Biomarkers of Cortical Impairment in Patients with ALS

Our long term objective is to identify biomarkers that demonstrate longitudinal changes and can be used to detect disease modifying effects in clinical trials of ALS using several state of the art MRI methods at 4Tesla. The study will be performed in two steps. We first will test the hypothesis that high resolution structural imaging, perfusion weighted imaging, or diffusion tensor imaging (DTI) can detect baseline differences in motor and frontal regions in ALS. This will be done with a cross-sectional study to determine which MRI techniques: structural, perfusion, or diffusion tensor MRI show the greatest differences between 23 ALS subjects and controls (data being acquired with other funding). Imaging differences will be correlated with appropriate clinical measures: corticospinal tract (CST) changes with clinical evidence of motor system abnormalities, and frontal lobe abnormalities with changes in cognition and behavior.

Our primary hypothesis will be tested by repeat scanning at six months. We predict that some imaging measure will show a significant change and an effect size adequate for use in clinical trial design. We will determine which measures represent the greatest rate of change over the six month period, for these are most suited for clinical trials. These measures will be validated by comparing and correlating them with clinical measures obtained over the same time frame.

We expect this project to be a step in the development of techniques for assessment, screening, monitoring, and quantifying treatment effects in ALS. The experience gained will facilitate further development of MRI in diagnosis and monitoring progression in this disease. It will also allow for direct comparisons of different imaging modalities with time.

PI: Johnathan Katz, Forbes Norris ALS Research Center
Funding Source: The Amyotrophic Lateral Sclerosis Association