Magnetic Resonance Spectroscopy In Patients Research Articles

Localized proton magnetic resonance spectroscopy in patients with adult adrenoleukodystrophy. Increase of choline compounds in normal appearing white matter.

To describe the changes in the results of magnetic resonance imaging and spectroscopy occurring in the normal-appearing white matter of patients with adult adrenoleukodystrophy and to present evidence of a particular change that may serve as a marker for the follow-up of the disease. Neurologic, magnetic resonance imaging, and localized proton spectroscopic examinations were performed in 11 patients with adult adrenoleukodystrophy and compared with 11 sex- and age-matched controls. Eleven patients with adult adrenoleukodystrophy participated in a trial of dietary therapy with glyceryl trioleate and glyceryl trierucate (Lorenzo's oil) in the Fédération de Neurologie and the Institut National de la Santé et de la Recherche Médicale, Unité 134, at the Hôpital de la Salpêtrière in Paris, France. The results of magnetic resonance imaging of the white matter were normal in 2 patients and showed areas of mild symmetrical hypersignals on T2-weighted images and fluid attenuated inversion recovery sequences, localized in the posterior white matter in 9 patients. The results of spectroscopy indicated that the peak of the area of choline-containing compounds was increased at long echo times in patients with adult adrenoleukodystrophy, which may reflect very long-chain fatty acid accumulation in this disease. The peak of the area of myo-inositol-containing compounds was increased at short echo times in patients with adult adrenoleukodystrophy, which may indicate a rise in this metabolite concentration. The N-acetylaspartate-creatine amplitude ratio was significantly decreased in patients with motor deficit. The significance of this finding remains to be established. The results of localized proton magnetic resonance spectroscopy show abnormalities in the cerebral white matter of patients with adult adrenoleukodystrophy, which may contribute to the understanding of the pathophysiologic characteristics of the disease. Although changes in the results of spectroscopy found in this disease are not specific, the increase of choline-containing compounds may reflect the accumulation of very long-chain fatty acids in the central nervous system. Localized proton magnetic resonance spectroscopy may prove a valuable technique, in addition to magnetic resonance imaging, for noninvasive investigation of patients with adult adrenoleukodystrophy undergoing future clinical trials.

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

The authors represent a cooperative group of 15 institutions that examined the feasibility of using metabolic features observed in vivo with 1H-magnetic resonance (MR) spectroscopy to characterize brain tumors of the glial type. The institutions provided blinded, centralized MR spectroscopy data processing long with independent central review of MR spectroscopy voxel placement, composition and contamination by brain, histopathological typing using current World Health Organization criteria, and clinical data. Proton 1H-MR spectroscopy was performed using a spin-echo technique to obtain spectra from 8-cc voxels in the tumor and when feasible in the contralateral brain. Eighty-six cases were assessable, 41 of which had contralateral brain spectra. Glial tumors had significantly elevated intensities of choline signals, decreased intensities of creatine signals, and decreased intensities of N-acetylaspartate compared to brain. Choline signal intensities were highest in astrocytomas and anaplastic astrocytomas, and creatine signal intensities were lowest in glioblastomas. However, whether expressed relative to brain or as intratumoral ratios, these metabolic characteristics exhibited large variations within each subtype of glial tumor. The resulting overlaps precluded diagnostic accuracy in the distinction of low-and high-grade tumors. Although the extent of contamination of the 1H-MR spectroscopy voxel by brain had a marked effect on metabolite concentrations and ratios, selection of cases with minimal contamination did not reduce these overlaps. Thus, each type and grade of tumor is a metabolically hetero-geneous group. Lactate occurred infrequently and in all grades. Mobile lipids, on the other hand, occurred in 41% of high-grade tumors with higher mean amounts found in glioblastomas. This result, coupled with the recent demonstration that intratumoral mobile lipids correlate with microscopic tumor cell necrosis, leads to the hypothesis that mobile lipids observed in vivo in 1H-MR spectroscopy may correlate independently with prognosis of individual patients.

Measurement of plasma 5-fluorouracil by high-performance liquid chromatography with comparison of results to tissue drug levels observed using in vivo 19F magnetic resonance spectroscopy in patients on a protracted venous infusion with or without interferon-α

To measure plasma 5-fluorouracil (5-FU) levels using high-performance liquid chromatography (HPLC) and compare the findings to the tissue metabolism of 5-FU evaluated using 19F magnetic resonance spectroscopy (MRS), during a protracted venous infusion (PVI) with or without interferon-alpha. Patients receiving PVI 5-FU (300 mg/m2/day) with or without interferon-alpha (5 x 10(6) units 3 times per week), had 2 weekly plasma 5-FU levels evaluated using reverse-phase ion-pairing HPLC. These samples were drawn just prior to the patient undergoing MRS using a 1.5T Siemens Magnetom whole body magnetic resonance system with a 16 cm surface coil placed over normal liver or metastatic tumour. Semi-quantitated MRS values were compared with the plasma 5-FU levels using linear regression analysis. Data were available from patients given interferon-alpha with PVI 5-FU from day 1 or at the point of 5-FU refractory disease. A total of 30 patients were studied. Plasma 5-FU concentrations while on a protracted venous infusion varied from <25 ng/ml (0.192 mu M) to 25,000 ng/ml (192 mu M). A high plasma 5-FU concentration was associated with an increase in patient toxicity. Patients given interferon-alpha with 5-FU had higher median plasma 5-FU levels higher than patients on 5-FU alone (6138 vs. 218 ng/ml; p = 0.03). There was no correlation between the plasma 5-FU concentration and tumour response. A comparison of the plasma 5-FU data to the MRS studies in normal liver revealed a positive correlation between plasma 5-FU and liver catabolite signal (r = 0.68; p = 0.016) but a negative correlation with the log plasma 5-FU concentration and 5-FU liver signal (r = -0.63; p = 0.022). The patients experiencing toxicity, in addition to having a higher plasma 5-FU concentration did not exhibit a liver 5-FU signal, while the reverse was true for those having no toxicity. Plasma 5-FU levels may show greater interpatient variation when given as a protracted venous infusion. Levels of 5-FU correlated with treatment toxicity but not with anti-tumour activity. The addition of interferon-alpha to 5-FU increases plasma 5-FU levels. MRS findings suggest patients with low plasma 5-FU levels have higher 5-FU levels in normal liver tissue than in those with higher plasma levels.

Brain fluoxetine measurements using fluorine magnetic resonance spectroscopy in patients with social phobia

Brain fluoxetine measurements using fluorine magnetic resonance spectroscopy in patients with social phobia

Reduced N-acetylaspartate in the brain observed on in vivo proton magnetic resonance spectroscopy in patients with mental retardation

Volume-selective proton magnetic resonance spectroscopy ( 1H-MRS) of the brain was performed with a 1.5T magnet in 28 patients with unclassified mental retardation (MR) and in 25 age-matched healthy children. Peaks of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), but not of lactate, were observed in both groups on 1H-MRS. In all our subjects of this age range, 1H-MRS revealed an increase with advancing age in the ratio of NAA/Cho ( P = .0031), but no developmental change in the NAA/Cr and Cho/Cr ratios. The NAA/Cho ratio was lower in patients with MR than in controls ( P = .0016). The NAA/Cr ratio tended to be lower in the MR group, and the Cho/Cr ratio did not differ between patients with MR and controls. These results suggest that in patients with MR, NAA decreases and a disorder and/or dysfunction of neurons in the brain exists.

Temporal lobe proton magnetic resonance spectroscopy of patients with first-episode psychosis.

The authors measured the ratio of N-acetyl aspartate (a putative neuronal marker) to creatine-phosphocreatine in patients with first-episode psychosis by using proton magnetic resonance spectroscopy (MRS). Temporal lobe 1H MRS was performed bilaterally on 13 patients with first-episode psychosis and 15 comparison subjects. The N-acetyl aspartate/creatine-phosphocreatine and choline/creatine-phosphocreatine ratios were determined. The N-acetyl aspartate/creatine-phosphocreatine ratio of the psychotic patients was significantly lower than that of the comparison subjects. These preliminary data suggest that abnormalities in temporal lobe N-acetyl aspartate concentration are present early in psychotic illness.

Limitations of magnetic resonance spectroscopy in patients with white matter disease

Limitations of magnetic resonance spectroscopy in patients with white matter disease

Cerebral phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy

Cerebral phosphorus-31 magnetic resonance spectroscopy was undertaken in 33 patients with biopsyproven cirrhosis: 6 had no evidence of neuropsychiatric impairment on standard clinical, psychometric and electrophysiological testing; 8 had evidence of subclinical hepatic encephalopathy; and 19 were classified as having overt hepatic encephalopathy. The reference population comprised 15 healthy volunteers. Unlocalized spectra were acquired from the entire head with a 45-degree pulse angle and repetition times of 1 and 5 sec. Spectra localized to the basal ganglia were acquired with a 45-degree pulse angle and a repetition time of 1 sec. Peak area ratios of phosphomonoesters, inorganic phosphate, phosphodiesters and phosphocreatine relative to β-ATP were measured in the spectra acquired. We noted no consistent change in the ratios of inorganic phosphate to ATP and phosphocreatine to ATP. Mean values of the ratios of phosphomonoesters to ATP and phosphodiesters to ATP were significantly lower in the total patient population than in the reference population, and they correlated with the patients' neuropsychiatric status. Thus we found no significant reductions in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients who were neuropsychiatrically unimpaired, but significant reductions were observed in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients with both subclinical and overt hepatic encephalopathy. The most marked reductions in these metabolite ratios were observed in patients with overt encephalopathy. (Hepatology 1994;20:1173–1178).

Cerebral Phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy

Cerebral phosphorus-31 magnetic resonance spectroscopy was undertaken in 33 patients with biopsy-proven cirrhosis: 6 had no evidence of neuropsychiatric impairment on standard clinical, psychometric and electrophysiological testing; 8 had evidence of subclinical hepatic encephalopathy; and 19 were classified as having overt hepatic encephalopathy. The reference population comprised 15 healthy volunteers. Unlocalized spectra were acquired from the entire head with a 45-degree pulse angle and repetition times of 1 and 5 sec. Spectra localized to the basal ganglia were acquired with a 45-degree pulse angle and a repetition time of 1 sec. Peak area ratios of phosphomonoesters, inorganic phosphate, phosphodiesters and phosphocreatine relative to beta-ATP were measured in the spectra acquired. We noted no consistent change in the ratios of inorganic phosphate to ATP and phosphocreatine to ATP. Mean values of the ratios of phosphomonoesters to ATP and phosphodiesters to ATP were significantly lower in the total patient population than in the reference population, and they correlated with the patients' neuropsychiatric status. Thus we found no significant reductions in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients who were neuropsychiatrically unimpaired, but significant reductions were observed in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients with both subclinical and overt hepatic encephalopathy. The most marked reductions in these metabolite ratios were observed in patients with overt encephalopathy.

The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-α using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: A pilot study

5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007). MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest.

Cellular energetics of dystrophic muscle

Cytosolic pH and phosphorus metabolite ratios in skeletal muscle were measured by 31P magnetic resonance spectroscopy in patients with Duchenne muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) and in Duchenne/Becker carriers. In resting dystrophin-deficient muscle, there was a decrease in phosphocreatine (PCr) and increase in orthophosphate (P i) relative to ATP, and an increase in calculated free [ADP]. Phosphomonester and phosphodiester were also increased relative to ATP. These changes were largest in DMD, smaller in BMD and small or absent in carriers. Cytosolic pH was increased substantially in DMD, moderately in BMD and slightly but significantly in gastrocnemius of carriers. Raised intracellular pH thus appears to be the most characteristic abnormality in dystrophin-deficient muscle. Responses to aerobic exercise were studied in the forearm muscle flexor digitorum superficialis of carriers. PCr depletion during exercise was greater than normal but the fall in pH was disproportionately small, resulting in increased [ADP]. This is likely to result either from reduced anaerobic glycogenolysis to lactic acid or from increased proton efflux (as is seen in mitochondrial myopathy). Detailed analysis suggests: (1) at the start of exercise, calculated lactic acid production was increased, as was the rate of PCr depletion, suggesting that there was no absolute defect of glycogenolysis. (2) At the start of recovery, calculated proton efflux was not increased, although as the pH at the end of exercise was higher than in controls and proton efflux is normally pH-dependent, an up-regulation of proton efflux cannot be excluded. (3) Recovery of PCr, P i and ADP after exercise were not impaired, suggesting that mitochondrial function is normal.

Brain lithium concentrations measured with lithium-7 magnetic resonance spectroscopy in patients with affective disorders: Relationship to erythrocyte and serum concentrations

Brain lithium concentrations weremeasured in eight patients with affective disorders using lithium-7 magnetic resonance spectroscopy (MRS). Brain lithium concentrations correlated better with serum concentrations ( n = 23, r = 0.66, p < 0.001) than with erythrocyte concentrations ( r = 0.44, p < 0.05). Because of previous data in animal experiments these results were unexpected, but the differences in cation transport mechanisms between neurons and erythrocytes may account for the results.

Combined magnetic resonance imaging and proton magnetic resonance spectroscopy of patients with acute stroke.

The prospect for a therapeutic window for treatment of ischemic stroke encourages the noninvasive investigation of metabolic changes in acute ischemia. Recently, localized proton spectroscopy became available at 1.5-T magnetic resonance systems. In this study we evaluated the usefulness of combined magnetic resonance imaging and spectroscopy on the diagnosis of acute and chronic infarctions. Combined magnetic resonance imaging and spectroscopy investigations were carried out with a 1.5-T system in 16 volunteers, eight patients with chronic infarction (greater than 8 months), and 10 patients with acute ischemic stroke (less than 8 hours). We used a stimulated echo sequence to acquire localized spectra from image-guided volumes of interest (16-27 ml). There were no significant interindividual differences of choline, creatine, phosphocreatine, and N-acetyl aspartate resonances in the spectra from volunteers. In chronic infarctions, N-acetyl aspartate was decreased in relation to choline. Acute ischemic infarctions were characterized by decreased N-acetyl aspartate resonances and elevation of lactate. The study demonstrates the feasibility of proton spectroscopy in stroke patients. Metabolic alterations in ischemic tissue can be monitored and can distinguish acute from chronic lesions.

Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura.

We studied brain and muscle energy metabolism by phosphorus 31 magnetic resonance spectroscopy (31P-MRS) in 12 patients affected by migraine with aura (classic migraine) in interictal periods. Brain 31P-MRS disclosed a low phosphocreatine content in all patients, accompanied by high adenosine diphosphate concentration, a high percentage of V/Vmax (adenosine triphosphate), and a low phosphorylation potential--features showing an unstable state of metabolism in classic migraine. Abnormal muscle mitochondrial function, in the absence of clinical signs of muscle impairment, was present in nine of the 12 patients examined.

In vivo 31P nuclear magnetic resonance spectroscopy in patients with old myocardial infarction.

To assess the usefulness of in vivo 31P nuclear magnetic resonance (NMR) spectroscopy, we investigated spectra from the myocardium in 6 patients with old Q-wave infarction (QMI), 6 with old non-Q-wave infarction (NQMI) and 9 controls by ECG-gated depth-resolved surface-coil spectroscopy. External hexamethylphosphoric triamide (HMPT) was used to quantify the signal intensities. Left ventricular weight in the region of interest (LVW) was estimated from 1H magnetic resonance images. The extent score by 201Tl scintigraphy was determined in 3 QMI and 4 NQMI patients. No significant differences were found among the 3 groups in peak area ratios of 31P NMR spectra to phosphocreatine (PCr) or adenosine triphosphate (ATP). Compared with controls, significant reductions were observed in values for the peak areas of PCr normalized by the standard HMPT (PCr/HMPT) or by both HMPT and LVW (PCr/HMPT/LVW) for QMI patients (p less than 0.05), and in ATP/HMPT and ATP/HMPT/LVW for QMI and NQMI patients (p less than 0.01). There was a significant negative correlation between ATP/HMPT and the 201Tl scintigraphy extent score (p less than 0.05). These findings suggest that in vivo 31P NMR spectroscopy can detect high-energy phosphate reduction in the infarcted myocardium and may be useful in evaluating myocardial viability.

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder

Measurements of the lithium concentration in the occipital pole of the head and calf muscle of nine patients with bipolar disorder in remission were performed using in vivo lithium-7 nuclear magnetic resonance spectroscopy ( 7Li NMR). 7Li NMR measurements were performed on a 1-m-bore, 1.85-T, superconducting magnet supplemented with a multinuclear spectrometer, using 11.5-cm-diameter surface coils. The average lithium concentration in the occipital pole was 0.36 ± 0.10 mEq/L, whereas in the muscle it was 0.50 ± 0.17 mEq/L, both lower than the average serum lithium concentration (0.79 ± 0.23 mEq/L). The average brain/serum lithium concentration ratio was 0.47 ± 0.12 whereas the average muscle/serum lithium concentration ratio was 0.66 ± 0.20. There was a positive correlation between the brain versus serum and brain versus muscle lithium concentrations. The hypothesis is advanced that the minimal effective concentration of brain lithium concentration for maintenance treatment of bipolar disorder is around 0.2–0.3 mEq/L.

Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine

The hypothesis that brain mitochondria are directly affected in several phenotypes associated with disordered oxidative phosphorylation was tested using phosphorus 31 (31P) magnetic resonance spectroscopy. Abnormal phosphorylation potentials in skeletal muscle have been demonstrated by 31P magnetic resonance spectroscopy in patients with mitochondrial cytopathies (heritable disorders of oxidative phosphorylation), but abnormalities of phosphorylation potentials in other organs have not been documented. Several lines of evidence suggest that these mutations may affect mitochondria in nonmuscle tissue. In this study we found that phosphocreatine-to-ATP ratios in brain were significantly reduced and that calculated brain ADP concentrations, phosphorylation potentials, and percentage of maximal rate of ATP synthesis were significantly altered in the 5 patients examined. This study indicates a primary abnormality of mitochondrial function in the brain, even in the absence of clinically evident cerebral dysfunction.

In vivo phosphorus-31 spectroscopic imaging in patients with global myocardial disease

The goals of this study were to determine whether abnormalities in phosphorus metabolism could be noninvasively detected using phosphorus-31 nuclear magnetic resonance spectroscopy in patients with dilated cardiomyopathy and left ventricular hypertrophy, and whether these patient groups could be distinguished from each other based on parameters obtained using this technique. Seventeen patients and 14 control subjects were studied using nuclear magnetic resonance spectroscopy. Spectra were obtained from the human heart at rest using 3-dimensional spectroscopic imaging as a localization technique. Data were acquired over an average volume of 48 cc in 26.3 minutes using a 2 tesla imaging and spectroscopy unit. The ratio of phosphocreatine to adenosine triphosphate was 0.89 ± 0.08 (mean ± standard error) in normal subjects and did not differ significantly in patients with dilated cardiomyopathy or left ventricular hypertrophy. A prominent peak in the phosphodiester region was seen much more frequently in patients with dilated cardiomyopathy, resulting in significantly higher ratios of phosphodiester to phosphocreatine (1.28 ± 0.35) and phosphodiester to adenosine triphosphate (0.79 ± 0.18) in this group compared to normal subjects (0.33 ± 0.08 and 0.29 ± 0.08, respectively). However, the various patient groups could not be reliably distinguished from each other based on spectral patterns. These studies demonstrate the feasibility of performing phosphorus-31 nuclear magnetic resonance spectroscopic imaging in patients with myocardial disease. The initial results indicate that, under resting conditions, the ratio of phosphocreatine to adenosine triphosphate is not consistently altered in patients with severe global cardiomyopathies or hypertrophy. Phosphodiesters are elevated in some patients with dilated cardiomyopathy, a finding that may signify abnormal phospholipid metabolism in this condition.

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder : Laszlo Gyulai, M.D., Steven W. Wicklund, B.S., Robert Greenstein, M.D., Mark Bauer, M.D., Patrick Ciccione, M.D., Peter Whybrow, M.D., Joanne Zimmerman, R.N., Gyula Kovachich, Ph.D. Department of Psychiatry, Hospital of Pennyylvania (L.G., R.G., M.B., P.W.), Department of Psychiatry, Veterans Affairs Medical Center (R.G., P.C.,

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder : Laszlo Gyulai, M.D., Steven W. Wicklund, B.S., Robert Greenstein, M.D., Mark Bauer, M.D., Patrick Ciccione, M.D., Peter Whybrow, M.D., Joanne Zimmerman, R.N., Gyula Kovachich, Ph.D. Department of Psychiatry, Hospital of Pennyylvania (L.G., R.G., M.B., P.W.), Department of Psychiatry, Veterans Affairs Medical Center (R.G., P.C.,

Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days after the beginning of treatment, before any response was seen in the haemoglobin concentration of peripheral blood. The spectral changes indicate an alteration in cellular composition of haemopoietic bone marrow with an increase in the amount of haemopoietic active tissue. One patient showed a major change in the spectrum four days after treatment began, indicating that MR spectroscopy may detect early changes in the cellular composition of the bone marrow. This noninvasive method may be useful in evaluating treatment effects of recombinant human haemopoietic growth factors in the bone marrow, as well as investigating bone marrow response from different modes of rHuEPO administration.