B display these same data as a maximum intensity projection on a transparent “glass brain.” The dashed lines indicate the extent of the brain that was covered by the ASL perfusion images.

Figure 2 Absolute forced vital capacity (FVC) positive correlation with arterial spin labeling (ASL) perfusion (left = ipsilateral) Voxels exhibiting increased ASL perfusion with increased absolute FVC. Voxels were only included if they were in clusters of at least 100 voxels (p < 0.001). The images in A project these voxels onto a 3-dimensional rendering of the Montreal Neurological Institute atlas. The images in B display these same data as a maximum intensity projection on a transparent “glass brain.” The dashed lines indicate the extent of the brain that was covered by the ASL perfusion images.

Figure 3 Amyotrophic Lateral Sclerosis Functional Rating Scale positive correlation with arterial spin labeling (ASL) perfusion (left = ipsilateral) Voxels exhibiting increased ASL perfusion with increased number of finger taps. Voxels were only included if they were in clusters of at least 100 voxels (p < 0.001). The images in A project these voxels onto a 3-dimensional rendering of the Montreal Neurological Institute atlas. The images in B display these same data as a maximum intensity projection on a transparent “glass brain.” The dashed lines indicate the extent of the brain that was covered by the ASL perfusion images.