This comment was solicited by the Alzheimer Research Forum.

There is a clear need for novel biomarkers that are sensitive to progression of disease in ALS and that could be used to facilitate monitoring in therapeutic trials and reduce the reliance on survival as the primary outcome measure. MRI, as a non-invasive technique with widespread availability for patients, has proved itself in providing several robust objective and quantitative markers of upper motor neuron involvement. There remain important challenges to apply it to the study of the lower motor neuron burden of disease which accounts for much of the disability in ALS.

Arterial spin labeling is a novel MRI technique that allows non-invasive measurement of cerebral perfusion. This study by Rule et al. has a sound rationale given what has been demonstrated already about the wider extra-motor cerebral involvement in ALS, and the need to find a potentially “functional” correlate for the more 'structural' analysis that diffusion tensor tractography can offer. Their results are encouraging in that regional...  Read more

This comment was solicited by the Alzheimer Research Forum.

There is a clear need for novel biomarkers that are sensitive to progression of disease in ALS and that could be used to facilitate monitoring in therapeutic trials and reduce the reliance on survival as the primary outcome measure. MRI, as a non-invasive technique with widespread availability for patients, has proved itself in providing several robust objective and quantitative markers of upper motor neuron involvement. There remain important challenges to apply it to the study of the lower motor neuron burden of disease which accounts for much of the disability in ALS.

Arterial spin labeling is a novel MRI technique that allows non-invasive measurement of cerebral perfusion. This study by Rule et al. has a sound rationale given what has been demonstrated already about the wider extra-motor cerebral involvement in ALS, and the need to find a potentially “functional” correlate for the more 'structural' analysis that diffusion tensor tractography can offer. Their results are encouraging in that regional alterations in perfusion appear to be linked to the 'bedside' functional rating scale for disability in ALS (the ALSFRS-R).

PET, involving radioactive tracers, has been the gold standard of perfusion imaging for many years. It is noteworthy, as a proof-of-concept, that this more practical, non-invasive MRI study confirms some of the regional resting-state findings of the PET study of blood flow in ALS undertaken by my predecessor John Kew in Professor Nigel Leigh's lab in London nearly 20 years ago, "Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study" (see Kew et al., 1993).

The authors acknowledge that there is no control group, and so this paper stands as a promising pilot study that needs repeating in a larger group of patients, with controls, and crucially with longitudinal data. Combination with diffusion imaging would also be useful. A wider point is that, despite the all-too-regular comments that MRI has had its day as a technology, it continues to be inventive and to push back the boundaries of neuroscience research. With high resolution cord imaging becoming a reality, there is much more to come in the next decade for MRI across a range of neurological disorders, and it is vital that the brightest physicists and image analysts continue to be drawn to the field.

View all comments by Martin R. Turner

A recent paper in Human Molecular Genetics also observed that TARDBPl compensates for the loss of TARDBP.

References:
Hewamadduma CA, Grierson AJ, Ma TP, Pan L, Moens CB, Ingham PW, Ramesh T, Shaw PJ. Tardbpl splicing rescues motor neuron and axonal development in a mutant tardbp zebrafish. Hum Mol Genet. 2013 Mar 3. Abstract

View all comments by Tennore Ramesh