phosphocreatine and Brain-Neoplasms

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

In this study a human glioma-derived intracerebral tumor model was analyzed histologically and examined by image-guided 1H NMR spectroscopy. It was shown that histological characteristics such as cellular subpopulation and necrosis of the primary tumor were preserved in the implants. Usually circumscript tumor growth was present with tumor cells invading the surrounding brain parenchyma. It was demonstrated that tumor growth and tumor metabolism could be monitored by image-guided 1H NMR spectroscopy in a longitudinal study. One of the initial changes noticed was the rise of the lactate signal in the tumor region followed by an increase of the choline and a decrease of N-acetyl-aspartate and phosphocreatine signals. Even before tumor invasion in brain adjacent to the central tumor area could be demonstrated by NMR imaging increased lactate and moderately increased choline signals were measured in these regions. By histopathological examination these areas were shown to be infiltrated by single tumor cells. These observations indicate that image-guided 1H NMR spectroscopy could play an important role in the study of brain tumor biology, especially in the case of changing tumor metabolism during growth.

Topics: Animals; Aspartic Acid; Brain Neoplasms; Choline; Energy Metabolism; Glioblastoma; Humans; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Necrosis; Neoplasm Invasiveness; Neoplasm Transplantation; Phosphocreatine; Rats; Rats, Nude; Skin Neoplasms; Transplantation, Heterologous

We tested the reliability of quantifying brain metabolite concentrations by MR spectroscopy. We employed a PRESS sequence and used a cyclohexane sample as an external standard. The signal intensity ratios of water and cyclohexane were measured by changing the geometrical arrangement of the cyclohexane sample and water phantom with various loading factors of the coil. Choline (Cho) concentrations were calculated from the signal intensity ratios of Cho and water and compared with actual Cho concentrations (1.0 to 2.6 mmol/L). The brain metabolites Cho, creatine/phosphocreatine (Cr/PCr) and N-acetylaspartate (NAA) were evaluated in five normal volunteers and six patients with metastatic brain cancer before (0 Gy), after 20 Gy and after 40 Gy of whole brain radiotherapy. Variation in the ratio of spectrum intensity between water and cyclohexane was less than 1.5% for various geometrical arrangements and loading factors. The error in quantification of Cho concentrations in the phantom study was 0.05 +/- 0.10 mmol/L. The concentrations measured in the volunteers were: Cho 1.6 +/- 0.4 mmol/L, Cr/PCr 6.4 +/- 1.1 mmol/L and NAA 8.2 +/- 0.1 mmol/L. There was no significant difference (p > 0.05) in these concentrations between the control group and the patients before, during, or after radiotherapy.

Topics: Adult; Aged; Aspartic Acid; Brain; Brain Neoplasms; Choline; Creatine; Cyclohexanes; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Models, Structural; Phosphocreatine; Reference Standards; Reproducibility of Results

Topics: Brain Neoplasms; Cell Line, Tumor; G2 Phase Cell Cycle Checkpoints; gamma-Aminobutyric Acid; Glioblastoma; Glucose; Glutamic Acid; Humans; Ions; Lactic Acid; Magnetic Resonance Spectroscopy; Neoplastic Stem Cells; Phosphocreatine; Photons; Radiation, Ionizing

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

We report a case, in which quantitative 1H-MR spectroscopy (MRS) was useful for the differentiation between radiation necrosis and a recurrent tumor. The present case is a 44-year-old man who underwent the subtotal removal of a mass lesion in the left frontal lobe. The histological diagnosis was anaplastic oligodendroglioma (WHO grade III). Postoperatively, a fractionated radiotherapy (total 64Gy) and chemotherapy were performed. MRI after the radiotherapy showed no contrast enhancing lesion. MRI, 5 years after the radiotherapy, showed a growing enhancing lesion and a T1 hypointensity lesion without enhancement, both of which indicated a recurrent tumor. MR spectroscopy was performed for the differential diagnosis of these lesions. The spectrum was acquired by the point resolved spectroscopy (PRESS) method by TR/TE=2,000 ms/68 ms, 136 ms, and 272 ms and evaluated with peak pattern and quantification value of metabolite. MRS of the enhancing lesion demonstrated a decrease of the Choline-containing compounds (Cho) concentration, disappearance of N-acetylaspartate (NAA), decrease of Creatine/ Phosphocreatine (t-Cr) and presence of Lipids (Lip) and Lactate (Lac), all of which are characteristic finding of a radiation necrosis. The histological diagnosis of this lesion showed evidence also of radiation necrosis. On the other hand, MRS of the T1 hypointensity lesion without enhancement showed, a marked high peak of the Cho concentration, which is characteristic for a recurrent tumor. The histological findings of this lesion showed a diffuse proliferation of recurrent tumor cells. Quantitative 1H-MRS is a useful tool for the differentiation between radiation necrosis and recurrent tumors.

Topics: Adult; Aspartic Acid; Brain Diseases; Brain Neoplasms; Choline; Creatine; Diagnosis, Differential; Frontal Lobe; Humans; Lactates; Lipids; Magnetic Resonance Spectroscopy; Male; Necrosis; Neoplasm Recurrence, Local; Oligodendroglioma; Phosphocreatine; Radiation Injuries

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

Topics: Abnormalities, Radiation-Induced; Aspartic Acid; Brain Neoplasms; Cell Proliferation; Choline; Creatine; Fatty Acids, Nonesterified; Humans; Inositol; Lactates; Magnetic Resonance Spectroscopy; Phosphocreatine; Photons

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

To determine the relative signal intensity ratios of choline (Cho), phosphocreatine (CR) and N-acetyl-aspartate (NAA) in MR spectroscopic imaging (proton-MRSI) for differentiating progressive tumors (PT) from non-progressive tumors (nPT) in follow-up and treatment planning of gliomas. Threshold values to indicate the probability of a progressive tumor were also calculated.. Thirty-four patients with histologically proven gliomas showing a suspicious brain lesion in MRI after stereotactic radiotherapy were evaluated on a 1.5 Tesla unit (Magnetom Vision, Siemens, Erlangen, Germany) using 2D proton MRSI (repetition time/echo time = 1500/135 msec, PRESS; voxel size 9 x 9 x 15 mm (3)). A total of 274 spectra were analyzed (92 voxel were localized within the suspicious brain lesion). Relative signal intensities Cho, Cr and NAA were measured and their ability to discern between PT and nPT was assessed using the linear discrimination method, logistic regression, and the cross-validation method. PT and nPT were differentiated between on the basis of clinical course and follow-up by MRI, CT and positron emission tomography.. The Cho parameter and the relative signal intensity ratios of Cr and NAA were most effective in differentiating between PT and nPT. The logistic regression method using the parameter ln(Cho/Cr) and ln(Cho/NAA) had the best predictive results in cross-validation. A sensitivity of 93.8 % and specificity of 85.7 % were achieved in the differentiation of PT from nPT by proton-MRSI.. (1)H-MRSI has a high sensitivity and specificity for differentiating between therapy-related effects and the relapse of irradiated gliomas. This method allows for assessment of the probability of radiotherapy response or failure.

Topics: Adult; Aspartic Acid; Astrocytoma; Brain; Brain Neoplasms; Chemotherapy, Adjuvant; Choline; Combined Modality Therapy; Contrast Media; Cranial Irradiation; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Gadolinium DTPA; Glioblastoma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oligodendroglioma; Phosphocreatine; Predictive Value of Tests; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant; Reference Values; Stereotaxic Techniques

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

Brain metabolism after surgery and postoperative radiotherapy (pRT) because of primary brain tumors was assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in vivo. The study was designed to reveal the impact of pRT on normal brain tissue metabolism, which may potentially help in delineating the target volumes for reirradiated patients.. Spectra of 43 patients ages 16-63 years treated with pRT for primary glial tumors in the Center of Oncology Maria Curie Memorial Institute Branch in Gliwice were analyzed. The control group consisted of spectra acquired for 30 healthy volunteers. All patients were treated with 3D conformal techniques using 6-20 MV photons to total doses of 60 Gy. Spectra were acquired from the control region before pRT and from three uninvolved regions 9-12 months after the end of pRT. Voxels were located in the region of low (<6 Gy), medium (29-39 Gy), and high radiation dose ( approximately 60 Gy). Relative intensities of the signals relating to N-acetyl-aspartate (NAA), choline-based compounds, creatine and phosphocreatine (Cr), mio-Inositol, lactate, and lipids were obtained.. The spectra of "normal brain" taken 9 months after pRT are significantly different from those obtained for control volunteers and from the spectra acquired before radiotherapy. The lactate and lipids signals are very strong; however, they are not correlated with absorbed dose. NAA/Cr ratios are significantly lower than before radiotherapy even for the low-dose regions. Differences increase with radiation dose: the NAA/Cr ratio is significantly lower for the regions of brain receiving a high dose of radiation than for the low-dose areas.. Combined treatment of primary brain tumors (surgery + postoperative radiotherapy) causes alteration of brain metabolism, even in regions of the brain far from the postoperative tumor bed and receiving relatively low total doses of radiation. Single voxel MRS spectroscopy in vivo cannot help in delineating target volumes for secondary irradiation.

Topics: Adolescent; Adult; Aspartic Acid; Brain; Brain Neoplasms; Combined Modality Therapy; Female; Humans; Lactic Acid; Lipids; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine

A century after the discovery of X-rays, the low-energy range of the electromagnetic spectrum also attained broad application in radiology. Radiofrequency waves allow excitation in a magnetic field of the magnetic resonance of spin-bearing nuclei in tissue. Using the intense signal of the water protons, morphological images of the human body can be obtained, while at a higher frequency resolution also endogenous metabolites as well as pharmaceuticals, which contain MR-visible nuclei (e.g., 1H, 13C, 19F, 31P), can be detected noninvasively and in vivo. Accordingly, in vivo MR spectroscopy is a technique which is sensitive to molecules and molecular properties and which can be applied to repeated examinations. Its major limitation is the low signal intensity vs noise, which implies long measurement times and poor spatial resolution. Using spectroscopic imaging, the distribution of metabolites within an organ can be monitored selectively and displayed as a molecular image.

Topics: Aspartic Acid; Brain; Brain Diseases; Brain Neoplasms; Choline; Energy Metabolism; Humans; Image Enhancement; Image Processing, Computer-Assisted; Inositol; Magnetic Resonance Spectroscopy; Phosphocreatine; Sensitivity and Specificity; Software; Water-Electrolyte Balance

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

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

It is often difficult to make a correct diagnosis of ring-like enhanced lesions on Gd-enhanced MR brain images. To differentiate these lesions using proton MR spectroscopy (1H-MRS), we retrospectively evaluated the correlation between the 1H-MR spectra and histopathological findings. We evaluated proton MR spectra obtained from the lesions in 45 patients, including metastasis (n = 19), glioblastoma (n = 10), radiation necrosis (n = 7), brain abscess (n = 5), and cerebral infarction (n = 4). The rate of misdiagnosis was found to be lowest at the threshold level of 2.48 for the (choline containing compounds)/(creatine and phosphocreatine) ratio (Cho/Cr) obtained from the whole lesions, which include the enhanced rim and the non-enhanced inner region. That is, the positively predictive values of a Cho/Cr greater than 2.48 for diagnosing metastasis or glioblastoma was 88.9 and 60.0%, respectively, and the positively predictive value of a Cho/Cr less than 2.48 for diagnosing radiation necrosis or cerebral infarction was 71.4 and 100%, respectively. For further differentiating between metastasis and glioblastoma, information about the presence and absence of an N-acetyl-aspartate (NAA) peak and lipid- or lactate-dominant peak was found to be useful. In 73.7% of metastasis cases a lipid-dominant peak was observed in the whole lesion without an NAA peak in the inner region, whereas the same pattern was observed in only 10% of the glioblastoma cases. Correlation with the histopathological findings showed that a high Cho signal is suggestive of neoplasm. Lipid signal in the non-enhanced central region was correlated to necrosis. Lactate signals were often observed in glioblastoma, abscess and sometimes metastasis, presumably reflecting the anaerobic glycolysis by the living cells in the ring-like enhanced rim. Single-voxel proton MR spectroscopy may serve as a potential tool to provide useful information of differentiation of ring-like enhanced lesions that cannot be diagnosed correctly using enhanced MR images alone.

Topics: Adult; Aged; Brain; Brain Abscess; Brain Diseases; Brain Neoplasms; Cerebral Infarction; Choline; Creatine; Diagnosis, Differential; Female; Glioblastoma; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Necrosis; Phosphocreatine; Radiation Injuries; Retrospective Studies

Most patients with a malignant glioma spend considerable time on a treatment protocol before their response (or nonresponse) to the therapy can be determined. Because survival time in the absence of effective therapy is short, the ability to predict the potential chemosensitivity of individual brain tumors noninvasively would represent a significant advance in chemotherapy planning.. Using proton magnetic resonance spectroscopic imaging (1H MRSI), we studied 16 patients with a recurrent malignant glioma before and during treatment with high-dose orally administered tamoxifen. We evaluated whether 1H MRSI data could predict eventual therapeutic response to tamoxifen at the pretreatment and early treatment stages.. Seven patients responded to tamoxifen therapy (three with glioblastomas multiforme; four with anaplastic astrocytomas), and nine did not (six with glioblastomas multiforme; three with anaplastic astrocytomas). Responders and nonresponders exhibited no differences in their age, sex, tumor type, mean tumor volume, mean Karnofsky scale score, mean number of weeks postradiotherapy, or mean amount of prior radiation exposure. Resonance profiles across the five metabolites measured on 1H MRSI spectra (choline-containing compounds, creatine and phosphocreatine, N-acetyl groups, lactate, and lipids) differed significantly between these two groups before and during treatment. Furthermore, linear discriminant analyses based on patients' in vivo biochemical information accurately predicted individual response to tamoxifen both before and at very early treatment stages (2 and 4 wk). Similar analyses based on patient sex, age, Karnofsky scale score, tumor type, and tumor volume could not reliably predict the response to tamoxifen treatment at the same time periods.. It is possible to accurately predict the response of a tumor to tamoxifen on the basis of noninvasively acquired in vivo biochemical information. 1H MRSI has potential as a prognostic tool in the pharmacological treatment of recurrent malignant gliomas.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Agents, Hormonal; Aspartic Acid; Astrocytoma; Brain Neoplasms; Choline; Creatine; Dose-Response Relationship, Drug; Female; Glioblastoma; Humans; Lipid Metabolism; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphocreatine; Tamoxifen; Treatment Outcome; Tumor Stem Cell Assay

The ability of magnetic resonance spectroscopy (MRS) to differentiate neoplastic brain cells and their metabolic and structural characteristics is evaluated. We examined 120 patients with brain tumors using a 1.5-tesla MRI unit and MRS. The peak areas of N-acetyl-aspartate (NAA), phosphocreatine-creatine (Pcr-Cr), choline-containing compounds (Cho), lactate, lipids, myoinositol, amino acids and the ratios of NAA/Pcr-Cr, NAA/Cho and Cho/Pcr-Cr were calculated by a standard integral algorithm. In normal brain tissue, the following metabolites were identified: NAA at 2.0 ppm, Pcr-Cr at 3.0 ppm and Cho at 3.2 ppm. The different concentrations of the metabolites examined and their role in the biochemical profile of different types of tumors are discussed. The confidence interval of the MRS versus pathology was between 0.9 and 0.954, while it was between 0.52 and 0.631 for MRI versus pathology. The Cho/Pcr-Cr ratio is a very important malignancy marker for histologic tumor grading of astrocytomas. The greater this ratio, the higher the grade of the astrocytoma. NAA/Pcr-Cr together with Cho/Pcr-Cr help specify the presence or absence of a neoplasm. Proton MRS is a useful and promising diagnostic modality not only in diagnosing but also in grading solid brain tumors.

Topics: Adult; Aged; Amino Acids; Aspartic Acid; Astrocytoma; Brain; Brain Abscess; Brain Neoplasms; Choline; Creatine; Glioblastoma; Humans; Lactates; Lipid Metabolism; Magnetic Resonance Spectroscopy; Meningioma; Middle Aged; Oligodendroglioma; Phosphocreatine; Reference Values

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

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 determine whether radiation necrosis can be differentiated from residual/recurrent tumor by proton MR spectroscopy.. We studied the effects of interstitial brachytherapy on the brains of healthy monkeys and in humans with glioblastoma multiforme. The effects of radiation therapy on normal brain tissue in monkeys were assessed with sequential proton MR spectroscopic studies 1 week to 6 months after brachytherapy. Proton MR spectroscopy was also performed in five patients with residual/recurrent glioblastoma multiforme (three of whom had radiation necrosis after brachytherapy), seven patients with newly diagnosed untreated glioblastoma multiforme, and 16 healthy volunteers, who served as a control group.. In monkeys, the ratio of N-acetylaspartate (NAA) to creatine-phosphocreatine (Cr) and the ratio of choline-containing compounds (Cho) to Cr of the reference point were significantly lower 1 week after brachytherapy than before treatment. The ratio of NAA to Cho of the irradiated area tended to be higher 1 week after brachytherapy than before irradiation. These peak metabolic ratios showed characteristic changes 6 months after treatment. In two of three monkeys, lipid signal was elevated 6 months after irradiation. In the clinical study, the ratio of NAA to Cho in the area of radiation necrosis was significantly different from that in glioblastoma multiforme when compared with the contralateral hemisphere after irradiation. In addition, lipid signal was detected in all patients with radiation necrosis.. It might be possible to use proton MR spectroscopy to differentiate radiation necrosis from residual/recurrent glioblastoma multiforme on the basis of comparisons with the contralateral hemisphere after radiation therapy.

Topics: Adult; Animals; Aspartic Acid; Brachytherapy; Brain; Brain Neoplasms; Choline; Cranial Irradiation; Creatine; Diagnosis, Differential; Energy Metabolism; Female; Glioblastoma; Humans; Macaca; Magnetic Resonance Spectroscopy; Male; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Phosphocreatine; Radiation Injuries; Radiation Injuries, Experimental

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

Phosphorus magnetic resonance spectroscopy has been used noninvasively to determine characteristic spectral parameters for untreated human brain tumors as a prelude to its use in clinical diagnosis.. The spectra, which reflect the relative amounts of phosphorus-containing compounds, and the pH within and surrounding the tumors, were obtained in vivo using the localization technique of one-dimensional chemical shift imaging applied with a surface coil. Phosphorus-31 chemical shift imaging was performed successfully in vivo on 9 volunteers and 27 patients with untreated brain tumors, including 7 with astrocytoma, 4 with glioblastoma, 3 with meningioma, and 11 with metastases. This study provides spectra from within and surrounding the brain tumors, and allows accountability for the heterogeneity of brain tumors by the selection of the maximum data point for each parameter.. The ratios of resonance areas, phosphodiesters over nucleoside triphosphate (NTP), and phosphomonoesters over NTP, were found to be higher in glioblastomas (2.55 +/- 0.22, 1.06 +/- 0.09) and astrocytomas (3.04 +/- 0.36, 1.28 +/- 0.36) than in normal brain (2.00 +/- 0.32, 0.79 +/- 0.22). The ratios of areas due to inorganic phosphate and NTP, and phosphocreatine and NTP, also were higher in astrocytomas (1.16 +/- 0.40, 1.17 +/- 0.41) compared with glioblastomas (0.68 +/- 0.01, 0.88 +/- 0.19) and normal brain (0.61 +/- 0.03, 0.77 +/- 0.03). The pH of brain tumors ranged from alkaline to neutral, with meningiomas consistently having alkaline pH.. These data show that there are statistically significant differences in the magnetic resonance parameters of the affected brain hemispheres of patients with astrocytomas, glioblastomas, meningiomas, and normal brain tissue, and underline the need for a multisite clinical trial to establish clinical criteria for diagnosis.

Topics: Adenosine Triphosphate; Adult; Aged; Astrocytoma; Brain; Brain Neoplasms; Female; Glioblastoma; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Organophosphates; Phosphates; Phosphocreatine; Phosphorus; Phosphorus Isotopes; Tomography, X-Ray Computed

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

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

1H magnetic resonance spectroscopy allows the regional quantitation of a number of metabolites from the brain in a noninvasive fashion. Spectra were obtained from 5 normal children and 25 children with brain tumors. Choline (Cho), N-acetylaspartate (NAA), creatine and phosphocreatine, and lactate were quantitated in the form of ratios. The brains of normal children showed relatively high concentrations of Cho and NAA and virtually no lactate, as has been shown in adults. Benign astrocytomas and ependymomas were characterized by an elevation of the Cho:NAA ratio and an abnormal accumulation of lactate. Intrinsic malignant tumors were remarkable for an even higher Cho:NAA ratio but had no more lactate than was found in the benign tumors. Proton magnetic resonance spectroscopy may prove useful in characterizing neoplastic tissue in conjunction with more conventional imaging modalities.

Topics: Adolescent; Aspartic Acid; Biomarkers, Tumor; Brain Neoplasms; Child; Child, Preschool; Choline; Creatine; Energy Metabolism; Female; Humans; Infant; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Nerve Tissue Proteins; Phosphocreatine

Image-guided localized proton magnetic resonance (MR) spectroscopy of intracranial tumors was performed to correlate spectral patterns and histologic findings. Thirty-six patients were examined prior to any specific treatment. Evaluation based on signal intensity ratios showed that all tumor spectra differed from spectra of healthy brain tissue. Ratios of creatine to choline-containing compounds (Cr/Cho) and nitrogen acetyl-aspartate to Cho (NAA/Cho) were reduced significantly in all tumor spectra compared with spectra of normal tissue in contralateral brain hemispheres (P less than .005). Noncerebral tumors typically showed a vanishing or missing NAA signal, strongly reduced Cr signal, and additional signals, assigned to alanine in meningiomas and lipids in metastases. In contrast, 11 gliomas of grades 2 and 3 exhibited NAA/Cho ratios and Cr/Cho ratios that were less than normal but that were significantly larger (P less than .01) than corresponding values in eight meningiomas. Ten glioblastomas displayed spectra with various signal ratios, so no significant differences between them and other tumor types could be established. In nine gliomas a clearly detectable lactate signal was present. However, no direct correlation between lactate level and histologic tumor grading was found.

Topics: Adult; Aspartic Acid; Brain; Brain Neoplasms; Choline; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Phosphocreatine

Magnetic resonance spectroscopy (MRS) may contribute to the characterization of intracranial tumors in vivo. Volume selective water suppressed proton spectroscopy offers the possibility to study a number of metabolites in the brain including choline (CHO), creatinine/phosphocreatinine (CR/PCR), N-acetylaspartate (NAA), and lactate. Using the stimulated echo technique we have studied 17 patients with intracranial tumors. In all cases the tumors were classified based on histologic evaluation. The tumor spectra differed considerably from those obtained in healthy brain tissue. The results indicate a relative decrease in the NAA and CR/PCR content. In many cases a lactate peak could be seen especially in the tumors with malignant growth characteristics. Our preliminary results suggest that proton spectroscopy may contribute to the differentiation of brain tumors with respect to benign or malignant growth. However, further research is warranted before a definite conclusion can be drawn.

Topics: Adult; Aged; Aspartic Acid; Astrocytoma; Brain Neoplasms; Choline; Creatine; Female; Humans; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Oligodendroglioma; Phosphocreatine

Fourteen children aged 1 week to 16 years, with a variety of large or superficial brain tumors, underwent localized in vivo 31P magnetic resonance spectroscopy of their tumor. Quantitative spectral analysis was performed by measuring the area under individual peaks using a computer algorithm. In eight patients with histologically benign tumors the spectra were considered to be qualitatively indistinguishable from normal brain. The phosphocreatine/inorganic phosphate ratio (PCr/Pi) averaged 2.0. Five patients had histologically malignant tumors; qualitatively, four of these were considered to have abnormal spectra, showing a decrease in the PCr peak. The PCr/Pi ratio for this group averaged 0.85, which was significantly lower than that seen in the benign tumor group (p less than 0.05). No difference between the two groups was seen in adenosine triphosphate or phosphomonoesters. It is concluded that a specific metabolic "fingerprint" for childhood brain tumors may not exist, but that some malignant tumors show a pattern suggestive of ischemia.

Topics: Adenosine Triphosphate; Adolescent; Brain Chemistry; Brain Neoplasms; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phosphorus Radioisotopes

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

Eleven normal volunteers and 17 subjects with brain tumors were studied by phosphorus-31 Magnetic Resonance (MR) spectroscopy. Measurements were performed by FROGS (Fast Rotating Gradient Spectroscopy) saturating nearly skin or muscle by Volume of Interest (VOI). This measurement took about 30 minutes for each case, including the imaging procedure, shimming and the measuring of spectroscopy. In phosphorus-31 MR spectroscopy, pH of the subjects with brain tumors showed a statistically significant elevation compared with that of the volunteers. In the subjects with benign tumors, only the elevation of pH was significant compared with that in volunteers. There was no other difference. This result suggests that benign tumors have an almost normal metabolic mechanism. Malignant brain tumors showed a decrease of PCr and an increase of Pi and PME. The increase of Pi indicates the increase of energy consumption. The increase of PME is connected with the acceleration of cell proliferation, there is a difference between malignant tumors and benign tumors. Phosphorus-31 spectroscopy has the potential to investigate the metabolism in vivo.

Topics: Astrocytoma; Brain Neoplasms; Energy Metabolism; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Meningioma; Organophosphates; Phosphocreatine; Phosphorus

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 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

We now report a mouse model system of brain tumor for 31P-NMR spectroscopic study of in vivo cerebral metabolism. In vivo 31P-NMR (109 MHz) spectra were taken on the 9th day by the Faraday shield method of the brain of mice (3-week-old) transplanted intracerebrally with mKS X A tumor cells. In tumor-bearing mice, the amount of creatine phosphate decreased markedly and that of inorganic phosphate plus sugar phosphate increased accordingly. Furthermore, the broadening and splitting of individual signals were also noted with tumor-bearing mice; this is interpreted as indicating a variety of changes in chemical shift occurring in the brain of the animals due to heterogeneous distribution of pH. Binding or detaching of divalent cations to and from phosphometabolites may also be responsible for these changes.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Neoplasms; Hydrogen-Ion Concentration; Magnesium; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Phosphocreatine; Phosphorus

31P surface coil NMR spectroscopy was used to evaluate in vivo high-energy phosphorus metabolism in the brains of mice with experimentally induced primary intracranial and subcutaneous KHT sarcomas. 31P spectra of subcutaneous KHT tumors revealed a lack of detectable phosphocreatine (PCr) levels in the tumor as compared to the relatively high endogenous levels of PCr in normal mouse brain. As the intracerebral tumor size increased, there was a reduction in spectral PCr levels over a 23-day postinoculation period in situ in the brain. No histologic or spectroscopic evidence of tumor-associated necrosis or hypoxia was found. This study demonstrates that surface coil 31P NMR spectroscopy can be used to monitor changes in high-energy phosphate metabolism associated with progressive growth of an experimentally induced mouse brain tumor in situ.

Topics: Animals; Brain; Brain Neoplasms; Female; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Phosphocreatine; Sarcoma, Experimental

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

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: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Biopsy; Brain Edema; Brain Neoplasms; Cerebral Cortex; Dogs; Energy Metabolism; Female; Freezing; Glycolysis; Humans; Lactates; Male; Methods; Nitrogen; Phosphocreatine; Potassium; Pyruvates; Sodium; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Brain; Brain Neoplasms; Cell Nucleus; Culture Techniques; Cytoplasm; Energy Transfer; Freeze Drying; Freezing; Glioblastoma; Glycolysis; Histocytochemistry; Methods; Mice; Microscopy, Electron; Microscopy, Electron, Scanning; Phosphocreatine; Radiation Effects; Subcellular Fractions; Time Factors

Topics: Adenosine Triphosphate; Animals; Brain Chemistry; Brain Neoplasms; Cell Nucleus; Centrifugation; Chromosomes; Culture Techniques; Cytoplasm; DNA, Neoplasm; Female; Freeze Drying; Glioblastoma; Glucose; Glycerol; Glycolysis; Histocytochemistry; Lactates; Methods; Mice; Microscopy, Electron, Scanning; Neoplasms, Experimental; Phosphocreatine; Potassium; RNA, Neoplasm; Sodium

Topics: Adenosine Triphosphate; Animals; Brain Neoplasms; Disease Models, Animal; Fluorometry; Freezing; Glioblastoma; Glucose; Glycogen; Histocytochemistry; Lactates; Mice; NAD; NADP; Neoplasm Transplantation; Neoplasms, Experimental; Neuroglia; Oxygen Consumption; Pentoses; Phosphates; Phosphocreatine; Transplantation, Homologous

Topics: Adenine Nucleotides; Adenosine Triphosphate; Body Fluids; Brain Edema; Brain Neoplasms; Central Nervous System; Cerebral Cortex; Extracellular Space; Glucose; Glycolysis; Humans; Lactates; Phosphates; Phosphocreatine; Pyruvates; Water-Electrolyte Balance

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; Adult; Aged; Animals; Astrocytoma; Brain; Brain Neoplasms; Cerebral Cortex; Craniopharyngioma; Fluorometry; Frontal Lobe; Glucose; Glycogen; Glycolysis; Humans; In Vitro Techniques; Ischemic Attack, Transient; Mice; Middle Aged; Oxygen Consumption; Parietal Lobe; Phosphocreatine; Spectrophotometry

Topics: Adenosine Triphosphate; Animals; Brain Neoplasms; Creatine Kinase; Glioblastoma; Glucose; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glutamate Dehydrogenase; Glycogen; Glycolysis; Hexokinase; Histocytochemistry; Ischemia; Lactates; Mice; NAD; NADP; Neoplasms, Experimental; Phosphates; Phosphocreatine; Phosphoglucomutase; Phosphogluconate Dehydrogenase

Topics: Adenosine Triphosphate; Brain Neoplasms; Coenzymes; Glucose; Glycogen; Glycolysis; Hexosephosphates; Ischemia; Lactates; Phosphates; Phosphocreatine; Research