Whole-body MR imaging and spectroscopy with a 4-T system

The clinical potential and limitations of magnetic resonance imaging and spectroscopy at 4 T were investigated with the use of a newly constructed system, which has been in use since January 1987. The magnet has a warm bore that measures 1.25 m in diameter, and its homogeneity in a sphere with a diameter of 50 cm is better than +/- 2.5 ppm. It was hypothesized that the improvement in the signal-to-noise ratio (S/N) afforded by the higher field strength would be useful in reducing imaging time and in improving spatial resolution. In experiments in human volunteers, believed to be the first in which an entire human body was exposed to a magnetic flux density of that magnitude, the subjects were exposed to 4 T for 10-30 minutes. They showed no changes in well-being or heart activity. The expected gain in spectral resolution due to chemical-shift scaling was achieved with the 4-T system, and an improvement in S/N was verified for phosphorus at 34 and 68 MHz. In sodium imaging, the high flux density appears to be useful in reducing imaging time, which should increase the usefulness of sodium imaging in evaluating brain tumors and strokes. In spectroscopy, the increase in flux density improves the quality of the spectra.     

Rapid-sequence phosphorus-31 magnetic resonance spectroscopy of the human heart using a 1.5-T clinical system

PURPOSE: To compare a 'standard' slow phosphorus-31 magnetic resonance spectroscopy (31P-MRS) sequence with two faster sequences in phantoms and healthy volunteers using a 1.5-T clinical system. MATERIAL AND METHODS: Complete 3D localization was performed using a 2D phosphorus chemical-shift imaging sequence in combination with 30-mm axial slice-selective excitation. Two 31P-MRS rapid sequences (RS8-4: 8 x 8 phase-encoding, with an average of 4 acquisitions, and RS16-1: 16 x 16 phase-encoding, 1 acquisition) were compared with the standard sequence (StdP: 16 x 16 phase-encoding, with an average of 8 acquisitions) in phantom and healthy volunteers. RESULTS: Acquisition time for the 31P-MRS procedure with StdP, RS8-4, and RS16-1 in the healthy volunteer studies ranged from 30 to 45, 3 to 5, and 3 to 5 minutes, respectively. Metabolite measurements of healthy volunteers obtained from 31P-MRS using RS8-4 correlated with values obtained using StdP (PCr r2=0.63, P<0.001; ATP r=0.41, P<0.01 and PCr/ATP ratio r2=0.25, P<0.05). There was no correlation between StdP and RS16-1 for either ATP or the PCr/ATP ratio (r2=0.03, P=0.60, and r2=0.11, p=0.26, respectively). Reproducibility (intensity of phosphorus signal) with RS16-1 was worse than that of RS8-4 or StdP. CONCLUSION: 31P-MRS using RS8-4 may be a valid diagnostic tool for patients with cardiac diseases.     

In vivo MR spectroscopy of human subjects with a 1.4-T whole-body MR imager

A 1.4-T magnetic resonance (MR) imager was modified to perform MR spectroscopy measurements. The implementation involved only a few additions in hardware and practically no change in software. Procedures for acquiring the MR spectra are similar to those for MR images. Both sensitivity and homogeneity were found to be adequate over a region 12 cm in diameter. Typical scanning times are 4.5 minutes for human brain, 2.8 minutes for muscle, and 20-35 minutes for solid tumors. Preliminary spectral studies of the metabolism of human brains, tumors, and a muscle of the forearm during exercise obtained with the modified system are presented.     

In vivo nuclear Overhauser effect in 31P-(1H) double-resonance experiments in a 1.5-T whole-body MR system

In 31P-(1H) MR experiments of humans in a 1.5-T whole-body system, signal intensity enhancements of 31P resonances of up to 68 +/- 4% (for phosphocreatine of the calf muscle) have been observed upon irradiation at proton frequency. This observation is explained as a nuclear Overhauser effect due to the dipolar coupling between 1H and 31P spins.     

31P-NMR spectroscopy of myopathies: clinical application of whole-body MR

Patients with myopathies were examined by 31P-NMR spectroscopy using a whole body MR system operating at 1.5 T. Spectra from the femoral muscles were measured as a function of time during a post-exercise recovery period. A 4-min scanning time was used to obtain a good S/N ratio and enable us to evaluate the relative intensity and position of each absorption line. The results were expressed by PCr/Pi ratio and pH value and compared with values before exercise. Clear changes were observed in the recovery process after workload depending on the stage of disease. We were able to observe the in vivo dynamic energy metabolism of myopathies by whole-body MR.     

Volume tracking cardiac 31P spectroscopy.

The limited reliability and accuracy of cardiac spectroscopy have been partly attributed to effects from respiratory motion. In this work, we developed a prospective volume tracking method for respiratory motion compensation based on multiple navigator echoes and demonstrated its application in cardiac (31)P spectroscopy. The sequence consists of two 2D selective excitation pulses preceding the spectroscopic experiment to sample respiratory motion components. The navigator information is evaluated in real-time to calculate the shift of the heart from respiration. Based on the displacement information, the spectroscopic volume and/or grid position is prospectively corrected to track the volume of interest. The method was validated with a moving compartment phantom simulating in vivo respiratory motion. With volume tracking, no signal contamination was apparent. Spectra obtained in 14 healthy volunteers were evaluated using time-domain fitting procedures. The fitting accuracy improved consistently with volume tracking compared to data from non-navigated reference acquisitions. Compared to other gating approaches available for spectroscopy, the current technique does not degrade the scan efficiency, thus allowing effective use of scan time.     

In vivo 31P magnetic resonance spectroscopy using a needle microcoil

Batch fabrication methods have been used to produce low‐cost microcoils for magnetic resonance spectroscopy (MRS) that could be discarded after applications such as insertion into tissue during interventional surgery. Needle‐shaped microcoils were constructed using electroplated conductors buried in shafts formed with different combinations of silicon and plastic and used to acquire in vivo ³¹P spectra of rat thigh muscle at 81 MHz. The designs in this study achieved a maximum signal‐to‐noise ratio (SNR) for phosphocreatine (PCr) of 10.4 in a 10‐min acquisition, with the three adenosine triphosphate (ATP) multiplets also clearly visible. An average 20% reduction in PCr occurred over a 60‐min period, and intracellular pH was estimated to be 6.6, which are both evidence of ischemia. A needle microcoil design could have applications in real‐time MRS of tumors or in evaluating pathology in general during surgical investigations. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

In vivo flow 31P FT-NMR spectroscopy of a nematode parasite

31P NMR spectroscopy of a parasitic nematode. Steinernema carpocapsae, is described. In vivo spectra were generated from nematode suspensions continuously circulating through the spectrometer. By flowing the organism, saturation effects were avoided and short interpulse delays significantly reduced spectral generation time. To maximize sensitivity, 90 degrees pulses were employed. Changes in energetic status in response to oxygen availability were easily and rapidly monitored in circulating nematodes.     

31P magnetic resonance spectroscopy of mesenteric ischemia

31P magnetic resonance spectroscopy (MRS) was performed in vivo on normal and ischemic rat intestine. Within 3 min after induction of ischemia, there is a dramatic fall in adenosine triphosphate (ATP) and rise in inorganic phosphate (Pi). Our results suggest that MRS may prove useful in the early detection of mesenteric ischemia.     

31P NMR spectroscopy of isolated perfused lungs

³¹P NMR spectra of isolated blood-perfused pig lungs were obtained by degassing the lungs in vivo to remove field inhomogeneities caused by air-tissue interfaces. The spectra show the presence of ATP, phosphodiester, inorganic phosphate, and phosphomonoester, but no phosphocreatine. All the metabolites remained stable for more than 4 h when the lungs were perfused with oxygenated blood. Blood gas tensions, glucose concentration, pH, and temperature were controlled throughout the experiment. During anoxia or isch-emia, ATP and intracellular pH declined and P_i increased but returned to control levels during subsequent normoxia or reperfusion. These results demonstrate the applicability of NMR spectroscopy to isolated perfused lungs, enabling studies of metabolic processes in normal and pathologic lungs, as well as establishment of optimal conditions for lung preservation for transplantation. © 1986 Academic Press, Inc.     

Rapid 31P NMR test of liver function

The 31P NMR spectrum of perfused rat liver was found to be dependent on the exogenous carbon available to the tissue. When pyruvate was supplied to liver initially perfused with lactate, Pi decreased, phosphoenol pyruvate and phosphomonoesters increased, and nucleotide pools remained the same. It is proposed that these changes can be used to evaluate liver function.     

31P NMR spectroscopy in chronic adriamycin cardiotoxicity

Abnormal cardiac energy metabolism has been postulated as a mechanism for adriamycin induced cardiotoxicity. This study was designed to determine high energy phosphate stores at rest and with hemodynamic stress in perfused rat hearts after animals had been chronically exposed to adriamycin (2 mg/kg weekly for 14 weeks). Morphologic and hemodynamic changes were mild in this model. Phosphorus-31 NMR determined intracellular pH and levels of inorganic phosphate (Pi) and ATP were comparable in treated and control hearts. Phosphocreatine (PCr) levels were markedly decreased in treated hearts (0.89 +/- 0.07 units/g versus 1.7 +/- 0.13 units/g, p less than 0.001). The PCr/Pi ratio decreased in both groups during hemodynamic stress. It recovered earlier in controls and there was a marked over-shoot after cessation of rapid pacing in this group which was not present in adriamycin treated hearts. These results suggest that metabolic regulation in response to hemodynamic stress is impaired after chronic adriamycin exposure. PCr depletion and delayed metabolic recovery after hemodynamic stress appear to be potentially useful markers for the effect of adriamycin on the heart.     

31P localized spectroscopy of fetal brain in utero

31-Phosphorus (³¹P) nuclear magnetic resonance (NMR) spectroscopy of fetal brain in utero was obtained entirely noninvasively in rat utilizing image selected in vivo spectroscopy (ISIS). The results were in excellent agreement with the data obtained using the surface coil method in the late stage fetus, namely, high phosphomonoester (PME), low phosphocreatine (PCr), and high intracellular pH. Localized spectroscopy provides unprecedented opportunities for the investigation of fetal brain metabolism in utero.     

Impact of salbutamol on muscle metabolism assessed by 31P NMR spectroscopy

The potential ergogenic effects of oral salbutamol intake were demonstrated for decades but the underlying mechanisms remain to elucidate. We hypothesized that improved exercise performance after acute oral salbutamol administration is associated with changes in muscle metabolism. Twelve healthy, nonasthmatic, moderately trained, male subjects were recruited to compare in a double‐blind crossover randomized study, an oral dose of salbutamol (4 mg) and a placebo. After treatment administration, subjects performed repetitive plantar flexions to exhaustion in a 3T magnet. Continuous ³¹P nuclear magnetic resonance spectroscopy assessment of the calf muscles was performed at rest, during exercise, and during recovery. No significant difference between treatments was detected in metabolite concentration at rest (P > 0.05). Creatine phosphate and inorganic phosphate changes during and immediately after exercise were similar between treatments (P > 0.05). Intramuscular pH (pHi) was significantly higher at rest, at submaximal exercise but not at exhaustion with salbutamol (pHi at 50% of exercise duration, 6.8 ± 0.1/6.9 ± 0.1 for placebo and salbutamol, respectively, P < 0.05). The maximal power (28 ± 7 W/23 ± 7 W; P = 0.001) and total work (1702 ± 442 J/1381 ± 432 J; P = 0.003) performed during plantar flexions were significantly increased with salbutamol. Salbutamol induced significant improvement in calf muscle endurance with similar metabolic responses during exercise, except slight differences in pHi. Other mechanisms than changes in muscle metabolism may be responsible for the ergogenic effect of salbutamol administration.     

31P NMR spectroscopy of the stomach by zig-zag coil

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic investigations of the rat stomach were performed utilizing a 1-cm2, three-turn, zig-zag coil. A zig-zag coil of this dimension produced an effective B1 field that extends only within a 4-mm distance from the plane of the surface coil, rendering it possible to obtain high-resolution 31P spectra localized to the stomach without contamination from surrounding tissues. Normal stomach showed a characteristic spectral pattern with resonances reflecting inorganic phosphate (Pi), phosphocreatine (PCr), and the alpha-, beta-, and gamma-phosphates of adenosine triphosphate (ATP). Ischemia-induced changes in Pi, PCr, and ATP resonances were readily followed in vivo with a time resolution of 2.13 min. Indomethacin-induced ulcer revealed a low intracellular pH and a decrease in the PCr to Pi ratio indicating the partially ischemic conditions of ulcerative lesions of the stomach as has been previously suggested. The present studies indicate that 31P NMR spectroscopy utilizing a zig-zag coil is a powerful tool to study local pathology of the gastrointestinal (GI) tract. Since zig-zag coils suitable for fiberscopic devices are easily constructed, clinical applications of the present technique are apparent.     

31P spectroscopy in thrombolytic treatment of experimental cerebral infarct

Ischemic changes produced by autogenous clot embolization of intracranial arteries were monitored by continuous surface-coil 31P spectroscopy in 12 rabbits: six were used as controls and six were treated intravenously with tissue-type plasminogen activator. The animals were sacrificed and the brains were fixed with intravital stains. The results indicate that spectral changes are reversible only when thrombolysis therapy is started within 30 min after ischemic changes are detected. The improvement of the 31P spectrum correlated with postmortem changes.     

Characterization of tumor hypoxia by 31P MR spectroscopy.

Tumor hypoxia is of considerable importance to the oncologist in selecting and optimizing cancer therapy, because hypoxia can determine the effectiveness of various therapies. The relationship between tumor hypoxia and tumor bioenergetics, assessed by 31P MR spectroscopy, is examined to determine whether 31P MR spectroscopy can be clinically useful to measure or characterize tumor hypoxia. Work with experimental tumors has suggested that several different types of hypoxia may exist and that 31P MR spectroscopy cannot be used to characterize all types. Metabolic hypoxia is the level of hypoxia that results in mitochondrial impairment in cells, and it is associated with declining cellular bioenergetic status, which can be measured by enzymatic assay of adenosine triphosphate (ATP). Because 31P MR spectroscopy is sensitive to levels of ATP, it is potentially sensitive to metabolic hypoxia in vivo and may provide a rapid and noninvasive technique for characterizing metabolic hypoxia in tumors. Radiobiologic hypoxia is the level of hypoxia that results in attenuated cell death due to radiation, because radiotoxicity is directly related to tissue levels of oxygen. Radiobiologic hypoxia of tumors thus has more impact on choice of therapy, yet the relationship between metabolic hypoxia and radiobiologic hypoxia remains to be elucidated. An analysis of published data suggests that 31P MR spectroscopy is directly sensitive to metabolic hypoxia in tumors, but it is only indirectly sensitive to radiobiologic hypoxia in tumors. Therefore, 31P MR spectroscopy may be unable to quantify the cell fraction of a tumor that has radiobiologic hypoxia. However, preliminary data suggest that MR spectroscopy may prove useful for determining the effectiveness of therapeutic interventions designed to manipulate radiobiologic hypoxia in tumors or for monitoring the kinetics of tumor reoxygenation after treatment.     

31P magnetic resonance spectroscopy of traumatic spinal cord injury

31P magnetic resonance spectroscopy (MRS) was applied in vivo to study metabolic changes in spinal cord after experimental traumatic injury. Severe trauma, resulting in spastic paraplegia, caused an early and sustained loss of high energy phosphates with profound intracellular acidosis. Early metabolic changes after traumatic spinal injury may predict irreversible tissue damage.