phosphocreatine and Glioblastoma

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

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

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

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

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

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

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

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

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: 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