The History of Nuclear Cardiology

Clinical nuclear medicine began in the mid-1960s when technologists used radioactive materials to provide important information about the anatomy and physiology of various organs and organ systems. In the decades since, researchers and clinicians have used nuclear medicine to detect and diagnose a host of diseases and disorders.
Nuclear medicine’s history originates in the 1920’s, with its first diagnostic application occurring in the field of cardiology. In 1927, Herman Blumgart used injectable solutions of radon gas and a Geiger tube to measure the “velocity of the circulation,” the time it took for the radioactivity to reach the heart, in normal volunteers. He subsequently studied patients with thyrotoxicosis, anemia, polycythemia vera, carcinoma, and heart disease. He examined the effects of physiologic and pharmacologic stresses and with his colleagues, and published 22 articles, chiefly in the Journal of Clinical Investigation.

Since then radiotracers, external radiation detection instruments and sophisticated processing software have been developed to give detailed quantitative information about cardiac function. Regional myocardial blood flow, metabolism, and innervation may be measured noninvasively in individuals with or at risk of diseases of the heart.

Georg de Hevesy used red blood cells labeled with Phosphorous-32 to measure red blood cell volume, inventing the “tracer principle,” the most fundamental in nuclear medicine. A major breakthrough was made by Werner Forssmann in Eberswald, Germany in 1929 when the human heart was first catheterized. In 1936 Paul Hahn used Iron-59 to measure total body hematocrit. Research conducted during World War II led to the introduction of Sulfur-35 as a tracer of plasma proteins. Fein and Seligman invented the radioiodine method for measuring plasma volume. By 1943, radioiodinated bovine albumin, the so-called “first true radiopharmaceutical” was used in humans. Storaasli replaced bovine albumin with human serum albumin (HSA), among the earliest commercially available “radiopharmaceuticals,” as radioactive tracers came to be known.

In 1951 the rectilinear scanner was invented by Benedict Cassen and subsequently used in cardiology to detect pericardial effusion and diagnose pulmonary embolism. This device was capable of rendering static, life-size images of organs which lacked resolution and did not yield quantitative measurements or volumetric data. Jeff Holter, the inventor of the Holter monitor to detect cardiac arrhythmias in ambulatory patients, had the idea to found the Society of Nuclear Medicine in 1954. Two important tools in Nuclear Medicine: the ”scintillation camera” by Hal Anger in 1958 and the commercial development of Technetium-99m in 1960, allowed for the imaging of radiotracers circulating through different portions of the heart in real time. Among the first uses was the detection of intracardiac shunts, soon followed by the measurements of regional myocardial perfusion and regional ventricular function.

The first radiotracer used to measure regional myocardial blood flow was Potassium-43. Exercise stress was developed for increasing the sensitivity of coronary heart disease detection, and in 1973 H. William Strauss introduced the first exercise stress myocardial perfusion exam. This expanded the world of nuclear medicine to include a new technology: Nuclear Cardiology. 201-Thallium was first introduced for myocardial perfusion imaging in 1973 by Elliot Lebowitz, but it was not available commercially until 1977 when New England Nuclear received FDA approval to distribute it for the diagnosis and location of myocardial infarction. Diagnosis was the primary role of nuclear cardiology at that time. Today, advances in technology and radiopharmaceuticals have made nuclear cardiology an important tool for diagnosis and risk stratification and management of patients with known or suspected coronary artery disease.

In 1979, Berger examined the “first pass” of 99mTc tracers through the heart to evaluate left and right ventricular function in patients with coronary heart disease, chronic obstructive lung disease, and congenital heart disease. Global ventricular function and regional contraction of the ventricles could be studied, and quantitative measurements of stroke volumes, ejection fractions, and ventricular filling and emptying rates could be calculated.

Hal Anger invented the positron and single photon multiplane tomographic scanners that have become such important tools for diagnostic cardiac imaging. Single photon emission tomography (SPECT) allowed us to electronically slice the left ventricle into the short axis, horizontal long and vertical long axis planes in order to evaluate regional perfusion. The application of positron emission tomography (PET) offers better spatial resolution and quantification than SPECT technology. Today there are a number of radiopharmaceuticals useful in the study of myocardial perfusion, glucose and fatty acid metabolism, and autonomic innervation of the heart. 15-O water is the most widely used positron emitter worldwide in nuclear cardiology but requires a cyclotron at the site of the examinations. 15N-ammonia is useful as a tracer of blood flow, but is not commercially available. 82-Rubidium, with properties similar to Thallium-201, is beginning to be more widely used for examining myocardial perfusion. Regional metabolic imaging with 18F-deoxyglucose is useful in detecting myocardial viability in patients being considered for surgical intervention. Heart failure and better care of patients with arrhythmias are likely to become major foci of nuclear cardiology in the near future. Newer techniques involving the detection of plaques on coronary arteries are being developed to help physicians screen for early coronary disease.