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The effect of cyclophosphamide (Cp) on the glycolytic rate of radiation-induced fibrosarcomas (RIF-1) was measured in vivo in C3H mice by following the production of [3-(13)C]lactate after tail vein infusion of labeled [1-(13)C]glucose. Cp administered i.p. at a dose of 300 mg/kg caused a significant drop in glycolytic rate 24 h after treatment (P0.01). This drop was accompanied by an increase in [C-3]/[C-4] glutamate ratio in perchloric acid extracts of the tumors, indicating an increase in the Kreb's cycle activity. Treatment with Cp led to a significant decrease (P0.01) in tissue pO(2), measured in vivo with an oxygen Eppendorf electrode. Increases in NADH levels were also observed in rapidly frozen excised tumors examined by three-dimensional optical redox scanning. A significant decrease in tumor pO(2) and an increase in the NADH levels are suggestive of an increase in oxygen consumption by these tumors after Cp treatment. Overall, these data indicate that the reduction in glycolytic rate of Cp-treated RIF-1 tumors is due to an increase in aerobic metabolism.

The possible relationships between intracellular Na+ (Na1+), bioenergetic status and intracellular pH (pH1) in the mechanism for ischemic preconditioning were studied using 23Na and 31P magnetic resonance spectroscopy in isolated Langendorff perfused rat heart. The ischemic preconditioning (three 5-min ischemic episodes followed by two 5-min and one 10-min period of reperfusion) prior to prolonged ischemia (20 min stop-flow) resulted in a decrease in ischemic acidosis and faster and complete recovery of cardiac function (ventricular developed pressure and heart rate) after 30 min of reperfusion. The response of Na1 during ischemia in the preconditioned hearts was characterized by an increase in Na+1 at the end of preconditioning and an accelerated decrease during the first few minutes of reperfusion. During post-ischemic reperfusion, bioenergetic parameters (PCr/P1 and βATP/P, ratios) were partly recovered without any significant difference between control and preconditioned hearts. The reduced acidosis during prolonged ischemia and the accelerated decrease in Na1+ during reperfusion in the preconditioned hearts suggest activation of Na+/H+ exchanger and other ion transport systems during preconditioning, which may protect the heart from intracellular acidosis during prolonged ischemia, and result in better recovery of mechanical function (LVDP and heart rate) during post-ischemic reperfusion.

Nuclear magnetic resonance (NMR) is the basic physical phenomenon in which certain nuclei absorb and emit radiofrequency (RF) radiation while in the presence of a magnetic field. The noninvasive nature of NMR techniques, including magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), has allowed explosive developments in biomedical applications since the late 1970s. MRI of protons is now a widely accepted clinical imaging technique, whereas MRS of various nuclei, including 31P, 1H, 13C, 23Na, and 19F, can provide a vast amount of metabolic and physiological information. MRI provides significant advantages over many other imaging techniques in terms of resolution, contrast, and its noninvasive nature. Although not as common in clinical medicine, MRS also provides valuable metabolic information that cannot be obtained by other techniques. This article reviews the fundamentals of spatial encoding, contrast, artifacts, and applications of MRI as well as some recent advances in the field. Some applications of biomedical MRS of various nuclei are also discussed.

We describe the characterization of a (23)Na temperature-dependent chemical shift and relaxation rates in the complex, Na(4)HTm[DOTP]. This is the first characterization of a (23)Na temperature-dependent chemical shift in a nonmetallic sample. The (23)Na temperature-dependent chemical shift coefficient is approximately -0. 5 PPM/ degrees C for both an aqueous solution and a 6% agarose gel of this compound. This is 50 times the magnitude of the temperature-dependent chemical shift coefficient of water protons. The relaxation times, T(1), T(2f), and T(2s) increased by 0.1, 0.01, and 0.05 ms/ degrees C, respectively. Applications of these unique properties for designing an MRI technique for monitoring heat deposition in tissue and tissue phantoms are discussed.

A method is presented to measure the absolute concentration of intracellular Na+([Na+]i) in vivo by using interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectroscopy and TmDOTP5− as shift reagent and chemical marker of tissue extracellular space (ECS). The technique was used to determine [Na+]iand relative ECS in livers of control rats (21 ± 3 and 0.11 ± 0.02 mM, respectively) and in rats exposed to carbon tetrachloride (103 ± 29 and 0.23 ± 0.03 mM, respectively). The NMR measurements were confirmed independently on excised tissue samples by using atomic absorption spectroscopy. The results confirm that TmDOTP5− can be used as a combined cation shift reagent and ECS marker, thereby allowing quantitation of [Na+]iin vivo by NMR.

Triple quantum (TQ)-filtered 23 Na NMR spectroscopy and the shift reagent, TmDOTP 5- , have been used to evaluate the contributions of intra- (Na i + ) and extracellular (Na e + ) sodium to the TQ-filtered signal in the rat liver, in situ. Na e + contributed significantly to the total TQ-filtered signal in live animals, and the intensity of this signal did not change postmortem. The TQ-filtered Na i + signal increased by approximately 380% over a period of 1 h postmortem, whereas the single quantum (SO) Na i + increased by 90%. The constancy of the TQ-filtered Na e + signal indicates that changes in total TQ-filtered 23 Na signal intensity in liver (without a shift reagent) may accurately reflect changes in TQ-filtered Na i + signal intensity. The large percent increase in the TQ-filtered Na i + signal as compared to the SO signal suggests that the fraction of Na i + interacting with macromolecules increases after death.

The authors used fluorine-19 inversion-recovery (IR) echo-planar imaging (EPI) to map oxygen tension on the basis of the spin-lattice relaxation rate (R1) of sequestered perfluorocarbon. R1 measured with IR-EPI varied as a linear function of oxygen tension and temperature, and the relationship agreed well with earlier spectroscopic findings. Oxygen tension maps of a mouse that had received a dose of perflubron emulsion were acquired before, during, and after the mouse breathed pure oxygen. Results showed low liver oxygen tension during air breathing, which increased during breathing of pure oxygen, with distinct regional heterogeneity, to 8-17% atm (60-130 torr [8.0-17.3 kPa]).

The use of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate (TmDOTP5-) as an in vivo 23Na NMR shift reagent for rat liver was evaluated by collecting interleaved 23Na and 31P spectra. Infusion of 80 mM TmDOTP5- without added Ca2+ produced baseline-resolved peaks from intra- and extracellular sodium without producing any changes in phosphate metabolite resonances or intracellular pH. Several key physiological parameters measured in parallel groups of animals confirmed that liver physiology is largely unaffected by this shift reagent. A direct comparison of TmDOTP5- versus DyTTHA3- showed that after infusion of 5-8 times more DyTTHA3-, the extracellular sodium peak shifted by the same amount as with TmDOTP5-, but the two 23Na resonances were very broad and not resolved. The baseline-resolved peaks with TmDOTP5- allowed us to measure the in vivo T1 and T2 relaxation characteristics of intra- and extracellular Na+. The measured T1, T2s, and T2f values and the relative contributions from the slow and fast T2 components for intracellular Na+ in liver did not differ significantly from the values reported for perfused frog heart. The T1 and T2 relaxation curves of the extracellular Na+ resonances fit a monoexponential function. Analysis of the relative contribution of the fast- and slow-relaxing T2 components from intracellular Na+ resulted in a calculated visibility factor of 69 +/- 4% and the intracellular Na+ concentration calculated from the NMR peak intensity ratio, the measured visibility factor, and literature values of intra- and extracellular volume was 19 mM. These results indicate that TmDOTP5- promises to be quite useful as an in vivo shift reagent for liver and other organs.