phosphocreatine and Glioma

Magnetic resonance imaging (MRI) is the neuroimaging method of choice for the noninvasive monitoring of patients with brain tumors due to the enormous amount of information it yields regarding the morphologic features of the lesion and surrounding parenchyma. Over the past decade, proton magnetic resonance spectroscopy (1H-MRS), which uses the same technology as MRI and can be performed during a routine clinical imaging examination, has been used to glean information about the metabolic status of the brain. Accurate interpretation of 1H-MRS data from individual patients requires an understanding of the various techniques for acquiring the data, the physiologic basis of the metabolic signatures obtained from different types of tumors, and the specificity of the technique. This review covers the basic physics of 1H-MRS, the spectral and physiological characteristics of the metabolites that are typically measured in various types of brain tumors, and the clinical utility of 1H-MRS with respect to diagnosis, therapeutic planning, and the assessment of response to treatment.

Topics: Alanine; Aspartic Acid; Brain Neoplasms; Choline; Creatine; Glioma; Glutamic Acid; Glutamine; Humans; Inositol; Lactic Acid; Lipid Metabolism; Magnetic Resonance Spectroscopy; Phosphocreatine

Of primary central nervous system tumors treated each year, the majority are glioma, followed by meningioma and then pituitary adenoma. While the use of magnetic resonance (MR) and computed tomographic imaging is well established in the diagnosis and management of such tumors, these techniques have a limited role in determining the metabolic state, either prior to or following therapy. Multinuclear MR spectroscopy, on the other hand, provides information on tumor metabolism and the effect of therapy on tumor viability. This paper reviews MR spectroscopic studies performed on patients with central nervous system tumors and discusses the impact that such studies have had on tumor diagnosis and management.

Topics: Adenoma; Adenosine Triphosphate; Adolescent; Adult; Aged; Blood Chemical Analysis; Brain Chemistry; Brain Neoplasms; Child; Child, Preschool; Energy Metabolism; Female; Glioma; Humans; Hydrogen-Ion Concentration; Incidence; Infant; Magnetic Resonance Spectroscopy; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Phosphocreatine; Phospholipids; Pituitary Neoplasms

To evaluate the ability of magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to distinguish neurofibromatosis Type 1 (NF-1) with brain stem enlargement from diffuse pontine glioma (PG) in pediatric patients.. A chart review was used to identify all patients with NF-1 and diffuse brain stem enlargement who were seen at our institution and who had undergone MRI. Comparison groups were as follows: 1) eight patients who did not have NF-1 but who did have diffuse PG, and 2) seven healthy children. Midsagittal diameters of the pons, midbrain, and medulla were measured in all patients, and the results were statistically analyzed. Two MRS variables were also statistically compared: N-acetyl aspartate and the vector sum of the metabolites choline and creatine/phosphocreatine.. In MRI-based measurements, only the pontine midsagittal diameter differed significantly between the NF-1 and PG groups (P = 0.002). Altogether, 21 children underwent MRS, including 6 in the NF-1 group. Measures of both MRS variables were significantly lower in patients with PG than in the others (P < or = 0.007). The two MRS variables classified the 21 children into the three respective groups with 100% accuracy. Of the seven patients with NF-1, four presented with symptoms attributable to brain stem involvement. The brain stems of all seven patients with NF-1 were hyperintense on T2-weighted magnetic resonance images, and five were isointense on T1-weighted images; only one exophytic tumor was identified. Four of the patients with NF-1 were followed up clinically without treatment; all remained alive and neurologically stable for a median of 40 months. All eight patients in the PG group were symptomatic at presentation, and all except one died despite therapy.. Both MRI measurements and MRS seem to be useful for distinguishing patients with NF-1 and diffuse brain stem enlargement from patients without NF-1 but with diffuse PG. They should be most helpful in differentiating symptomatic patients with NF-1 from patients with PG, thereby minimizing aggressive treatment and its side effects in patients destined to have better outcomes.

Topics: Adolescent; Aspartic Acid; Brain Neoplasms; Brain Stem; Child; Child, Preschool; Choline; Creatine; Diagnosis, Differential; Female; Glioma; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mesencephalon; Neurofibromatosis 1; Phosphocreatine; Pons

The objective of this study was to elucidate the influence on quantitative analysis using LCModel with the condition of echo time (TE) longer than the recommended values in the spectrum acquisition specifications.. A 3T magnetic resonance system was used to perform proton magnetic resonance spectroscopy. The participants were 5 healthy volunteers and 11 patients with glioma. Data were collected at TE of 72, 144 and 288ms. LCModel was used to quantify several metabolites (N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds). The results were compared with quantitative values obtained by using the T2-corrected internal reference method.. In healthy volunteers, when TE was long, the quantitative values obtained using LCModel were up to 6.8-fold larger (p<0.05) than those obtained using the T2-corrected internal reference method. The ratios of the quantitative values obtained by the two methods differed between metabolites (p<0.05). In patients with glioma, the ratios of quantitative values obtained by the two methods tended to be larger at longer TE, similarly to the case of healthy volunteers, and large between-individual variation in the ratios was observed.. In clinical practice, TE is sometimes set longer than the value recommended for LCModel. If TE is long, LCModel overestimates the quantitative value since it cannot compensate for signal attenuation, and this effect is different for each metabolite and condition. Therefore, if TE is longer than recommended, it is necessary to account for the possibly reduced reliability of quantitative values calculated using LCModel.

Topics: Aspartic Acid; Brain; Brain Neoplasms; Choline; Creatine; Glioma; Humans; Image Processing, Computer-Assisted; Models, Theoretical; Phosphocreatine; Proton Magnetic Resonance Spectroscopy; Reproducibility of Results

To evaluate if metabolic changes in WHO grades II and III gliomas measured in vivo with proton magnetic resonance spectroscopic imaging ((1)H-MRSI) correlate with progression-free survival (PFS).. (1)H-MRSI and MRI were performed before surgery in 61 patients with histopathological proven WHO grades II and III gliomas. Averaged (av) and maximum (max) metabolite concentrations of creatine/phosphocreatine (tCr) and choline-containing compounds (tCho) from the tumor were normalized to contralateral brain tissue. In 50 patients with a median follow-up of 34 (WHO grade II) and 19.5 (WHO grade III) months, spectroscopic data as well as the extent of tumor resection, histopathological subtype, adjuvant therapy and patients' ages were analysed for PFS times with Cox regression analysis. Kaplan-Meier method was performed with categorized tCr values (cutoff: 0.93) to estimate the median PFS time.. The normalized tCr(av) was prognostic for the PFS in patients with WHO grades II and III gliomas (p<0.0001 and p=0.034, respectively). For WHO grade II gliomas, tCr(max) (p=0.008) and the patients' ages (p=0.006) were also prognostic. The multivariate analysis provided tCr(av) (p=0.001) as single independent prognostic factor for the PFS of WHO grade II gliomas. Patients with WHO grades II and III gliomas revealing a normalized tCr(av) greater than 0.93 had a significant shorter PFS.. Potential tumor progression in WHO grades II and III gliomas is best indicated by the normalized tCr(av). Normalized tCr(av) >0.93 seems to indicate gliomas with earlier progression.

Topics: Adult; Aged; Brain Neoplasms; Choline; Creatine; Disease Progression; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Protons; Retrospective Studies; ROC Curve; Statistics, Nonparametric; Treatment Outcome; World Health Organization; Young Adult

Differential diagnosis between radiation necrosis and tumor recurrence is important in the clinical management of glioma. Multi-modality imaging including proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) with L-[methyl-(11)C]methionine (MET) was evaluated. Eighteen patients underwent sequential (1)H-MRS and MET-PET. The expressions of metabolites including choline-containing compounds (Cho), creatine phosphate (Cre), and lactate (Lac) were calculated as the ratios of Cho to Cre (Cho/Cre) and Lac to Cho (Lac/Cho). The uptake of MET was determined as the ratio of the lesion to the contralateral reference region (L/R). The final diagnoses were determined by histological examination and/or follow-up MR imaging and clinical course. The Lac/Cho ratio was 0.63 +/- 0.25 (mean +/- standard deviation) in recurrence (7 cases) and 2.35 +/- 1.81 in necrosis (11 cases). The Lac/Cho ratio was significantly different between the two groups (p < 0.01). Consecutive investigation of (1)H-MRS revealed temporary elevation of Cho in 4 of 9 cases of necrosis, which could be identified as false positive findings for recurrence. Including those cases, MET-PET demonstrated significant difference in the L/R ratio between the two groups (2.18 +/- 0.42 vs. 1.49 +/- 0.35, p < 0.01). According to a 2 x 2 factorial table analysis, the borderline values of Lac/Cho and L/R to differentiate recurrence from necrosis were 1.05 and 2.00, respectively. (1)H-MRS is reliable and accessible for the differentiation of recurrence and necrosis, although the temporary elevation of Cho in the course of necrosis should be recognized. Additional MET-PET imaging can establish the diagnosis.

Topics: Adolescent; Adult; Aged; Biomarkers; Brain; Brain Neoplasms; Carbon Radioisotopes; Choline; Diagnosis, Differential; Fatal Outcome; Female; Glioma; Humans; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Methionine; Middle Aged; Necrosis; Phosphocreatine; Positron-Emission Tomography; Predictive Value of Tests; Radiation Injuries; Radiotherapy; Retrospective Studies; Young Adult

The aim of this study was to explore the diagnostic effectiveness of magnetic resonance (MR) spectroscopy with diffusion-weighted imaging on the evaluation of the recurrent contrast-enhancing areas at the site of treated gliomas.. In 55 patients who had new contrast-enhancing lesions in the vicinity of the previously resected and irradiated high-grade gliomas, two-dimensional MR spectroscopy and diffusion-weighted imaging were performed. Spectral data for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid (Lip), and lactate (Lac) were analyzed in conjunction with the apparent diffusion coefficient (ADC) in all patients. Diagnosis of these lesions was assigned by means of follow-up or histopathology.. The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor than in regions of radiation injury (p < 0.01). The ADC value and ADC ratios (ADC of contrast-enhancing lesion to matching structure in the contralateral hemisphere) were significantly higher in radiation injury regions than in recurrent tumor (p < 0.01). With MR spectroscopic data, two variables (Cho/NAA and Cho/Cr ratios) were shown to differentiate recurrent glioma from radiation injury, and 85.5% of total subjects were correctly classified into groups. However, with discriminant analysis of MR spectroscopy imaging plus diffusion-weighted imaging, three variables (Cho/NAA, Cho/Cr, and ADC ratio) were identified and 96.4% of total subjects were correctly classified. There was a significant difference between the diagnostic accuracy of the two discriminant analyses (Chi-square = 3.96, p = 0.046).. Using discriminant analysis, this study found that MR spectroscopy in combination with ADC ratio, rather than ADC value, can improve the ability to differentiate recurrent glioma and radiation injury.

Topics: Adult; Aged; Aspartic Acid; Brain; Brain Neoplasms; Choline; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Discriminant Analysis; Female; Glioma; Humans; Lactic Acid; Lipid Metabolism; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphocreatine; Radiation Injuries

We describe the magnetic resonance (MR) imaging characteristics of dysembryoplastic neuroepithelial tumors (DNT) and discuss their differential diagnosis.. Proton MR spectroscopy (TE 30 and 136 ms), diffusion-weighted and perfusion images were retrospectively evaluated in 22 patients with pathologically proven DNT (17 male and 5 female, mean age 18.7 years) and 14 control subjects (10 male and 4 female, mean age 16.9 years). The results from the DNT patients and from the control subjects were compared using an independent sample t-test and the degree of correlation was tested by Pearson's correlation.. All DNTs were solitary and in a supratentorial cortical or subcortical location (ten temporal, eight frontal and four parietal). They had low-signal on T1-weighted images and high-signal on T2-weighted images without a prominent mass effect. Additionally a cystic appearance (six patients, 27.3%), cortical dysplasia (six patients, 27.3%) and contrast enhancement (four patients, 18.2%) were also noted. No significant differences were detected in NAA/Cho, NAA/Cr, NAA/Cho+Cr or Cho/Cr ratios between DNT and normal brain. DNTs had a significantly higher mI/Cr ratio and apparent diffusion coefficient (ADC) values and lower cerebral blood values than normal parenchyma (P < 0.001). ADC had the highest correlation with the diagnosis of DNT (r = 0.996) followed by relative cerebral blood volume (rCBV) (r = -0.883) and mI/Cr ratio (r = 0.663).. Proton MR spectroscopy, diffusion-weighted and perfusion imaging characteristics of DNTs provide additional information to their MR imaging findings. The MR spectrum showing a slight increase in mI/Cr ratio, and higher ADC and lower rCBV values than normal parenchyma help to differentiate DNTs from other cortical tumors, which had higher rCBV and lower ADC values than DNTs.

Topics: Adolescent; Adult; Blood Flow Velocity; Choline; Creatine; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Echo-Planar Imaging; Energy Metabolism; Female; Glioma; Humans; Image Processing, Computer-Assisted; Inositol; Magnetic Resonance Angiography; Magnetic Resonance Spectroscopy; Male; Malformations of Cortical Development; Neovascularization, Pathologic; Neuroectodermal Tumors, Primitive; Parietal Lobe; Phosphocreatine; Reference Values; Regional Blood Flow; Retrospective Studies; Supratentorial Neoplasms; Temporal Lobe

Echo time (TE) can have a large influence on the spectra in proton MR spectroscopy ((1)H-MR spectroscopy). The purpose of this study was to comparatively assess the diagnostic value of 3T single-voxel (1)H-MR spectroscopy with short or intermediate TEs in grading cerebral gliomas.. Single voxel (1)H-MR spectroscopy was performed at 3T in 35 patients with cerebral glioma. The spectra were obtained with both short (35 ms) and intermediate TEs (144 ms). Metabolite ratios of choline (Cho)/creatine (Cr), Cho/N-acetylaspartate (NAA), lipid and lactate (LL)/Cr and myo-inositol (mIns)/Cr were calculated and compared between short and intermediate TEs in each grade. After receiver operating characteristic curve analysis, diagnostic accuracy for each TE in differentiating high-grade glioma from low-grade glioma was compared.. At short TE, Cho/Cr and Cho/NAA ratios were significantly lower, and LL/Cr and mIns/Cr were significantly higher, compared with those at intermediate TE, regardless of tumor grade. Lactate inversion at intermediate TE was found in only 2 patients. At both TEs, there were significant differences in Cho/Cr and LL/Cr ratios between low- and high-grade gliomas. Diagnostic accuracy was slightly higher at short TE alone or combined with intermediate TE than intermediate TE alone (85.7% versus 82.9%).. Metabolite ratios were significantly different between short and intermediate TE. Cho/Cr and LL/Cr ratios at either TE were similarly useful in differentiating high-grade gliomas from low-grade gliomas. If only a single spectroscopic sequence can be acquired, short TE seems preferable because of poor lactate inversion at intermediate TE on 3T single-voxel (1)H-MR spectroscopy.

Topics: Adult; Aged; Aspartic Acid; Brain Neoplasms; Choline; Creatine; Echo-Planar Imaging; Female; Glioma; Humans; Hydrogen; Image Enhancement; Inositol; Lactates; Lipids; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Time Factors

The aim of this study was to detect the non-neoplastic white-matter changes vs. time after irradiation using 1H nuclear magnetic resonance (NMR) spectroscopy in vivo.. A total of 394 1H MR spectra were acquired from 100 patients (age 19-74 years; mean and median age, 43 years) before and during 2 years after radiation therapy (the mean absorbed doses calculated for the averaged spectroscopy voxels are similar and close to 20 Gy).. Oscillations were observed in choline-containing compounds (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center of gravity (CG) of the lipid band in the range of 0.7-1.5 ppm changes over time reveal oscillations. The parameters have the same 8-month cycle period; however the CG changes precede the other by 2 months.. The results indicate the oscillative nature of the brain response to irradiation, which may be caused by the blood-brain barrier disruption and repair processes. These oscillations may influence the NMR results, depending on the cycle phase in which the NMR measurements are performed in. The earliest manifestation of radiation injury detected by magnetic resonance spectroscopy is the CG shift.

Topics: Adult; Aged; Aspartic Acid; Blood-Brain Barrier; Brain; Brain Neoplasms; Choline; Creatine; Female; Glioma; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Radiation Injuries; Statistics, Nonparametric

In proton magnetic resonance spectroscopic imaging (1H MRSI), the recorded spectra are often linear combinations of spectra from different cell and tissue types within the voxel. This produces problems for data analysis and interpretation. A sophisticated approach is proposed here to handle the complexity of tissue heterogeneity in MRSI data. The independent component analysis (ICA) method was applied without prior knowledge to decompose the proton spectral components that relate to the heterogeneous cell populations with different proliferation and metabolism that are present in gliomas. The ability to classify brain tumours based on IC decomposite spectra was studied by grouping the components with histopathology. To this end, 10 controls and 34 patients with primary brain tumours were studied. The results indicate that ICA may reveal useful information from metabolic profiling for clinical purposes using long echo time MRSI of gliomas.

Topics: Algorithms; Aspartic Acid; Astrocytoma; Brain Neoplasms; Cell Proliferation; Choline; Creatine; Glioblastoma; Glioma; Humans; Hydrogen; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Lactic Acid; Lipids; Magnetic Resonance Imaging; Oligodendroglioma; Phosphocreatine

In vivo magnetic resonance spectroscopy (MRS) studies of glial brain tumours reported that higher grade of astrocytoma is associated with increased level of choline-containing compounds (Cho) and decreased levels of N-acetylaspartate (NAA) and creatine and phosphocreatine (Cr). In this work, we studied the metabolism of glioma tumours by in vitro proton magnetic resonance spectroscopy (1H-MRS). 1H-MR spectra were recorded in vitro from perchloric acid extracts of astrocytoma (WHO II) and glioblastoma multiforme (WHO IV) samples. We observed differences between astrocytoma and glioblastoma multiforme in the levels of Cho, alanine, lactate, NAA, and glutamate/glutamine. In astrocytoma samples, we found higher MR signal of NAA and lower signal of Cho and alanine. MR spectra of glioblastoma samples reported significantly higher levels of lactate and glutamate/glutamine. In contrast, levels of Cr were the same in both tumour types. We also determined NAA/Cr and Cho/Cr ratios in the tumour samples. The NAA/Cr ratio was higher in astrocytomas than in glioblastomas multiforme. Conversely, the Cho/Cr ratio was higher in glioblastoma multiforme. The results indicate that MRS is a promising method for distinguishing pathologies in human brain and for pre-surgical grading of brain tumours.

Topics: Aspartic Acid; Astrocytes; Astrocytoma; Brain; Brain Neoplasms; Choline; Chromium; Creatine; Glioblastoma; Glioma; Humans; In Vitro Techniques; Magnetic Resonance Spectroscopy; Neoplasms; Phosphocreatine; Spectrophotometry

Gliomas can display marked changes in the concentrations of energy metabolism molecules such as creatine (Cr), phosphocreatine (PCr) and lactate, as measured using magnetic resonance spectroscopy (MRS). Moreover, the BOLD (blood oxygen level dependent) contrast enhancement in functional magnetic resonance imaging (fMRI) can be reduced or missing within or near gliomas, while neural activity is not significantly reduced (so-called neurovascular decoupling), so that the location of functionally eloquent areas using fMRI can be erroneous. In this paper, we adapt a previously developed model of the coupling between neural activation, energy metabolism and hemodynamics, by including the venous dilatation "Balloon model" of Buxton and Frank. We show that decreasing the cerebral blood flow (CBF) baseline value, or the CBF increase fraction, results in a decrease of the BOLD signal and an increase of the lactate peak during a sustained activation. Baseline lactate and PCr levels are not significantly affected by CBF baseline reduction, but are altered even by a moderate decrease of mitochondrial respiration. Decreasing the total Cr and PCr concentration reduces the BOLD signal after the initial overshoot. In conclusion, we suggest that the coupled use of BOLD fMRI and MRS could contribute to a better understanding of the neurovascular and metabolic decoupling in gliomas.

Topics: Adenosine Triphosphate; Blood-Brain Barrier; Brain Neoplasms; Cerebrovascular Circulation; Energy Metabolism; Glioma; Hemodynamics; Humans; Lactic Acid; Magnetic Resonance Imaging; Models, Neurological; Oxygen; Phosphocreatine; Sodium

NMR-visible mobile lipid (ML) has been observed in aggressive tumors and also in in vitro tumor cell models subjected to growth-inhibiting conditions, such as confluence or low-pH stress. The aim of the present study was to determine if ML production after confluence or low pH stress in a cultured cell model of brain tumor is due to growth arrest alone. ML was observed in situ by one- and two-dimensional (1)H NMR in viable but growth-arrested C6 glioma cells superfused for a period of 48 h after harvesting. The rate of ML production in cells harvested at subconfluence was compared to the rate in cells confluent for one cell cycle and to the rate in subconfluent-harvested cells superfused at low pH (pH 6.1). Confluent-harvested cells produced ML at a markedly greater rate than that of cells harvested at subconfluence, suggesting the involvement of prior cell-cell contact rather than simple growth arrest. A high rate was also observed in subconfluent-harvested cells subjected to low pH, indicating that ML in pH-stressed cells also does not arise from growth arrest alone. Furthermore, two-dimensional data on the degree of unsaturation of the ML fatty acyl chains and one-dimensional (31)P and two-dimensional (1)H NMR data on the GPC content of the cells suggest distinct metabolic pathways for the production of ML following confluence and low-pH stress.

Topics: Adenosine Triphosphate; Cell Communication; Energy Metabolism; Fatty Acids, Unsaturated; Glioma; Hydrogen-Ion Concentration; Kinetics; Lipids; Magnetic Resonance Spectroscopy; Phosphocreatine; Tumor Cells, Cultured

The effects of chemotherapy [25 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea administered with a single i.p. injection] on cellular energetics by 31P nuclear magnetic resonance (NMR) spectroscopy, total tissue sodium by single-quantum (SQ) 23Na NMR spectroscopy, and intracellular sodium by triple-quantum-filtered (TQF) 23Na NMR spectroscopy were studied in the s.c. 9L glioma. Animals were studied by NMR 2 days before therapy and 1 and 5 days after therapy. Destructive chemical analysis was also performed 5 days after therapy to validate the origin of changes in SQ and TQF 23Na signals. One day after treatment, there was no significant difference between control and treated tumors in terms of tumor size or 23Na and 31P spectral data. Five days after therapy, treated tumors had 28 +/- 16% (P < 0.1) lower SQ 23Na signal intensity, 46 +/- 20% (P < 0.05) lower TQF 23Na signal intensity, 125 +/- 51% (P < 0.05) higher ATP:Pi ratio, 186 +/- 69% (P < 0.05) higher phosphocreatine:Pi ratio, and 0.17 +/- 0.06 pH units (P < 0.05) higher intracellular pH compared with control tumors. No significant differences in TQF 23Na relaxation times were seen between control and treated tumors at any time point. Destructive chemical analysis showed that the relative extracellular space of control and treated tumors was identical, but the treated tumors had 21 +/- 8% (P < 0.05) lower total tissue Na+ concentration and 60 +/- 24% (P < 0.05) lower intracellular Na+ concentration compared with the controls. The higher phosphocreatine:Pi and ATP:Pi ratios after 1,3-bis(2-chloroethyl)-1-nitrosourea treatment indicate improved bioenergetic status in the surviving tumor cells. The decrease in SQ and multiple-quantum-filtered 23Na signal intensity was largely attributable to a decrease in Na(i)+ because the treatment did not change the relative extracellular space. The improved energy metabolism could decrease the intracellular concentration of Na+ by increasing the activity of Na+-K+-ATPase and decreasing the activity of Na+/H+. Although both 23Na and 31P spectra were consistent with improved cellular metabolism in treated tumors, the 23Na methods may be better suited for monitoring response to therapy because of higher signal:noise ratio and ease of imaging the single 23Na resonance.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents, Alkylating; Brain Neoplasms; Carmustine; Glioma; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Neoplasm Transplantation; Phosphocreatine; Phosphorus; Rats; Rats, Inbred F344; Sodium

To add metabolic information during stereotactic biopsy target selection, the authors adopted proton chemical shift imaging (1H CSI)-directed stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique has been reported in stereotactic biopsy. We performed 1H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, and evaluated the pathological results.. The 1H CSI-directed stereotactic biopsy was performed in four patients. 1H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic frame. After reconstructing the metabolic maps of N-acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were selected as target sites in the stereotactic MR images.. 1H CSI is possible with the stereotactic headframe in place. No difficulty was experienced performing 1H CSI or making a diagnosis. Pathological samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathological samples taken from areas of increased Lac/Cr ratio showed predominant feature of necrosis.. 1H CSI was feasible with the stereotactic headframe in place. The final pathological results obtained were concordant with the local metabolic information from 1H CSI. We believe that 1H CSI-directed stereotatic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting.

Topics: Adult; Aspartic Acid; Biopsy, Needle; Brain; Brain Neoplasms; Creatine; Diagnosis, Differential; Energy Metabolism; Female; Glioblastoma; Glioma; Humans; Image Processing, Computer-Assisted; Lactic Acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Necrosis; Phosphocreatine; Phosphorylcholine; Stereotaxic Techniques

High-grade brain tumors are known to have a high rate of glucose (Glc) consumption. Postmortem measurements have suggested that Glc content in experimental brain tumors is relatively low. We used magnetic resonance spectroscopy to investigate this, in vivo, in the brains of seven rats bearing intracerebral C6 gliomas. We combined the high spectral resolution allowed by two-dimensional proton nuclear magnetic resonance with spatial encoding by magnetic field gradient pulses to obtain in vivo maps of Glc, alanine, hypotaurine, aspartate, phosphoethanolamine, Glu/Gln, N-acetylaspartate (NAA), phosphocreatine/creatine (PCr/Cr), choline-containing compounds, and lactate (Lac) (some of which are involved in energy metabolism). Compared with normal brain tissue, the main differences found in the gliomas were that Glc, NAA, PCr/Cr, and aspartate concentrations were much lower, whereas concentrations of alanine, hypotaurine, phosphoethanolamine, and Lac were higher, whatever the extent of necrosis. A striking observation is the similarity of the NAA and Glc images: the concentrations of both metabolites are lower in the tumor than they are in the contralateral brain. If Glc was completely absent from the tumor tissue, and if the residual Glc level was due only to a partial volume effect like that for NAA, a neuronal marker, the ratio [Glc]tumor/[Glc]contralateral tissue, should be similar to that found for NAA. The ratio for Glc was 0.48 +/- 0.22 (+/- SD; n = 6), a ratio similar to that found for PCr/Cr (0.50 +/- 0.19) but significantly higher than that obtained for NAA (0.29 +/- 0.07). This observation indicates that a measurable Glc concentration is still present in the tumor tissue. Intense glycolysis in tumor cells may explain the increased production of Lac and alanine and decreased amount of Glc. These nuclear magnetic resonance measurements of metabolite concentrations are complementary to positron emission tomography, which measures Glc consumption.

Topics: Alanine; Animals; Aspartic Acid; Brain Neoplasms; Choline; Creatine; Ethanolamines; Female; Glioma; Glucose; Glutamic Acid; Glutamine; Glycolysis; Lactic Acid; Magnetic Resonance Imaging; Phosphocreatine; Rats; Rats, Sprague-Dawley; Taurine; Tumor Cells, Cultured

The value of extracellular pH (pH(e)) in tumors is an important factor in prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). (1)H SI also allowed us to map metabolites, and, to better understand the determinants of pH(e), we compared maps of pH(e), metabolites, and the distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of four Wistar rats gave rise to gliomas of approximately 10 mm in diameter. Three mmols of IEPA were injected in the right jugular vein from t = 0 to t = 60 min. From t = 50 min to t = 90 min, spin-echo (1)H SI was performed with an echo time of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 microl). IEPA resonances were detected only within the glioma and were intense enough for pH(e) to be calculated from the chemical shift of the H2 resonance in almost all voxels of the glioma. (1)H spectroscopic images with an echo time of 136 ms were then acquired to map metabolites: lactate, choline-containing compounds (tCho), phosphocreatine/creatine, and N-acetylaspartate. Finally, T(1)-weighted imaging after injection of a bolus of Gd-DOTA gave a map indicative of extravasation. On average, the gradient of pH(e) (measured where sufficient IEPA was present) from the center to the periphery was not statistically significant. Mean pH(e) was calculated for each of the four gliomas, and the average was 7.084 +/- 0.017 (+/- SE; n = 4 rats), which is acid with respect to pH(e) of normal tissue. After normalization of spectra to their water peak, voxel-by-voxel comparisons of peak areas showed that N-acetylaspartate, a marker of neurons, correlated negatively with IEPA (P < 0.0001) and lactate (P < 0.05), as expected of a glioma surrounded by normal tissue. tCho (which may indicate proliferation) correlated positively with pH(e) (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001), phosphocreatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate is exported from cells in association with protons, within the gliomas, no evidence was observed that pH(e) was significantly lower where lactate concentration was higher. These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which pr

Topics: Animals; Aspartic Acid; Brain Neoplasms; Buffers; Choline; Contrast Media; Creatine; Extracellular Space; Female; Glioma; Heterocyclic Compounds; Hydrogen-Ion Concentration; Imidazoles; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Organometallic Compounds; Phosphocreatine; Propionates; Protons; Rats; Rats, Wistar

Biopsies of 6 malignant gliomas (grade 3 or 4) and 11 low-grade meningiomas were extracted with perchloric acid or methanol/water, and the fully-relaxed 1H-MRS spectra of the extracts containing water-soluble metabolites and a concentration and chemical shift standard were recorded at 11.4 T. The resonance signals assigned to inositol (Ino), glycerophospho- and phosphocholine (GPC + PC), choline (Cho), creatine and phosphocreatine (Cr + PCr), glutamate (Glu), acetate (Ac), alanine (Ala) and lactate (Lac) were integrated, and analyzed by two methods. First, the concentrations of the aforementioned substances in the bioptates were estimated from their resonance signals in the extracts. Second, these signals were normalized to the Cr + PCr resonance signal. The Mann-Whitney U-test was used to verify statistical significance between the data sets obtained for gliomas and meningiomas. When the first method of analysis was used, the only difference was in the Ala concentration, which in meningiomas was on average 4 times higher than in gliomas (P < 0.01). However, when the second method of analysis was applied, gliomas expressed lower normalized resonance signals of Ala and Glu (P < 0.001, ranges not overlapping), Lac (P < 0.005), as well as Ino and GPC + PC (P < 0.05). In proton MR spectra of brain tumor tissue extracts containing water soluble metabolites, the resonance signals normalized to that of total creatine may provide a very good discrimination between malignant gliomas and low-grade meningiomas.

Topics: Biopsy; Brain; Brain Neoplasms; Creatine; Diagnosis, Differential; Energy Metabolism; Glioma; Humans; Magnetic Resonance Spectroscopy; Meningeal Neoplasms; Meninges; Meningioma; Phosphocreatine; Predictive Value of Tests; Prognosis; Reference Values

This study reports the MR spectroscopic patterns of two patients with bithalamic glioma. In one patient, phosphorus (31P) MR spectroscopy was performed. In both patients, the proton MR spectroscopic scans showed an increased creatine-phosphocreatine peak in the tumor. In the patient who underwent 31P-MR spectroscopy, an increased phosphocreatine peak was also observed. This group of thalamic tumors may be distinguished from other gliomas clinically, radiologically, and metabolically.

Topics: Adult; Brain Chemistry; Brain Neoplasms; Creatine; Glioma; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Thalamic Diseases; Thalamus

The present experiments were conducted to investigate the direct effects of ethanol on the energy metabolism of astrocytes and C6-glioma cells. Primary astrocytes were prepared from cerebral cortices of neonatal rats, and C6-glioma cells were purchased from American Type Culture Collection (ATCC). These cells were exposed to different concentrations of alcohol (100 mM, 200 mM, and 300 mM) for 15 minutes and 24 hours. The amount of ATP and PCr was measured by the method of Lowry and Passonneau (1972). Following 15 minutes treatment with different doses of ethanol the amount of ATP and PCr increased, in both cell types. Only the increase of ATP concentration with varying doses of ethanol (100 mM, 200 mM, and 300 mM) was statistically significant. Following 24 hours treatment of astrocytes with different doses of ethanol the concentration of ATP and PCr decreased. The decrease in concentration of ATP was significant with all three doses of ethanol, but the decrease of PCr concentration was only statistically significant with 300 mM ethanol. Following 24 hours treatment of C6-glioma cells to varying doses of ethanol, the concentration of PCr and ATP decreased. The decrease of PCr was statistically significant with all three doses of ethanol and the decrease of ATP concentration was only significant with 300 mM ethanol.

Topics: Adenosine Triphosphate; Animals; Astrocytes; Cells, Cultured; Energy Metabolism; Ethanol; Glioma; Phosphocreatine; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured

Brain tissue cells have been shown to use two predominant pathways for energy production. The first of these is the pentose phosphate shunt, and the second is glycolysis, followed by the TCA cycle. Inhibition of these pathways can result in a reduction of ATP, and changes in the concentration of various metabolites. In the present study, the acute and chronic effect of 6-aminonicotinamide (6-AN) (0.01, 0.02, and 0.03 mg/ml) was examined on astrocytes and C6-glioma cells. Following this treatment, glucose, lactate, glutamate, ATP, and PCr were assayed according to the procedures of Lowry and Passonneau. Our data indicated that following 15 minutes treatment of astrocytes and C6-glioma with 6AN there was no significant difference in the concentration of metabolites measured. However, following 24 hours treatment there was a significant increase in glucose concentration and significant reduction in the concentration of ATP, PCr, lactate and glutamate in both cell types. Morphological changes appeared later following 48 hours treatment with 6-AN in both cell types. Glucose accumulation can be explained by the fact that it is the precursor to both glycolysis and the pentose phosphate shunt. If these processes are inhibited, glucose will obviously accumulate and products like ATP, PCr, lactate and glutamate will decrease. Additionally, there was significant differences in concentration of glucose and lactate between astrocytes and C6-glioma cells. The significance of these differences has been discussed.

Topics: 6-Aminonicotinamide; Adenosine Triphosphate; Animals; Animals, Newborn; Astrocytes; Brain Neoplasms; Cells, Cultured; Enzyme Inhibitors; Glioma; Glucose; Glutamic Acid; Lactic Acid; Nerve Tissue Proteins; Phosphocreatine; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured

The authors tested the hypothesis that proton magnetic resonance spectroscopy (1H-MRS) imaging can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of low- to high-grade malignant transformation or posttherapeutic recurrence. Twenty-seven patients with cerebral gliomas verified on histological examination were studied repeatedly with 1H-MRS imaging over a period of 3.5 years. At the time of each 1H-MRS imaging study, clinical examination, MR imaging, positron emission tomography with 18F-fluorodeoxyglucose, and biopsy findings (when available) were used to categorize each patient as having either stable or progressive disease. Measures of the percentage changes in the choline (Cho) 1H-MRS imaging signal intensity between studies, which were obtained without knowledge of the clinical categorization, allowed the investigators to segregate the groups with a high degree of statistical significance. All progressive cases showed a Cho signal increase between studies of more than 45%, whereas all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. The authors conclude that increased Cho levels coincide with malignant degeneration of cerebral gliomas and therefore may possibly be used as a supportive indicator of progression of these neoplasms.

Topics: Adult; Aged; Aspartic Acid; Biomarkers, Tumor; Biopsy; Brain Neoplasms; Cell Transformation, Neoplastic; Choline; Creatine; Deoxyglucose; Disease Progression; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Follow-Up Studies; Glioma; Humans; Hydrogen; Lactic Acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphocreatine; Prognosis; Protons; Radiopharmaceuticals; Tomography, Emission-Computed

To test clinical proton MR spectroscopy as a noninvasive method for predicting tumor malignancy.. Water-suppressed single-voxel point resolved spectroscopy in the frontal white matter of 17 healthy volunteers and 25 patients with brain tumors yielded spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cre), and lactate. These peak intensities were semiquantitated as a ratio to that of the external reference. The validity of the semiquantitation was first evaluated through phantom and volunteer experiments.. The variation in measurements of the designated region in the volunteers was less than 10%. Normal ranges of NAA/reference, Cho/reference, and Cre/reference were 3.59 +/- 0.68, 1.96 +/- 0.66, and 1.53 +/- 0.64 (mean +/- SD), respectively. In 17 gliomas, the Cho/reference value in high-grade gliomas was significantly higher than in low-grade gliomas. Levels of NAA/reference were also significantly different in low-grade and high-grade malignancy. In eight meningiomas (four newly diagnosed and four recurrent), the level of Cho/reference was significantly higher in recurrent meningiomas than in normal white matter or in newly diagnosed meningiomas.. Higher grades of brain tumors in this study were associated with higher Cho/reference and lower NAA/reference values. These results suggest that clinical proton MR spectroscopy may help predict tumor malignancy.

Topics: Adolescent; Adult; Aged; Aspartic Acid; Brain Neoplasms; Choline; Creatine; Energy Metabolism; Female; Glioma; Humans; Image Processing, Computer-Assisted; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Meningioma; Middle Aged; Phantoms, Imaging; Phosphocreatine; Protons; Reference Values; Reproducibility of Results

We studied the feasibility of characterizing brain tumor tissue by localized proton magnetic resonance spectroscopy (1H-MRS). Twenty-six newly diagnosed tumors were examined by in-vivo 1H-MRS. The NAA (N-acetylaspartate)/Cho (choline) ratio of Grade 2 astrocytoma was higher than that of Grade 4. The Cho/Cr (creatine and phosphocreatine) ratio of meningioma was considerably higher than that of glioma of all grades. We have experienced only two cases of ependymoma and the Cho/Cr ratios of both were lower than that of glioma. It seems likely that 1H-MRS can be used to differentiate Grade 2 from Grade 4 in most cases of astrocytoma based on the NAA/Cho ratio, though a few cases will overlap. Meningioma can be distinguished easily from glioma, and the results of our study suggest that ependymoma shows a characteristic pattern on 1H-MRS, different from those of other brain tumors.

Topics: Aspartic Acid; Astrocytoma; Brain Neoplasms; Choline; Creatine; Ependymoma; Glioma; Humans; Magnetic Resonance Spectroscopy; Meningioma; Phosphocreatine

Under full nutrient in vitro conditions, the cellular adenylate energy charge of six different rodent and human tumor cell types was identical, i.e., 0.94 +/- 0.01, suggesting the potential utility of this parameter as a cell (and tissue) independent marker of nutrient deprivation and hypoxia, across tumor types. The adenylate energy charge values of tumors, arising from these cells, was reduced and variable ranging from 0.72 to 0.91 for the various tumor types. However, neither the tumor adenylate energy charge, NTP/Pi, nor PCr/Pi ratios correlated with the radiobiologic hypoxic cell fractions across tumor types. The reduced adenylate energy charge in vivo suggests varying degrees of nutrient deprivation in the different tumor types, however, factors other than or in addition to hypoxia likely contribute to tumor energy status.

Topics: Adenine Nucleotides; Animals; Carcinoma, Squamous Cell; Cell Hypoxia; Cell Line; Cell Survival; Energy Metabolism; Female; Glioma; Humans; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Mice, Nude; Neoplasms; Neoplasms, Experimental; Pharyngeal Neoplasms; Phosphates; Phosphocreatine; Ribonucleotides; Sarcoma, Experimental; Transplantation, Heterologous; Tumor Cells, Cultured; Whole-Body Irradiation

F98 gliomas, E367 neuroblastomas, and RN6 Schwannomas in rat brain were studied non-invasively in vivo by localized proton MR spectroscopy (MRS). The spectra obtained from homotopic brain contralateral to the tumors were qualitatively indistinguishable from those of normal rat brain in vivo and showed resonance lines assigned to N-acetylaspartate, glutamate, total creatine (creatine and phosphocreatine), choline, glucose, and myo-inositol. The tumor spectra displayed marked differences compared to those obtained from contralateral brain. There were increases in choline, myo-inositol and lipids, which are presumably associated with increased membrane turnover. The presence of lactate indicated anaerobic glycolysis. Other differences included the absence of signals from NAA resulting from the destruction or displacement of neuronal tissue by the tumor. There was also a loss of total creatine. Although the spectra of all three tumor types were distinct from contralateral brain, there were no obvious differences between the different tumor types.

Topics: Animals; Aspartic Acid; Blood Glucose; Brain Edema; Brain Neoplasms; Caudate Nucleus; Cell Line; Choline; Creatinine; Energy Metabolism; Glioma; Glutamic Acid; Inositol; Magnetic Resonance Imaging; Male; Neoplasm Transplantation; Neurilemmoma; Neuroblastoma; Phosphocreatine; Rats; Rats, Inbred F344

In a prospective study, proton (1H) and phosphorus (31P) nuclear magnetic resonance spectroscopy were used to search for effects of brain tumor radiotherapy on normal human central nervous system. Phosphorus spectroscopy data at 1.5 T seems to suggest that any radiation induced damage that may occur as a result of therapeutic brain irradiation, does not alter the relative concentrations of phosphorus metabolites or the intracellular pH beyond the limits of normal variation (approximately +/- 20%). Proton spectroscopy, on the other hand, detects post radiation changes in the ratios of certain nuclear magnetic resonance visible metabolites following radiotherapy, particularly choline/N-acetylaspartate, and especially in regions of brain receiving high doses of radiation. Such changes may be indicative of the release of membrane bound choline during radiation induced demyelination of brain. Of interest, we have found elevated metabolite ratios of 31P in normal central nervous system prior to radiotherapy, which persisted throughout the time span of the study in both the ipsilateral and contralateral cerebral hemispheres.

Topics: Adenoma; Adenosine Triphosphate; Brain; Brain Neoplasms; Energy Metabolism; Glioma; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Oligodendroglioma; Phosphates; Phosphocreatine; Phosphorus; Pituitary Neoplasms; Prospective Studies; Reference Values

The mechanism behind the relative increase in high-energy phosphates observed by MRS in many tumors following chemotherapy is poorly understood. To test the hypothesis that this metabolic activation is associated with a decrease in tumor hypoxia, tumor blood flow and oxygenation were measured in tumors that were also analyzed by MRS. 31P MR spectra were acquired with a GE 2T CSI spectrometer from subcutaneous 9L tumors in rats 4 days following treatment with BCNU (10 mg/kg) and from age-matched sham-treated control tumors. BCNU-treated tumors (n = 13) underwent a significant improvement in bioenergetic state compared to control tumors (n = 14), showing a relative increase in high-energy phosphate (Pi/phosphocreatine) (p less than 0.01), and a relative decrease in Pi (Pi/alpha nucleoside biphosphate) (p less than 0.01). Gamma camera imaging of 133Xe washout, following injection of 133Xe in saline into control and treated 9L tumors 4 days after treatment, was used to measure tumor perfusion. Sham-treated control tumors (n = 21) were perfused at a rate of 35.4 (+/- 6.4 SE) mL/100 g/min, while BCNU-treated tumors (n = 20) were perfused at a rate of 55.1 (+/- 7.5 SE) mL/100 g/min (T = 1.96; p less than 0.05). The partial pressure of oxygen (pO2), measured with a polarographic electrode was found to be significantly higher in treated 9L than in sham-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Carmustine; Cell Hypoxia; Female; Glioma; Magnetic Resonance Spectroscopy; Oxygen; Perfusion; Phosphates; Phosphocreatine; Rats; Rats, Inbred F344

Patients with intracranial tumors (gliomas) were examined by means of localized water-suppressed 1H NMR single volume spectroscopy and spectroscopic imaging. The 1H NMR spectra of the tumors exhibit signal intensities of the N-acetyl aspartate, choline compounds, and creatine plus phosphocreatine resonance lines that are different from the corresponding intensities observed on normal brain tissue. Also, for 6 out of the 10 patients examined so far, lactate resonance lines were detected in the tumor spectra. For one patient, abnormal 1H NMR spectra were obtained of a hemisphere which appeared normal with 1H NMR imaging. Metabolic heterogeneity of the tumorous regions could be demonstrated with 1H NMR spectroscopic imaging, using a spatial resolution in the order of 1 cm. These results suggest a spectrum of metabolic observations that may ultimately provide an important means for characterizing brain tumors.

Topics: Adult; Aspartic Acid; Astrocytoma; Brain; Brain Neoplasms; Creatine; Glioma; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Phosphocreatine

Glioma are often histologically heterogenous. As many of these tumors are not removable in toto, due to their localisation, the most malignant part of the tumor may be missed and information for optimum therapeutic management is incomplete. Furthermore, low grade gliomas tend to become more malignant in their development; additional surgical intervention is often not possible. Non-invasive measurement of tumor glucose metabolism with (F-18)-2-fluoro-2-deoxyglucose (FDG) and positron-emission-tomography (PET) may be used to evaluate tumor malignancy. Malignant gliomas (astrocytoma III degree and glioblastoma) frequently showed increased peak metabolic rates (in comparison with normal white matter) and uncoupling of FDG transport and phosphorylation. Preliminary experiences with image-guided localized phosphorus-31 MR spectroscopy (P-31 MRS) demonstrated a decrease of phosphodiesters in malignant gliomas, whereas the phosphomonoesters showed an increase in several cases. The phosphocreatine peak was often reduced. A more active therapy of low grade gliomas might be indicated when signs of hypermetabolism in FDG-PET and alteration of energy-rich phosphates or membrane-phosphates in P-31 MRS are found.

Topics: Adenosine Triphosphate; Adult; Blood Glucose; Brain Neoplasms; Deoxyglucose; Energy Metabolism; Female; Fluorodeoxyglucose F18; Glioma; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus; Tomography, Emission-Computed

A recently developed method for image-selected localized hydrogen-1 magnetic resonance (MR) spectroscopy was assessed in the differential diagnosis of nine primary and secondary cerebral tumors, including four gliomas, two meningiomas, one neurilemoma, one arachnoid cyst, and one metastasis of breast cancer. Well-resolved H-1 MR spectra of these tumors were obtained in vivo with a conventional 1.5-T whole-body MR imaging system. All tumor spectra were remarkably different from spectra from normal brain tissue. Spectra obtained from different tumors exhibited reproducible differences, while histologically similar tumors yielded characteristic spectra with only minor differences. The observed spectral alterations reflect variations in concentrations and relaxation times of the H-1 MR sensitive pool of free (mobile) metabolites within the tissues. In most cases, the concentrations of N-acetyl-aspartate and creatine/phosphocreatine are reduced below detectability, whereas choline-containing compounds are generally enhanced. The spectral differences between the tumors are mainly due to the differing concentrations of lipids, lactic acid, and carbohydrates. Localized H-1 MR spectroscopy may become an important clinical tool for the differentiation of tumors as well as for therapeutic control.

Topics: Adult; Aspartic Acid; Brain Chemistry; Brain Diseases; Brain Neoplasms; Choline; Creatinine; Cysts; Diagnosis, Differential; Female; Glioma; Glutamine; Humans; Inositol; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neurilemmoma; Phosphocreatine

The energetic metabolism of perfused C6 glioma cells anchored and cultured on polystyrene microcarrier beads has been studied by phosphorus-31 nuclear magnetic spectroscopy (NMR). The observation of intracellular phosphorylated compounds demonstrates the metabolic long-lasting viability of the perfused cells. The effect of glucose deprivation on energetic metabolism and intracellular pH illustrates the existence of an active aerobic glycolysis. The non-invasive study of anchored C6 cells by NMR provides a direct means to investigate the metabolism of glioma cells.

Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Glioma; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Microspheres; Phosphates; Phosphocreatine; Polystyrenes; Rats; Tumor Cells, Cultured

In vivo 31P nuclear magnetic resonance spectroscopy was used to examine the bioenergetics of the rat 9L gliosarcoma during untreated growth and in response to chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Tumor growth was associated with a decline in the phosphocreatine and nucleoside triphosphate resonances, consistent with an increase in tumor hypoxia during untreated growth. Following chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (10 mg/kg), tumor levels of phosphocreatine and nucleoside triphosphate rebounded while the level of inorganic phosphate in the tumor declined. Histological comparison of treated and untreated tumor sections 4 days posttreatment showed that the treated tumor had a lower proportion of necrotic cells, a higher proportion of viable cells, and a 5-fold higher level of interstitial space than the control tumor.

Topics: Animals; Carmustine; Energy Metabolism; Extracellular Space; Glioma; Magnetic Resonance Spectroscopy; Necrosis; Nucleotides; Phosphocreatine; Rats

The in vivo high-energy phosphorus metabolic profile and pH of an experimental intracerebral C6 glioma in rats was examined using surface coil 31P NMR spectroscopy. Initially, phosphorus-containing metabolites of the glioma were characterized by in vivo 31P surface coil spectroscopy of subcutaneously implanted tumors and by high-resolution NMR studies of perchloric acid (PCA) extracts of both freeze-clamped subcutaneous tumor tissue and cultured cells. These studies demonstrated that the C6 glioma has reduced levels of phosphocreatine (PCr) compared to the levels found in normal rat brain. Thus, reduced spectral PCr levels were useful as a metabolic indicator for monitoring the spatial selectivity of tumor metabolism distinct from that of adjacent normal brain tissue. To maximize 31P NMR signals from intracerebral tumors, tumor cells were stereotaxically placed superficially in the brain. Proton magnetic resonance imaging (1H MRI) was used to determine the size and location of the resultant brain tumors in order to preselect rats with large superficial tumors for spectroscopic study. 31P NMR spectra of the glioma tumors revealed a consistent reduction in the PCr/ATP ratio, an increase in the Pi/ATP ratio, and a slightly increased tissue pH. No correlation was found between levels of Pi/ATP and tumor pH in subcutaneous or intracerebral gliomas and the amount of necrosis as determined histologically. This study demonstrates that phosphorus metabolites of an experimental brain tumor in the rat can be monitored in vivo with minimal contributions from adjacent normal brain tissue metabolites using surface coil 31P NMR spectroscopy.

Topics: Adenosine Triphosphate; Animals; Brain Neoplasms; Female; Glioma; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Neoplasm Transplantation; Phosphocreatine; Rats; Rats, Inbred F344

The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by fluorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I-III gliomas had a glucose consumption rate of 2-3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by 18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measured in situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the glioma-derived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomas in situ and (2) are significantly altered in several aspects of their glycolytic metabolism.

Topics: Adenosine Triphosphate; Energy Metabolism; Glioma; Glucose; Humans; Phosphocreatine; Pyruvates; Pyruvic Acid; Tumor Cells, Cultured

In vivo phosphorus-31 magnetic resonance (MR) spectra were obtained by a surface coil method from rat glioma tissue inoculated subcutaneously in CD Fisher rats, and the effects of photoradiation therapy on tumors were evaluated by sequentially observing spectral changes. In the control group, the nucleoside triphosphate (NTP) and phosphomonoester peaks were large, the phosphocreatine peak was small, and the inorganic phosphate (Pi) peak was intermediate. In all eight cases in the group in which a dose of 10 mg/kg of hematoporphyrin derivatives (HpD) was given before photoirradiation, NTP peaks decreased, and the Pi peak increased remarkably within 1 hour after the 60-minute white-light irradiation. Spectral changes were observed before histologic changes were apparent. Histologic examinations 3 days after irradiation showed extensive necrosis in the tumor tissue. With preinjection of 5 mg/kg HpD, three of the eight cases showed spectrum changes after the irradiation. No spectrum changes were observed in the group with preinjection of 2.5 mg/kg. In vivo P-31 MR spectra measurements are useful not only to investigate the energy metabolism of tumor tissue in vivo but also to evaluate the effects of photoradiation therapy on tumors.

Topics: Animals; Brain Neoplasms; Energy Metabolism; Evaluation Studies as Topic; Glioma; Hematoporphyrin Photoradiation; Magnetic Resonance Spectroscopy; Necrosis; Phosphates; Phosphocreatine; Photochemotherapy; Purine Nucleotides; Rats

Prostaglandin E1 receptor sites were measured in homogenates of NG108-15 neuroblastoma-glioma hybrid cells after exposure of intact cells to PGE1. Scatchard analysis of competitive binding studies showed that incubation of NG108-15 cells in the presence of 2.5 microM PGE1 for 16 h resulted in a loss of PGE1 receptors and an increase in the dissociation constant of the remaining receptors. Thus, cells challenged with PGE1 not only lose adenylate cyclase activity, but also lose PGE1 receptors and decreased the affinity of the remaining receptors for PGE1.

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Alprostadil; Animals; Cyclic AMP; Cytidine Triphosphate; Glioma; Guanylyl Imidodiphosphate; Hybridomas; Neuroblastoma; Phosphocreatine; Prostaglandins E; Receptors, Cell Surface; Receptors, Prostaglandin; Receptors, Prostaglandin E; Time Factors

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Adolescent; Adult; Aged; Brain Neoplasms; Child; Creatine Kinase; Energy Metabolism; Female; Glioma; Glycogen; Humans; Lipids; Male; Meningioma; Middle Aged; Neurilemmoma; Phosphates; Phosphocreatine; Uridine Triphosphate

Topics: Adenine Nucleotides; Adenosine Triphosphate; Brain; Brain Neoplasms; Fluorometry; Frontal Lobe; Glioma; Glucose; Glycogen; Glycolysis; Hexoses; Humans; In Vitro Techniques; Ischemia; Lactates; Phosphocreatine; Spectrophotometry; Tissue Extracts

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Fluorometry; Glioma; Glucose; Glycogen; Ischemic Attack, Transient; Lactates; Methylcholanthrene; Mice; Neoplasms, Experimental; Phosphocreatine