Developing pathology specific imaging biomarkers in ALS: integrating postmortem neuropathology and multimodal ex-vivo MRI

In ALS, motor neurons in the brain gradually break down, but researchers still don’t fully understand how this cellular damage corresponds to what appears on MRI scans of living people. This project by Dr. Zeighami and team takes a unique approach by using high‑resolution MRI scans on donated ALS brain tissue. These ultra‑detailed images will be paired with microscopic examinations of the same brain areas to reveal exactly how MRI signals correspond to real cellular damage. By building these connections, the research team hopes to pinpoint MRI features that reliably reflect ALS‑related changes in brain structure and function.

Ultimately, this work could potentially lay the groundwork for developing better MRI‑based biomarkers that could be used in people with ALS to understand the cellular disease pathology in real time. These tools could help diagnose ALS sooner, monitor the disease more accurately, and improve the design of future clinical trials.

Yashar Zeighami, PhD, is an Assistant Professor and FRQS Junior 1 Scholar in Artificial Intelligence and Digital Health at the Douglas Research Centre, Department of Psychiatry, McGill University. He received his undergraduate degree in Electrical Engineering and his Master’s in Biomedical Engineering from the University of Tehran, and completed his PhD in Neuroscience at McGill University in 2018. He subsequently completed an internship at the Allen Institute for Brain Science and a postdoctoral fellowship at McGill focused on brain aging.In January 2022, he started his own research group, the AGING Lab.

His research integrates molecular neuroscience, large-scale neuroimaging, clinical data, and advanced computational modeling to investigate brain changes across the lifespan in health and disease. His work aims to uncover the mechanisms underlying healthy brain aging and identify risk factors that contribute to deviations from this trajectory in neurodegenerative disorders.