Emergence of an imaging biomarker for amyotrophic lateral sclerosis: is the end point near?

A diagnostic and treatment biomarker for amyotrophic lateral sclerosis (ALS) remains a holy grail.1 ,2 From a neuroimaging perspective, diffusion tensor imaging (DTI) has been increasingly utilised to identify brain-related upper motor neuron changes in ALS. In particular, the corticospinal tract, anterior corpus callosum and hippocampal fractional anisotropy (FA) white matter changes have been closely linked with ALS pathology3 ,4 and associated with the underlying neuropathological spread of TAR DNA binding protein 43 (TDP-43).5 Thus, DTI emerges as an ideal neuroimaging biomarker end point for disease-modifying trials in ALS. However, most advanced trials are run on a multicentre basis, and currently it is not clear how DTI signatures across centres in ALS hold-up, in particular with varying imaging sequences and scanner variabilities.