Proton magnetic resonance spectroscopy in primary blepharospasm

Single-volume proton magnetic resonance spectroscopy, localized to basal ganglia, was carried out in 10 patients with primary blepharospasm (PB) to assess the levels of N-acetyl aspartate (NAA), creatine-phosphocreatine, and choline-containing compounds. NAA was reduced significantly in patients compared with control subjects. This result suggests a striatal neuronal loss in PB.     

Proton magnetic resonance spectroscopy of linear nevus sebaceus syndrome

OBJECTIVE: The potential effect of ethnicity on the serum lipid profile and lipoprotein(a) [Lp(a)] was studied in a population with chronic spinal cord injury (SCI). STUDY DESIGN: The distribution and correlates of high density lipoprotein (HDL) cholesterol and Lp(a) were studied in a population of 600 subjects with chronic SCI. RESULTS: Mean +/- SEM serum HDL cholesterol was significantly higher in the African American group than in the white and Latino groups (47 +/- 1 vs 40 +/- 1 and 38 +/- 1 mg/dL, p < .0001, respectively). The African American group had a lower serum total to HDL cholesterol ratio than white and Latino groups (4.46 +/- .153 vs 5.18 +/- .168 and 5.40 +/- .140 mg/dL, p < .01, respectively). Mean serum Lp(a) levels were significantly higher in the African American group than in Latino or white groups (29 +/- 2 vs 18 +/- 1 and 15 +/- 1 mg/dL, p < .0001, respectively). Age, duration of SCI, and level and completeness of lesion had no significant effect on serum Lp(a) level. CONCLUSIONS: In a population with chronic SCI, those in the African American group had the highest serum HDL cholesterol concentrations, the lowest serum total to HDL cholesterol ratios, and elevated levels of serum Lp(a) compared with the Latino and white groups. In a population of individuals with chronic SCI, ethnicity was shown to have a major effect on serum lipids and may be used to assist in the determination of cardiovascular risk.     

Proton magnetic resonance spectroscopy in children with Sturge-Weber syndrome

Quantitative proton magnetic resonance spectroscopy was performed on six children with Sturge-Weber syndrome following gadolinium enhanced magnetic resonance imaging (MRI). MRI revealed only unilateral involvement in all cases. The mean concentration (mmol/kg wet weight) of the neuronal marker N-acetyl-aspartate was significantly reduced by 37% in the ipsilateral gadolinium enhanced volume of interest compared to a similarly placed contralateral volume of interest (5.39 +/- 1.70 [SD] vs 8.50 +/- 1.14, P < .005, two-tailed paired Student's t-test). Decreased N-acetyl-aspartate in the ipsilateral volume of interest was observed in all patients studied. No significant differences were found in the concentrations of creatine/phosphocreatine or choline compounds between the ipsilateral and contralateral volumes of interest. These findings give possible new insight into the pathophysiology of this disease and suggest that quantitative proton magnetic resonance spectroscopy may be useful for the early characterization and monitoring of neuronal dysfunction or loss in infants and children with Sturge-Weber syndrome.     

Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study

Budding yeast (Saccharomyces cerevisiae) Rap1p has been expressed in fission yeast (Schizosaccharomyces pombe) under the control of the regulatable fructose bisphosphatase (fbp) promoter. When the fbp promoter was derepressed, cells containing the complete RAP1 gene failed to show any significant growth, suggesting that Rap1p is toxic. A derivative of Rap1p that has a temperature-sensitive mutation in the DNA-binding domain was not toxic in cells grown at 37 degrees C, a temperature at which DNA binding by rap1p(ts) is severely inhibited. Removal of a short region downstream of the DNA-binding domain, including a region previously shown to be essential for Rap1p toxicity in budding yeast, also abolished the toxic effect. The toxic effect of Rap1p has therefore been conserved between two distantly related yeasts. In budding yeast, overexpression of Rap1p also caused changes to the lengths of the telomeric repeats. No effects on telomeres were detected in fission yeast.     

Cardiac magnetic resonance spectroscopy

The article reviews cardiac magnetic resonance spectroscopy (MRS) in Canada. 31P MRS has been used to study cardiac energetics and intracellular pH in hearts subjected to ischemia-reperfusion and to evaluate the effects of pharmacological interventions. 23Na, 87Rb, and 7Li MRS have provided unique probes to study ion balance and fluxes in intact tissue under normal and stressful physiological conditions. 1H MRS has been used to monitor the accumulation of lactate and lipids in hearts subjected to ischemia-reperfusion and follow the effects of diet on cardiac lipid levels and function. The isolated rat heart has been used most commonly to study the effects of pharmacological agents on energy balance, pH, ion fluxes, and contractile function of the heart subjected to ischemia-reperfusion. The pig heart has been developed as an alternative to the rodent heart because its metabolism is more similar to that of the human heart. Human atrial appendages have been useful in evaluating the effects of preservation strategies (temperature, composition of preservation solutions) on energy levels. The pig heart model has been useful in evaluating the effects of preservation solutions on cardiac function of hearts destined for transplantation. An isolated blood-perfused pig heart model has been developed to assess the effects of cardioplegic strategies on the preservation of contractile function of hearts following surgery on the heart. An in vivo canine model has been used to study myocardial infarction and the effects of therapies to reduce the infarct zones and areas of the heart at risk of infarction. Studies of human hearts in vivo have provided insight into the metabolic adaptations that occur in individuals living at high altitudes.     

Proton magnetic resonance studies of bradykinin antagonists

Bradykinin (BK) is a peptide hormone with sequence Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9 and has been implicated in a multitude of pathophysiological processes such as the ability to lower systemic blood pressure and stimulate pain. BK analogues having bulky, beta-branched D-aliphatic residues at position 7 combined with bulky L-aliphatic residues at position 8 have now been observed to be strong antagonists. Conformational studies based on two-dimensional nmr experiments in methanol/water (80/20 v/v) were carried out on several such active antagonists in a polar solvent. Included in this study were the very active antagonists, [D-Arg0,Hyp3,Thi5,D-Cpg7,Cpg8]-BK [Cpg: alpha-cyclo-pentyl-glycine; Hyp: trans-4-hydroxy-L-proline; Thi: beta-(2-thienyl)-L-alanine] (I), [D-Arg0,Hyp3,D-Cpg7,Cpg8]-BK (II), as well as its variant with D-Cpg7 replaced by Cpg7, namely [D-Arg0,Hyp3,Cpg7,Cpg8]-BK (III). A turn-like structure, which coexists with the extended conformation, was observed between residues 2 and 5 for the most active antagonists I and II, in direct correlation with the peptide activities. No turn-like structure was found for residues 6-9. In peptide III, a turn-like structure was not identified. The existence of a turn at the C-terminal end of bradykinin and its analogues has been predicted by empirical calculations and supported by nmr measurements. But the present nmr study on the most active antagonists (I, II) does not support this hypothesis. Instead, the data suggest that a turn-like structure between residues 2 and 5 could be important for antagonist activity. Finally, one weak inhibitor [D-Cpg7]-BK (IV) showed no defined secondary structure.     

Clinical applications of magnetic resonance spectroscopy

Neurospectroscopy measures a neuronal marker, energy and redox state, specific fuels of tissue respiration, maturation, and possibly myelination. It provides diagnostic patterns of altered neurochemistry. Current clinical uses range from intensive care in neonates to dementia in the elderly and include tumor and stroke management, prognosis in hemorrhage and trauma, white matter, inflammatory diseases, and AIDS. Inborn errors, metabolic and systemic diseases, subclinical hepatic encephalopathy, hyponatremia, and "coma" have been elucidated. Automation, single-voxel MRS, chemical shift imaging, quality control, and outcome analyses are discussed. With no remaining impediments to clinical use, neurospectroscopy has changed the way we look at diseases of the brain.     

Proton nuclear magnetic resonance studies on dideoxyribonucleoside methylphosphonates

A series of dideoxyribonucleoside methylphosphonates, d-ApA, d-ApT, d-TpA, and TpT, were synthesized chemically and the diastereoisomers of each dimer were separated [Miller, P. S., Yano, J., Yano, E., Carroll, C., Jayaraman, K., & Ts'o, P. O. P. (1979) Biochemistry 18, 5134]. The 1H NMR spectra of these compounds are similar to those of their parent diester compounds. Specifically, the assignments of the 1H resonances of the two diastereoisomers of d-ApA (designated as 1 and 2) were reaffirmed by comparing with the unmodified, parent d-ApA. The absolute configuration of the phosphonate methyl group of the two isomers (d-ApA)1 and (d-ApA)2 was determined by the NOE technique. The 1H NMR spectra of the diastereoisomers of d-ApA, as well as the corresponding monomer components dAp and CH3pdA, and TpT were analyzed by spectrum simulation techniques. Thus, all the coupling constants and chemical shifts of the proton resonances of the deoxyribofuranose ring and the phosphonate methyl group could be precisely determined. These data provide the information for an analysis of the sugar puckering and backbone conformations of these novel nonionic nucleic acid analogues. It was found that the conformations of the sugar-phosphate backbones of each isomer are similar to each other and are similar to the conformations of the parent dinucleoside monophosphates. The average adenine stacking conformations of (d-ApA)1 and (d-ApA)2 were described in numerical coordinates derived from a computer analysis which included both ring-current magnetic anisotropy and atomic diamagnetic anisotropy effects. The two computer-derived conformational models are similar to those derived from the graphic approximation based only on the ring-current effects. For each pair of dimer analogues, the base stacking mode of isomer 1 is similar to that of its parent diester while the extent of base overlap in isomer 2 is less than that in isomer 1. The results of the conformational analysis based on NMR data are consistent with the results obtained from ultraviolet and circular dichroism measurements on these dimers.     

Proton magnetic resonance spectroscopy: a metabolic approach of cerebral tumors and their follow-up after external radiation therapy

The same physical principles are the basis of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). Proton MRS is easily performed with clinical magnets (> or = 1.5 T) and may be added to routine MRI studies to provide metabolic information on pathological tissues. It represents an important tool to detect several metabolic compounds. The article will review the current status of proton MRS with a particular emphasis upon its clinical utility for the diagnosis of brain tumors and for the evaluation of the efficacy of radiotherapy.     

Proton magnetic resonance spectroscopy in the evaluation of children with congenital heart disease and acute central nervous system injury

We studied nine infants and children, aged 1 week to 42 months, with severe acute central nervous system injuries associated with cardiac disease or corrective operations by means of single-voxel proton magnetic resonance spectroscopy to determine whether this technique would be useful in predicting neurologic outcome. Proton magnetic resonance spectroscopic data were acquired from the occipital gray and parietal white matter (8 cm3 volume, stimulated echo-acquisition mode sequence with echo time of 20 msec and repetition time of 3.0 seconds) a median of 9 days after operation (range 3 to 42 days). Data were expressed as ratios of areas under metabolite peaks, including N-acetyl compounds, choline-containing compounds, creatine and phosphocreatine, and lactate. Four patients had cerebral insults before operation, one had both a preoperative and a perioperative insult, three had perioperative insults, and one had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome Scale scores) were assigned at discharge and 6 to 12 months after injury. Six patients were in a vegetative state or had severe impairment at discharge, and two still had severe impairment at 6- to 12-month follow-up. Proton magnetic resonance spectroscopy showed lactate in these two patients, along with markedly reduced ratios of N-acetyl compounds to creatine compounds. The other four patients with severe impairment recovered to a level of mild disability at follow-up. Proton magnetic resonance spectroscopy showed no lactate in these four patients; however, one patient showed moderately reduced ratio of N-acetyl compounds to creatine compounds. The three patients who had mild or moderate impairment at discharge showed no lactate and mild or no changes in metabolite ratios; follow-up revealed normal or mild outcomes. Overall, we found that the presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine compounds were predictive of severe outcomes at discharge and long-term follow-up, whereas no lactate and mild or no changes in ratios suggested potential for recovery with at least a mild disability. Continuing investigations are in progress to determine the optimal selection of candidates and timing of proton magnetic resonance spectroscopic studies.     

Quantitative proton magnetic resonance spectroscopy of childhood adrenoleukodystrophy

Cerebral metabolic disturbances in patients with childhood adrenoleukodystrophy (ALD) were assessed by quantitative localized proton MRS. Patient monitoring by follow-up MRS studies served to identify putative markers for disease onset and progression. Whereas normal-appearing white matter of neurologically asymptomatic patients is characterized by slightly elevated concentrations of choline-containing compounds (Cho), an increase of both Cho and myo-inositol (Ins) seems to indicate the onset of demyelination. Markedly elevated concentrations of Cho, Ins, and glutamine in affected white matter reflect active demyelination and glial proliferation. A simultaneous reduction of the concentrations of N-acetylaspartate and glutamate is consistent with neuronal damage or loss. The observation of elevated lactate is in line with inflammation and/or macrophage infiltration. The more severe metabolic disturbances in cerebral ALD correspond to progressive demyelination, neuroaxonal loss and gliosis leading to clinical deterioration and eventually death. The detection of MRS abnormalities before the onset of neurological symptoms may help in the selection of patients for bone marrow transplantation (BMT). Stabilization and partial reversal of metabolic abnormalities is demonstrated in a patient after BMT.     

Silicon-29 nuclear magnetic resonance spectroscopy detection limits

We show that an unmodified, commercially available high-field (17.61T) NMR spectrometer using the DEPT pulse sequence is capable of detecting silicon-containing species down to concentrations of 150 ng/mL (150 ppb) per spin site. This is in the range given for the concentration of silicon in the blood of silicone breast implant recipients, as determined by ICP analysis, and demonstrates that, contrary to the view expressed in the literature, in theory 29Si NMR may be sufficiently sensitive to be of use in determining the nature of the silicon-containing species present. A summary of the factors affecting the detection limits in NMR spectroscopy is given.     

Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements

OBJECTIVES: To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations. MATERIALS AND METHODS: We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years. The control group included 20 healthy volunteers and 4 patients with multifocal motor neuropathy. Proton magnetic resonance spectroscopy determined levels of the brain metabolites N-acetylaspartate (NAA), choline, inositol-containing compounds, glutamate/glutamine, and phosphocreatine. RESULTS: Patients with ALS showed a significant reduction in the NAA-choline (P <.001) and NAA-phosphocreatine (P <.005) metabolite ratios and significantly elevated choline-phosphocreatine (P <.005) ratios compared with controls. Inositol-phosphocreatine ratios were also elevated in case patients, but the increase was less pronounced (P <.05). No differences in glutamate/glutamine-phosphocreatine ratios were detected between case patients and controls. An analysis of subgroups demonstrated less significant differences in NAA-choline metabolite ratios (P<.05), even in patients with pure lower motor neuron syndrome (suspected ALS). No changes in metabolite T1 and T2 relaxation times were observed. Patients with multifocal motor neuropathy showed normal metabolic ratios. Progressive alterations in affected metabolite ratios could be documented in the follow-up examinations. CONCLUSIONS: Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.     

Functional and metabolic evaluation of the athlete's heart by magnetic resonance imaging and dobutamine stress magnetic resonance spectroscopy

BACKGROUND: The question of whether training-induced left ventricular hypertrophy in athletes is a physiological rather than a pathophysiological phenomenon remains unresolved. The purpose of the present study was to detect any abnormalities in cardiac function in hypertrophic hearts of elite cyclists and to examine the response of myocardial high-energy phosphate metabolism to high workloads induced by atropine-dobutamine stress. METHODS AND RESULTS: We studied 21 elite cyclists and 12 healthy control subjects. Left ventricular mass, volume, and function were determined by cine MRI. Myocardial high-energy phosphates were examined by 31P magnetic resonance spectroscopy. There were no significant differences between cyclists and control subjects for left ventricular ejection fraction (59+/-5% versus 61+/-4%), left ventricular cardiac index (3.4+/-0.4 versus 3.4+/-0.4 L x min(-1) x m[-2]), peak early filling rate (562+/-93 versus 535+/-81 mL/s), peak atrial filling rate (315+/-93 versus 333+/-65 mL/s), ratio of early and atrial filling volumes (3.0+/-1.0 versus 2.6+/-0.6), mean acceleration gradient of early filling (5.2+/-1.4 versus 5.8+/-1.9 L/s2), mean deceleration gradient of early filling(-3.1 +/- 0.9 versus -3.2 +/- 0.7 L/s2), mean acceleration gradient of atrial filling (3.6+/-1.8 versus 4.5+/-1.7 L/s2), and atrial filling fraction (0.23+/-0.06 versus 0.26+/-0.04, respectively). Cyclists and control subjects showed similar decreases in the ratio of myocardial phosphocreatine to ATP measured with 31P magnetic resonance spectroscopy during atropine-dobutamine stress (1.41+/-0.20 versus 1.41+/-0.18 at rest to 1.21+/-0.20 versus 1.16+/-0.13 during stress, both P=NS). CONCLUSIONS: Left ventricular hypertrophy in cyclists is not associated with significant abnormalities of cardiac function or metabolism as assessed by MRI and spectroscopy. These observations suggest that training-induced left ventricular hypertrophy in cyclists is predominantly a physiological phenomenon.     

Quantitation of 5-fluorouracil catabolism in human liver in vivo by three-dimensional localized 19F magnetic resonance spectroscopy

The development of clinical applications of 19F magnetic resonance (MR) spectroscopy of 5-fluorouracil (5-FU) has been limited by the inability to localize 19F spectra to specific regions of interest, making it difficult to quantitate drug and metabolite concentrations accurately. To develop methodology for quantitation, we studied the liver of patients receiving rapid bolus i.v. injections of 5-FU. In serial studies, 5-FU disappeared from the liver within 17-26 min, and its catabolite, alpha-fluoro-beta-alanine (FBAL), rose to reach a plateau after 40 min. A high peak level of fluoro-ureido-propionic acid preceded that of FBAL in only one patient, and dihydrofluorouracil was never observed. During the plateau, we obtained MR imaging-directed 19F MR spectra localized using three-dimensional chemical shift imaging. The spin-lattice relaxation time of FBAL in liver, measured using a variable nutation angle method, was 1.6 +/- 0.2 s (mean +/- SD; n = 5). The concentration of FBAL at 60 +/- 10 min after injection was 1.0 +/- 0.2 mm in liver (mean +/- SD; n = 7). This amount represents approximately 20% of the injected dose and 1.4 times the initial hepatic 5-FU concentration. Our approach may permit one to obtain molar concentrations of fluoropyrimidine metabolites simultaneously in hepatic cancers and surrounding liver, and it helps expand pharmacokinetic modeling of fluoropyrimidine catabolism.     

Proton nuclear magnetic resonance spectral profiles of urine in type II diabetic patients

Serial urine samples of 33 type II diabetic patients and 20 control subjects were examined by 1H nuclear magnetic resonance (NMR). Metabolites including lactate, citrate, glycine, alanine, hippurate, trimethylamine-N-oxide, and dimethylamine were identified in all subjects although in higher concentrations in diabetic patients. Other analytes, such as creatine, acetate, betaine, and ketone bodies, were found more frequently and in greater concentrations in diabetics than in controls. In addition, although lactate, citrate, alanine, and hippurate concentrations increased with increasing glycosuria and glycohemoglobin, trimethylamine-N-oxide and dimethylamine were present at high concentrations even in diabetics with good metabolic control. 1H NMR spectroscopy permitted us to explore the relationships among the metabolites present in the urine samples and to obtain information about the disease status in type II diabetic patients.     

Functional radiology of the liver: magnetic resonance imaging

Magnetic Resonance (MR) images sensitive to the flowing blood are defined as images of MR angiography. Proton movement within a magnetic field modifies both the intensity and the phase of Nuclear Magnetic Resonance (NMR) signal; two techniques of MR angiography are thus distinguished: (TOF) the "time of flight" (intensity) and the "phase-contrast" (phase) technique. In the time of flight MR angiography the blood may appear as hypointense or hyperintense compared to stationary tissues. Blood hypointensity in vessels is due to the flow void phenomenon while hyperintensity is due to the phenomenon of flow-related enhancement. In phase contrast MR angiography, protons moving within a magnetic field modify their phase directly proportional to the displacement velocity and gradient intensity. Moreover, MRI allows noninvasive measurement of blood flow. Flow velocity is measured with TOF sequences or phase-contrast sequences. In TOF sequences quantitative measurement is performed with the bolus tracking procedure. In contrast-phase sequences the velocity is measured based on the extent of signal phase modification induced by the proton displacement velocity. The recent use of liver-specific contrast media supplies information on parenchymal liver function.