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At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography (PET) and, more recently, magnetic resonance imaging (MRI). The signal used by PET is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. PET provided a level of precision in the measurement of blood flow that opened up the modern era of functional human brain mapping. Further, the discovery with PET that these changes in blood flow are unaccompanied by quantitatively similar changes in oxygen consumption has paved the way for the explosive rise in the use of MRI in functional brain imaging. The remarkable success of this enterprise is a fitting tribute to men like Michel Ter-Pogossian. He pioneered the use of positron emitting radionuclides in biology and medicine when most had abandoned them in favor of more conventional nuclear medicine radionuclides. Importantly, also, he welcomed into his laboratory young scientists with a broad range of talents, many of whom subsequently became leaders in imaging the mind in research centers throughout the world.

The development of positron emission tomography (PET) illustrates how advances in basic science translates into benefits for human beings. In 1930 Ernest Lawrence and co-workers conceived of the cyclotron. By 1938 Lawrence, Livingston, et al had designed a "medical cyclotron." The subsequent production of C-11, N-13, O-15, and F-18 found many uses in medical and physiologic research. The introduction of F-18 deoxyglucose represents another major step toward practical clinical use of positron-emitting tracers. We have now achieved the transition from the postulation of the existence of positrons to their use in a wide variety of diseases.

Nuclear medicine translates advances in molecular biology into the care of patients. In the future, diseases will be characterized at the molecular rather than the cellular level, often before detectable structural changes have occurred. Position emission tomography (PET) will play a major role in the study of intercellular communication by making it possible to characterize the actions of "molecules with messages." Diseases will be characterized by defects in intercellular communication. Treatment will be planned based on molecular abnormalities, and the response to treatment will be monitored with molecular probes. PET studies of the brain, heart, and cancer will be extended to all organs of the body. Pharmacology will be strongly influenced by PET because most drugs act by stimulating or blocking "recognition sites" on the surface of cells. In the next century, will single photon emission computed tomography (SPECT) makes PET unnecessary? The answer is no, because both PET and SPECT will have achieved a permanent role in medical practice; both make it possible to examine regional in vivo chemistry in human beings. Carbon-11 and fluorine-18 will continue to lead the way, but many drugs, and some body constituents such as proteins, can be radiolabeled with iodine-123 and technetium-99m. Today, PET is limited by the need to make one's own radiotracers. This is likely to change when regional radiopharmacies become widespread.(ABSTRACT TRUNCATED AT 250 WORDS)

The development of positron emission tomography (PET) took place through the combination of the following recognitions: (1) a handful of short-lived, positron-emitting radionuclides, carbon-11, nitrogen-13, and oxygen-15, exhibit chemical properties that render them particularly suitable for the tracing of important physiological pathways, and (2) the radiation emitted as a result of the annihilation of positrons in matter exhibited physical properties that made it well-suited for nuclear medicine imaging, particularly for tomographic reconstruction. The scientific building blocks that were necessary for the structure of PET were contributed over a period of several decades by many investigators in physics, mathematics, chemistry, and fundamental biology.