Spatial localization techniques are necessary for in vivo NMR spectroscopy involving heterogeneous organisms. Localization by surface coil NMR detection alone is generally inadequate for deep-lying organs due to contaminating signals from intervening surface tissues. However, localization to preselected planar volumes can be accomplished using a single selective excitation pulse in the presence of a pulsed magnetic field gradient, yielding depth-resolved surface coil spectra (DRESS). Within selected planes, DRESS are spatially restricted by the surface coil sensitivity profiles to disk-shaped volumes whose radii increase with depth, notwithstanding variations in the NMR signal density distribution. Nevertheless, DRESS is a simple and versatile localization procedure that is readily adaptable to spectral relaxation time measurements by adding inversion or spin-echo refocusing pulses or to in vivo solvent-suppressed spectroscopy of proton (1H) metabolites using a combination of chemical-selective RF pulses. Also, the spatial information gathering efficiency of the technique can be improved to provide simultaneous acquisition of spectra from multiple volumes by interleaving excitation of adjacent planes within the normal relaxation recovery period. The spatial selectivity can be improved by adding additional selective excitation spin-echo refocusing pulses to achieve full, three-dimensional point resolved spectroscopy (PRESS) in a single excitation sequence. Alternatively, for samples with short spin-spin relaxation times, DRESS can be combined with other localization schemes, such as image-selected in vivo spectroscopy (ISIS), to provide complete gradient controlled three-dimensional localization with a reduced number of sequence cycles.

The longitudinal (T1) and transverse (T2) hydrogen (1H) nuclear magnetic resonance (NMR) relaxation times of normal human and animal tissue in the frequency range 1-100 MHz are compiled and reviewed as a function of tissue type, NMR frequency, temperature, species, in vivo versus in vitro status, time after excision, and age. The dominant observed factors affecting T1 are tissue type and NMR frequency (V). All tissue frequency dispersions can be fitted to the simple expression T1 = AVB in the range 1-100 MHz, with A and B tissue-dependent constants. This equation provides as good or better fit to the data as previous more complex formulas. T2 is found to be multicomponent, essentially independent of NMR frequency, and dependent mainly on tissue type. Mean and raw values of T1 and T2 for each tissue are tabulated and/or plotted versus frequency and the fitting parameters A, B and the standard deviations determined to establish the normal range of relaxation times applicable to NMR imaging. The mechanisms for tissue NMR relaxation are reviewed with reference to the fast exchange two state (FETS) model of water in biological systems, and an overview of the dynamic state of water and macromolecular hydrogen compatible with the frequency, temperature, and multicomponent data is postulated. This suggests that 1H tissue T1 is determined predominantly by intermolecular (possibly rotational) interactions between macromolecules and a single bound hydration layer, and the T2 is governed mainly by exchange diffusion of water between the bound layer and a free water phase. Deficiencies in measurement techniques are identified as major sources of data irreproducibility.

Shortly after the introduction of 1 H MRI, fluorinated molecules were tested as MR-detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine ( 19 F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, 19 F MRI of 'hotspots' of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants.

The heart consumes more energy per gram than any other organ, and the creatine kinase (CK) reaction serves as its prime energy reserve. Because chemical energy is required to fuel systolic and diastolic function, the question of whether the failing heart is ''energy starved'' has been debated for decades. Despite the central role of the CK reaction in cardiac energy metabolism, direct measures of CK flux in the beating human heart were not previously possible. Using an image-guided molecular assessment of endogenous ATP turnover, we directly measured ATP flux through CK in normal, stressed, and failing human hearts. We show that cardiac CK flux in healthy humans is faster than that estimated through oxidative phosphorylation and that CK flux does not increase during a doubling of the heart rate-blood pressure product by dobutamine. Furthermore, cardiac ATP flux through CK is reduced by 50% in mild-to-moderate human heart failure (1.6 ؎ 0.6 vs. 3.2 ؎ 0.9 mol͞g of wet weight per sec, P < 0.0005). We conclude that magnetic resonance strategies can now directly assess human myocardial CK energy flux. The deficit in ATP supplied by CK in the failing heart is cardiac-specific and potentially of sufficient magnitude, even in the absence of a significant reduction in ATP stores, to contribute to the pathophysiology of human heart failure. These findings support the pursuit of new therapies that reduce energy demand and͞or augment energy transfer in heart failure and indicate that cardiac magnetic resonance can be used to assess their effectiveness.heart failure ͉ magnetic resonance spectroscopy ͉ metabolism A TP provides the chemical energy that fuels myocardial contractile function. Relatively large rates of ATP synthesis are required to sustain normal systolic and diastolic function. The ''energy starvation'' hypothesis of heart failure suggests that inadequate ATP supply underlies the contractile dysfunction present in heart failure (1, 2). Large-scale clinical trials demonstrating that pharmacologic agents such as beta-blockers and angiotensin-converting enzyme inhibitors that reduce metabolic demand improve outcomes in heart failure, whereas those such as positive inotropic agents that increase energetic demand worsen outcomes (3) are consistent with the energy-starvation hypothesis. However, the ability to test the energy-starvation hypothesis has been limited, in part, by an inability to directly measure ATP synthesis in the human heart.Creatine kinase (CK) is central to mammalian energy metabolism and serves as the prime energy reserve of the heart. CK reversibly converts ADP and creatine phosphate (PCr) to ATP and creatine (Cr). This reaction allows tight control of ADP and ATP concentrations in cardiac and skeletal muscle as well as in brain, providing a rapid source of ATP during ischemia and burst activity in skeletal muscle (4-6). It is also hypothesized that the CK reaction serves as an intracellular spatial energy shuttle, facilitating the transfer of high-energy phosphates from the mitochondria (where AT...