Magnetic coupling between water and creatine protons in human brain and skeletal muscle, as measured using inversion transfer (1)H-MRS

Using the inversion transfer technique, the possible magnetic coupling between water protons and the protons of low-molecular weight metabolites was investigated in human brain and skeletal muscle at 1.5 T. The localized (1)H-MR spectra were recorded at different times after selective inversion of the water resonance. Water inversion led to a significant transient reduction in the signal intensity of the methyl protons of creatine/phosphocreatine, in both tissues. This is indicative of magnetic coupling between the protons of water and those of creatine/phosphocreatine. Neither the choline and N-acetylaspartate protons in brain nor the protons of the trimethylammonium pool in skeletal muscle showed a significant magnetic coupling to mobile water.     

Proton and phosphorus magnetic resonance spectroscopy of human astrocytomas in vivo. Preliminary observations on tumor grading

We have obtained localized, water-suppressed proton magnetic resonance spectra from eleven astrocytomas in vivo. Localized phosphorus spectra were also obtained from three of these tumors. All tumors were examined prior to surgery, radiotherapy or chemotherapy. Examinations were performed with a commercially available 1.5 Tesla combined imaging and spectroscopy system using a stimulated echo pulse sequence for protons and an ISIS pulse sequence for phosphorus. A relatively high lactate resonance intensity correlated with a more malignant histological tumor grade and more aggressive behaviour. The resonance intensity of N-acetylaspartate/creatine was decreased and choline/creatine was increased, but these did not reliably discriminate between tumor grades. Other unidentified resonances not present in spectra of normal brain were sometimes seen. Proton magnetic resonance spectroscopy provides a new method for determining the metabolic behaviour of astrocytomas that may be useful in the clinical assessment of patients with these tumors.     

Non-invasive in vivo localized 1H spectroscopy of human astrocytoma implanted in rat brain: regional differences followed in time

Human astrocytoma cells were cultured and inoculated into the rat brain. From the pre-clinical to the terminal state, tumour growth was monitored by in vivo MR imaging and by localized water-suppressed 1H spectroscopy (0.12-0.15 cm3 volumes) and spectroscopic imaging (0.01 cm3 voxels) employing the ACE localization technique. The MR experiments were conducted completely non-invasively, leaving the scalp intact. Brain spectra were obtained, showing distinct resonances for more than five different brain metabolites; they were not contaminated with lipid signals because of the adequate localization. Tumour progression, monitored in a selected volume of interest, was reflected in the corresponding spectra by decreasing intensities for resonances of N-acetyl aspartate and (phospho)creatine and increasing intensities for resonances of choline compounds and lactate. From spectroscopic imaging experiments metabolic heterogeneity could be deduced within the tumorous region. At particular times during tumour development spectra were obtained greatly resembling localized 1H MR spectra obtained from patients with astrocytomas by the use of similar localization methods. This emphasizes the relevance of animal model study for the evaluation of MR spectroscopic investigations in human brain tumour diagnosis and therapy evaluation.     

Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects

This study compared the effects of short-term creatine supplementation on muscle phosphocreatine, blood and urine creatine levels, and urine creatinine levels in elderly and young subjects. Eight young (24 +/- 1.4 years) and seven old (70 +/- 2.9 years) men ingested creatine (20 g day-1) for 5 days. Baseline muscle phosphocreatine measurements were taken pre- and post-supplementation using nuclear magnetic resonance spectroscopy (NMR). On the first day of supplementation subjects had blood samples taken immediately before and hourly for 5 h following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine levels was conducted. Twenty-four hour urine collections were conducted for 2 days prior to the supplementation period and for 5 days during supplementation. Old subjects had significantly higher baseline plasma creatine levels than young subjects (68.5 +/- 12.5 vs. 34.9 +/- 4.7 micromol L-1; P < 0.02). There were no significant differences between groups in plasma creatine pharmacokinetic parameters (i.e. area under the curve, elimination rate constant, absorption rate constant, time to maximum concentration, and maximum concentration) following the 5 g oral creatine bolus. Urine creatine, assessed pre and on 5 days of supplementation, increased (P < 0.001), with no difference between groups. Urine creatinine did not change as a result of creatine supplementation. Young subjects showed a significantly greater increase in muscle phosphocreatine compared with old subjects, and post-supplementation muscle phosphocreatine levels were greater in young subjects (young 27.6 +/- 0.5; old 25.7 +/- 0.8 mmol kg-1 ww) (P=0.02). There were no differences in blood or urine creatine between groups in response to supplementation, but old subjects had a relatively small increase (young 35% vs. old 7%) in muscle phosphocreatine after supplementation.     

Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle

Deficiency of guanidinoacetate methyltransferase (GAMT), the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate in brain. This results in epilepsy, mental retardation, and extrapyramidal movement disorders. Investigation of skeletal muscle by proton and phosphorus magnetic resonance spectroscopy before therapy demonstrated the presence of considerable amounts of creatine and phosphocreatine, and accumulation of phosphorylated guanidinoacetate in a 7-year-old boy diagnosed with GAMT deficiency, suggesting separate mechanisms for creatine uptake and synthesis in brain and skeletal muscle. The combination of creatine supplementation and a guanidinoacetate-lowering therapeutic approach resulted in improvement of clinical symptoms and metabolite concentrations in brain, muscle, and body fluids.     

磁共振波谱评价大脑半球代谢物的偏侧优势

为了利用无创性的磁共振波谱成像技术研究大脑半球代谢物的非对称性,本研究对56例正常成年人行磁共振波谱成像,主要对双侧大脑半球的4个解剖区域:额叶、颞叶、枕叶及顶叶的代谢物天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)进行测量,并以Cr为内参照物比较NAA和Cho相对含量(NAA/Cr、Cho/Cr)的侧别差异。结果表明:双侧额叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异;在双侧颞叶之间,这2种比值均存在显著性差异;双侧枕叶之间Cho/Cr存在显著性差异,而NAA/Cr无显著性差异;双侧顶叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异。本研究结果提示双侧大脑半球的代谢物存在偏侧优势。     

In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement

It is often difficult to make a correct diagnosis of ring-like enhanced lesions on Gd-enhanced MR brain images. To differentiate these lesions using proton MR spectroscopy (1H-MRS), we retrospectively evaluated the correlation between the 1H-MR spectra and histopathological findings. We evaluated proton MR spectra obtained from the lesions in 45 patients, including metastasis (n = 19), glioblastoma (n = 10), radiation necrosis (n = 7), brain abscess (n = 5), and cerebral infarction (n = 4). The rate of misdiagnosis was found to be lowest at the threshold level of 2.48 for the (choline containing compounds)/(creatine and phosphocreatine) ratio (Cho/Cr) obtained from the whole lesions, which include the enhanced rim and the non-enhanced inner region. That is, the positively predictive values of a Cho/Cr greater than 2.48 for diagnosing metastasis or glioblastoma was 88.9 and 60.0%, respectively, and the positively predictive value of a Cho/Cr less than 2.48 for diagnosing radiation necrosis or cerebral infarction was 71.4 and 100%, respectively. For further differentiating between metastasis and glioblastoma, information about the presence and absence of an N-acetyl-aspartate (NAA) peak and lipid- or lactate-dominant peak was found to be useful. In 73.7% of metastasis cases a lipid-dominant peak was observed in the whole lesion without an NAA peak in the inner region, whereas the same pattern was observed in only 10% of the glioblastoma cases. Correlation with the histopathological findings showed that a high Cho signal is suggestive of neoplasm. Lipid signal in the non-enhanced central region was correlated to necrosis. Lactate signals were often observed in glioblastoma, abscess and sometimes metastasis, presumably reflecting the anaerobic glycolysis by the living cells in the ring-like enhanced rim. Single-voxel proton MR spectroscopy may serve as a potential tool to provide useful information of differentiation of ring-like enhanced lesions that cannot be diagnosed correctly using enhanced MR images alone.     

Magnetization transfer MRS

This review deals with magnetization transfer (MT) effects observed in in vivo NMR spectroscopy. The basic experimental methods of MT experiments, the underlying kinetic mechanisms as well as the evaluation of measured data by fits to two- or three-pool models are described. Experimental results of both (31)P and (1)H in vivo MRS are reviewed showing the potential of MT experiments to characterize kinetic equilibrium reactions. This includes reactions where all involved components are MR visible, as well as situations where one indirectly measures pools of bound spins which cannot directly be observed in vivo. In particular, MT effects are described which have been observed in in vivo (1)H NMR spectra measured on the animal or human brain or on skeletal muscle. Possible mechanisms for the strong MT effects observed for the signals of creatine/phosphocreatine, lactate, alcohol and other metabolites are discussed. It is also emphasized that MT effects caused by water suppression techniques may lead to systematic errors in the quantification of in vivo (1)H NMR spectra.     

Brain Creatine Kinase with Aging in F-344 Rats: Analysis by Saturation Transfer Magnetic Resonance Spectroscopy

We measured in vivo forward flux of the creatine kinase reaction in rat forebrain in young (Y: 6 month, n = 13), mid-aged (M: 12 month, n = 7) and aged (O: 27 month, n = 10) animals using 31P magnetic resonance saturation transfer. Forward flux was reduced in the aged rats (Y: 0.42 ± 0.08; M: 0.41 ± 0.10; O: 0.31 ± 0.03 s⁻¹ ± SD; p = 0.008 O vs. Y). In vitro studies in a subset of the same rats showed a parallel decline in CK activity (Y: 2.16 ± 0.40; M: 2.17 ± 0.25; O: 1.56 ± 0.06 IU ±S.D.; p = 0.002 O vs. Y). The in vivo spectroscopic and in vitro biochemical measures were significantly correlated. Reduced creatine kinase activity could account for the observed decreased forward flux in aging brain. Intracellular pH, phosphocreatine/inorganic phosphate ratio, and phospocreatine/γ-adenosine triphosphate ratio did not differ between groups. Forward flux may represent a better measure of brain energy function than relative phosphocreatine or adenosine triphosphate levels observable in vivo.     

Magnetization transfer attenuation of creatine resonances in localized proton MRS of human brain in vivo

To assess putative magnetization transfer effects on the proton resonances of cerebral metabolites in human brain, we performed quantitative proton magnetic resonance spectroscopy (2.0 T, STEAM, TR/TE/TM = 6000/40/10 ms, LCModel data evaluation) of white matter (7.68 mL, 10 healthy young subjects) in the absence and presence of fast repetitive off-resonance irradiation (2.1 kHz from the water resonance) using a train of 100 Gaussian-shaped RF pulses (12.8 ms duration, 120 Hz nominal bandwidth, 40 ms repetition period, 1080 degrees nominal flip angle). A comparison of pertinent metabolite concentrations revealed a magnetization transfer attenuation factor of the methyl and methylene resonances of creatine and phosphocreatine of 0.87 +/- 0.05 (p < 0.01). No attenuation was observed for the resonances of N-acetylaspartate and N-acetylaspartylglutamate, glutamate and glutamine, choline-containing compounds, and myo-inositol. The finding for total creatine is in excellent agreement with data reported for rat brain. The results are consistent with the hypothesis of a chemical exchange of mobile creatine or phosphocreatine molecules with a small immobilized or 'bound' pool.     

Improved high-performance liquid chromatographic assay for the determination of "high-energy" phosphates in mammalian skeletal muscle. Application to a single-fibre study in man.

A sensitive and reproducible method for the determination of adenine nucleotides (ATP, IMP) and creatine compounds [creatine (Cr), phosphocreatine (PCr)] in freeze-dried single human muscle fibre fragments is presented. The method uses isocratic reversed-phase high-performance liquid chromatography of methanol extracts. Average retention times (min) of ATP, IMP and PCr, Cr from standard solutions were 10.6+/-0.42, 2.11+/-0.06 (n=6) and 10.5+/-0.31 and 1.19+/-0.02 (n=9), respectively. Detection limits in extracts from muscle fibre fragments were 2.0, 1.0, 3.0 and 2.0 mmol/kg dm, respectively. The assay was found successful for analysis of fibre-fragments weighing > or = 1 microg.     

Noninvasive measurement of viable cell number in tissue-engineered constructs in vitro, using 1H nuclear magnetic resonance spectroscopy

Noninvasive monitoring of tissue-engineered constructs is of critical importance for accurate characterization of constructs and their remodeling in vitro and in vivo. This study investigated the utility of (1)H NMR spectroscopy to noninvasively quantify viable cell number in tissue-engineered substitutes in vitro. Agarose disk-shaped constructs containing betaTC3 cells were employed as the model tissue-engineered system. Two construct prototypes containing different initial cell numbers were monitored by localized, water-suppressed 1H NMR spectroscopy over the course of 13 days. (1)H NMR measurements of the total choline resonance at 3.2 ppm were compared with results from the traditional cell viability assay MTT and with insulin secretion rates. Results show a strong linear correlation between total choline and MTT (R (2) = 0.86), and between total choline and insulin secretion rate (R (2) = 0.90). Overall, this study found noninvasive measurement of total choline to be an accurate and nondestructive assay for monitoring viable betaTC3 cell numbers in tissue-engineered constructs. The applicability of this method to in vivo monitoring is also discussed.     

Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy

Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague-Dawley rats (n = 10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P < 0.001). The changes were nearly prevented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetylaspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P < 0.01) and MK-801 (P < 0.05) still showed significant reduction as compared with sham controls. Thus we conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides a better neuroprotective effect than MK-801. With a better therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application.     

Heat production and chemical change during isometric contraction of rat soleus muscle.

1. Methods are described whereby the soleus muscle of the rat may be used for the investigation of initial processes in the absence of oxidative recovery. 2. The anaerobic conditions employed had no effect on the concentration of phosphocreatine in resting muscle or the mechanical response during contraction. 3. Muscles were stimulated tetanically for 10 s at 17-18 degrees C. Measurements were made of the heat production and metabolic changes that occurred during a 13 s period following the first stimulus. 4. There was no detectable change in the concentration of ATP. Neither was there detectable activity of adenylate kinase or adenylate deaminase. The changes in the concentration of glycolytic intermediaries were undetectable or very small. 5. The change in the concentration of phosphocreatine was large and amounted to -127 +/- 11-4 mumol/mmol Ct (mean and S.E. of the mean, negative sign indicates break-down, Ct = free creatine + phosphocreatine) which is equivalent to about -2-13 mumol/g wet weight of muscle. The heat production was 6549 +/- 408 mJ/mmol Ct (mean and S.E. of mean) which is equivalent to about 110 mJ/g. 6. About 30% of the observed energy output is unaccounted for by measured metabolic changes. 7. The ratio of heat production (corrected for small amounts of glycolytic activity) to phosphocreatine hydrolysis was -49-7 +/- 5-6 kJ/mol (mean and S.E. of mean), in agreement with previous results using comparable contractions of frog muscle, but different from the enthalpy change associated with phosphocreatine hydrolysis under in vivo conditions (-34 kJ/mol). 8. The results support the notion that the discrepancy between energy output and metabolism is an indication of an unidentified process of substantial energetic significance that is common to a number of species.     

Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy.

The absolute concentrations of the three major brain metabolites observable by in vivo proton spectroscopy--N-acetylaspartate(NAA), creatine and phosphocreatine (Cr and PCr) and choline (Cho)--have been measured at four standardized localizations in 34 healthy volunteers by in vivo localized proton spectroscopy using an external reference sample. The results show that the concentration of Cr and PCr as observed by in vivo MRS (5-6 mmol/L) is lower than that measured by other methods. The results are concordant with the hypothesis, that the Cr and PCr resonance as observed by proton spectroscopy is due mainly to PCr, whereas Cr remains invisible by being attached to a larger molecule. It is also demonstrated, that Cr and PCr is higher in the cerebellum than in the cerebrum, whereas NAA remains constant within the margin of error (8-9 mmol/L).     

Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle

Skeletal muscle is a biological structure with a high degree of organization at different spatial levels. This order influences magnetic resonance (MR) in vivo-in particular 1H-spectra-by a series of effects that have very distinct physical sources and biomedical applications: (a) bulk fat (extramyocellular lipids, EMCL) along fasciae forms macroscopic plates, changing the susceptibility within these structures compared to the spherical droplets that contain intra-myocellular lipids (IMCL); this effect leads to a separation of the signals from EMCL and IMCL; (b) dipolar coupling effects due to anisotropic motional averaging have been shown for 1H-resonances of creatine, taurine, and lactate; (c) aromatic protons of carnosine show orientation-dependent effects that can be explained by dipolar coupling, chemical shift anisotropy or by relaxation anisotropy; (d) limited rotational freedom and/or compartmentation may explain differences of 1H-MR-visibility of the creatine/phosphocreatine resonances; (e) lactate 1H-MR resonances are reported to reveal information on tissue compartmentation; (f) transverse relaxation of water and metabolites show multiple components, indicative of intra-, extracellular and/or macromolecular-bound pools, and in addition dipolar or J-coupling lead to a modulation of the signal decay, hindering straightforward interpretation; (g) diffusion weighted 31P-MRS has shown restricted diffusion of phosphocreatine; (h) magnetization transfer (MT) indicates that there is a motionally restricted proton pool in spin-exchange with free creatine; reduced availability or restricted motion of creatine is particularly important for an estimation of ADP from 31P-MR spectra, and in addition MT effects may alter the signal intensity of creatine 1H-resonances following water-suppression pulses; (i) transcytolemmal water-exchange can be studied in 1H-MRS by contrast-agents applied to the extracellular space; (k) transport of glucose across the cell membrane has been studied in diabetes patients using a combination of 13C- and 31P-MRS; and l residual quadrupolar interaction in 23Na MR spectra from human skeletal muscle suggest that sodium ions are bound to ordered muscular structures.     

The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds

Hereditary creatine transporter deficiency causes brain damage, despite the brain having the enzymes to synthesize creatine. Such damage occurring despite an endogenous synthesis is not easily explained. This condition is incurable, because creatine may not be delivered to the brain without its transporter. Creatine-derived compounds that crossed the blood-brain barrier in a transporter-independent fashion would be useful in the therapy of hereditary creatine transporter deficiency, and possibly also in neuroprotection against brain anoxia or ischemia. We tested the double hypothesis that: (1) the creatine carrier is needed to make creatine cross the plasma membrane of brain cells and (2) creatine-derived molecules may cross this plasma membrane independently of the creatine carrier. In in vitro mouse hippocampal slices, incubation with creatine increased creatine and phosphocreatine content of the tissue. Inhibition of the creatine transporter with 3-guanidinopropionic acid (GPA) dose-dependently prevented this increase. Incubation with creatine benzyl ester (CrOBzl) or phosphocreatine-Mg-complex acetate (PCr-Mg-CPLX) increased tissue creatine content, not phosphocreatine. This increase was not prevented by GPA. Thus, the creatine transporter is required for creatine uptake through the plasma membrane. Since there is a strong indication that creatine in the brain is mainly synthesized by glial cells and transferred to neurons, this might explain why hereditary transporter deficiency is attended by severe brain damage despite the possibility of an endogenous synthesis. CrOBzl and PCr-Mg-CPLX cross the plasma membrane in a transporter-independent way, and might be useful in the therapy of hereditary creatine transporter deficiency. They may also prove useful in the therapy of brain anoxia or ischemia.     

Reduced brain glutamate in patients with Parkinson's disease

An understanding of the role played by glutamate (Glu) in idiopathic Parkinson's disease (PD) has remained somewhat elusive. Animal models of PD suggest that over-activity of Glu receptors complicates the motor symptoms of PD and that Glu blockade may be a pharmacologic target in PD, whereas patient autopsy studies have proved less convincing for changes in Glu. No previous 1H MRS patient studies have documented changes in glutamate. All but one of these previous studies were performed at 1.5 T. We performed 3 T 1H MRS of the posterior cingulate gyrus in 12 non-demented patients with PD and 12 age-matched, neurologically normal control participants. Glu, N-acetylaspartate (NAA) and choline-containing compounds (Cho) measured in reference to creatine + phosphocreatine (Cr) were determined from single-voxel proton MR spectra measured by PRESS at TE of 80 ms. The results show that the Glu/Cr ratio was reduced in patients with PD compared with controls (t = 2.54; P = 0.019), whereas no differences were observed in NAA/Cr or Cho/Cr ratios. These findings suggest that a reduction in Glu occurs in the cerebral cortex of patients with PD. (1)H MRS at 3 T should be investigated in future studies as a means of tracking the course of metabolic brain changes in association with progression of disease in patients with PD.     

Effect of paramagnetic manganese cations on (1)H MRS of the brain

Manganese cations (Mn(2+)) can be used as an intracellular contrast agent for structural, functional and neural pathway imaging applications. However, at high concentrations, Mn(2+) is neurotoxic and may influence the concentration of (1)H MR-detectable metabolites. Furthermore, the paramagnetic Mn(2+) cations may also influence the relaxation of the metabolites under investigation. Consequently, the purpose of this study was to investigate the effect of paramagnetic Mn(2+) cations on (1)H-MR spectra of the brain using in vivo and phantom models at 4.7 T. To investigate the direct paramagnetic effects of Mn(2+) cations on the relaxation of N-acetylaspartate (NAA), creatine and choline, T(1) relaxation times of metabolite solutions, with and without 5% albumin, and containing different Mn(2+) concentrations were determined. Relaxivity values with/without 5% albumin for NAA (4.8/28.1 s(-1) mM(-1)), creatine (2.8/2.8 s(-1) mM(-1)) and choline (1.8/1.1 s(-1) mM(-1)) showed NAA to be the most sensitive metabolite to the relaxation effects of the cations. Using an in vivo optic tract tracing imaging model, we obtained two adjacent regions of interest in the superior colliculi with different water T(1) values (Mn(2+)-enhanced = 1.01 s; unenhanced = 1.14 s) 24 h after intravitreal injection of 3 microL 50 mM MnCl(2). Using phantom and in vivo water relaxation time data, we estimated the in vivo Mn(2+) concentration to be 2-8 microM. The phantom data suggest that limited metabolite relaxation effects would be expected at this concentration. Consequently, this study indicates that, in this model, the presence of Mn(2+) cations does not significantly affect (1)H-MR spectra despite possible toxic and paramagnetic effects.     

Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)