Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine

This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. METHODS: Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. CONCLUSION: Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.     

Correlation of glucose consumption and tumor cell density in astrocytomas. A stereotactic PET study

To determine histological correlates of the variability of glucose consumption in astrocytomas, the authors performed positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and matched the PET scans three-dimensionally with computerized tomography scans obtained in a stereotactic frame before biopsy. Ten patients with astrocytomas of World Health Organization Grade 2 or 3 were studied; patients with glioblastomas, oligodendrogliomas, or oligoastrocytomas were excluded from the study to avoid any confounding effects of different cell types and necroses. In samples of pure tumor, glucose consumption correlated significantly with cell density, but not with nuclear polymorphism. It is concluded that tumor cell density is a major determinant of glucose consumption in astrocytomas. The use of PET with FDG may help to locate the highest cell density and thus improve the diagnostic yield of stereotactic biopsy.     

Expression of oligodendrocytic mRNAs in glial tumors: changes associated with tumor grade and extent of neoplastic infiltration

We examined the expression of glial- and neuronal-specific mRNAs within human gliomas using in situ hybridization. We found that low-grade astrocytomas contained a high number of proteolipid protein (PLP) mRNA-positive cells and that the number of PLP-stained cells decreased markedly with increasing tumor grade. Interestingly, the ratio of PLP mRNA-stained cells:myelin basic protein (MBP) mRNA-stained cells in normal white matter and low-grade astrocytoma was about 2:1 but approached 1:1 with increasing tumor grade. This parameter appeared to be a good indicator of tumor infiltration in astrocytomas, so we tested this in the analysis of other gliomas. Unlike astrocytomas, oligodendrogliomas were found consistently to contain few PLP mRNA- or MBP mRNA-expressing cells. In contrast, gemistocytic astrocytomas, typically highly invasive tumors, contained high numbers of PLP-positive cells and a ratio of PLP mRNA:MBP mRNA-stained cells of about 1.5:1, similar to low-grade astrocytomas. Nonradioactive in situ hybridization also enabled the morphological identification of specific cells. For example, gemistocytic astrocytes, which were found to be strongly vimentin mRNA positive, contained little glial fibrillary acidic protein mRNA and did not stain for PLP or MBP mRNAs. Neuronal mRNAs, such as neurofilament 68, were observed in small numbers of entrapped neurons within gliomas but were uninformative with respect to predicting tumor grade. Our results suggest that oligodendrocytes survive low-grade tumor infiltration and that glial tumor cells, unlike cell lines derived from them, do not express oligodendrocyte or neuronal mRNAs. In addition, the expression of mRNAs for the two major myelin protein genes, PLP and MBP, could be used to predict the grade and extent of tumor infiltration in astrocytomas.     

11C-methionine PET for differential diagnosis of low-grade gliomas

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.     

Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas

The 10q25-26 region between the dinucleotide markers D10S587 and D10S216 is deleted in glioblastomas and, as we have recently shown, in low-grade oligodendrogliomas. We further refined somatic mapping on 10q23-tel and simultaneously assessed the role of the candidate tumor suppressor gene PTEN/MMAC1 in glial neoplasms by sequence analysis of eight low-grade and 24 high-grade gliomas. These tumors were selected for partial or complete loss of chromosome 10 based on deletion mapping with increased microsatellite marker density at 10q23-tel. Three out of eight (38%) low-grade and 3/24 (13%) high-grade gliomas exclusively target 10q25-26. We did not find a tumor only targeting 10q23.3, and most tumors (23/32, 72%) showed large deletions on 10q including both regions. The sequence analysis of PTEN/MMAC1 revealed nucleotide alterations in 1/8 (12.5%) low-grade gliomas in a tumor with LOH at l0q21-qtel and in 5/21 (24%) high-grade gliomas displaying LOH that always included 10q23-26. Our refined mapping data point to the 10q25-26 region as the primary target on 10q, an area that also harbors the DMBT1 candidate tumor suppressor gene. The fact that we find hemizygous deletions at 10q25-qtel in low-grade astrocytomas and oligodendrogliomas - two histologically distinct entities of gliomas - suggests the existence of a putative suppressor gene involved early in glial tumorigenesis.     

Myocardial 18F-FDG-PET. Experiences with the euglycemic hyperinsulinemic clamp technique

Myocardial positron emission tomography (PET) with 18F-Fluordeoxyglucose (FDG) is increasingly used for the detection of viable tissue in the infarcted myocardium. Previous studies show that the variable metabolic conditions determine the regional distribution of this tracer and that the inhomogeneities of uptake often observed even in the normal myocardium may relate to substrate availability. The authors tried to stimulate the myocardial FDG uptake by either the technically easier method of glucose loading or by the euglycemic hyperinsulinemic clamp (EHC) technique. In their hands both methods could be considered as equally practicable but differing in some important details in regard to both the study protocol (tracer dose, optimal scanning time) and the reproducibility of results. The EHC allows a quick stabilization of the metabolic environment and resulted in an earlier and markedly increased FDG uptake. However, the important standardization of the method was performed by a computer-controlled system only for the glucose and insulin infusions. Their experiences show that the EHC provides a useful framework for assessing altered cardiac metabolism and possibly describes changes after therapeutic interventions more precisely than the commonly used glucose-loading technique.     

Telomerase activity in human gliomas

OBJECTIVE: Telomerase activity, which is undetectable in most mature normal tissues, has been identified in many types of human cancers, including neuroblastomas and oligodendrogliomas. These findings suggest that a novel mechanism in addition to activation of oncogenes and inactivation of tumor suppressor genes may play an important role in tumorigenesis. The goal of the present study was to assess and correlate the telomerase activity in astrocytic gliomas of different grades. METHODS: Telomere repeat amplification protocol and Southern blot hybridization with telomere-specific probes were used to detect telomerase activity and to measure terminal restriction fragment length, respectively. RESULTS: Telomerase activity was detected in 3 of 9 (33%) low-grade astrocytomas (World Health Organization Grade II), 5 of 11 (45%) anaplastic astrocytomas (World Health Organization Grade III), 36 of 41 (89%) glioblastomas multiforme (World Health Organization Grade IV), 3 of 4 (75%) oligodendrogliomas, and none of 4 normal brain specimens. CONCLUSION: We demonstrated that telomerase activity is absent in normal brain tissues while present in most glioma samples (72%). The frequency of such activity increases with malignancy. These results suggest that telomerase activity may be used as a tumor marker and that the activation of telomerase may correlate with initiation and malignant progression of astrocytic tumors.     

Management of malignant brain tumors

This review is made up of two parts. The first section describes techniques and methods used in the treatment of malignant brain tumors, stressing the most recent developments. The second part reviews the therapeutic modalities in malignant gliomas, where an attempt is made to consider separately glioblastomas, anaplastic astrocytomas and oligodendrogliomas, low-grade glioma, medulloblastoma, primary brain lymphoma, and brain metastases. A decision making algorithm is suggested for each tumor type.     

Clonal analysis of gliomas

In malignant gliomas, the characteristically heterogeneous features and frequent diffuse spread within the brain have raised the question of whether malignant gliomas arise monoclonally from a single precursor cell or polyclonally from multiple transformed cells forming confluent clones. Although monoclonality has been shown in surgically resected tissues, these may not include the full spectrum of patterns seen on autopsy material. Little is known about the clonality of low-grade gliomas from which malignant gliomas may sometimes arise. We sought to investigate the clonality of low-grade and malignant gliomas by using and comparing surgical and autopsy material with a Polymerase chain reaction (PCR)-based assay for nonrandom X chromosome inactivation. For that, purpose, archival surgical and autopsy material from 15 female patients (group A) (age 4 to 73 years; median, 45) with malignant gliomas (12 glioblastomas, one gliosarcoma, one anaplastic oligoastrocytoma, one gliomatosis cerebri), surgical material only from 21 female patients (group S) (age 6 to 78 years; median, 60) with low-grade and malignant gliomas (four low-grade astrocytomas, three oligoastrocytomas, two anaplastic astrocytomas, one gemistocytic astrocytoma, four oligodendrogliomas, seven glioblastomas) were analyzed. In group A, representative areas (mean = 5/patient; median = 7) were microdissected from tissue sections and assayed by PCR amplification of a highly polymorphic microsatellite marker locus of the human androgen receptor gene (HUMARA) in the presence of alpha32P with and without predigestion with a methylation-sensitive restriction enzyme (HhaI). Products were resolved by denaturing gel electrophoresis and autoradiographed. In group S, selected tumor areas were used for the assay. Each patient's normal brain tissue was used for control. The band intensity of alleles were measured by densitometric scanning. In group A, 13 of 15 cases were informative (heterozygous). The same pattern of nonrandom X chromosome inactivation was present in all areas of solid dense and moderate tumor infiltration in eight including all components of the gliosarcoma. Two of eight also showed focal loss of heterozygosity (LOH). One of 13 presented global LOH. Two of 13 showed microsatellite instability, one of which in a patient with Turcot syndrome, the other in gliomatosis cerebri. Opposite skewing patterns were seen in distant areas of gliomatosis cerebri consistent with oligoclonal derivation. Clonality remained indeterminate in one glioblastoma and in the anaplastic oligoastrocytoma because of skewed lyonization in the normal control. In group S, 19 of 21 cases were informative. Fifteen of 19 were monoclonal (four low-grade astrocytomas, one anaplastic astrocytoma, one gemistocytic astrocytoma, two oligodendrogliomas, one oligoastrocytoma, six glioblastomas). Four of 19 were indeterminate. We conclude that (1) Low-grade and malignant gliomas are usually monoclonal tumors, and extensively infiltrating tumors must result from migration of tumor cells (2) Gliomatosis cerebri may initiate as an oligoclonal process or result from collision gliomas (3) Biphasic gliomas likely arise from a single precursor cell. (4) LOH at the HUMARA locus is probably related to partial or complete deletion of an X-chromosome, which occurs in malignant gliomas during clonal evolution.     

Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome

Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone.     

Tumour blood flow and partition coefficients: correlation with grade of cerebral gliomas using xenon-enhanced computed tomography

It is possible to underestimate the grade of nonenhancing cerebral tumours on conventional contrast-enhanced MRI or CT. Differentiation of high- and low-grade gliomas by measurement of the brain-blood partition coefficient lambda (T lambda) with Xe-enhanced CT (XeCT) has been reported. We assessed the practical applications of XeCT in suspected low-grade astrocytomas. We examined 15 patients with tumours which showed no contrast enhancement on conventional MRI and CT, using XeCT. Tumour blood flow (TBF) and T lambda were calculated. Fourteen patients underwent surgery, one patient had a biopsy. We recognized three histological groups. While T lambda differed significantly between them, TBF did not. Group 1 contained grade II-III astrocytomas and T lambda was 0.77; group 2 contained grade I-II astrocytomas with T lambda 1.14, and group 3 four oligodendrogliomas in which a T lambda of 1.50 was found.     

Precentral glioma location determines the displacement of cortical hand representation

OBJECTIVE: Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS: We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS: Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION: Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.     

Upregulation of 5''-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit

Eighteen patients with intracranial skull base tumours diagnosed at CT or MR as neuromas or meningiomas were studied with positron emission tomography (PET) using L-(methyl-11C) methionine. Compared with normal cerebellar tissue, the uptake of methionine in the tumours increased more rapidly and reached a higher level, and showed a slow decline after a peak occurring about 5 min after the injection. All the meningiomas exhibited considerably higher accumulation of the tracer compared with the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding structures (tumour to cerebellum ratios 2.62-5.37, mean 3.63). The uptake was homogeneous in all meningiomas, which were all of the syncytial type. The neuromas showed lower contrast against the cerebellum (tumour to cerebellum ratios 1.1-1.87, mean 1.48). Some neuromas displayed an irregular pattern with regions of decreased tracer uptake corresponding to small cystic areas within the neuroma. There was no overlap in methionine uptake between the two tumour groups. The results indicate that PET-methionine may contribute to the evaluation, treatment planning and follow-up of patients with skull base meningiomas and neuromas.     

Positron emission tomography in diagnosing brainstem vascular lesions that cause abnormal eye movements

PURPOSE: To evaluate the efficacy of positron emission tomography (PET) in aiding in the diagnosis of brainstem infarctions that cause abnormal eye movements. METHOD: Cerebral glucose metabolism was examined by PET with 18F-fluorodeoxyglucose as a tracer in five normal control subjects and six patients with abnormal eye movements. The PET images were registered to and superimposed on magnetic resonance images (MRIs). RESULTS: All control subjects showed little asymmetry of glucose metabolism in the brainstem, whereas all six patients demonstrated areas of low glucose metabolism in the brainstem. Areas of low metabolism seen by PET were wider than they appeared to be by MRI; MRIs even appeared normal in some patients. Asymmetry index measurements at the level of the ischemic lesion ranged between 19% and 45%. CONCLUSIONS: Positron emission tomography detected metabolic abnormality in patients with brainstem lesions that caused abnormal eye movements. Superimposing PET images on MRIs accurately localized abnormally low metabolism in the brainstem. Combined imaging with PET and MRI can be used to diagnose ischemic lesions in the brainstem from functional (PET) and morphologic (MRI) viewpoints.     

Use of 2-[18F]fluoro-2-deoxyglucose as a potential agent in the prediction of graft rejection by positron emission tomography

BACKGROUND: We investigated the potential of predicting allograft rejection by measuring the ability of graft-infiltrating cells to take up 2-[18F]fluoro-2-deoxyglucose ([18F]FDG). This molecule is a positron emitting glucose analogue that is taken up by metabolically active cells and can be detected using positron emission tomography. METHODS: Uptake of [18F]FDG during an alloresponse was measured both in vitro in mixed lymphocyte cultures and in vivo using allogeneic and syngeneic skin grafts. RESULTS: Uptake of [18F]FDG was seen in a mixed lymphocyte reaction. Using a mouse skin graft model, we found that mean [18F]FDG uptake was 1.5-2 times higher in allografts than in syngeneic grafts; the increase in uptake correlated with the level of T-cell infiltrate seen histologically. CONCLUSION: Assessing the metabolic activity of graft-infiltrating cells with [18F]FDG may be useful in the prediction of graft rejection episodes.     

Genetic analysis of protein C deficiency in nineteen Japanese families: five recurrent defects can explain half of the deficiencies

OBJECTIVE: The lack of sensitivity and specificity of conventional imaging techniques based on morphological critera is responsible for considerable limitations in the staging and surveillance of oral cancer. Therefore, this study investigates the contribution of [F18]-2-fluordesoxyglucose (FDG) positron emission tomography (PET) to tumor management with special regard to lymphnode involvement and therapeutic monitoring after radiotherapy. DESIGN: Prospective observational study. PATIENTS: Twenty-one patients with advanced oral cancer, predominantly T3/T4. INTERVENTION: FDG-PET scans before and after preoperative radio(chemo)therapy. Standardized uptake values (SUV) were determined for the tumor site and lymphnode areas. PET scans were correlated to histological findings after ablative tumor surgery. RESULTS: FDG-PET yielded superior sensitivity and specificity for tumor and lymphnode assessment. The effect of radiotherapy was reflected by the metabolic activity of the tumor, which shows a close correlation between the decrease of FDG uptake and histologic tumor regression. PET detected distant metastases and simultaneous tumors. CONCLUSION: FDG-PET is a challenging imaging technique with the potential to improve staging procedures for oral cancer. In the monitoring of metabolic activity of the tumor in the course of radio(chemo)therapy, FDG-PET allows objective measurement of the treatment response.     

Contraction and relaxation velocities of the normal left ventricle using pulsed-wave tissue Doppler echocardiography

OBJECTIVE: To investigate whether atrophy of the corpus callosum is associated with cognitive impairment and cerebral cortical hypometabolism in corticobasal degeneration. DESIGN: Prospective clinicoradiological correlation with magnetic resonance imaging and positron emission tomography. SETTING: A university hospital. PATIENTS: Eight right-handed patients with clinically diagnosed corticobasal degeneration (mean+/-SD age, 64+/-8 years). MAIN OUTCOME MEASURES: Midsagittal corpus callosum area-skull area ratio (on T1-weighted magnetic resonance images), the sum of the scaled scores of the 6 subtests on the Wechsler Adult Intelligence Scale-Revised (Digit Span, Arithmetic, Picture Arrangement, Object Assembly, Block Design, and Digit Symbol), and cerebral metabolic rate of glucose (measured with positron emission tomography by using fludeoxyglucose F 18 as a tracer). RESULTS: Compared with 36 age-matched right-handed control subjects, the patients had significantly decreased callosal area-skull area ratio. The reduction in this ratio was greatest in the middle half of the corpus callosum. The atrophy of the corpus callosum was accompanied by a decreased mean cortical glucose metabolic rate with hemispheric asymmetry and a decrease in the sum of the scaled subtest scores of the Wechsler Adult Intelligence Scale-Revised. CONCLUSIONS: Atrophy of the corpus callosum with middle predominance is present in corticobasal degeneration, and this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism with hemispheric asymmetry. Atrophy of the corpus callosum might reflect the severity of the disconnection between cortical regions, and this may be an important factor in the development of cerebral cortical dysfunction in corticobasal degeneration.     

Cerebral networks and functional brain asymmetry: evidence from regional metabolic changes during word repetition

Word repetition causes a significant bilateral metabolic increase in both superior temporal cortices. Frontal speech areas are less activated despite their presumable speech competence. We investigated in this study the relationship between frontal and temporal cortical areas during word repetition. We measured regional cerebral metabolic rates of glucose (CMRGI) in 15 normal subjects with positron emission tomography (PET) at rest and during word repetition. Significant correlations connected frontal and temporal areas of both hemispheres, notwithstanding their different levels of mean metabolic activation. The left planum temporale was a hub of significant interregional correlations, in contrast to its contralateral mate. This study indicates that an asymmetric network of significant connections orchestrates the speech-relevant cortical areas according to the actual needs of speech processing.     

Clinical studies of oral antiemetic drugs on delayed emesis induced by cancer chemotherapy]

BACKGROUND AND PURPOSE: Our purpose was to develop a classification scheme and method of presentation of in vivo single-voxel proton spectroscopic data from astrocytomas that most closely match the classification scheme determined from biopsy specimens. Since in vivo proton spectroscopy is noninvasive, it may be an attractive alternative to intracranial biopsy. METHODS: Single-voxel spectra were acquired using the point-resolved spectroscopic pulse sequence as part of the Probe spectroscopy package on a G.E. 1.5-T Signa scanner. Subjects consisted of 27 patients with biopsy-confirmed brain tumors (13 with glioblastoma multiforme, six with anaplastic astrocytoma, and eight with low-grade astrocytoma). The patients were divided into groups based on the histologic subtype of their tumor for different treatment protocols. RESULTS: Metabolic peak areas were normalized for each metabolite (choline, creatine, N-acetylaspartate, lactate) to the area of the unsuppressed water peak and to the area of the creatine peak. Kruskal-Wallis nonparametric analysis of variance (ANOVA) tests showed statistically significant differences among the tumor groups for all the area ratios. The lactate/water ratio could be used to distinguished all three tumor groups, whereas the choline/water ratio distinguished low-grade astrocytomas from the two high-grade groups. Both the choline and lactate ratios could be used to separate the high-grade from the low-grade tumors. CONCLUSION: Specific relative metabolic peak area ratios acquired from regions of contrast-enhancing brain tumor can be used to classify astrocytomas as to histopathologic grade.