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We performed 31P magnetic resonance spectroscopy of gastrocnemius muscle at rest in 7 normal volunteers and 12 patients with sickle cell disease (7 with leg ulcers and 5 without leg ulcers but with painful crises). We measured intracellular pH and ratios of Pi to ATP, PCr to ATP and PCr to Pi (Pi = inorganic phosphate, ATP = adenosine triphosphate, and PCr = phosphocreatine). Magnetic resonance arteriograms were also performed. Significant differences were found for PCr/Pi ratios between normals and sickle cell disease patients with leg ulcers (p < 0.008). Magnetic resonance arteriograms were normal in volunteers and patients with sickle cell disease. The altered high energy phosphate metabolism in sickle cell disease with leg ulcers is consistent with muscle ischemia or hypoxia.

Determination of the chemical shift and integral of the myocardial intracellular inorganic phosphate (Pi) resonance by 31P magnetic resonance spectroscopy (MRS) is often precluded due to a large overlapping signal from 2,3-diphosphoglycerate (2,3-DPG) from chamber and myocardial blood. This report demonstrates the use of radiofrequency (RF) magnetic field gradient echoes (RFGE) to eliminate signals from 2,3-DPG in flowing blood, while retaining signals from intracellular myocardial Pi, ATP, and phosphocreatine (PCr). The ECG-triggered 31P spectra were acquired from the myocardium of open chest pigs using a Philips Gyroscan 2-T magnetic resonance spectrometer. A 2.5-cm-diameter surface coil attached to the myocardium was used to provide the RF gradient as well as for excitation and detection of signals. Optimal performance of the RFGE pulse sequence was obtained when the RF gradient pulses were centered at peak diastole or peak systole. Under these conditions, 2,3-DPG signals were completely suppressed, and sensitivity was usually sufficient to allow detection of a well-resolved Pi signal. Myocardial pH determined from RFGE experiments was 7.16 +/- 0.10, and the ratio of the integrals of the Pi and ATP resonances (Pi/ATP) was 0.24. The mean signal-to-noise ratio (S/N) for PCr in control spectra acquired in 4 min was 19/1, while the mean S/N for PCr in RFGE-edited spectra acquired in 15 min was 11/1, demonstrating that the present implementation of the RFGE method results in significant loss in sensitivity. These experiments demonstrate that RFGE-editing allows accurate determination of the chemical shift and integral of the Pi resonance in blood-perfused myocardium in situ.

Previous studies have noted that myocardial blood flow and high energy phosphates are heterogeneous across the myocardial wall during ischemia. In order to determine whether differences in metabolites between the subendocardium and subepicardium could be detected using 31P magnetic resonance spectroscopy, the Fourier series window (FSW) experiment was implemented on a porcine model of graded regional ischemia. FSW experiments using a planar phantom showed a 46% improvement in localization to the subendocardium compared to a one-pulse experiment. Animal studies of graded ischemia demonstrated a gradient in the phosphocreatine to inorganic phosphate ratio in the myocardium that paralleled the gradient in blood flow. These studies demonstrate the ability of spatially localized 31P magnetic resonance spectroscopy to detect regional changes in myocardial high energy phosphates localized to the subepicardium and subendocardium.

The changes in myocardial high energy phosphates and pH during regional ischemia, and their potential role in mediating functional abnormalities, is unclear. To determine the degree of regional blood flow reduction required to induce changes in high energy phosphates and pH, and to correlate these metabolic changes with alterations in blood flow, 31P nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional blood flow and phosphate compounds were made during various steady-state degrees of regional ischemia in which subendocardial blood flow was reduced by as much as 80%. ATP did not fall over the total range of graded ischemia, while phosphocreatine (PCr), inorganic phosphate (Pi), and pH all changed progressively after blood flow was reduced below 50% of normal. The ratio of PCr/Pi (a measure of the energy reserve of the myocardium) was strongly correlated to subendocardial blood flow (r = 0.94) and declined by 25% when blood flow was reduced by only 21% below normal. These findings indicate that PCr/Pi is a sensitive marker of ischemia and support the hypothesis that the in vivo energy status of the myocardium is closely coupled to myocardial blood flow.

Localized phosphorus-31 magnetic resonance (MR) spectroscopy in humans has previously been accomplished with surface coils by means of depth-resolved surface coil spectroscopy or rotating frame experiments, in which the extent of tissue sampled critically depends on surface coil placement. The authors' goal was to modify the surface coil image-selected in vivo spectroscopy (ISIS) experiment to accomplish three-dimensional volume selection through application of selective pulses in the presence of B0 gradients. Advantages of ISIS include the ability to use proton images to define the volume of interest (VOI) and reduced dependence on exact positioning of the surface coil. However, rapid replication of the surface coil ISIS experiment can cause spectral contamination from signals originating outside the VOI. A modified version of the ISIS experiment was developed to alleviate contamination under conditions of rapid replication. Applications of localized P-31 MR spectroscopy for observation of high-energy phosphorus metabolites are presented in human liver, heart, and transplanted and normal kidney.

Magnetic resonance spectroscopy (MRS) is a valuable tool for the study of myocardial ischemia. Phosphorus (31P) MRS can detect changes in high-energy phosphates resulting from ischemia and has been used to determine the sensitivity of metabolic changes to ischemia as well as to investigate the metabolic factors important for myocardial dysfunction. The mechanisms mediating postischemic dysfunction have been investigated using 31P MRS, as have interventions to limit metabolic and functional damage from ischemia. These investigations have laid the groundwork for human cardiac studies. While abnormalities following myocardial infarction have been shown in man, further work must be performed to reliably acquire localized spectra under conditions of ischemia.

In in vivo phosphorus magnetic resonance spectroscopy (MRS), spectroscopic imaging (SI) can be used as a flexible localization technique, producing spectra from multiple volumes in a single examination. Presented here are phosphorus SI studies of human organs in which a selective-volume SI reconstruction was used rather than the usual array-format SI reconstruction. A linear predictor technique was used to estimate the initial points of the free induction decay missing because of the delay needed for phase-encoding gradients, significantly reducing the baseline artifacts which commonly complicate interpretation of SI spectra. In studies of heart, brain, liver, and kidney, the performance of SI was found to compare favorably with that of ISIS. SI phosphorus metabolite intensity images from a brain tumor patient were obtained at 2 X 2-cm in-plane resolution (with "slice" thickness of roughly 16 cm, determined by coil sensitivity) in 34 min, demonstrating the feasibility of obtaining clinically useful metabolite images in clinically reasonable examination times.