Value Of Magnetic Resonance Spectroscopy Research Articles

EXTH-20. HYPERPOLARIZED [2-13C] PYRUVATE TO [5-13C] GLUTAMATE AS BIOMARKERS OF IDH1 MUTANT GLIOMA RESPONSE TO TEMOZOLOMIDE THERAPY

Abstract Low-grade gliomas, driven by mutations in the cytosolic isocitrate dehydrogenase 1 (IDH1) gene, are less aggressive than primary glioblastoma, but nonetheless always recur and ultimately lead to patient death. The treatment of IDH1 mutant patients with Temozolomide (TMZ) improves survival, but there remains a need for complementary imaging methods to assess response to therapy at an early time point. The goal of this study was, therefore, to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic imaging biomarkers for detection of response to treatment. To this end we investigated NHA and U87 cells expressing IDH1 R132H mutant gene (NHAIDHmut and U87IDHmut) and first used 1H MRS combined with chemometrics to examined the metabolic alterations that occurred following treatment with the IC50 value of TMZ. We observed a significant increase in 2-hydroxyglutarate (2-HG), glutamate, and glutamine, and metabolic pathway analysis showed tricarboxylic acid (TCA) cycle and pyruvate metabolism to be significantly altered pathways following TMZ treatment compared to DMSO control. To confirm changes in TCA cycle flux and to assess the metabolic pathways contributing to the increase in 2-HG and glutamate/glutamine, cells were then labelled with [1-13C] glucose and [3-13C] glutamine. Our data indicated that both glucose flux via the TCA to glutamate and 2HG, and the contribution of glutamine to glutamate and 2HG were increased following TMZ treatment. Finally, we used hyperpolarized 13C-MRS to dynamically probe the metabolism of hyperpolarized [2-13C] pyruvate and its conversion to hyperpolarized [5-13C] glutamate via the TCA cycle. Consistent with our previous findings, we observed that hyperpolarized [5-13C] glutamate synthesis was significantly higher in TMZ-treated cells compared to controls. Collectively, our findings identify 1H MRS-detectable elevation of 2-HG and glutamate/glutamine as well as hyperpolarized 13C-MRS-detectable [5-13C] glutamate production from [2-13C] pyruvate as potentially translatable metabolic biomarkers of response to TMZ therapy in mutant IDH1 glioma.

Abstract 5263: 1H and 13C MRS-based metabolic markers of IDH1 mutant glioma response to temozolomide therapy

Abstract Low-grade gliomas, driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene, are less aggressive than primary glioblastoma (GBM), but nonetheless always recur and ultimately lead to patient death. To improve patient survival, one therapeutic strategy is treatment with the alkylating chemotherapeutic agent Temozolomide (TMZ), previously reserved for the treatment of primary GBM. Though the treatment of IDH1 mutant patients with TMZ improves survival, early detection of treatment-associated effects remains challenging. The goal of this study was, therefore, to determine the value of magnetic resonance spectroscopy (MRS)-based biomarkers for detection of response to treatment. To this end, we examined the global metabolic alterations that occurred following TMZ treatment in a genetically engineered IDH1 mutant immortalized Normal Human Astrocyte (NHAIDHmut)-based cell model using 1H MRS combined with chemometrics and 13C MRS combined with labeling of cells with [1-13C]-glucose and [3-13C]-glutamine. Cells were treated either with the IC50 value of TMZ (100 μM; N=5), or with DMSO (0.2%; N=5) for 72 hours. Then, metabolites were extracted from cells using the dual-phase extraction method. 1H-MRS and proton-decoupled 13C-MRS spectra were acquired using a 500 MHz Bruker Avance spectrometer. 1H MRS data was subjected to multivariate analysis using SIMCA. Specific metabolites were also quantified using Mnova7, integrals normalized to TSP and to cell number and statistical significance of differences determined using unpaired Student’s t-test. Pathway enrichment analysis of dysregulated metabolites was performed using MetPA. principal component analysis score plot showed separation of TMZ-treated from DMSO-treated control cells. Further, improved separation between the groups was obtained by orthogonal-partial least squares discriminant analysis. Most significant metabolites contributing to class separation were identified using correlation ≥0.6 and variable importance in projection score ≥1. Glutamine, glutamate, 2-hydroxyglutarate (2-HG), pyruvate, succinate, glucose, phosphocholine, isoleucine, valine, lysine, phenylalanine, NAD(P)+ and AMP/ADP/ATP were observed to be significantly higher in TMZ-treated cells as compared to controls. Based on pathway impact score, tricarboxylic acid (TCA) cycle was identified to be the significantly altered pathway following treatment Further, there was a significant increases in glucose- and glutamine-derived glutamate and 2-HG, indicating an increase in flux to the TCA cycle following treatment. These findings demonstrate that IDH1 mutant glioma show a clear metabolomic fingerprint in response to TMZ therapy, which, combined with complementary hyperpolarized 13C MRS approaches, may help assess early response to TMZ therapy in mutant IDH1 glioma. Note: This abstract was not presented at the meeting. Citation Format: Elavarasan Subramani, Chloe Najac, Georgios Batsios, Pavithra Viswanath, Marina Radoul, Anne Marie Gillespie, Russell O. Pieper, Sabrina M. Ronen. 1H and 13C MRS-based metabolic markers of IDH1 mutant glioma response to temozolomide therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5263.

Magnetic resonance spectroscopy data in the prognosis of consciousness recovery in patients with vegetative state

To study the prognostic value of magnetic resonance spectroscopy (MRS) in patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Thirty-four patients with VS/UWS underwent multi-voxel MRS (thalamus, globus pallidus, putamen, internal capsules, fornix, brainstem, temporal and frontal cortex). Subjects were grouped according to etiology: 22 patients with traumatic brain injury (TBI) (group 1) and 12 patients with a hypoxia (group 2). The groups were matched by age and duration of UWS (mean 2, 3 months). The CRS-R was used to identify the first signs of consciousness during hospitalization and 6-12 months later. Outcomes of the patients with TBI were as follows: chronic VS/UWS (n=6), minimally conscious state (MCS) plus (n=9), emergence from MCS (EMCS) (n=7). Outcomes of the patients with hypoxia were: chronic vegetative state (n=10), minimally conscious state (MCS) (n=2). The decrease in the NAA/Cr ratio in thalamus, capsula interna, temporal cortex are correlated with poor outcome in both groups. Higher rates of NAA/Cr in these structures are correlated with further recovery of consciousness. The decrease in the ratio of NAA Cr and NAA/NAA+Cho+Cr in the midbrain is correlated with poor outcome only in UWS with hypoxia. The results suggest that the MRS allows to more accurately predicting the outcome in VS/UWS patients with hypoxic brain damage, as well as in UWS patients with TBI, who have recovered consciousness to the level of EMCS.

Evaluation of the INTERPRET decision-support system: can it improve the diagnostic value of magnetic resonance spectroscopy of the brain?

PurposeWe evaluated in a clinical setting the INTERPRET decision-support system (DSS), a software generated to aid in MRS analysis to achieve a specific diagnosis for brain lesions.MethodsThe material consisted of 100 examinations of focal intracranial lesions with confirmed diagnoses. MRS was obtained at 1.5 T using TE 20–30 ms. Data were processed with the LCModel for conventional analysis. The INTERPRET DSS 3.1. was used to obtain specific diagnoses. MRI and MRS were reviewed by one interpreter. DSS analysis was made by another interpreter, in 80 cases by two interpreters. The diagnoses were compared with the definitive diagnoses. For comparisons between DSS, conventional MRS analysis, and MRI, the diagnoses were categorised: high-grade tumour, low-grade tumour, non-neoplastic lesion.ResultsInterobserver agreement in choosing the diagnosis from the INTERPRET database was 75%. The diagnosis was correct in 38/100 cases, incorrect in 57 cases. No good match was found in 5/100 cases. The diagnostic category was correct with DSS/conventional MRS/MRI in 67/58/52 cases, indeterminate in 5/8/20 cases, incorrect in 28/34/28 cases. Results with DSS were not significantly better than with conventional MRS analysis. All definitive diagnoses did not exist in the INTERPRET database. In the 61 adult patients with the diagnosis included in the database, DSS/conventional MRS/MRI yielded a correct diagnosis category in 48/32/29 cases (DSS vs conventional MRS: p = 0.002, DSS vs MRI: p = 0.0004).ConclusionUse of the INTERPRET DSS did not improve MRS categorisation of the lesions in the unselected clinical cases. In adult patients with lesions existing in the INTERPRET database, DSS improved the results, which indicates the potential of this software with an extended database.

The value of magnetic resonance spectroscopy as a supplement to MRI of the brain in a clinical setting.

BackgroundThere are different opinions of the clinical value of MRS of the brain. In selected materials MRS has demonstrated good results for characterisation of both neoplastic and non-neoplastic lesions. The aim of this study was to evaluate the supplemental value of MR spectroscopy (MRS) in a clinical setting.Material and methodsMRI and MRS were re-evaluated in 208 cases with a clinically indicated MRS (cases with uncertain or insufficient information on MRI) and a confirmed diagnosis. Both single voxel spectroscopy (SVS) and chemical shift imaging (CSI) were performed in 105 cases, only SVS or CSI in 54 and 49 cases, respectively. Diagnoses were grouped into categories: non-neoplastic disease, low-grade tumour, and high-grade tumour. The clinical value of MRS was considered very beneficial if it provided the correct category or location when MRI did not, beneficial if it ruled out suspected diseases or was more specific than MRI, inconsequential if it provided the same level of information, or misleading if it provided less or incorrect information.ResultsThere were 70 non-neoplastic lesions, 43 low-grade tumours, and 95 high-grade tumours. For MRI, the category was correct in 130 cases (62%), indeterminate in 39 cases (19%), and incorrect in 39 cases (19%). Supplemented with MRS, 134 cases (64%) were correct, 23 cases (11%) indeterminate, and 51 (25%) incorrect. Additional information from MRS was beneficial or very beneficial in 31 cases (15%) and misleading in 36 cases (17%).ConclusionIn most cases MRS did not add to the diagnostic value of MRI. In selected cases, MRS may be a valuable supplement to MRI.

Diagnostic Value of Magnetic Resonance Spectroscopy in Differentiation of Benign and Malignant Salivary Gland Tumors in Comparison with Pathology Results

Diagnostic Value of Magnetic Resonance Spectroscopy in Differentiation of Benign and Malignant Salivary Gland Tumors in Comparison with Pathology Results

Three-dimensional proton magnetic resonance spectroscopy and diffusion-weighted imaging in the differentiation of incidental prostate carcinoma from benign prostate hyperplasia.

The present study evaluated three-dimensional proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) features in differentiating incidental prostate carcinoma (IPCa) and benign prostate hyperplasia (BPH) in the central gland of the prostate. The clinical and imaging data of 9 patients with IPCa, 118 patients with BPH [including those with glandular hyperplasia (GH), stromal hyperplasia (SH) and mixed hyperplasia (MH)], were retrospectively analyzed. The mean (choline + creatine)/citrate (CC/C) value of 3D MRS, the apparent diffusion coefficient (ADC) value and the minimal ADC value of DWI were compared between carcinoma and non-carcinoma tissues. The mean CC/C values were 1.04±0.28, and 1.09±0.58 in IPCa and BPH, respectively (t=-0.205, P=0.838). No significant difference in CC/C values (χ2=2.595, P=0.458) could be detected between IPCa, GH, SH and MH groups. The ADC values of the central gland only differed between IPCa (1.48±0.18) ×10-3 and GH (1.60±0.16) ×10-3 mm2/sec (P=0.037). The minimal ADC values were similar between IPCa (1.15±0.10) ×10-3 and BPH (1.14±0.11) ×10-3 mm2/sec, no significant differences could be detected between IPCa and GH (P=0.930), IPCa and SH (P=0.192), and IPCa and MH (P=0.544). Although the ADC values of the central gland of the prostate differed between IPCa and GH, the findings of the present study therefore indicate that combining 3D MRS with DWI cannot potentially improve the detection of IPCa.

Magnetic resonance spectroscopy for assessment of brain injury in the rat model of sepsis.

The diagnostic value of magnetic resonance spectroscopy (MRS), T2-weighted imaging (T2WI) and serum markers of brain injury in a rat model of sepsis were investigated. Rats were randomly divided into the control group and 6, 12 and 24 h after lipopolysaccharide-injection groups. Brain morphology and metabolism were assessed with T2WI magnetic resonance imaging (MRI) and MRS. Serum and brain tissue samples were then collected to examine the concentrations of neuron-specific enolase (NSE) and S100-β protein. Brain T2WI showed no differences between the groups. N-acetylaspartate/choline (NAA/Cr) ratio measured by MRS showed different degrees of decrease in the sepsis groups, and serum NSE and S100-β concentrations were increased compared with the control group. Apoptosis rates were measured in the right hippocampal area, and there were statistically significant differences between the indicated groups and the control group (p<0.05). The correlation between apoptosis rate and NAA/Cr ratio was closer than that between apoptosis rate and NSE or S100-β (−0.925 vs. 0.434 vs. 0.517, respectively). In conclusion, MRS is a sensitive, non-invasive method to investigate complications of brain injury in septic rats, which may be utilized for the early diagnosis of brain injury caused by sepsis.

Biologic target volume delineation and the application of three-dimensional ultrasound image system in hypofractional radiotherapy for prostate cancer.

e16585 Background: To investigate the value of magnetic resonance spectroscopy (MRS) and positron emission computed tomography (PET-CT) in biological target volume(BTV) delineation of prostate cancer using hypofractional intensity modulated radiotherapy (HF-IMRT) with simultaneously integrated boost(SIB), and the preliminary efficacy and adverse effects of 3D ultrasound (3DUS) guided imaging in the treatment of prostate cancer using HF-IMRT and SIB. Methods: Between August 2015 and May 2016, 13 patients diagnosed with mid-high risk prostate cancer were retrospectively enrolled. All the eligible patients had underwent MRI MRS and PET-CT(18F-FDG or 11C-CHO) examination before radiotherapy. 5 patients had explicit BTV by examinations mentioned above. Radiation oncologists fused 3DUS and CT images and delineated tumor target volume referring to MRS and PET-CT. The target volumes were named as GTVMRI BTVMRS BTVPET-CT respectively and the volume were recorded. 3DUS guided HF-IMRT were applied during the radiotherapy. Results: The volumes of GTVMRI BTVMRS BTVPET-CT among the 5 patients were different. The mean volume of GTVMRI BTVMRS and BTVPET-CT were 3.52±1.69cm3, 6.64±2.27cm3 and 5.47±2.60cm3,respectively. Significant difference was only observed between GTVMRI and BTVMRS( P = 0.046). Compared to GTVMRI, the average increasing volumes of BTVMRS and BTVPET-CT were 89.07% and 55.52%. The prescription dose and biological effective dose(BED) of BTVMRS were 70.09-73.45Gy and 129.06-135.54Gy. The prescription dose and BED of the whole prostate were 66.02-69.40Gy and 113.32-124.82Gy. The dose of bladder and rectum were within safe control. The prostate specific antigen (PSA) were significantly decreased after radiotherapy. No local recurrence or distant metastasis was observed. Conclusions: MRS and PET-CT can be applied to delineation of the BTV of prostate cancer. With the help of multi-modal image guidance, dose painting for prostate cancer is feasible. 3DUS guided HF-IMRT with SIB is an alternative for radiation oncologists based on BTVMRS. With shortened time and less cost, this technique is safe and non-radioactive compared to CBCT guidance.

Magnetic resonance spectroscopy for quantitative analysis of fatty liver disease: a systematic review

Introduction: Magnetic resonance spectroscopy (MRS) is a sensitive and non-invasive imaging method that provides information about the metabolite variations due to pathological damages. In this study, we aimed to systematically review studies in which the MRS had been used for quantitative analysis of steatohepatitis.Methods: PubMed and Scopus were methodically searched in June 2015 with following search method (((magnetic resonance spectroscopy OR MR spectroscopy OR MRS)) AND (hepatic steatosis OR steatohepatitis OR fatty liver)) AND Quantitative) to find relevant documents in which the diagnostic value of MRS had been investigated in patients with hepatic steatosis. Obtainable information were extracted and used for further evaluation based on the main purpose of this study.Results: Of 88 articles found in the PubMed and 328 found in the Scopus, only 10 relevant documents were selected and used for data extraction according to inclusion/exclusion criteria. Of total 2963 participants enrolled in the selected studies, 1428 were male and 1535 were female. The results of this review showed that MRS is reliable technique for quantitative assessment of steatohepatitis.Conclusion: Findings showed that MRS as a non-invasive imaging method can quantitatively determine even small changes of metabolites due to pathological damages. As well, findings suggested that the results obtained by MR spectroscopy can be considered as reference standard in quantitative analysis. Based on the results of studied documents, MRS as a sensitive tool is helpful in the quantitative assessment of patients with fatty liver disease.

Diagnostic Value of magnetic resonance spectroscopy in Morphometrical Analysis of basal ganglia in patients with Idiopathic Generalized Epilepsy

ntroduction: Idiopathic generalized epilepsy (IGE) is a kind of epilepsy that has tonic-colonic characteristic and myocolonic tensions and its clinical symptom starts from the first 20 years of the life. Proton magnetic resonance spectroscopy (H1-MRS) technique applies as a noninvasive procedure to find metabolic disorders by evaluating brain metabolites. Purpose of this study was metabolical and morphological analysis of the thalamus using MRS imaging in patients with IGE. Materials and Methods: Applying H1-MRS (technique: PRESS-CSI), we evaluated thalamus images of 63 people (35 controls: 23 males, 12 females, ranging in age 19-46 years, average: 34.8±0.62 years) and 28 IGE patients (10 males, 18 females, ranging in age 20-49 years, average: 37.4±1.04 years). The data analyzed by SPSS (v.20). Results: Comparing the average NAA/Cr for the right thalamus, a significant reduction was seen between the control group and the IGE patients (p<0.0001). Likewise, for the left thalamus, the NAA/Cr was significantly decreased when we compared it for the control group and the IGE patients (p<0.001). Conclusion: H1-MRS could be a suitable diagnostic technique to evaluate epilepsy in IGE patients. The possible alteration of neuronal pathways in the thalamo-cortical circuit seems to play a critical role in epileptogenesis of IGE.

Prognostic value of magnetic resonance spectroscopy in patients with diffuse axonal injury: a systematic literature review

Introduction: Magnetic resonance spectroscopy (MRS) is an imaging technique that provides spectroscopic information about changes in biological markers. Studies suggest that MRS can be helpful in determining the prognosis of patients with diffuse axonal injury (DAI).Methods: The PubMed and Scopus databases were systematically searched in June 2015 using following search strategy: (“Magnetic resonance spectroscopy” OR MRS OR “MR spectroscopy”) AND [(“Diffuse axonal injury” OR DAI] AND Prognosis) to find relevant articles in which the prognostic value of MRS had been investigated in patients with traumatic DAI. All relevant information was extracted from the identified articles and used to synthesize the data for the purpose of this study.Result: In total, 19 articles were found in PubMed and 151 in Scopus. Of these, eight documents were selected for further data extraction following the application of the inclusion/exclusion criteria. The total number of patients who participated in the research studies described in the selected documents was 197. All of the selected documents showed that MRS can be used to quantitatively assess metabolite changes in patients with DAI.Discussion: The results of the studies indicate that MRS imaging as a sensitive method can quantitatively determine even small variations in metabolites. Any changes in the metabolite level of the brain after traumatic injury may be a useful predictor of a patient’s outcome; therefore, if the sensitivity of MRS is proven, this method can have prognostic value when employed with patients with DAI.Conclusion: Based on the results of this systematic review, MRS is a sensitive tool that is helpful in determining the prognosis of patients with DAI.

Diagnostic Value of Magnetic Resonance Spectroscopy in Radiation Encephalopathy Induced by Radiotherapy for Patients with Nasopharyngeal Carcinoma: A Meta-Analysis.

In this study, articles in English and Chinese were selected from available electronic databases prior to September 2014. The metabolic concentrations and patterns of N-acetylaspartic acid (NAA), Choline (Cho), Creatine (Cr), NAA/Cr, NAA/Cho, and Cho/Cr ratios in radiotherapy-induced radiation encephalopathy by proton magnetic resonance spectroscopy were extracted. A meta-analysis was performed to quantitatively synthesize findings of these studies. Weighted mean difference (WMD) and 95% confidence intervals (95%CIs) were calculated using random or fixed effective models. Heterogeneity between studies was assessed using the Cochrane Q test and I 2 statistics. The results indicated that a total of 4 researches involving 214 patients met inclusion criteria. Depending on methodologies of selected studies, control groups were referred to as healthy subjects. The combined analysis revealed that there was no significant difference in value of Cr between radiotherapy group and healthy control group (WMD = −1.483, 95% CI: −67.185–64.219, p = 0.965). However, there were significant difference in values of NAA (WMD = −18.227, 95%CI: −36.317–−0.137, p = 0.048), Cho (WMD = 38.003, 95%CI: 5.155–70.851, p = 0.023), NAA/Cr (WMD = −1.175, 95%CI: −1.563–−0.787, p = 0.000), NAA/Cho (WMD = −1.108, 95%CI: −2.003–0.213, p = 0.015), and Cho/Cr (WMD = −0.773, 95%CI: 0.239–1.307, p = 0.005). In conclusion, MRS can be regarded as an effective and feasible imaging test for radiotherapy-induced radiation encephalopathy in NPC patients.

P75 – 2430: Diagnostic value of magnetic resonance spectroscopy and cerebrospinal fluid lactate in identifying children with mitochondrial disorders

Objective To determine whether MRS (magnetic resonance spectroscopy) and CSF (cerebrospinal fluid) lactate value are diagnostic markers for identifying children with mitochondrial disease. Methods Eighty-eight children were included in whom MRS was performed, because of clinical suspicion of mitochondrial disease or neurometabolic disease in general (median age 3.94 years). Patients were divided into 4 groups “definite” (n=17, ≥1 major criteria, i.e. mitochondrial DNA mutation and/or enzymatic complex deficiency in muscle biopsy), “probable” (n=10, ≥2 minor criteria, i.e. ATP production speed Results MRS lactate values and MRS lactate/creatine ratios values were significantly higher in the definite group than in the control group (p=0.015 and p=0.001, respectively). The probable group had significantly higher values of MRS lactate/creatine ratio than the control group (p=0.030). No significant differences were found for CSF lactate values between all groups. Conclusion MRS lactate and MRS lactate/creatine ratio values seem to be diagnostic markers for identifying mitochondrial disease in children. Elevated CSF lactate was not a significant indicator for mitochondrial disease in children.

Multiparameter magnetic resonance imaging in the diagnosis of prostate cancer

Multiparametric magnetic-resonance imaging study was performed on 89 patients in magnetic-resonance imager 3 T. In 61 of them identified prostate cancer. Identified opportunities and the role of the complex magnetic resonance imaging in the clinical diagnostic algorithm for cancer of the pancreas, compared the diagnostic value of magnetic resonance spectroscopy, diffusion-weighted imaging and dynamic contrast-enhanced magnetic-resonance imaging. Dynamic contrast-enhanced magnetic-resonance imaging is one of the important methods for diagnosis of prostate cancer, specifying the location and staging of neoplastic process. Multiparametric magnetic-resonance imaging study of patients of prostate cancer has a great advantage compared with other clinical and diagnostic radiation methods in determining the localization of the true size of the tumor and its degree of aggressiveness.

TM-07 * 13C MRS DETECTS METABOLIC FLUX ADAPTATION IN IDH MUTANT GLIOMA CELLS

The isocitrate dehydrogenase (IDH)1 mutation is associated with accumulation of 2-hydroxyglutarate (2-HG), but the metabolic fluxes associated with 2-HG production and cellular reprogramming of mutant IDH1 cells are not fully understood. The objective of this study was to use 13C magnetic resonance spectroscopy (MRS) to probe the fate of 13C-labeled metabolites (at thermal polarization and hyperpolarized by dynamic nuclear polarization) and to monitor the glycolytic pathway, the TCA cycle, and glutamine metabolism in wild-type and mutant IDH1 glioma cells. To achieve this goal, U87 cells expressing mutant IDH1 and wild-type IDH1 were generated by transduction with a lentiviral vector coding for mutant or wild-type IDH1 respectively. MRS studies were performed using a cell perfusion (bioreactor) system. Live cells were exposed to hyperpolarized 1-13C or 2-13C-labeled pyruvic acid, 1-13C glucose or 3-13C glutamine and cell metabolism was probed using 13C MRS. We found that in mutant IDH1 cells pyruvate flux to lactate was increased relative to wild-type cells, and pyruvate flux to glutamate and 2-HG was decreased compared to pyruvate flux to glutamate in wild-type IDH1 cell. Glutamine flux to glutamate in wild-type cells, or to glutamate and 2-HG in mutant IDH1 cells was comparable. Accordingly, the total intracellular glutamate pool was reduced in mutant IDH1 cells. The drop in pyruvate flux to the TCA cycle was mediated by a significant drop in pyruvate dehydrogenase (PDH) activity, which was due to significantly increased inhibitory PDH phosphorylation. When considering 2-HG synthesis, our data also indicate that, consistent with previous work, the majority of 2-HG is produced from glutamine (82%). However in our cells a significant portion (18%) was also derived from glucose. Our findings thus point to metabolic reprogramming in IDH1 mutant cells beyond 2-HG production and highlight the value of MRS for characterizing the metabolic changes associated with the IDH1 mutation.

Magnetic resonance spectroscopic imaging of brain injury after nasopharyngeal cancer radiation in early delayed reaction.

This study aimed to investigate the value of magnetic resonance spectroscopy (MRS) imaging in assessing nasopharyngeal carcinoma radiotherapy during the early delayed reaction period. Eighty cases of nasopharyngeal cancer treated with radiotherapy within the same period underwent MRS imaging before or after radiotherapy. Of the 80 cases, 47 underwent MRS imaging on the 3rd, 4th, 6th, and 12th months after radiotherapy. The trends of the primary metabolite concentration at different time points were monitored and compared with the corresponding data after radiotherapy. Repeated measures analysis of variance was performed. At the end of radiotherapy, the N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and NAA/Cho ratios were reduced to the lowest levels after 3 months. However, increasing trends were observed from the 4th to the 12th month. On the 12th month, stable levels were reached with statistically significant differences (F = 316.02, 53.84, 286.68; P < 0.01). MRS reflected the radiation injury-repair process in the brain of a nasopharyngeal cancer patient during early delayed reaction. This non-invasive monitoring of changes in brain tissue metabolite concentrations provides valuable information for prognosis.

3 Tesla magnetic resonance spectroscopy: cerebral gliomas vs. metastatic brain tumors. Our experience and review of the literature

The aim of the present study is to report about the value of magnetic resonance spectroscopy (MRS) in differentiating brain metastases, primary high-grade gliomas (HGG) and low-grade gliomas (LGG). MRI (magnetic resonance imaging) and MRS were performed in 60 patients with histologically verified brain tumors: 32 patients with HGG (28 glioblastomas multiforme [GBM] and 4 anaplastic astrocytomas), 14 patients with LGG (9 astrocytomas and 5 oligodendrogliomas) and 14 patients with metastatic brain tumors. The Cho/Cr (choline-containing compounds/creatine–phosphocreatine complex), Cho/NAA (N-acetyl aspartate) and NAA/Cr ratios were assessed from spectral maps in the tumoral core and peritumoral edema. The differences in the metabolite ratios between LGG, HGG and metastases were analyzed statistically. Lipids/lactate contents were also analyzed. Significant differences were noted in the tumoral and peritumoral Cho/Cr, Cho/NAA and NAA/Cr ratios between LGG, HGG and metastases. Lipids and lactate content revealed to be useful for discriminating gliomas and metastases. The results of this study demonstrate that MRS can differentiate LGG, HGG and metastases, therefore diagnosis could be allowed even in those patients who cannot undergo biopsy.

The value of magnetic resonance spectroscopy and diffusion tensor imaging in characterization of gliomas growth patterns and treatment efficiency

The objective of the study was to assess the usefulness of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in detection of vital tumor cell infiltration presence in peritumoral brain areas and determination of biochemical changes in the brain parenchyma after received treatment. 73 patients with present, morphologically conformed brain gliomas and 77 gliomas patients in remission stage after combined therapy underwent magnetic resonance imaging (MRI) including MRS and DTI. Fractional anisotropy (FA) and metabolite ratios—choline/creatine (Cho/Cr), myoinositol/creatine (MI/Cr), lactate-lipid/creatine (LL/Cr), N-acetyl aspartate/creatine (NAA/Cr)—were measured in the tumor, perifocal edema zone, distant and contra-lateral normal appearing white matter. We observed gradual reduction of Cho/Cr, MI/Cr, LL/Cr mean ratios and step-by-step increase of NAA/Cr, FA mean values in the direction from the tumor to the distant and contra-lateral normal-appearing white matter. LL/Cr ratios within distal normal appearing white matter decreased in patients after radiotherapy/chemotherapy. Our study suggests that MRS and DTI in combination with structural MRI sequences enhance vital glial tumor cells areas and possible infiltration border. MRS and DTI quantitative measurements in the glioma peritumoral area reveal pathological changes, despite the normal signal intensity in structural MRI. We suggest that increased LL/Cr ratios and decreased FA values may have the superior implications in the detecting of glial tumors extent along the white matter tracts. NAA/Cr reduction and Cho/Cr increase may provide additional diagnostic value. LL/Cr ratio in distal normal signal intensity area could be used as radiation/chemotherapy effectiveness criteria, as this will reduce after the received treatment and in remission period.

Editorial Comment

No AccessJournal of UrologyAdult Urology1 Feb 2013Editorial Comment Alessandro Sciarra Alessandro SciarraAlessandro Sciarra More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.08.269AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, 189(2), p. 499 References 1 : Value of magnetic resonance spectroscopy and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin Cancer Res2010; 16: 1875. Google Scholar Prostate Unit, University Sapienza, Rome, Italy© 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 2February 2013Page: 499 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alessandro Sciarra More articles by this author Expand All Advertisement PDF downloadLoading ...