Researchers at Western University’s Western Institute for Neuroscience (WIN) in London, Ontario, have received a $4.1 million grant from the Canada Foundation for Innovation to develop an advanced imaging platform intended to map the brain and enhance disease detection. The Ontario Research Foundation is providing the researchers a matching grant of $4.1 million, and vendors are awarding them a $2.0 million in-kind grant, for a total of $10.2 million.

This research will focus on integrating the testing for three types of disease biomarkers (fluids, imaging, and cognition tests) using live and deceased humans to better detect and understand brain diseases such as Alzheimer’s and Parkinson’s diseases. By these means, the researchers hope to create detailed maps that indicate the location of disease-related molecules within brain tissue.

“This project is the first to undertake brain mapping to this degree and with this level of resolution and sophistication,” Shawn Whitehead, PhD, professor of medical sciences at Western University and director of WIN, told Medscape News Canada.

University Health Network and University of Ottawa in Ottawa are collaborating on the project, which includes more than 80 scientists. Whitehead, who is recognized as an international leader in mass spectrometry, emphasized that this project has assembled a multidisciplinary team of clinicians, basic scientists, bioinformatics specialists, computational scientists, and imaging experts.

Seeking a Comprehensive Approach

The challenge in diagnostics is that researchers typically look at individual biomarkers in specific domains, Whitehead explained. “In brain research, we examine the cognitive domain of someone who might be at risk for Alzheimer’s disease or Parkinson’s disease to determine what their behavioral or cognitive symptoms are. Or MRI or a PET scan might be performed. However, what’s lacking is the full picture.”

This aim of the research project is to enable a more comprehensive approach to neurologic disease. There are few known diagnostic biomarkers with high predictive value for Alzheimer’s disease, for example. The disease has multiple comorbidities, such as cerebrovascular disease and diabetes. Accurate diagnosis has been challenging because of difficulties in biomarker mapping. “Until now, there hasn’t been a platform to integrate new image-guided diagnostic markers from postmortem studies into existing studies,” said Whitehead.

The researchers also are developing highly sensitive self-specific fluid biomarkers. “Currently, with a blood draw, we identify brain inflammation by examining the biomarkers circulating in the blood. However, restricting ourselves to that alone doesn’t tell us if the biomarkers are in the brain or elsewhere,” added Whitehead.

Whitehead noted that in many cases, clinical trial design uses one or two modalities, such as MRI, PET scan, a blood draw, or cerebrospinal fluid draw, which results in predictive and retrospective imaging. What is needed is a platform that can image patients and be used to validate biomarker candidates, according to Whitehead. Fluid biomarkers can be detected and imaging can be performed during a longitudinal study. The problem with the fluid biomarkers is that it’s impossible to locate Alzheimer’s disease in the body at a molecular level until the patient has died. This platform will enable the identification of novel diagnostic markers that can be incorporated into ongoing clinical trials.

Historically, researchers have relied upon preclinical animal model development. Now, Whitehead and his colleagues are ready to apply their research to clinical trials in the human population.

No Screening for Brain Disease

Accurate diagnostic tests can’t be achieved with imaging alone, Whitehead pointed out. In diseases such as Alzheimer’s and dementia, brain changes occur decades before the disease is clinically apparent. A patient in their forties or fifties with normal cognition might not consent to a routine MRI, PET scan, or spinal tap. But blood-based fluid biomarkers can be extremely powerful if incorporated into routine diagnostic care, said Whitehead. 

“From a screening perspective, once a person turns age 50 years, they’re screened for breast and colon cancer,” he said. “However, no screening exists for brain disease. It can’t be based solely on animal models and clinical trials. We can’t just look at a particular timepoint and then ignore postmortem work, or vice versa. This is where the integration across blood markers, imaging markers, and cognitive markers needs to be done in an intentional way. Otherwise, we can’t find the right markers to start testing.

“If you have the right targets [ie, diagnostic biomarkers] that you’ve identified in a longitudinal sense and you’ve integrated them across the three biomarker modalities of imaging, cognition, and fluids, then you can start to stratify patients for existing clinical trials.” A database of patients who have been stratified according to the three biomarker modalities should be used in the design of clinical trials, he added. “That’s really what we’re missing, and that’s what this this proposal is aiming to support building,” concluded Whitehead.

Whitehead reported having no relevant financial relationships.

Evra Taylor is a widely published freelance medical writer and reporter with 20 years’ experience covering a broad range of therapeutic sectors, including family health, cardiology, psychiatry, ophthalmology, and dermatology.