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PubMed2000

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.

Animals↗
PubMed1990

Monitoring tumor growth and regression by 31P magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) uniquely provides noninvasive access to chemistry in vivo. 31P MRS can be used to monitor the high energy phosphates--phosphocreatine (PCr) and ATP, and their breakdown product--Pi, in situ in animals or patients. In several experimental tumor lines in animals it has been shown that the PCr/ATP and other related ratios steadily decline as the tumor increases in size, and that this effect is reversed when the tumor is treated with a therapeutic modality to which it responds. Acid extracts of freeze-clamped tumors at different stages of growth have confirmed these MRS observations and give additional information on related compounds such as creatine and ADP. Results show that, in the tumors studied, at least 80% of the ADP and about 40% of the Pi are bound and not in solution in the cytosol. Histological sections have indicated that the MRS response to endocrine therapy, in an NMU-induced estrogen-sensitive mammary tumor model, precedes any histological changes or any measurable regression. If these findings can be translated into a clinical setting, this may mean that MRS can be used in the clinic as an early predictor of tumor responsiveness to treatment. In untreated tumor growth, the cause of the decrease in PCr and ATP relative to Pi is probably due to the tumors outgrowing their blood supply and the cells becoming increasingly hypoxic. The PCr is lost more rapidly than ATP, indicating that the equilibrium in the creatine kinase reaction is maintained in these tumors. When the tumor is treated, cellular growth ceases and the requirement for oxygen and other nutrients is greatly reduced. This would allow the cellular energy reserves to be repleted and thus lead to the paradoxical improvement in the high energy phosphate status of a tumor that is about to regress.

Adenine Nucleotides↗
PubMedDate not supplied

Brain lesions with elevated lactic acid peaks on magnetic resonance spectroscopy.

Magnetic resonance (MR) spectroscopy is a noninvasive imaging tool that provides information on various metabolite concentrations within brain lesions. The biochemical information obtained with MR spectroscopy, along with the morphologic appearance of a lesion on MR imaging, allows for better characterization and improved diagnostic ability. Lactic acid is an end product of anaerobic metabolism. Under conditions of anaerobic metabolism or inflammation, lactate levels become elevated and a characteristic peak at 1.3 ppm is detected on MR spectroscopy. This review will discuss the significance of lactate as a metabolite and will describe various brain lesions and disease conditions in which elevated lactate levels are detected.

Brain↗
PubMed2004

Discrimination between neurochemical and macromolecular signals in human frontal lobes using short echo time proton magnetic resonance spectroscopy.

Magnetic resonance spectra from large (35 cm3) frontal lobe voxels in vivo were analyzed using LCModel, with and without subtraction of a "metabolite nulled" spectrum with an inversion time of 650 ms to characterize the macromolecule baseline. Baseline subtraction decreased the signal to noise ratio (SNR), but improved the reliability of LCModel quantification of most metabolites, as reflected in the Cramer-Rao lower bounds, in particular for glutamate and glutamine. The reported concentrations increased for glutamine, creatine, and lactate, and decreased for glutamate, myo-inositol and NAAG, but the sum of all metabolites remained constant, as did the standard deviation of the concentrations in the control group. Macromolecule subtraction is worthwhile when SNR is high, as in the characterization of normal-appearing tissue in the brain.

Algorithms↗
PubMed2004

Determination of grade and receptor status from the primary breast lesion by magnetic resonance spectroscopy.

Magnetic resonance spectra (MRS) from fine needle aspiration biopsies (FNAB) from primary breast lesions were analysed using a pattern recognition method, Statistical Classification Strategy, to assess tumor grade and oestrogen receptor (ER) and progesterone receptor (PgR) status. Grade 1 and 2 breast cancers were separated from grade 3 cancers with a sensitivity and specificity of 96% and 95%, respectively. The ER status was predicted with a sensitivity of 91% and a specificity of 90%, and the PgR status with a sensitivity of 91% and a specificity of 86%. These classifiers provide rapid and reliable, computerized information and may offer an objective method for determining these prognostic indicators simultaneously with the diagnosis of primary pathology and lymph node involvement.

Breast Neoplasms↗
PubMed2001

Magnetic resonance spectroscopy and magnetic resonance imaging findings in Krabbe's disease.

Two twins with late infantile globoid cell leukodystrophy of Krabbe's disease were studied with conventional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy. Brain MRI demonstrated brain atrophy with extensive bilateral symmetric abnormal T2 signal in the posterior periventricular white matter, parietal lobes, corona radiata, centrum semiovale, and splenium of the corpus callosum. Magnetic resonance imaging-guided proton magnetic resonance spectroscopy revealed prominent peaks from choline-containing compounds, total creatine, and inositols. The N-acetylaspartate peak was markedly reduced, and the choline-to-N-acetylaspartate ratio was abnormally high; in one of the twins, lactic acid was also detected. The constellation of magnetic resonance spectroscopy findings is indicative of extensive demyelination, gliosis, and loss of axons in the involved white matter; the latter two events occur in the later stages of globoid cell leukodystrophy. In conjunction with brain MRI, these magnetic resonance spectroscopy findings may alert clinicians to the possibility of leukodystrophy in children with progressive encephalopathy.

Aspartic Acid↗
PubMed2000

Observation of intramyocellular lipids by 1H-magnetic resonance spectroscopy.

Magnetic resonance (MR) methods are increasingly being used to investigate the physiology of human muscle. Although MR imaging (MRI) reveals the morphology of muscles in great detail, for example, for determining their volume and fiber orientation, MR spectroscopy (MRS) provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the observation of high-energy phosphates (31P-MRS), glycogen (13C-MRS), or intramyocellular lipids (1H-MRS), to give only a few examples. 1H-MRS of human skeletal muscle requires special techniques because 1H nuclei in water or adipose tissue are far more concentrated than in any other metabolite of human tissue. The strong signal from water can be suppressed by special prepulses, whereas large signals from fat in adipose tissue can be reduced by carefully selecting the region of interest. Until recently, it was presumed that only a few metabolites would be visible underneath the large resonances of water and subcutaneous fat. Meanwhile, it was clear that 1H-MR spectra of human muscle reveal much metabolic and structural information. The determination of intramyocellular lipids (IMCL) by 1H-MRS was initiated by the observation of two compartments of triacylglycerols with a resonance-frequency shift of approximately 0.2 ppm. The two resonances can be attributed to CH2 protons of lipids in fat cells, and to lipids inside muscle cells (IMCL). 1H-MRS examinations are noninvasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace biopsy to follow-up IMCL levels; however, biopsy still has the advantage that other methods, such as molecular biology, can be applied to the sample. It can be shown that IMCL levels (expressed in mMol/kg wet weight and volume %) are muscle specific and vary with diet and physical activity. In addition, it has been reported that IMCL levels are correlated with insulin sensitivity. A comparison of different methods for assessing IMCL levels, including MRS, chemical analysis, and morphometry, revealed a satisfactory correlation among them and a superior correlation of MRS with the average of the three methods. The observation of IMCL levels by means of 1H-MRS is extremely promising, but several methodological limitations and pitfalls need to be considered.

Adipose Tissue↗
PubMed1997

Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging.

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In addition, patients showed a significant reduction (P = .024) in white matter choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy (P < .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N-acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal-systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.

Adult↗
PubMed1999

Short echo time single-voxel 1H magnetic resonance spectroscopy in magnetic resonance imaging-negative temporal lobe epilepsy: different biochemical profile compared with hippocampal sclerosis.

Single-voxel proton magnetic resonance spectroscopy (1H MRS) has shown abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Many TLE patients, however, do not have HS or other lesions on quantitative magnetic resonance imaging (MRI) (MRI-negative). Fifteen control subjects, 15 patients with unilateral HS, and 15 MRI-negative TLE patients underwent 1H MRS at an echo time of 30 msec on a 1.5-T GE Signa scanner. Voxels were tailored to the individual hippocampi. N-Acetylaspartate (NAA), creatine, choline, total glutamate plus glutamine (Glx), and myo-inositol (Ins) were quantitated by using an external standard and LCModel, a user-independent quantitation method. Normal ranges were defined as the control mean +/- 2.5 SD. In HS patients, 12 of 15 had abnormally low NAA in sclerotic hippocampi; 3 of these 12 also had abnormally low NAA contralaterally. Abnormally low NAA/Ins ratios lateralized the side affected by HS in 7 of 15 patients, without any bilateral abnormalities. In 15 MRI-negative TLE patients, 4 had abnormally low hippocampal NAA ipsilateral to seizure onset, 1 of whom had abnormally low NAA bilaterally. Analysis of groups of subjects showed a bilateral decrease in NAA, most marked in patients with HS and on the side of seizure onset. The mean NAA/Ins ratio was lower in patients with HS than in control subjects and in MRI-negative patients. The concentration of Glx was higher ipsilateral to seizure onset in MRI-negative patients than in HS patients. Quantitative short echo time 1H MRS identified abnormalities in 87% of patients with HS and 27% of MRI-negative TLE patients in concordance with other lateralizing data. In individual and group comparisons, 1H MRS described a metabolite profile in the hippocampi of MRI-negative TLE patients that was different from patients with HS, with an increase in Glx and a less marked decrease in NAA than was seen in HS.

Adult↗
PubMed2004

Functional investigations of exercising muscle: a noninvasive magnetic resonance spectroscopy-magnetic resonance imaging approach.

Muscle fatigue, which is defined as the decline in muscle performance during exercise, may occur at different sites along the pathway from the central nervous system through to the intramuscular contractile machinery. Historically, both impairment of neuromuscular transmission and peripheral alterations within the muscle have been proposed as causative factors of fatigue development. However, according to more recent studies, muscle energetics play a key role in this process. Intramyoplasmic accumulation of inorganic phosphate (P(i)) and limitation in ATP availability have been frequently evoked as the main mechanisms leading to fatigue. Although attractive, these hypotheses have been elaborated on the basis of experimental results obtained in vitro, and their physiological relevance has never been clearly demonstrated in vivo. In that context, noninvasive methods such as 31-phosphorus magnetic resonance spectroscopy and surface electromyography have been employed to understand both metabolic and electrical aspects of muscle fatigue under physiological conditions. Mapping of muscles activated during exercise is another interesting issue which can be addressed using magnetic resonance imaging (MRI). Exercise-induced T2 changes have been used in order to locate activated muscles and also as a quantitative index of exercise intensity. The main results related to both issues, i.e. the metabolic and electrical aspects of fatigue and the MRI functional investigation of exercising muscle, are discussed in the present review.

Animals↗
PubMed2004

Proton magnetic resonance spectroscopy and magnetic resonance imaging findings in a patient with central nervous system paracoccidioidomycosis.

The authors describe a patient with brain paracoccidioidomycosis whose magnetic resonance image (MRI) showed multiple hypointense lesions on T2-weighted images with peripheral enhancement after gadolinium injection. Single-voxel proton magnetic resonance spectroscopy (1H-MRS) of one of the lesions showed 2 peaks at 0.9 and 1.32 ppm, corresponding to lipid signals, indicating intense necrosis. The other characteristic peaks of 1H-MRS were undifferentiated from baseline. These findings, although not specific, may help to differentiate fungal abscess from tumoral lesions and other types of abscess.

Adult↗
PubMedDate not supplied

[Magnetic resonance spectroscopy and functional magnetic resonance images: non-invasive alternatives for identifying epileptogenic foci].

Magnetic resonance spectroscopy and functional magnetic resonance images are new non-invasive techniques which have the potential for localization of the epileptogenic focus in patients with refractory focal epilepsy, who are candidates for surgery. Determination of patterns of asymmetry of the N-acetyl-aspartic acid (NAA) between homologous regions of the temporal lobes, using magnetic resonance spectroscopy contributes to preoperative lateralization in patients with temporal lobe epilepsy. This technique may become a method for localization if its usefulness in the differentiation of mesial temporal lobe epilepsy from neocortical epilepsy is validated. Functional magnetic resonance images triggered by epileptiform discharges on the EEG, when combined with methods for localizing the source, permit the site of the epileptogenic focus to be found. This would particularly benefit patients with non-lesional extra-temporal epilepsy who are potential candidates for invasive recordings. The use of magnetic resonance spectroscopy and functional magnetic resonance images in the preoperative evaluation of patients with refractory focal epilepsy, especially if it is used together with the relevant clinical data and that from other structural and functional imaging techniques, will reduce invasive monitoring and increase the accessibility to surgical treatment for this condition.

Animals↗
PubMed1995

Analysis of brain tumors using 1H magnetic resonance spectroscopy.

BACKGROUND: Magnetic resonance imaging (MRI) is superior in delineating anatomic and pathologic information and has subsequently been married to the ability of magnetic resonance spectroscopy (MRS) to provide insight into the biochemical changes underlying pathology. Proton magnetic resonance spectroscopy (1H MRS) allows the non-invasive in vivo collection and measurement of chemical information from a selected volume of tissue (voxel). METHODS: We conducted a prospective trial in 23 patients with brain mass lesions and 16 normal subjects using proton magnetic resonance spectroscopy (1H MRS). The spectra were analyzed for N-acetyl-aspartate (NAA), choline compounds (Cho), creatine (Cr), and lactate (Lac). The ratios of the compounds in tumors were compared to normals. RESULTS: The tumors showed significant decreases in the mean peak height ratios of NAA/Cho, NAA/Cr, and significant increases in Cho/Cr when compared to tissue from normal subjects. Cho was elevated in all of the meningiomas and gliomas. In benign tumors, Cho was usually elevated while in metastases Cho was often normal or decreased. The four metastatic tumors showed NAA/Cho, NAA/Cr, and Cho/Cr that were similar to controls. Lac varied with tumor type and was elevated in many malignant primary brain tumors. CONCLUSIONS: 1H MRS is a powerful tool for safe, noninvasive analysis of tissue chemistry in vivo. Analysis of intracranial tumors reveals significant trends that might eventually be used in the classification of tumor histology and evaluation of the efficacy of tumor treatment.

Adult↗
PubMed1981

Recent developments in nuclear magnetic resonance spectroscopy.

Nuclear magnetic resonance spectroscopy is a powerful and versatile technique that yields information related to molecular structure, interactions, and dynamics. Methods are currently being developed for real-time monitoring of metabolic processes in vivo and for noninvasive detection of disease and abnormality in living animals. Other nuclear magnetic resonance techniques are providing entirely new approaches for analyses of complex chemical systems. The increased power and popularity of nuclear magnetic resonance spectroscopy today are due to many developments in instrumentation and methods that have occurred over the 35-year history of the technique. The most important single advance, particularly in recent years, has been increased sensitivity. Concurrent improvements in effective spectral resolving power and an array of new methods and applications have also contributed to elevating nuclear magnetic resonance spectroscopy to its present position as one of the premier analytical techniques.

Fourier Analysis↗
PubMed1989

Cardiovascular applications of nuclear magnetic resonance spectroscopy.

Nuclear magnetic resonance spectroscopy has great potential for defining noninvasively the metabolic status of the heart and skeletal muscle. This technique uses the spin properties of certain nuclei (such as phosphorus-31, hydrogen-1 and carbon-13) to measure high energy phosphates, intracellular pH, lactate and glycogen. Animal studies have formed the basis for human investigations and have demonstrated well-defined changes in high energy phosphates during myocardial ischemia and reperfusion, as well as in cardiomyopathies. Human studies have been limited by issues of sensitivity and localization, although techniques such as rotating frame, depth-resolved surface coil spectroscopy, image-selected in vivo spectroscopy and spectroscopic imaging have been used to acquire phosphorus-31 spectra from the human heart. The few human studies of patients with disease have demonstrated elevated inorganic phosphate peaks after myocardial infarction and abnormal phosphodiester peaks in patients with hypertrophic cardiomyopathy. Studies of patients with heart failure have shown that these patients acidify their peripheral muscles with exercise more easily than do control subjects. Clinical application of nuclear magnetic resonance spectroscopy will depend on technical advances and the demonstration of sensitivity of metabolic changes with disease.

Animals↗
PubMed2001

Non-invasive studies of glycogen metabolism in human skeletal muscle using nuclear magnetic resonance spectroscopy.

Nuclear magnetic resonance spectroscopy provides non-invasive and real-time assessment of the metabolic fluxes in skeletal muscle during exercise, recovery from exercise and stimulation by insulin. Carbon-13 nuclear magnetic resonance spectroscopy has proved that reduced glycogen synthesis is a consistent feature of insulin-resistant type 2 diabetic patients, their offspring, and obesity. Low intracellular glucose and glucose-6-phosphate concentrations indicate that decreased glucose transport is mainly responsible for common insulin resistance. An elevation of plasma free fatty acids causes similar alterations of muscle glucose metabolism, and could play a central role in the development of impaired muscle glucose transport associated with insulin resistance.

Carbon Isotopes↗
PubMed1986

Nuclear magnetic resonance spectroscopy.

Nuclear magnetic resonance spectroscopy has progressed far since the original description of the phenomenon (30,31) and now permits noninvasive and harmless measurements to be repeatedly made of tissue biochemistry. Currently, there is a paucity of NMR data on normal human metabolism and the interpretation of spectra recorded from diseased tissues must be circumspect. This is further complicated by the inability of NMR spectroscopy to render accurate quantitative measurements and all observations must be considered to be compatible with, rather than diagnostic of, specific diseases. Nevertheless, NMR is an important addition to the clinician's armamentarium and these relatively expensive instruments should be situated in regional referral centres. Undoubtedly the most significant advances in NMR will only occur following the successful combination of the imaging and spectroscopic techniques, since that will enable anatomical and metabolic data to be obtained from a single site without the need for biopsy. Nuclear magnetic resonance spectroscopy has much to offer and the practical hazards appear to be few. In the next few years we will undoubtedly see an improvement in the quality of the data obtainable an a growing diversity of clinical applications.

Humans↗