Solvent-suppression NMR techniques are combined with a pulsed magnetic field gradient and surface coil detection method of spatial localization. The result is a technique that enables observation of metabolites in the hydrogen (1H) NMR chemical-shift spectra from preselected disk-shaped volumes of biological tissue in vivo. Localized spectra are recorded from the normal human brain and forearm and from a dog in acquisition periods of 2 s using a 1.5-T imaging/spectroscopy system. This is several hundredfold faster than acquiring similar state-of-the-art 31P NMR spectra of brain metabolites in vivo. Spectroscopy experiments are followed by conventional surface coil imaging sequences to precisely defrne the selected volume. Contamination of spectra by lipid resonances is a problem.Localized phosphorus (31P) NMR is proving a valuable tool in the in vivo investigation of animal models of stroke (1-5), myocardial ischemia (6-8), tumors (9, 10), and the efficacy of drug therapy (11, 12) as well as human muscular metabolic diseases (13-15) and cerebral disorders in neonates (16). Its value resides in the ability to detect and monitor intracellular pH and in vivo concentrations of metabolites such as phosphocreatine (PCr), ATP, and Pi, which directly measure the state of health of tissue. A major impediment limiting utility of this technology in clinical medicine is the low sensitivity of the 31P resonance. Thus, data acquisition times are typically of the order 10 min for a single coarsely resolved localized volume of the order 20 cm3 in the currently available large-aperture, 1.5-to 2-T, magnet-based spectroscopy systems (16)(17)(18).Nucleus for nucleus, the hydrogen (1H) resonance offers a 15-fold improvement in signal-to-noise ratio (19, 20) or a reduction by a factor of 227 in signal averaging time over 31p NMR at the same magnetic field strength. 1H NMR spectra can reveal the relative concentrations of the total PCr/creatine (Cr) pool, phosphocholine (PCho), N-acetylaspartate (N-AcAsp), some lipid (-CHY-), and lactate metabolites.Such resonances have been detected in vivo in rat brain (21) and isolated perfused heart spectra at 8.5 T (22) and recently in rabbit brain at 1.9 T (23), all with spectral averaging times of 2-2.5 min and sample volumes of the order 1-10 cm3. The amplitude of the lactate (-CH3) resonance appears as sensitive to hypoxia and ischemia as the Pi resonance in 31p spectra and contains 3-fold as many nuclei. Thus, localized in vivo 1H NMR spectroscopy could provide spectacular sensitivity/scan time advantages over 31p for certain metabolic studies and clinical applications.Key difficulties encountered with the implementation of in vivo 1H metabolic spectroscopy are the suppression of H20 and lipid -CH2-resonances (21-23) and the method of spatial localization. The H20 resonance is of order 10,000-fold more intense than the metabolites and normally swamps the spectrum. Solvent-suppression techniques that rely on avoiding excitation of the H20 resonance (24) are unsuitable for localized...