Following 11th grade and without graduating from high school, Pettigrew accepted an early admission scholarship from Charles E. Merrill, Jr., to attend Morehouse College in Atlanta, Georgia.

In 1983, Pettigrew undertook a position as clinical research scientist at Picker International, Inc., where he began work in developing nuclear magnetic resonance imaging, later called MRI, specifically for the heart.

In 1984, Pettigrew received a fellowship from the Robert Wood Johnson Foundation (RWJF) in their Harold Amos Medical Faculty Development Program, created to help achieve more appropriate representation and inclusion of minority scientists and scholars in academia.

This talk, titled Four Dimensional Cardiac MRI: Diagnostic Procedure of the Future, predicted the advanced medial technological approach being realized and built upon today.

In the 1990s, through appointments as professor in the Department of Cardiology at the Emory University School of Medicine, where he directed the Emory Center for Magnetic Resonance Research, and in the Department of Bioengineering at the Georgia Institute of Technology, his research continued to focus on applying MRI to the diagnosis of a variety of cardiac disorders, quantifying heart-wall function, imaging coronary arteries, and in quantifying blood flow across heart valves and in vessels, including congenital heart anomalies.

In 2002, Pettigrew was named the first director[3] of NIBIB, after contentious and prolonged effort by the national medical imaging[4] and bioengineering communities to establish an NIH institute that is dedicated to advancing health through these catalytic fields, known to be engines of scientific progress.

Pettigrew also conceived the NIBIB Quantum Grants Program, designed to target major medical problems that would be transformative for health care and could be solved by technological innovation over a decade.

In remarks[7] made in 2007, Pettigrew called the Quantum Program awards "Medical Moonshots," an analogy to President Kennedy's 1961 challenge to land a man on the moon before the end of the decade.

On behalf of NIH, Pettigrew currently also serves as the liaison to the U.S. Department of Energy and to the National Aeronautics and Space Administration (NASA), and is co-chairman of the Interagency Working Group on Medical Imaging, convened by the White House Office of Science & Technology Policy (OSTP).

He was elected to the National Academy of Engineering (NAE) in 2010 for "the use of MRI in human blood-flow studies and for leading advancements in bioengineering research and education as the initial director of NIBIB.