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Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.

Aspartic Acid↗

Preclinical metabolic changes in mouse prion diseases detected by 1H-nuclear magnetic resonance spectroscopy.

Magnetic resonance spectroscopy studies in animal models of prion disease are very few and concern terminal stages of infection. In order to study earlier stages of the disease, we used in-vivo magnetic resonance spectroscopy in a mouse model of scrapie and, for the first time, in mice infected with a bovine spongiform encephalopathy strain. In bovine spongiform encephalopathy-infected mice, we observed an increase in myo-inositol preceding clinical signs by 20 days, followed by a decrease in N-acetylaspartate at advanced stages. In scrapie-infected mice, changes in N-acetylaspartate and myo-inositol were detected at the beginning of the symptomatic phase. These results show that magnetic resonance spectroscopy is a valuable tool for detecting subtle metabolic changes associated to gliosis and neuronal dysfunction in prion diseases.

Animals↗

In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS), an application of the methods of nuclear magnetic resonance (NMR), is a functional imaging modality that provides a view of localized biochemistry in vivo. A number of studies applying MRS to the neurochemistry of schizophrenia have been reported, which encompass a range of patient populations, states of medication, anatomic regions, nuclear species, and MRS techniques. A brief review of the history and methodology of NMR and MRS is presented. Comparison is made of MRS capabilities with other functional imaging modalities. Aspects of the neurochemistry of schizophrenia relevant to MRS studies are reviewed, as are the reported MRS studies involving patients with schizophrenia. Areas of consistent findings include decreased phosphomonoesters and increased phosphodiesters in frontal lobes, and decreases in the putative neuronal cell marker, N-acetylaspartate, in temporal lobes. Studies of neurotransmitters such as glutamate, gamma-aminobutyric acid, and glutamine have generated inconsistent results. New insights into alterations in neurochemistry in schizophrenia have been provided by MRS. Studies of neurotransmitters have future potential with improvements in field strength and in spectral editing techniques. MRS has the potential to measure brain medication levels and simultaneous effects on neurochemistry. MRS may assist in characterizing high-risk populations, and ultimately guide medication use.

Brain Chemistry↗

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is noninvasive and may be readily combined with magnetic resonance imaging (MRI). Attention has focussed on proton (1H) and phosphorus (31P) MRS, and studies have been undertaken by using single voxels or many voxels simultaneously (chemical-shift imaging, magnetic resonance spectroscopic imaging). The latter is more difficult and prone to artefact but potentially yields significantly more information. 1H MRS has principally yielded data on concentrations of N-acetyl aspartate (NAA), choline, creatine, and phosphocreatine. NAA is located primarily within neurons, and reduction of the ratio of NAA to choline, creatine, and phosphocreatine is a marker of neuronal loss and dysfunction. This technique may be useful as a noninvasive tool for localizing epileptogenic foci, but its role requires further evaluation. As with all functional imaging methods, coregistration with high-quality MRI is essential for interpreting data. 1H MRS can be used also to estimate cerebral concentrations of several neurotransmitters: glutamate, glutamine, and gamma-aminobutyric acid (GABA). This may prove useful for characterizing the neurometabolic profiles of patients with different epilepsy syndromes and for evaluating the effects of medical and surgical treatments. 31P MRS can detect adenosine triphosphate, phosphodiesters, phosphomonoesters, phosphocreatine, and inorganic phosphate, and estimate intracerebral pH. Abnormalities that have been associated with epileptogenic brain areas include increased inorganic phosphate, reduced phosphomonoesters, and increased pH. Only small numbers of patients have been studied, however, so that conclusions are not definitive, and the clinical role of this technique is not yet established.

Aspartic Acid↗

Cardiac magnetic resonance spectroscopy.

Magnetic resonance spectroscopy provides information about metabolic processes in living tissues. The resulting information may be more sensitive and specific than that obtained using techniques that rely on functional or structural measurements. Although the preponderance of applications to date have been in physiologic investigations in animals, clinical applications are emerging. Reports in the past two years have appeared evaluating the clinical use of phosphorus spectroscopy to detect ischemic heart disease, cardiomyopathy, and cardiac transplant rejection. Active research using nuclei other than phosphorus for spectroscopy will expand the potential clinical applications. Technical developments, including improved surface coil design, wider use of high-field magnets and new pulse sequences, will allow improved sensitivity and spatial localization in the future.

Animals↗

Advances in human in vivo magnetic resonance spectroscopy.

Magnetic resonance spectroscopy holds promise as another tool for functional and metabolic assessment in diagnosis and in monitoring therapy. Although the maturation and acceptance of MR spectroscopy as a clinical tool lags significantly behind that of MR imaging, important technical and methodologic advances continue at a rapid pace. Some of the advances that have occurred recently are described in this review.

Data Display↗

Monitoring pharmacokinetics of anticancer drugs: non-invasive investigation using magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) offers the unique advantage of detecting, identifying and quantifying chemicals deep within the living body in a totally non-invasive manner. In studies on pharmacology and toxicology of anticancer drugs, MRS and the closely related technique magnetic resonance imaging (MRI) have many uses. MRS in particular, despite its low sensitivity, offers unique insights into pharmacokinetics (the changing concentration of the drug at its site of action) which can be monitored, and metabolism (both activation and detoxification) can be detected in real time. This review considers some recent work on (19)F, (31)P, (1)H and (13)C MRS of anticancer drugs. Future possibilities for (13)C MRS and (1)H MRS studies of drugs and their metabolites are considered in detail.

Antineoplastic Agents↗

Impact of evidence-based medicine on magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is a robust, non-invasive means of defining aspects of human neurochemistry. After more than two decades, it is clear that in addition to its scientific interest, MRS has diagnostic value in tumor diagnosis, prognosis, therapeutic outcome, dementia diagnosis and prognosis, multiple sclerosis, infections, trauma, development, stroke, perinatal ischemia, xenobiotics and inborn errors (as determined from a meta-analysis included in this paper). However, in many healthcare systems, a new radiological technique requires evidence-based medicine (EBM) before it is recommended for reimbursement. Much of the reason why MRS is thought to be non-reimbursable in the USA is due to recent announcements that this 15-year-old technique is still considered 'investigational' by these EBM assessments. An analysis is presented of the technology assessments that brought about this situation. Based on the conclusions of the EBM assessments, strategies are suggested that involve all entities responsible for spectroscopy including the scientists' role in ensuring the future for clinical spectroscopy.

Clinical Trials as Topic↗

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy, like PET, allows cerebral function to be assessed neuro-anatomically. In addition to being noninvasive and not requiring ionizing radiation, this technique can be performed with equipment available at most medical centers. Initial studies suggest both proton and phosphorous spectroscopy will be useful adjunctive presurgical tests for the localization of the epileptogenic foci in patients with partial epilepsy, especially those with extratemporal foci. Furthermore, MRS imaging may prove to be a useful tool for studying the response to medical treatment and the pathophysiologic basis of epilepsy.

Brain↗

Assessment of ganciclovir toxicity to experimental intracranial gliomas following recombinant adenoviral-mediated transfer of the herpes simplex virus thymidine kinase gene by magnetic resonance imaging and proton magnetic resonance spectroscopy.

Magnetic resonance imaging and in vivo localized H magnetic resonance spectroscopy were used to evaluate a gene therapy approach for treating experimental brain tumors. This approach involved the use of an adenoviral vector to transfer the herpes simplex virus thymidine kinase (HSVtk) gene into intracerebral 9L gliosarcomas in rats followed by systemic administration of the antiherpetic agent ganciclovir. Magnetic resonance imaging quantitation of changes in intracranial 9L tumor doubling times revealed a significant variation in therapeutic response. Localized H magnetic resonance spectra of 9L tumors treated with Ad.RSVtk/ganciclovir revealed a dramatic increase in the resonance intensity at 0.9-1.3 ppm, corresponding to mobile lipids and/or lactate. Changes in intracranial tumor doubling times correlated with changes in H tumor magnetic resonance spectra, suggesting that specific changes in tumor metabolite levels may be predictive of the effectiveness of this gene therapy approach.

Animals↗

Evaluation of the effects of photodynamic therapy with phosphorus 31 magnetic resonance spectroscopy.

Magnetic resonance spectroscopy in situ was used to study changes in phosphorus 31 metabolism after photodynamic therapy (PDT) of transplanted HeLa cell tumours. Tumours were irradiated 2 h after administration of ATX-S10 (8-formyloximethylidene-7-hydroxy-3-ethenyl-2,7,12,18, tetramethyl-porphyrin-13,17-bispropionil aspartate), a new photosensitizer and chlorin derivative. Nuclear magnetic resonance spectra were measured prior to illumination and 1, 3, 7, 14, 21 and 28 days after PDT on each mouse. A drastic decrease in adenosine triphosphate (ATP) and a concomitant increase in inorganic phosphate (Pi) were evident on the first day after PDT in all cases. The beta-ATP/total phosphate (P) ratio was 0.64 +/- 0.29% (average +/- s.d.) in complete response, 0.67 +/- 0.30% in recurrence and 2.45 +/- 0.93% in partial response. Comparison of this ratio to the histological findings revealed that the beta-ATP/total P ratio reflects the HeLa cell tumours which survived PDT. In other words, partial response on the one hand was distinguished from complete response and recurrence on the other with this ratio 1 day after PDT (P < 0.05). In addition, the ratio of phosphomonoester (PME) to Pi rose beyond 1.0 when macroscopic recurrence occurred, while it stayed under 1.0 in complete response. This finding suggests that the recurrence of HeLa cell tumours can be detected by the PME/Pi ratio.

Adenosine Triphosphate↗

Response of tumors to therapy studied by 31P magnetic resonance spectroscopy.

Magnetic resonance (MR) methods have been used to study the metabolic and vascular response of model tumors to tumor necrosis factor (TNF). Magnetic resonance measurements demonstrated acute reductions in tumor blood flow, measured from tumor uptake of D2O, and in tumor adenosine triphosphate (ATP), measured by 31P magnetic resonance spectroscopy (MRS) following administration of TNF. The decrease in ATP generally followed reduction in tumor blood flow, and therefore was probably due to ischemia caused by damage to tumor vasculature. Superficial human tumors have been studied by MRS to characterize their 31P spectra, and to measure metabolic changes during therapy. The ratio of the intensities of the phosphomonoester (PME) and ATP resonances (PME/ATP) was much higher in tumors than in the normal tissue displaced by the tumors. During therapy, decreases in PME/ATP were detected that paralleled, but did not anticipate, decreases in tumor size. In some cases, a transient increase in PME/ATP was detected during therapy, which did not correlate with changes in tumor size, and which may reflect stimulation of cell growth in some tumor zones.

Adenosine Triphosphate↗

[In vivo magnetic resonance spectroscopy].

Magnetic resonance tomography (MR) has become a highly useful tool for diagnostic imaging. The technology is in a process of rapid development with new and better methods emerging for the imaging of anatomic and pathologic aspects. With some additional equipment, the MR instrument may also be used for in vivo magnetic resonance spectroscopy (MRS). In vivo MRS provides biochemical information about metabolites in a given tissue volume. This type of biochemical information can be extracted from volumes the size of a sugar lump within a recording period of about five minutes. New technologies also allow extracting such information from several volumes during one recording in which the information is processed as metabolic pictures. The method has found clinical applications in several fields, including the evaluation of brain tumours and epilepsy. The use of in vivo MRS will probably increase in the years ahead, especially, perhaps, for the follow-up of various therapeutic regimens. All suppliers of MR equipment now provide in vivo MRS sets and routines for recording and data analysis have become very user-friendly.

Astrocytoma↗

Liver transplantation: current and potential applications of magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) allows the noninvasive measurement of whole organ metabolism due to the presence of the MR-sensitive nucleus phosphorus 31 in adenosine triphosphate (ATP), its precursors, and break-down products. In small animal liver transplant studies it has been used to analyze the metabolic effects of cold and warm ischemia, hypothermic reperfusion, and the relative efficacy of different organ preservation solutions. In recent large animal studies MRS has been developed to provide continuous dynamic information on ATP metabolism during graft reperfusion and the bioenergetic consequences of altering preservation solutions. These basic experimental data need to be critically evaluated in human liver transplantation. Encouraging preliminary data on many possible clinical applications have already been obtained, such as the assessment of human donor liver viability and posttransplant graft function. At present, the cost and technically demanding nature of MRS may restrict its application to research units.

Animals↗

Differentiation among metastatic brain tumors, radiation necroses, and brain abscesses using proton magnetic resonance spectroscopy.

Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) were evaluated for differentiating metastatic brain tumors, radiation necroses, and brain abscesses. Twelve histologically verified lesions in 12 patients were studied using preoperative MRI and proton MRS. The signal intensities of four major metabolites, N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and lactate (Lac), were observed over the region of interest. Metastatic brain tumors showed a decrease in NAA/Cr and an increase in Cho/Cr ratios. Radiation necroses showed a decrease in NAA/Cr and no change in Cho/Cr ratios. Brain abscesses showed an increase in Lac/Cr ratio. Correlation with histopathologic findings showed that a high Cho signal was suggestive of a metastatic brain tumor. Lac signals were observed in brain abscesses, presumably reflecting the anerobic glycolysis of living cells. Although more cases and studies are necessary, metabolic information provided by proton MRS combined with MRI is useful for differentiating among metastatic brain tumors, radiation necroses, and brain abscesses.

Adult↗

Clinical applications of magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is a new tool for evaluation of patients with epilepsy, demonstrating abnormalities of energy and lipid metabolism ictally and, more recently, interictally. These metabolic abnormalities include increased inorganic phosphate, pH, and decreased phosphomonoesters as determined by 31P MRS, as well as decreased N-acetylaspartate determined by 1H MRS. Furthermore, increased lactic acid has been detected postictally. These metabolic changes appear to be confined to the region of seizure origination and can be detected interictally. Therefore, they can be used for lateralization of the epileptogenic focus. Ongoing research suggests that these abnormalities may also be useful in localization of the focus, demonstrating metabolic alterations in temporal lobe epilepsy (TLE) similar to those in neocortical epilepsy. However, further technical development will be required before the goal of using these techniques for localization of the epileptogenic focus can be realized. For TLE lobe epilepsy at least, the clinical utility of 1H MRS to lateralize the seizure focus has clearly been demonstrated by several centers. The consistent findings in TLE suggest that 1H MRS is ready to become part of the evaluation process of patients with medically refractory epilepsy being evaluated for seizure surgery.

Aspartic Acid↗

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

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.

Diet↗