The pioneering accomplishments and vision of Charles A. Mistretta in developing digital subtraction angiography (DSA), time-resolved magnet resonance angiography (MRA), and accelerated imaging algorithms have transformed diagnostic radiology. During the 1970s, screen film X-rays were the standard for radiography and angiography. However, film angiograms were limited due to interference from overlying anatomy. Mistretta recognized the importance that electronic subtraction in imaging could play in providing vascular images that were free of obscuring anatomy. Incorporating a hand-made, custom-designed digital image processor, Mistretta introduced his DSA technique. He went on to refine and optimize DSA to provide virtually real-time visualization of vascular structures without obstructions, revolutionizing angiography with a safer and more effective technology that is now found in practically every medical center. DSA is also considered an enabling technology that made minimally invasive vascular therapeutic procedures such as angioplasty and stenting possible. During the 1990s, Mistretta applied DSA technology to overcome the limitations of slow magnetic resonance data acquisition in contrast-enhanced MRA techniques. He developed the time-resolved imaging of contrast kinetics (TRICKS) method for three-dimensional visualization of previously difficult-to-image vascular beds. TRICKS provides clinicians with dynamic vascular information and eliminates the timing uncertainty associated with single-image contrast-enhanced MRA. This radiation-free MRA method uses less toxic contrast material and is performed intravenously rather than intra-arterially for enhanced safety and effectiveness. Mistretta’s recent efforts include work on image acceleration. His highly constrained reconstructions from projections (HYPR) method provides rapid accelerations of dynamic or parametric imaging by using imaging data acquired over a short time interval to weight an image acquired over a much longer time interval.
A member of the U.S. National Academy of Engineering, Mistretta is a professor with the Department of Medical Physics, Radiology, and Biomedical Engineering at the University of Wisconsin-Madison, Madison, WI, USA.
Takuo Aoyagi’s development of the fundamental principles of pulse oximetry has led to an indispensable clinical tool for noninvasive monitoring of blood oxygen levels that has improved patient safety during anesthesia and practically all other facets of healthcare. In 1972, while investigating a noninvasive cardiac output device, Dr. Aoyagi discovered that arterial pulsatile “noise” interfering with the accurate dye dilution curve carried important information about the oxygenation of arterial blood. This led him to establish the principle of pulse oximetry using light signals of two different wavelengths. Based on his discovery, in 1975 he introduced the first commercially available pulse oximeter. Consisting of a probe containing a light-emitting device and two photodetectors, Dr. Aoyagi’s pulse oximeter could pass two wavelengths of light through the earlobe to the photodetectors to measure the changing absorbance at each of the wavelengths based on pulsing arterial blood. The device’s ability to rapidly and noninvasively assess the hemodynamic and respiratory condition of patients allows clinicians to detect abnormalities earlier and avoid patient harm as well as gauge the effectiveness of clinical interventions in real time. All of today’s pulse oximeters are based on Dr. Aoyagi’s original principles of pulse oximetry. Dr. Aoyagi has continued to advance the development of oxygen monitoring technologies and inspire generations of medical technology innovators around the world. Pulse oximetry is now considered the standard of care for patients undergoing anesthesia and for treatment in emergency rooms and intensive care units and for home care. In 2007, the World Health Organization included pulse oximetry as an essential component of its Surgical Safety Checklist for reducing complications.
An IEEE member and recipient of the Gravenstein Lifetime Achievement Award from the Society for Technology in Anesthesia (2013), Dr. Aoyagi is currently senior manager of the Aoyagi Research Laboratory at Nihon Kohden Corporation, Nakano-ku, Tokyo, Japan.
Leroy Hood’s development of five groundbreaking instruments, including the automated DNA sequencer, has helped unlock the mysteries of human biology and provided the foundation for the field of genomics, revolutionizing our understanding of genetics in the process. Moreover, two of these instruments—the automated DNA sequencer and the ink-jet DNA synthesizer—led to the concepts of high throughput biology and big data. A pioneer in bringing engineering to biology, Dr. Hood’s development of the DNA sequencer in 1986 allowed the rapid automated sequencing of human genomes. This instrument became the driving force of the Human Genome Project, enabling the reading of the entire human genetic code. Prior to the DNA sequencer, it took 30 years to map the genome of the cold virus. With the DNA sequencer, genomes of some viruses can now be mapped in less than an hour. Dr. Hood’s creation of the DNA synthesizer in 1987 made it possible to synthesize DNA fragments for sequencing and cloning complete genes. His development of the inkjet DNA synthesizer in 2004 enabled the creation of DNA chips that can measure the expression levels of tens of thousands of genes. Dr. Hood also developed a protein synthesizer (1981) and protein sequencer (1985) that helped establish the field of proteomics. His protein sequencer made it possible to determine the amino acid sequence of proteins present at vanishingly small concentrations. This resulted in the characterization of many new proteins and the cloning of their corresponding genes—opening up many new biological fields including the identification of the first oncogene. His protein synthesizer enabled the creation of an AIDS protease inhibitor, which was highly effective in treating AIDS. Dr. Hood has combined his genomic and proteomic expertise with mathematical modeling to form the discipline of systems biology, which has transformed biology and will be a key enabler of predictive and personalized medicine.
One of only 15 individuals elected to all three U.S. National Academies (the National Academy of Science, the National Academy of Engineering, and the Institute of Medicine), Dr. Hood is president and co-founder of the Institute for Systems Biology, Seattle, WA, USA.
Robert S. Langer is considered the single greatest contributor to medical nanotechnology for his pioneering research and inventions that have provided innovative methods to improve the diagnosis and treatment of disease for countless patients. Dr. Langer’s development in 1976 of principles enabling the use of polymers for the slow delivery of large molecules, such as peptides, has provided the foundation for much of today’s drug-delivery technology. Considered seminal to the field of “controlled release” for treating diseases, Dr. Langer’s work has led to drug-delivery systems providing numerous therapies to over a hundred million patients every year that otherwise would not be possible. Dr. Langer developed the first localized, long-acting chemotherapy treatment for brain cancer providing direct delivery to the tumor. His localized delivery concepts have also been applied to polymer-coated stents for treating cardiovascular disease and eliminating restenosis. Dr. Langer is responsible for creating the field of tissue engineering, helping develop the first approach to creating systems that deliver cells on three-dimensional polymer systems. He also discovered approaches to controlling stem-cell differentiation and stem-cell growth. Thousands of scientists today are creating life-saving tissue-engineered products based on Dr. Langer’s research.
An IEEE member, Dr. Langer is one of a very few individuals elected to the U.S. Institute of Medicine, the U.S National Academy of Engineering, and the U.S. National Academy of Sciences. Dr. Langer’s many awards include the Charles Stark Draper Award (2002), the Albany Medical Center Prize (2005), the U.S. National Medal of Science (2007), the U.S. National Medal of Technology and Innovation (2011), and the Wolf Prize in Chemistry (2013). Dr. Langer is the David H. Koch Institute Professor at the Massachusetts Institute of Technology, Cambridge, MA, USA.
Savio L-Y. Woo’s pioneering biomechanics research has profoundly impacted sports medicine and the management of ligament and tendon injuries, leading to improved patient recovery. From research at the cellular and tissue level to developing computer and robotic models of joints, Dr. Woo, together with his six hundred students, post-doctoral fellows, and colleagues, has provided key insight to understanding the function of bone and connective tissue and has led sports medicine and orthopedic surgery into the 21st Century. Dr. Woo helped develop the “controlled motion is good” concept, showing the benefits of joint movement and early weight-bearing activities during rehabilitation compared to immobilization following surgery. His approach to robotic testing of knee and shoulder movement helped define the beneficial effects of motion. He applied computer modeling and robotic technology to study joint mechanics and the effects of injury on joint function. Dr. Woo used robots to produce motions that occur during everyday activities and to determine the forces that the motions generate in the ligaments of the joints. Dr. Woo’s work has resulted in much faster recovery time for patients with soft-tissue injuries. More recently, he has focused on using novel functional tissue engineering to heal and regenerate ligaments and tendons at the cellular, tissue, and organ levels using bioscaffolds.
Dr. Woo began his career at the University of California, San Diego, as a professor of surgery and bioengineering in 1970 and moved to the University of Pittsburgh in 1990, where he founded the Musculoskeletal Research Center (MSRC). Dr. Woo is currently a Distinguished University Professor and Director of the MSRC within the University of Pittsburgh’s Department of Bioengineering and Swanson School of Engineering, Pittsburgh, Pa.
Considered one of the top imaging scientists in the world for his knowledge of the underlying physics and mathematics of biomedical imaging, Harrison H. Barrett has broadly impacted the field with contributions to instrumentation, reconstruction algorithms, and image quality assessment. He has provided a rigorous theoretical basis and clearly defined experimental and computational paradigms for the assessment and optimization of image quality. His work led to improved understanding of single photon emission computed tomography (SPECT) imaging, which uses gamma rays to provide three-dimensional imaging of the brain, tumors, and bone. Dr. Barrett’s research on image quality assessment has revolutionized how medical imaging systems are evaluated. He implemented numerical observers that allow a computer to analyze images instead of using human observers, overcoming what can be a lengthy process. Quantitative image quality assessment is now a requirement for practically all biomedical imaging. As early as 1972, he published some of the first results on using coded apertures for high-resolution tomographic imaging in nuclear medicine. During the 1980s and 1990s, he developed methods to improve the resolution-sensitivity trade-off in SPECT systems. He developed a stationary hemispherical SPECT system for human brain imaging and the FastSPECT and FastSPECT II systems for fast dynamic imaging in small animals. Recent developments include semiconductor arrays for high-resolution gamma-ray imaging. He co-founded the University of Arizona Center for Gamma-Ray Imaging in 1998.
An IEEE Fellow, Dr. Barrett is currently Regents Professor and director of the Center for Gamma-Ray Imaging at the University of Arizona, Tucson.
The creation of the hybrid positron emission tomography (PET)/computed tomography (CT) scanner by Ronald Nutt and David W. Townsend revolutionized diagnostic medical imaging and has enabled earlier detection of cancer and better monitoring of treatment efficacy. Introduced in 1999, the PET/CT scanner incorporates the individual strengths of existing CT and PET technology while overcoming their respective stand-alone limitations. The hybrid PET/CT scanner provides precise spatial registration of anatomy and function in a single diagnostic imaging examination. The original idea for the PET/CT scanner came when Drs. Nutt and Townsend, while working together on a PET scanner design, recognized the opportunity for integrating CT components into the gantry of an existing PET design. Dr. Townsend led the academic efforts to develop PET/CT methods and conduct the first human studies using the scanner. Dr. Nutt was instrumental in building the first prototype PET/CT system as well as developing the first commercial versions. The PET/CT scanner was named “Medical Invention of the Year” in 2000 by Time magazine. The technology was quickly adopted by industry, with more than 95% of all PET scanners sold in 2004 being PET/CT scanners. By 2006, practically all stand-alone PET scanners had been replaced by PET/CT scanners.
Dr. Nutt also was the co-developer and inventor of the gamma-ray detector known as the “block” detector that has been standard in PET for the past 20 years. An IEEE Fellow, he is currently the chairman of the Board of Advanced Biomarker Technologies, Knoxville, Tenn.
Dr. Townsend is considered the leading authority on hybrid imaging systems as well as one of the pioneers of three-dimensional PET and its required reconstruction algorithms. An IEEE Fellow, he is currently head of PET and SPECT development for the Singapore Bio-imaging Consortium under the Agency for Science, Technology and Research and Professor of Radiology, National University of Singapore.