PROJECT SUMMARY
This K23 project will prepare the Principal Investigator, Justin M. Canada, PhD, to develop as an
independent clinical/translational researcher who is expert in a novel form of cardiopulmonary exercise stress
measurement – cardiovascular magnetic resonance imaging (MRI) – to identify factors that reduce peak
oxygen consumption (VO2) in patients with heart failure. Peak VO2 reflects peak exercise capacity, a prime
determinant of outcomes among patients with cardiovascular disease (CVD). This noninvasive methodology
does not require intravenous contrast or ionizing radiation, eliminating possible side effects among patients in
poor health. It also accurately measures exercise-associated cardiac output—a fundamental contributor to
overall exercise capacity—that can be targeted with therapeutic interventions to improve overall peak exercise
capacity.
This project is a collaborative multi-disciplinary effort among oncologists, exercise physiologists, biomedical
engineers, and cardiovascular experts to address an important issue in the emerging field of cardio-oncology.
The proposal focuses on patients receiving allogeneic hematopoietic stem cell transplantation (HCT) for
hematologic malignancies. Treatment-associated reductions in peak VO2 can exclude candidates from life-
saving HCT. Among survivors of hematologic malignancies, reduced peak VO2 is associated with impaired
quality of life and elevated risk of death not related to relapse. At present, there is no reliable method to identify
those at risk for these serious adverse events.
In addition to a strong, supportive environment that includes international experts, the largest HCT program
in Virginia, and state-of-the-art equipment co-located within the Cancer Center that serves the HCT
community, the proposal is buttressed by highly supportive preliminary data and a robust career development
plan for Dr. Canada. This plan provides mentored training in the translational fundamentals of MRI theory:
conduct, interpretation, and MRI application in cardiovascular and cardio-oncology clinical management. This
includes expertise in the technical aspects, analysis, interpretation, and utilization of an innovative exercise
stress-associated cardiovascular MRI technique to discern the mechanism of reduced exercise capacity in
other heart failure syndromes.
This patient-oriented mentored research training plan incorporates a highly innovative technique and an
excellent training environment to develop and test a methodology that identifies the causes of reductions in
peak exercise capacity, a primary determinant of HCT outcomes. The outstanding mentor team will guide the
Candidate’s progress in professional milestones (publications and presentations) and oversee his continued
exposure to responsible conduct of research training. At completion of this K23, Dr. Canada will be well-
qualified to contribute meaningfully to an emerging field of growing research interest.
