Optimizing Brain Imaging for Dementia
Spotlight On: Dr. Stephen C. Strother
March 9, 2022
In a 45 year career spanning New Zealand, the United States, and Canada, TDRA investigator Dr. Stephen C. Strother has left a lasting impact on the field of dementia research. As he prepares to enter retirement, we spoke with Dr. Strother about his fascinating work in dementia and imaging science, and discussed some important insights yielded through his research.
Neuroimaging (i.e., brain imaging) is extremely helpful in the diagnosis and understanding of dementia. Dr. Strother’s work has focused on optimizing all aspects of neuroimaging techniques (e.g., CT scans, PET scans, and MRI scans). His research in this regard has taken on three major themes: 1) technical, mathematical, and statistical studies about how images of the brain are captured, processed, and analyzed, 2) application of optimized brain imaging techniques to study brain functions and disease, and 3) translation of findings to commercial drug trials and related studies with a focus on dementia.
To start from the beginning, Dr. Strother was born in New Zealand, where he received his Bachelor of Science (BSc) and Master of Science (MSc) degrees in physics and mathematics. Between his BSc and MSc, Dr. Strother spent a year in medical school, and worked as an apprentice medical physicist at Auckland hospital. At the hospital, Dr. Strother helped to evaluate and install New Zealand’s first CT scanner, which convinced him that he wanted to be a medical physicist, not a doctor. He left medical school, pursued his MSc in medical physics while continuing to work at Auckland hospital, and won a Rotary International Scholarship to the Montreal Neurological Institute at McGill University, Montreal, Canada. There he completed his PhD in electrical engineering, with a thesis on quantitative neuroimaging using positron emission tomography (PET).
Dr. Strother then completed his postdoctoral fellowship in neurological PET at Memorial Sloan Kettering Cancer Center, New York, USA. This was during the early days of the HIV epidemic in the 1980s; he was involved in the first behavioural and metabolic imaging studies of HIV-associated dementia, which was his first exposure to dementia imaging. Through his team’s study of HIV-associated dementia, it was discovered that an increased rate of metabolic activity (‘hypermetabolism’) in a specific region of the brain was a marker of subclinical (no symptoms yet) central nervous system (CNS) disease in HIV infection, and that it was possible to link certain characteristics of brain networks to specific diseases. This is an important finding that continues to guide studies related to neurological diseases (e.g., Alzheimer’s disease). For example, more recently, Dr. Strother contributed to a study which showed that behavioural variant frontotemporal dementia (FTD) and semantic dementia are associated with disrupted and elevated connections in different regions of the brain.
Following his postdoc, Dr. Strother spent some time working as a Senior Medical Physicist at the VA Medical Center, Minneapolis, USA, and as an Assistant Professor at the University of Minnesota before moving to Toronto, Canada. Since 2004, Dr. Strother has worked as a Senior Scientist at the Rotman Research Institute at Baycrest, and as a Professor of Medical Biophysics at the University of Toronto. Because of the collaborative environment available, it was in Toronto that Dr. Strother began to focus significant efforts on dementia research. This was building on his previous involvement in dementia research through a company that he co-founded in Chicago in 2001 (now called ADMdx Inc).
Throughout all the locations and institutions mentioned, Dr. Strother’s work and research continually evolved. For the first 15 years of his career, he focused on CT and PET imaging with an emphasis on optimizing the performance of the scanners (i.e., maximizing information gain for minimal radiation dose). By the late 1990s, his focus broadened to more statistically-oriented studies in the field of neuroinformatics, an area of research that uses data analysis and computer modelling to make new discoveries about the brain. This included a shift toward optimizing MRI as a replacement for PET imaging, and using what are now called data science and machine learning (artificial intelligence) techniques. The technical studies he contributed to during this time led to two important discoveries. First, proving that using multivariate analysis techniques (statistical analysis of two or more variables) to detect brain networks, as opposed to standard univariate analyses (statistical analysis of a single variable), is important in optimizing detection sensitivity and interpretation of neuroimaging studies. Second, when conducting multivariate analyses, brain-pattern reliability measures were shown to be a powerful tool for improving analysis techniques.
His focus broadened again in the late 2000s to include big data and databases with less emphasis on neuroimaging. With the establishment of the Ontario Brain Institute (OBI), Dr. Strother was able to use his knowledge to help build OBI’s data repository, Brain-CODE, which helps more than 160 researchers at over 20 institutions across Ontario share their data. Since its establishment, Dr. Strother has been the Primary Investigator of the neuroimaging platform for Brain-CODE. Dr. Strother further contributed to the big data space through his work in developing and maintaining the TDRA’s foundational project, the Memory Clinics Research Database. Dr. Strother refers to this as his greatest contribution toward the advancement of dementia prevention and care. This project built the infrastructure to support the ongoing sharing of consented, clinical patient data between memory clinics in Toronto that use OBI’s Brain-CODE. ‘Without such infrastructure, it is impossible to realize the vision of accelerating scientific learning from the many dementia patients that are seen at the TDRA clinics yearly’, said Dr. Strother. Brain-CODE and the Memory Clinics Research Database would not have been possible without extensive multi-laboratory and multi-institutional collaboration. Dr. Strother is an advocate for collaborative research and open science, explaining that many of the technical insights, discoveries, and developments during his career would not have been possible without it.
A central underlying theme and a big part of Dr. Strother’s research has been reducing the ‘replicability crisis’ in modern neuroscience. ‘One of the fundamental requirements for a scientific result to be considered valid, at least for the time being until it is possibly overturned by new data and results, is to be able to replicate the result’, he explains. This idea was introduced in the 17th century, but has been largely forgotten in the 20th century for many reasons. Throughout his career, Dr. Strother worked to address this via numerous replication studies and initiatives. Most impactful was the development of a neuroimaging standard that improved the ability of scientists to exchange and read each other’s neuroimages. This was an initiative of the Data Format Working Group of the Neuroimaging Informatics Technology Initiative (NIfTI), which Dr. Strother chaired at the National Institutes of Health in the USA. More recently, Dr. Strother was part of a team of Canadian researchers who developed a set of standardized MRI imaging protocols for dementia studies, which are now used by several large organizations in Canada.
As for the future of dementia research, Dr. Strother speculated on some trends. He believes that carefully standardized and targeted clinical and behavioural measures, electronically collected at the point-of-care will become more important, as will some forms of molecular measures from body fluids. These approaches will have to be pursued in multi-institutional, collaborative team settings to obtain the sample sizes necessary to truly understand the differences in early dementia cases. Lastly, he believes that translation of academic science into non-academic settings is a critical component of advancing dementia prevention and care across all fronts.
