Inside the Science: Imaging and ALS

Brain imaging is one of the most powerful tools to help us study ALS. By providing a way to look inside people living with ALS, imaging techniques are giving researchers a unique understanding of what is happening in the disease, what areas of the brain are affected, and how the disease progresses over time. Recent studies show how imaging can potentially be used as a source of biomarkers that may help us understand and track disease progression, evaluate new potential therapeutics in clinical trials, and someday lead to a more timely diagnosis.

Magnetic resonance imaging (MRI)

Magnetic resonance imaging (MRI) is one of the most widely used imaging techniques in ALS research. In an MRI test, to capture images of the brain, the person will usually need to lie still inside a machine that surrounds them. Scientifically, a strong magnet aligns the hydrogen atoms of the body so that radio signals can allow the machine to label their exact location and assemble cross-sectional brain images using a mathematical formula. (In a simpler explanation, an MRI machine will make very loud noises while you need to stay very still. After long minutes that feel like hours, you will have your brain on a computer screen!)

More specialized forms of MRI, like diffusion tensor imaging (DTI) can also provide even greater insights, by highlighting the connectivity and communication between different brain regions.

Positron emission tomography (PET) scans 

Another form of imaging is positron emission tomography (PET), which uses safe radioactive tracers to highlight biological processes. In ALS, PET can help detect neuroinflammation and abnormal protein accumulation, both of which are hallmarks of the disease.  

Tracking and understanding disease progression

Tools that are used to currently track ALS progression, like the ALSFRS-R scale, can’t show us what is happening in the brain and have long been debated on their limitations. Imaging could step in as a powerful tool allowing scientists and clinicians to see the disease in more detail.

Over the past decade, several studies have attempted to establish imaging as a potential source of prognostic biomarkers, which would aid in predicting clinical worsening, as well as distinguishing fast from slow progressors. As recent evidence, a study led by ALS Canada-Brain Canada awardee Dr. Isabelle Lajoie showed how specific areas of the brain underwent atrophy (shrinkage) that was tied to a higher risk of death or need for long-term breathing support. By gathering data from people living with ALS and applying mathematical techniques, other imaging measures have also been shown to help predict respiratory changes and survival. When combined with clinical information, the predictive ability of the imaging biomarkers increases significantly.

Interestingly, additional MRI and PET studies also suggest that there might be a way to help identify non-motor aspects of ALS, such as cognitive and behavioural changes, or ALS-FTD diagnoses. A recent study also reviewed how neuroimaging offers insights into sensory manifestations of ALS, such as pain and paraesthesia (tingling or numbness in the skin).

How the brain changes before diagnosis

Another potential application of imaging is assisting earlier diagnosis, as it may have the potential to reveal changes in the brain before major symptoms appear. For example, in a recent study  by Dr. van Veenhuijzen et al., researchers studied brain scans of asymptomatic  C9orf72 variant carriers to better understand and gain insights into when and how ALS or ALS-FTD develops. Through imaging, researchers found that variant carriers who went on to develop the disease showed distinct brain atrophy (shrinkage) patterns up to six years before the onset of symptoms, compared to other asymptomatic carriers.

Looking into the brain before an ALS diagnosis can bring us great insights into how disease develops and where it starts. Understanding the causes of ALS is how we will one day find a treatment that can alter its progression – as evident with Qalsody, the first treatment for ALS that actually targets a root cause of the disease for SOD1 genetic variant carriers.

Additionally, some researchers are investigating muscle scans in addition to neuroimaging. A recent study was able to detect ALS in people with early symptoms with nearly 90% accuracy using ultrasound imaging of muscle, adding to the evidence that these types of tests could be promising as an effective tool to aid in more timely diagnosis of the disease.

Promising research is being conducted worldwide, investigating different aspects of imaging, but there is still work to be done to establish standardized protocols and techniques, making results more reliable and comparable. Toward this collaborative effort, the Neuroimaging Society in ALS (NiSALS), founded by Dr. Martin Turner in 2010, aims to set clear standards for collecting and processing MRI data, making it easy for researchers to share their scans. Since its first meeting in 2010, neuroimaging experts from around the world have continued to gather annually to discuss imaging as a key tool for understanding ALS.

In Canada, we also have the Canadian ALS Neuroimaging Consortium (CALSNIC), a multidisciplinary team of experts across multiple academic centres, led by globally respected ALS imaging expert, Dr. Sanjay Kalra, from the University of Alberta. One of CALSNIC’s goals is the discovery of MRI-based biomarkers that will impact the lives of people living with ALS. As of 2025, the CALSNIC study remains one of the only multi-sites, longitudinal neuroimaging studies ever in ALS research, providing valuable information to the global effort to understand and treat the disease. CAPTURE ALS is another, larger study, capturing the same comprehensive information and adding biosamples (blood, CSF, etc.) from Canadians living with ALS. One of the biggest differentiators of this platform from others outside Canada is the imaging collection. Using data from the initiative, many studies are already looking into tracking progression and understanding how the disease advances in the brain.

However, despite all the promising advancements in imaging, some factors still limit its application. Costs and accessibility are aspects that restrict usage, as not every facility or research centre is equipped with the same technology. It should also be considered that not every person living with ALS could tolerate multiple MRIs, as there might be travel involved, assisted ventilation complications, or discomfort during the test. All these factors need to be addressed to reduce patient burden, if one day imaging tests will be used as a routine method to help track or diagnose ALS.

Still, with further analysis and by combining various imaging approaches and databases, researchers are coming closer to being able to pinpoint disease patterns to use imaging as a source of valuable biomarkers for ALS. Neuroimaging is also being considered in clinical trials, where it may have potential in helping with participant selection and grouping, as well as providing more precise indicators of disease progression. Better, more objective tracking of the disease is urgently needed in trials, and if imaging can help provide this, it will certainly enhance our ability to find therapies that are providing significant benefit to people living with ALS.

To cut a long story short, we are coming closer to imagining reliable ALS biomarkers and a better understanding of the disease.  

Inside the Science 

In our blog series, Inside the Science, we break down and discuss trending topics in ALS research, making complex science accessible to anyone affected by ALS.