Innovative Multimodal 7T MR Imaging to Assess Cortical Excitability and Disease Subtypes in ALS

In our brain, a delicate balance is maintained between chemicals that stimulate (excitatory) and calm (inhibitory) neuronal activity. A hallmark feature of ALS, thought to occur even before symptoms appear, is that motor neurons in the brain become overexcited (or hyperexcitable). This change occurs at the cellular level and can’t be noticed by people experiencing it, but researchers have found evidence of hyperexcitability in both electrical recordings from the brain and markers in the cerebrospinal fluid of people with ALS. However, researchers have also found that some people living with ALS have cortical inexcitability, which may signal different stages or subtypes. Understanding these differences could be key to improving our knowledge of ALS and developing more effective treatments.

In this project, Dr. de Castro will use ultra-high field 7T MRI, a much stronger type of Magnetic Resonance Imaging (MRI), combined with other advanced techniques, including structural imaging, transcranial magnetic stimulation (TMS), and clinical assessments to study people living with ALS. By comparing two groups, those with corticospinal hyperexcitability and those with inexcitability, they aim to uncover differences in brain chemistry, structure, and disease severity. Dr. de Castro and team will also validate a new Magnetic Resonance Spectroscopy (MRS) method to measure neurochemicals across a large brain area.

This is the first Canadian study using 7T MRI in ALS, integrating imaging and excitability measures to better understand differences in disease. Findings from this research can help refine patient stratification and guide targeted therapies.

Dr. Saldanha de Castro completed his residency at one of Brazil’s most respected neurology programs before moving to Canada to deepen his focus on ALS. Now at the Sunnybrook ALS Clinic, he has spent years supporting people affected by ALS, while also contributing to novel clinical trials. Combined with his passion for neuroimaging research, Pedro is committed to achieving a deeper understanding of ALS pathophysiology, therapeutic development, and improved quality of life.

The ALS Canada Research Program has previously supported exciting work led by Dr. Abrahao and the Sunnybrook team, including an innovative trial testing a new technology to noninvasively deliver treatments through the blood-brain barrier.

Funding for this award was made possible through Shionogi Canada (previously Tanabe Pharma Canada).