In memoriam: R. Mark Henkelman, 1946–2024

R. Mark Henkelman, a distinguished Canadian biophysics researcher renowned for his pioneering contributions to MRI, passed away on June 28, 2024. Mark is survived by wife Jannie and children Jonathan, Graeme, and Erika. He leaves behind a legacy of scientific innovation dedicated to advancing imaging in medicine and research. Mark was born on December 1, 1946, to Victor Albert and Jean Elizabeth (née Alloway) Henkelman, both teachers. From an early age, he loved the outdoors, taking frequent canoe trips through Algonquin Park in Ontario. He is also remembered as a child to have asked of everything, “How does it work?” This investigative spirit led him to pursue theoretical physics for both an undergraduate degree at the University of Toronto (1969) and a MSc degree at McMaster University (1970). He subsequently pursued a PhD (1973). For his thesis work, Mark developed an energy filter for electron microscopy that enabled imaging of biological samples. His supervisor, Peter Ottensmeyer, recalls recognizing very early that Mark had both “brain power” and “gifted hands,” and that his best course of action was to “not interfere with [Mark's] research.” Following his PhD, Mark moved across the country to join the University of British Columbia (BC) and the BC Cancer agency, where he worked on the pion beam line at TRIUMF and conducted initial studies of its biological effects on cells and animals. His work involved measuring the energy deposited by the pion beam at a microscopic level and explored its potential effectiveness in cancer treatment. BC also proved a wonderful place for Mark and his family to explore the outdoors. They enjoyed lengthy camping vacations up and down the west coast, finding a favorite spot on the Oregon Coast near Tillamook (Figure 1). While Mark was in BC, new needs and opportunities developed in Toronto. The Ontario Cancer Institute at Princess Margaret Hospital (PMH) and the Department of Medical Biophysics at the University of Toronto were growing rapidly. Leadership was needed to harness the exploding field of medical imaging and—though new to the area—Mark was the perfect candidate. He returned to Toronto in 1979, quickly becoming a scientific leader as associate chair in medical biophysics (1982) and building imaging excellence over the next decade. Mark faced an uphill battle when he arrived back in Toronto with a vision that MRI was going to change imaging and medicine. There was not yet an MRI system in Canada, and initial efforts to fund one met with rejection after rejection. With persistence, Mark and Mike Bronskill convinced the Ontario provincial government to fund Canada's first operational MR facility at PMH. Mark quickly became an early leader in the field, developing technical aspects of MRI, identifying and reducing artifacts—including pioneering work in motion correction and truncation artifacts, and understanding tissue contrast. These developments helped to extend the use of MRI in various disease settings, including cancer and neurosurgery. MRI became a major component of the Medical Physics PhD program, and through this program Mark trained and influenced many young scientists, a number of whom have become leaders in the field. Mark also fostered excellence in ultrasound, CT, and digital X-ray imaging. Soon other institutions were taking note, and the feelers were out nationally and internationally to recruit him away from PMH, which at the time faced restructuring and uncertainty. This led Mark to explore leading an entirely new research enterprise as vice president of research at Sunnybrook Health Sciences Centre, an institution in Toronto that at the time had almost no research but did have a board of directors with bold ideas. To say that their trust in Mark paid off is a major understatement. Today, Sunnybrook is Canada's ninth-largest medical research enterprise with over $135 M in annual funding. Despite the plethora of administrative duties at Sunnybrook, Mark continued to pursue his research. The 1990s was one of the most successful decades in MRI research with adaptation of various novel techniques for both research and the clinic. These included fMRI, perfusion, magnetization transfer, DTI, current density imaging, and more. Mark's contributions to these new, exciting MRI techniques were remarkable, including a theoretical framework for magnetization transfer, quantitative diffusion, intravoxel incoherent motion, etc (Figure 2). For this seminal work, Mark received the International Society for Magnetic Resonance in Medicine (ISMRM) Gold Medal in 1998 (the first and only researcher to date at a Canadian Institution to get this award). After over 10 years at Sunnybrook, Mark stepped down in 2000 to focus full-time on the science he loved. As the new millenium dawned, Mark and colleagues Janet Rossant and Stuart Foster recognized the importance of the Human Genome Project and the potential for imaging technology to help understand gene function. Mark and Stuart visited leading-edge labs around North America and formulated a plan that was taken to the board of directors of the Hospital for Sick Children (SickKids) in Toronto. At the meeting, Mark famously slammed a stack of modified telephone books on the board table and said: “This is the directory of mouse genes, and we need to define their roles in normal physiology and in models of human disease if we are going to make meaningful progress on new therapies!” The Mouse Imaging Centre (MICe) was funded almost immediately to develop the MRI, micro-CT, optical, and ultrasound tools needed for phenotyping of genetically engineered mice (Figure 3). In 2007, MICe moved into the Centre for Phenogenomics (TCP), which remains a national resource today. After 17 wonderful years at SickKids, Mark retired in 2017. Mark excelled as a mentor, collaborator, and team builder. He was careful in teaching the scientific method and uncompromising in scientific integrity. He was a true motivator and always made time to dig into data and brainstorm new ideas. He was frank and quick-witted, strict and supportive, proud and generous. Mark valued collaboration building and discussion of new ideas, which he worked hard to foster. This culminated in annual retreats at his family's cottage on Lake Rosseau in Ontario (called “MICe in Muskoka” in later years). These memorable getaways included community building and excellent food. Mark was organizer, host, and chef—he marinated the salmon days in advance! These retreats were a place to “think big” about imaging science and for trainees to learn informally about the keys for a good collaboration, a good manuscript, and a good career. Along with his busy professional schedule, Mark maintained an active personal one. When not traveling for science, he was often traveling for family adventures: scuba diving trips with his children, biking through Holland with his wife Jannie (mostly in the rain!), and family hiking or canoeing trips—the last one through Yoho National Park, combined with kayaking down the Bow River. He also loved books and the London theater. Throughout his illustrious career, Mark received numerous accolades, including the above-mentioned ISMRM Gold Metal (1998), the Robert L. Noble Prize (2008), and the Izaak Walton Killam Memorial Prize (2010). He was appointed a Fellow of the Royal Society of Canada in 2005 and an Officer of the Order of Canada in 2019. Mark finished his career as professor emeritus and university professor at the University of Toronto's Department of Medical Biophysics. Mark's research has had a lasting impact on imaging in medicine and science, advancing both the technology and its applications in diagnosing, treating, and studying diseases. His contributions continue to influence current research and clinical practices. He was always uniquely himself, and larger than life. His passion and research continue to inspire future scientists.