A comparison of MR-based attenuation correction in PET versus SPECT.

Attenuation correction (AC) is a critical step in the reconstruction of quantitatively accurate positron emission tomography (PET) and single photon emission computed tomography (SPECT) images. Several groups have proposed magnetic resonance (MR)-based AC algorithms for application in hybrid PET/MR systems. However, none of these approaches have been tested on SPECT data. Since SPECT/MR systems are under active development, it is important to ascertain whether MR-based AC algorithms validated for PET can be applied to SPECT. To investigate this issue, two imaging experiments were performed: one with an anthropomorphic chest phantom and one with two groups of canines. Both groups of canines were imaged from neck to abdomen, one with PET/CT and MR (n = 4) and the other with SPECT/CT and MR (n = 4), while the phantom was imaged with all modalities. The quality of the nuclear medicine reconstructions using MR-based attenuation maps was compared between PET and SPECT on global and local scales. In addition, the sensitivity of these reconstructions to variations in the attenuation map was ascertained. On both scales, it was found that the SPECT reconstructions were of higher fidelity than the PET reconstructions. Further, they were less sensitive to changes to the MR-based attenuation map. Thus, MR-based AC algorithms that have been designed for PET/MR can be expected to demonstrate improved performance when used for SPECT/MR.

Effects of recovery time on phosphocreatine kinetics during repeated bouts of heavy-intensity exercise.

The purpose of this study was to examine the kinetics of phosphocreatine (PCr) breakdown in repeated bouts of heavy-intensity exercise separated by three different durations of resting recovery. Healthy young adult male subjects (n = 7) performed three protocols involving two identical bouts of heavy-intensity dynamic plantar flexion exercise separated by 3, 6, and 15 min of rest. Muscle high-energy phosphates and intracellular acid-base status were measured using phosphorus-31 magnetic resonance spectroscopy. In addition, the change in concentration of total haemoglobin (Delta[Hb(tot)]) and deoxy-haemoglobin (Delta[HHb]) were monitored using near-infrared spectroscopy. Prior exercise resulted in an elevated (P < 0.05) intracellular hydrogen ion ([H(+)](i)) after 3 min (182 +/- 72 (SD) nM; pH 6.73) and 6 min (112 +/- 19 nM; pH 6.95) but not after 15 min (93 +/- 8 nM; pH 7.03) compared to pre-exercise in Con (90 +/- 3 nM; pHi 7.05). The on-transient time constant (tau) of the PCr primary component was not different amongst the exercise bouts. However, in each of the subsequent bouts the amplitude of the PCr slow component, total PCr breakdown, and rise in [H(+)](i) were reduced (P < 0.05). At exercise onset, Delta[Hb(tot)] was increased (P < 0.05) and the Delta[HHb] kinetic response was slowed (P < 0.05) in the exercise after 3 min, consistent with improved muscle perfusion. In summary, neither the level of acidosis or muscle perfusion at the onset of exercise appeared to be directly related to the time course of the on-transient PCr primary component or the magnitude of the PCr slow component during subsequent bouts of exercise.

Phenolic acid content and composition in leaves and roots of common commercial sweetpotato (Ipomea batatas L.) cultivars in the United States.

Phenolic acids in commercially important sweet potato cultivars grown in the United States were analyzed using reversed-phase high-performance liquid chromatography (HPLC). Caffeic acid, chlorogenic acid, 4,5-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 3,4-di-O-caffeoylquinic acid were well separated with an isocratic elution in less than 25 min compared to about 120 min for analyzing and re-equilibrating the column with a gradient method. The isocratic elution order of these caffeoylquinic acid derivatives was confirmed by LC-MS/MS. Chlorogenic acid was the highest in root tissues, while 3,5-di-O-caffeoylquinic acid and/or 4,5-di-O-caffeoylquinic acid were predominant in the leaves. Steam cooking resulted in statistically nonsignificant increases in the concentration of total phenolics and all the individual phenolic acids identified. Sweetpotato leaves had the highest phenolic acid content followed by the peel, whole root, and flesh tissues. However, there was no significant difference in the total phenolic content and antioxidant activity between purees made from the whole and peeled sweet potatoes.

Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise.

The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity plantar flexion exercise. Male subjects (n = 7) performed trials consisting of 20-min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco(2) (Pet(CO(2))) approximately 33 mmHg] and Hyp (Pet(CO(2)) approximately 17 mmHg) conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were used simultaneously to monitor intramuscular acid-base status, high-energy phosphates, and muscle oxygenation. Resting intracellular hydrogen ion concentration ([H(+)](i)) was lower (P < 0.05) in Hyp [90 nM (SD 3)] than Con [96 nM (SD 4)]; however, at end exercise, [H(+)](i) was greater (P < 0.05) in Hyp [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (tau) of PCr breakdown during transition from rest to exercise was greater (P < 0.05) in Hyp [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater (P < 0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or deoxymyoglobin (HHb) tau was similar between Hyp [13 s (SD 8)] and Con [10 s (SD 3)]; however, the amplitude was increased (P < 0.05) in Hyp [40 arbitrary units (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation during moderate-intensity exercise. In addition, the increased amplitude of the HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.

Cross-relaxation bottleneck in water-lysozyme proton magnetization exchange.

The proton spin-lattice relaxation parameters in natural and deuterated lysozyme solutions have been measured as a function of temperature (0-50 degrees C). The variation of the apparent magnitudes of the water proton magnetizations in the solutions with temperature indicates that magnetic coupling mixes protein and water proton magnetizations. The results are consistent with an exchange cross-relaxation model (Hills, B. P., Mol Phys 1992, 76, 489-508) in which the cross-relaxation acts between the labile and nonlabile protons, rather than between water and protein protons. Although this cross-relaxation pathway clearly affects the observed magnetization fractions in this protein solution, its influence on the relaxation rates is less apparent.

Two-dimensional time correlation relaxometry of skeletal muscle in vivo at 3 Tesla.

A hybrid two-dimensional relaxometry (2DR) sequence was used to simultaneously measure both the spin-spin (R2) and spin-lattice relaxation rates (R1) of skeletal muscle in vivo. The 2DR sequence involved a 180 degrees inversion pulse followed by a variable delay time (30 values from 40 to 7000 ms); a projection presaturation (PP) scheme to localize a 16-ml cylindrical voxel; and a CPMG sequence (950 even echoes, effective echo spacing = 1.2 ms, equilibrium time = 12 s). The 2DR data were collected at 3.0 Tesla from the flexor digitorum profundus of eight healthy males, 26 +/- 2 years old. Analysis was performed with a 2D version of the non-negative least-squares algorithm and a one-way ANOVA. All subjects exhibited at least three spin-groups (R2 < 200 s(-1)), designated B, C, and D, with R2 values of 42.7, 26.5, and 8.1 s(-1), and fractional volumes of 52, 35, and 7%, respectively. The R1 values of B and C were similar, congruent with0.7 s(-1), but different from that of D (P < 0.001), which had an R1 of 1.0 s(-1). The results suggest that exchange between B and C ranges from 0.7-16.2 s(-1), while exchange between either of these spin-groups with D is slower. If the data are interpreted with a compartment model, in which spin-groups with short and long R2 values are attributed to extra- and intracellular fluid, respectively, the exchange of water across the cell membrane in living skeletal muscle is slow or intermediate relative to both R1 and R2.

Effects of exercise on muscle transverse relaxation determined by MR imaging and in vivo relaxometry.

The purpose of this study was to determine the effects of intense exercise on the proton transverse (T(2)) relaxation of human skeletal muscle. The flexor digitorium profundus muscles of 12 male subjects were studied by using magnetic resonance imaging (MRI; 6 echoes, 18-ms echo time) and in vivo magnetic resonance relaxometry (1,000 echoes, 1.2-ms echo time), before and after an intense handgrip exercise. MRI of resting muscle produced a single T(2) value of 32 ms that increased by 19% (P < 0.05) with exercise. In vivo relaxometry showed at least three T(2) components (>5 ms) for all subjects with mean values of 21, 40, and 137 ms and respective magnitudes of 34, 49, and 14% of the total magnetic resonance signal. These component magnitudes changed with exercise by -44% (P < 0.05), +52% (P < 0.05), and +23% (P < 0.05), respectively. These results demonstrate that intense exercise has a profound effect on the multicomponent T(2) relaxation of muscle. Changes in the magnitudes of all the T(2) components synergistically increase MRI T(2), but changes in the two shortest T(2) components predominate.

Multicomponent T2 relaxation of in vivo skeletal muscle.

In vivo spin-spin (T2) relaxation measurements were acquired from the flexor digitorum profundus (FDP) of 13 subjects. A standard imaging T2 measurement technique [number of points (N) = 6, TE = 18 msec, signal-to-noise ratio (SNR) approximately equal to 300] yielded a single T2 value of 31 msec. A novel technique, projection presaturation combined with a CPMG sequence, was used to acquire data (N = 1000, TE = 1.2 msec, SNR 3500) from a cylindrical voxel (2 cm diameter, 5 cm length) within the FDP. All 13 subjects had at least four T2 components, at < 5, 21 +/- 4, 39 +/- 6, and 114 +/- 31 msec, with fractional areas of 11 +/- 2, 28 +/- 15, 46 +/- 12, and 11 +/- 5% respectively. The shortest and longest components have been observed in ex vivo muscle studies, probably corresponding to water associated with macromolecules and extracellular water, respectively. The middle T2 components are suggestive of an organization of in vivo intracellular water.

Evaluation of muscle oxidative potential by 31P-MRS during incremental exercise in old and young humans.

The purpose of this study was to compare muscle oxidative capacity between moderately active young and old humans by measuring intracellular threshold (IT) during exercise with 31P-magnetic resonance spectroscopy (31P-MRS). Changes in phosphocreatine, inorganic phosphate, and intracellular pH were measured by 31P-MRS during a progressive unilateral ankle plantar flexion exercise protocol in groups of moderately active old (n = 12, mean age 66.7 years) and young (n = 13, mean age 26.2 years) individuals. From muscle biopsy samples of the lateral gastrocnemius, citrate synthase (CS) activity was determined in six subjects from each group, and fibre type composition was determined in nine old and ten young subjects. The old group had a lower IT for pH, as a percentage of peak work rate (P < 0.05), despite a similar CS activity compared to the young. IT was significantly correlated with CS activity (R = 0.59; P < 0.05), but not with fibre type composition. It was concluded that metabolic responses to exercise are affected by ageing, as indicated by a lower IT in old compared to young individuals.

The effects of age on kinetics of oxygen uptake and phosphocreatine in humans during exercise.

We compared the kinetics of oxygen uptake (VO2) and phosphocreatine (PCr) during the adjustment to and recovery from plantar flexion exercise in moderately active older (n = 10, 66.9 years) and younger (n = 10, 27.5 years) individuals. VO2 kinetics were similar in the two groups, with time constants (tau) averaging 46.3 +/- 10.2 s (younger, on-transient), 38.1 +/- 14.4 s (younger, off-transient), 46.3 +/- 17.8 (older, on-transient) and 40.7 +/- 19.2 s (older, off-transient). These were similar to corresponding PCr kinetics, measured by 31P nuclear magnetic resonance spectroscopy, which averaged 50.6 +/- 24.0 s (younger, on-transient), 42.0 +/- 16.1 s (younger, off-transient), 39.8 +/- 22.0 s (older, on-transient) and 37.6 +/- 21.6 s (older, off-transient). On-transient tau values for VO2 and PCr were correlated, for combined groups (r = 0.53; P = 0.015). We conclude that: (1) VO2 and PCr kinetics during exercise of a muscle group accustomed to daily activity are not compromised in physically active older humans, and (2) PCr kinetics reflect the kinetics of muscle O2 consumption, and are expressed at the lung (VO2 kinetics) after a transit delay.

Noninvasive assessment of pharmaceutical intervention during myocardial ischemia-reperfusion in a canine model using two-dimensional 31P chemical shift imaging.

The metabolic effects during myocardial ischemia and sustained reperfusion of the antianginal agents diltiazem (n = 10) and propranolol (n = 10) were monitored with noninvasive phosphorus nuclear magnetic resonance spectroscopy to establish any correlation between metabolic changes and infarct size. Spectroscopy followed changes in high-energy phosphate concentrations and myocardial intracellular pH during 2 h of left anterior descending coronary artery occlusion and 3 subsequent weeks of reperfusion, in a closed chest canine infarct model. Gadolinium-DTPA enhanced magnetic resonance imaging was used to assess the extent of myocardial injury (infarct size). Microspheres were used to document the zone at risk and the success of reperfusion. Whereas diltiazem appeared to reduce the derangement in high-energy phosphates during coronary occlusion, there was no significant change in infarct size when compared with a previously studied control group. Propranolol, which produced a lesser decline in pH during occlusion and smaller pH changes during early reperfusion, was associated with a significant reduction in the degree of tissue necrosis (compared with controls). There was an inverse correlation (r = -0.51) between the change in myocardial pH (occlusion end to immediate reperfusion) and the recovery index (an index of myocardial salvage). By 1 h into reperfusion, there was a stronger inverse correlation between pH and infarct size (r = -0.75), implying a protective effect of delaying pH recovery during early reperfusion and indicating the potential use of this parameter as a predictor of tissue viability.

Myocardial infarction in a canine model monitored by two-dimensional 31P chemical shift spectroscopic imaging.

We have developed a closed chest animal model that allows noninvasive monitoring of cardiac high energy phosphate metabolism before, during, and for at least 3 weeks after a myocardial infarction. Ten beagles underwent 2 h of coronary occlusion followed by 3 weeks of reperfusion. Myocardial high energy phosphates from 12-ml voxels were noninvasively tracked using 31P two-dimensional chemical shift imaging. Gadolinium enhanced 1H MRI identified the zone at risk, and radioactive microspheres assessed regional blood flow and partition coefficients. Occlusion of the left anterior descending coronary artery produced infarcts that were 13.7+/-8.8% (mean+/-SD) of the left ventricular volume. Rapid changes in the phosphocreatine and inorganic phosphate levels were observed during occlusion, whereas adenosine triphosphate levels decreased more slowly. All metabolites recovered to base-line levels 2 weeks after occluder release. Multiple inorganic phosphate peaks in the infarct voxel spectra indicated that more than one metabolically compromised tissue zone developed during occlusion and reperfusion. Microsphere data indicating three distinct blood flow zones during ischemia and reperfusion (<0.3, 0.3-0.75, and >0.75 ml/min/g) supported the grouping of pH values into three distinct metabolic distributions.

Controlled reperfusion after myocardial ischemia in a canine model monitored by two-dimensional phosphorus 31 chemical shift spectroscopic imaging.

Phosphorus 31 magnetic resonance spectroscopy at 2 T was used to monitor high-energy phosphate metabolism over a 3-week period in a canine model of myocardial infarction and reperfusion. Twenty animals were divided into two groups: group 1 (n = 11) received intravenous nitroglycerin beginning at the onset of coronary occlusion; group 2 (n = 9) received a 105-minute infusion of superoxide dismutase (SOD) beginning at the onset of reperfusion. A metabolic protective effect was observed (vs controls) with both agents, manifested by a reduction in the degree of pH decline from baseline values and preservation of the adenosine triphosphate/total phosphate ratio during occlusion and reperfusion. Further, both treatments, compared with controls, produced a lower infarct/zone at risk ratio: controls, 1.5 +/- 1.2; nitroglycerin, 0.52 +/- 0.50; and SOD, 0.64 +/- 0.40. The technique of 31P magnetic resonance spectroscopy demonstrated its use for the noninvasive assessment of myocardial metabolism in response to therapeutic intervention.

Kinetics of pulmonary oxygen uptake and muscle phosphates during moderate-intensity calf exercise.

The purpose of this study is to directly compare the dynamic responses of phosphocreatine (PCr) and P(i) to those oxygen uptake (VO2) measured at the lung during transitions to and from moderate-intensity exercise. Changes in PCr and P(i) were measured by 31P-nuclear magnetic resonance spectroscopy, and changes in VO2 were measured breath by breath by mass spectroscopy during transitions to and from moderate-intensity square-wave ankle plantar flexion exercise in 11 subjects (7 men and 4 women; mean age 27 yr). Three repeated transitions were averaged for improvement in signal-to-noise ratio of phosphate data, and 12 transitions were averaged for VO2 measurements. Averaged transitions were fit with a monoexponential curve for determination of the time constant (tau) of the responses. Mean tau values for on transients of PCr, P(i), and phrase 2 VO2 were 47.0, 57.7, and 44.5 s, respectively, whereas means tau values for off transients were 44.8, 42.1, and 33.4 s, respectively. There were no significant differences between tau values for phosphate- and VO2-measured transients or on and off transients. The similarity of on and off kinetics supports linear first-order respiratory control models. Measurement of phase 2 pulmonary VO2 kinetics to and from moderate-intensity small-muscle-mass exercise reflect muscle phosphate kinetics (and muscle oxygen consumption).

Early detection of cancer cachexia in the rat using 31P magnetic resonance spectroscopy of the liver and a fructose stress test.

The dynamic metabolic effects of a fructose infusion challenge on hepatic intracellular levels of adenosine 5'-triphosphate (ATP), inorganic phosphate (Pi) and phosphomonoesters (PME) were monitored noninvasively by 31P MRS in a remote tumour-bearing rat model. Fisher male rats were inoculated with a methylcholanthrene-induced sarcoma. Seventeen rats were randomized into three groups: control (n = 6), low tumour burden (LTB, n = 6), or moderate tumour burden (MTB, n = 5). The LTB group had tumour burdens of 0.2-2.0% while the MTB group had tumour burdens of 2.6-5.7%. All rats were in the pre-clinical phase of cancer cachexia as determined by food intake and body weight. Rats were infused with 1.2 g/kg of fructose i.v. and the metabolic response of the liver was monitored with time over 1 h via 31P MRS. In all groups an immediate increase in hepatic levels of PME was noted, which returned to baseline values over the course of the experiment, reflecting the phosphorylation of fructose to fructose 1-phosphate. For the MTB rats, the return to baseline levels was more rapid than in the control or LTB group. All groups experienced a 20% decrease in hepatic ATP levels which did not return to baseline over the 1 h observation period. As well, all groups experienced an initial fall in Pi, which recovered to prefructose levels or greater. MTB rats demonstrated a 30-40% increase in Pi concentration and a 60-70% increase in Pi/ATP ratio after infusion with fructose as compared to LTB and control rats (ANOVA;p<0.05). This is consistent with cachexia-induced enhancement of hepatic gluconeogenic activity, and hence more rapid release of Pi from the phosphorylated metabolites in the MTB rats. Thus fructose infusion and hepatic 31P MRS permit pre-clinical detection of cancer cachexia as reflected by increased Pi generation and more rapid removal of PME.

Metabolic response of forearm muscle to graded exercise in type II diabetes mellitus: effect of endurance training.

In this study, 31P nuclear magnetic resonance spectroscopy was used to monitor muscle metabolism in Type II diabetic subjects (n = 10) during an incremental exercise test. Also the exercise responses of diabetic subjects (n = 4) following submaximal endurance training were assessed and compared to healthy controls (n = 5). Responses to incremental exercise in the diabetic subjects were consistent over time despite minor fluctuations in metabolic control. In the diabetic and control groups, after 12 weeks of training the forearm flexor muscles, power output at the intracellular threshold of acidosis (IT) increased (p < .01) similarly: T0 versus T12: 0.90 +/- 0.09 versus 1.20 +/- 0.13 and 1.03 +/- 0.07 versus 1.22 +/- 0.10 W, respectively. Minimum intracellular pH reached at peak exercise was unchanged after training. The control group, however, became more acidic versus the diabetic group (p < .05) in response to progressive exercise. This difference was maintained over time. Endurance training elicited similar adaptations in forearm muscles of Type II diabetic and control subjects, although there were differences between the two groups in intracellular pH during exercise.

Effect of anaemia correction on skeletal muscle metabolism in patients with end-stage renal disease: 31P magnetic resonance spectroscopy assessment.

Skeletal muscle metabolism during exercise was compared in 5 patients with end-stage renal disease (ESRD) and 8 healthy controls, using a noninvasive technique, 31P magnetic resonance spectroscopy (MRS). After 3 months of anaemia correction with recombinant human erythropoietin (rHuEPO) these patients were re-evaluated. Maximal power achieved by the ESRD patients during a dynamic wrist flexion exercise test was 33% lower (p < 0.05) than the controls. Similarly in the ESRD group, the power at the onset of metabolic acidosis (the intracellular threshold) was 29% less than controls. The metabolic differences observed in the patients indicated a lower aerobic capacity. Three months of rHuEPO treatment resulted in a 55% increase in mean haematocrit but conferred no significant improvement in metabolic parameters at rest or during exercise. The lack of any significant changes in muscle metabolism following the correction of anaemia suggests that oxygen availability is not the exclusive limiting factor for aerobic metabolism in ESRD patients.

An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients.

The level of the 1H metabolites in the left dorsolateral prefrontal region of schizophrenia patients at different stages of illness were measured in vivo using a short echo time spectroscopy technique. During both the early onset and chronic stages, normal N-acetylaspartate levels were observed, which suggests that these patients had no significant neuronal cell damage and/or loss. The in vivo measurements of glutamate in the first-episode, drugnaive patients failed to provide convincing evidence for the involvement of the glutamatergic system in the dorsolateral prefrontal region. Significant differences in the glutamine levels were observed in the acutely medicated and chronic patients; however, the interpretation of these differences requires further study.

The use of a priori knowledge to quantify short echo in vivo 1H MR spectra.

In vivo 1H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8-cm3 volume of interest (VOI) and a 4-cm3 VOI positioned within the 8-cm3 VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho(t)) between spectra from the 8- and 4-cm3 VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from 1H images). Correcting for the T1 and T2 relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho(t), Glu, and glutamine were consistent with previous in vivo and in vitro reports.

An in vivo study of the prefrontal cortex of schizophrenic patients at different stages of illness via phosphorus magnetic resonance spectroscopy.

BACKGROUND: In this study, phospholipid metabolism of cell membranes, high-energy phosphate metabolism, and intracellular free magnesium concentration in the prefrontal cortex of first-episode drug-naive schizophrenic patients and medicated schizophrenic patients at different stages of illness were compared with those of controls. METHODS: Localized in vivo phosphorus 31 magnetic resonance spectra of the left dorsolateral prefrontal cortex of 11 drug-native, eight newly diagnosed medicated, and 10 chronic medicated patients with schizophrenia were compared with controls of similar gender, education, parental education, and handedness. RESULTS: Significantly decreased levels of phosphomonoesters in drug-native, newly diagnosed medicated, and chronic medicated patients and significantly increased levels of phosphodiesters in drug-native patients were observed when compared with controls. There were no significant differences in the levels of high-energy phosphate metabolites between the groups except for a significant decrease in the inorganic orthophosphate levels of newly diagnosed medicated patients. A significant increase in the intracellular free magnesium concentration was observed in drug-naive, newly diagnosed medicated, and chronic medicated patients compared with controls. There were no correlations between the patients' negative and positive symptoms and the observed phosphorus-containing metabolites. CONCLUSIONS: A reduction in precursors of membrane phospholipid are observed during the early and chronic stages of the schizophrenia illness, and breakdown products of membrane phospholipids are increased at the early stage of illness before medication treatment.