Single-voxel PRESS Research Articles

Amino acid metabolism in glioma: in vivo MR-spectroscopic detection of alanine as a potential biomarker of poor survival in glioma patients.

Reprogramming of amino acid metabolism is relevant for initiating and fueling tumor formation and growth. Therefore, there has been growing interest in anticancer therapies targeting amino acid metabolism. While developing personalized therapeutic approaches to glioma, in vivo proton magnetic resonance spectroscopy (MRS) is a valuable tool for non-invasive monitoring of tumor metabolism. Here, we evaluated MRS-detected brain amino acids and myo-inositol as potential diagnostic and prognostic biomarkers in glioma. We measured alanine, glycine, glutamate, glutamine, and myo-inositol in 38 patients with MRI-suspected glioma using short and long echo-time single-voxel PRESS MRS sequences. The detectability of alanine, glycine, and myo-inositol and the (glutamate + glutamine)/total creatine ratio were evaluated against the patients' IDH mutation status, CNS WHO grade, and overall survival. While the detection of alanine and non-detection of myo-inositol significantly correlated with IDH wildtype (p = 0.0008, p = 0.007, respectively) and WHO grade 4 (p = 0.01, p = 0.04, respectively), glycine detection was not significantly associated with either. The ratio of (glutamate + glutamine)/total creatine was significantly higher in WHO grade 4 than in 2 and 3. We found that the overall survival was significantly shorter in glioma patients with alanine detection (p = 0.00002). Focusing on amino acids in MRS can improve its diagnostic and prognostic value in glioma. Alanine, which is visible at long TE even in the presence of lipids, could be a relevant indicator for overall survival.

MR spectroscopy differences between lipomatosis of nerve and neuromuscular choristoma: a potential adjunctive diagnostic tool.

To describe differences between lipomatosis of nerve (LN) and neuromuscular choristoma (NMC) evaluated with MR spectroscopy (MRS). Eight patients were included in this prospective pilot study: three patients with LNs and five with NMCs. Single voxel PRESS MRS of the tumors were acquired with 3T MRI. MRS data were processed with LCModel version 6.3-1J using the internal "lipid-8" basis set. From individual lipid peak and water content measurements, total fatty acid molecules (TFAM), unsaturated fatty acid molecules (UFAM), and glycerol molecules (GM) were computed and analyzed, as well as ratios of UFAM/TFAM, TFAM/GM, and a fatty-acid chain-length index (CLI). The LN group included two men and one woman (average age 58.3years); the NMC group included two men and three women (average age 20.4years). Lipid composition analysis showed that LN had considerably more fat than NMC: TFAM: LN = 15.29 vs NMC = 7.14; UFAM: LN = 4.48 vs NMC = 2.63; GM: LN = 5.20 vs NMC = 1.02. Both tumors had a similar fraction of unsaturated fatty acids: UFAM/TFAM: LN = 0.29 vs NMC = 0.37. LN had the usual number of FA molecules/glycerol molecule, while NMC had considerably more: TFAM/GM: LN = 2.94 vs NMC = 6.98. Finally, average FA chains were longer in NMC: CLI: LN = 17.39 vs NMC = 22.55. Our analysis suggests measurable differences in the amount and composition of lipid in LN and NMC. While a larger, statistically powered study is needed, these initial findings may be helpful to properly diagnose ambiguous cases and thereby avoid surgical intervention such as biopsy.

Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy

Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy

In vivo 2-hydroxyglutarate-proton magnetic resonance spectroscopy (3 T, PRESS technique) in treatment-naïve suspect lower-grade gliomas: feasibility and accuracy in a clinical setting.

To investigate the clinical feasibility of MRS for in vivo detection and quantification of 2HG on consecutive treatment-naïve suspect LGG patients and to compare MRS accuracy with tissue IDH1/2 analysis. MRS spectra at 3 T were acquired with 1H-MRS single-voxel PRESS 2HG-tailored sequences with TE 30 (group 1) or TE 97 (groups 2A and B). Voxel sizes were 1.5 × 1.5 × 1.5 cm3 for group 1 (n = 13) and group 2A (n = 14) and 2 × 2 × 2 cm3 for group 2B (n = 32). Multiple metabolites' concentrations were analyzed with LCModel. Tumors were assessed for IDH status and main molecular markers. 2HG levels in urine/blood were measured by liquid chromatography-mass spectrometry. The larger voxel TE 97 sequence resulted in highest specificity (100%), sensitivity (79%), and accuracy (87%). Urine and blood 2HG did not result predictive. Our data confirm that 2 × 2 × 2-cm3 voxel TE 97 MRS shows high accuracy for 2HG detection, with good sensitivity and 100% specificity in distinguishing IDH mutant gliomas. Main limits of the technique are small tumor volume and low cellularity. Integrating 2HG-MRS with other metabolites may help non-invasive diagnosis of glioma, prognostic assessment, and treatment planning in clinical setting.

Proton MR spectroscopy of human pancreas allografts

ObjectiveTo estimate pancreas graft relaxation times and concentrations of total fat, and the intracellular lipids of non-adipose pancreatic cells (NAPC) using proton (1H) magnetic resonance spectroscopy (MRS) during cold preservation.Materials and methodsGrafts from 11 human donors were investigated. Each pancreas was perfused in situ with histidine-tryptophan-ketoglutarate (HTK) or with University of Wisconsin solution and placed into a transport container. Temperature of the grafts was maintained at 4 ± 2 °C during transport to our hospital and MR scanning. A 1.5 T clinical scanner was used for the measurements. Single-voxel PRESS spectra were acquired using transmit–receiver head coil.ResultsRelaxation times were measured for lipid (–CH2–)n (T1, 287 ± 60 ms; T2, 27 ± 4 ms), and tissue water (T1, 670 ± 69 ms; T2, 77 ± 17 ms). Average total fat, and intracellular lipids of NAPC concentrations were 79.2 ± 100.8 (range 2.4–304.4), and 2.9 ± 1.2 mmol/kg ww, respectively.ConclusionWe have shown that 1H-MRS is a useful tool for the estimation of pancreas graft lipid concentrations. Total pancreatic fat and especially content of intracellular lipids of NAPC are valuable measures for inspection of graft quality prior to transplantation or islet of Langerhans isolation.

Intra- and inter-site reproducibility of human brain single-voxel proton MRS at 3T.

Clinical trials that involve participants from multiple sites necessitate standardized and reliable quantitative MRI outcomes to detect significant group differences over time. Metabolite concentrations measured by proton MRS (1 H-MRS) provide valuable information about in vivo metabolism of the central nervous system, but can vary based on the acquisition and quantitation methods used by different MR sites. Therefore, we investigated the intra- and inter-site reproducibility of metabolite concentrations measured by 1 H-MRS on MRI scanners from a single manufacturer across six sites. Five healthy controls were scanned twice within 24h at six participating 3T MR sites with large single-voxel PRESS (TE/TR/NSA=36ms/4000ms/56) and anatomical images for voxel positioning and correction of partial volume relaxation. Absolute metabolite concentrations were calculated relative to the T1 and T2 relaxation corrected signal from water. Intra- and inter-site reproducibility was assessed using Bland-Altman plots and intra- and inter-site coefficient of variation (CoV) as well as intra- and inter-site intra-class correlation coefficient. The median intra-site CoVs for the five major metabolite concentrations ([NAA], [tCr], [Glu], [tCho] and [Ins]) were between 2.5 and 5.3%. Inter-site CoVs were also low, with the median CoVs for all metabolites between 3.7 and 6.4%. Metabolite concentrations were robust to small inconsistencies in voxel placement and site was not the driving factor in the variance of the measurement of any metabolite concentration. Between-subject differences accounted for the majority of the concentration variability for creatine, choline and myo-inositol (42-65% of the variance). A large single-voxel 1 H-MRS acquisition from a single manufacturer's MRI scanner is highly reproducible and reliable for multi-site clinical trials.

18. Quality assurance in proton magnetic resonance spectroscopy: Final results of an intercomparison of 18 clinical scanner systems

Purpose Quality assurance in advanced and quantitative magnetic resonance techniques is strongly recommended [1] , [2] , [3] . The aim of this study was to propose and validate across various clinical scanner systems a straightforward quality assurance procedure for proton Magnetic Resonance Spectroscopy (MRS). Methods Eighteen clinical 1.5 T and 3 T scanners for MRS were enrolled in the study. The protocol included 3 sets of single voxel PRESS acquisitions without water signal suppression, repeated 4/5 times within approximately 2 months and performed using a standard water phantom supplied to all centres. Water peak linewidth (LW), water peak area (AP) and phantom T2 were estimated. Results LW values ranged from 0.4 Hz to 1.6 Hz, with 3 T and 1.5 T scanner systems showing similar performances. Coefficient of variation (CV) of LW values for repeated measurements were lower than 35% (except for only 3 scanners). AP showed significant (p 0.99 and 0.95 for 1.5 T and 3 T scanner systems, respectively). CV of AP for different spatial positions was less than 25%, and no relevant difference was observed between 3 T and 1.5 T scanners. Mean phantom T2 value and CV for repeated measurements were 1147 ms and 4%, respectively, for 1.5 T scanners, and 1010 ms and 9%, respectively, for 3 T scanners. Conclusions We proposed a straightforward multiparametric and not time consuming quality control protocol for MRS, which can be included in routine quality assurance procedures. The protocol has been validated and proven to be feasible in a multicentre intercomparison study of 18 clinical 1.5 T and 3 T scanner systems.

Fitting algorithms and baseline correction influence the results of non-invasive in vivo quantitation of 2-hydroxyglutarate with 1 H-MRS.

1 H-MRS enables non-invasive detection of 2-hydroxyglutarate (2-HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes. Reliable 2-HG quantitation requires reproducible post-processing, deployment of fitting algorithms and quantitation methods. We prospectively enrolled 38 patients with suspected or recently diagnosed gliomas (IDH mutated n=26). The MRI protocol included a 1 H single voxel PRESS sequence with volumes of usually 8mL or more (20×20×20mm3 ) at TE =97ms and 180° pulse spacing. Our aim was to evaluate the reliability of 2-HG quantitation comparing two frequently used software tools and their respective options of baseline correction (jMRUI with the time domain methods AQSES and QUEST, and LCModel, which analyzes the frequency domain data). For AQSES, degrees of freedom for baseline correction constrains were varied. For LCModel, baseline correction was obtained with and without correction of the unknown background term (predefined macromolecules, lipids). Tissue concentrations were calculated based on the phantom replacement method. Quantitation of 2-HG levels showed similar mean 2-HG tissue concentrations for IDH mutated tumors (2.65mM, range 3.06-2.20) for all methods. Bland-Altman plots (difference plots) did not reveal a systematic bias (fixed bias) for any of the algorithms tested, and we were able to show a significant correlation regarding 2-HG concentration at the same echo time with few statistical outliers (parametric correlation). However, evaluation of outliers suggested that in vivo quantitation of 2-HG is affected not only by the fitting domain (time or frequency), but also by the baseline correction, which is a major contributing factor to the result of 2-HG fitting. Clinical application of 2-HG quantitation as a prognostic or predictive biomarker, particularly in multicenter trials, requires standardized use of fitting methods and baseline correction procedures.

Simultaneous two-channel MR imaging, single voxel spectroscopy and chemical shift imaging by reconfiguration of a 'standard' Biospec spectrometer

Simultaneous two channel array proton imaging, single voxel PRESS and CSI acquisitions were demonstrated after reconfiguration and minimum hardware modification of a standard 4.7T BioSpec® spectrometer. Validation of the reconfiguration was assessed in phantoms and in a mouse brain. The modified configuration used the X channel exhibiting similar SNR performances compared to the 1H channel. The SNR gain for the two channel array coil was up to 1.3 compared to the SNR obtained with a reference surface coil. Compared to regular two element coil with quadrature combination, the SNR was improved with an additional gain of 1.3. These modifications could also be applied for any X nucleus

Reliability Of Glutamate And Gaba Quantification Using Magnetic Resonance Spectroscopy

Proton magnetic resonance (MR) spectroscopy is a non-invasive technique used to determine relative concentrations of target metabolites in the brain. PURPOSE: The aim of this study was to determine the reliability of glutamate and GABA measures using a single-voxel proton MR spectroscopy protocol in healthy men and women. METHODS: Seven (4 female) healthy college age participants were tested at two time points separated by two weeks. The study was performed at 3T using a single voxel PRESS sequence for glutamate (TR/TE=1500/30ms) and an adapted MEGA-PRESS sequence for GABA (TR/TE=2000/68ms). Quantitation of glutamate and GABA was performed at two regions of interest, the primary motor cortex and the dorsolateral prefrontal cortex (DLPFC). Reliability across days was assessed with the intraclass correlation coefficient (ICC 2,1). RESULTS: There was no significant difference across time or region for glutamate (p=0.50 and p=0.06 respectively) or GABA (p=0.57 and p=0.91 respectively). There were no significant time-by-region interactions for glutamate (p=0.19) or GABA (p=0.26). Reliability across days was very strong for both glutamate (R=0.96) and GABA (R=0.88). CONCLUSIONS: These results support the use of MR spectroscopy measurements to reliably quantify concentrations of glutamate and GABA within the motor cortex and DLPFC.

Role of MR Spectroscopy (H1-MRS) of the Testis in Men with Semen Analysis Altered

Purpose: Proton magnetic resonance spectroscopy (1 H-MRS) has been proposed as a tool to assess male infertility providing metabolic signatures related to the spermatogenesis in the testis. This study sought to identify the role of 1 H-MRS in the diagnosis of infertility in patients with semen analysis altered. Materials and Methods: 14 patients (27 testicles) with fertility problems and with an altered semen analysis (5 oligospermia, 3 asthenospermia, 6 oligoasthenospermia) and 9 controls (18 testicles) with normal spermatogenesis assessed (men with prior paternity and normal semen analysis) and normal testicles at magnetic resonance (MR) and ultrasonography (US) with colour Doppler (CD) examination were included. All patients underwent testis US and CD investigation, conventional MR examination at 1.5T including T1 and T2 weighted images in three orthogonal planes and proton magnetic resonance spectroscopy (1 H-MRS) with single-voxel PRESS (TR 2000 ms / TE 31 ms). Major metabolites peaks (choline, creatine, lipids, lactate) were calculated and compared between the patients and controls. Results: Mean choline peak in the semen analysis altered group was statistically significantly lower than the normal group (0.69 vs 1.34, 95% CI: 0.52 - 0.85; p < 0.001). 18 testicles within semen analysis altered group (66,7%) had both MR and US examination negative but mean choline peak lower then controls (1.09 vs 1.34, p < 0.001). 7 testicles of those presented also varicocele at CD investigation. Conclusion: 1 H-MRS revealed a significant shift towards lower choline peak in patients with semen analysis altered compared to controls with normal spermatogenesis. Moreover 1 HMRS provided to find out spermatogenesis disorder in patients with normal testis at MR and US examination.

A MRS study of metabolic alterations in the frontal white matter of major depressive disorder patients with the treatment of SSRIs.

BackgroundProton magnetic resonance spectroscopy provides a non-invasive technology to study brain metabolite levels in vivo, which can be used to measure biochemical compounds or metabolite concentrations in circumscribed brain regions. Previous research has highlighted the role of glial cells in brain white matter. It has been assumed that antidepressant treatment with SSRIs not only affects neurons, but also activates glial cells. This study focused on the observation of any potential changes in the metabolite levels of the ventral prefrontal white matter in major depressive disorder (MDD) patients who have received antidepressant treatment.Methods17 female patients diagnosed as MDD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria with the scores of 18 and above on the 24-item Hamilton Depression Rating Scale (HDRS) were recruited. MRS studies were performed on a 3.0 T MR system, single voxel PRESS spectroscopy with chemical-shift selective saturation water suppression. The volume of interest was localized at the bilateral ventral prefrontal white matter regions (voxel size: 2 × 2 × 2 mm3). The spectral data analysis was performed by using the instrument manufacturer supplied software.ResultsThe bilateral ventral prefrontal white matter of MDD patients showed significantly lower Cho/Cr (p < 0.05) before receiving treatment. The HDRS, as the indicator of treatment response, showed a significant decrease in patients who had gone through 12 weeks treatment (p < 0.01). The bilateral Cho/Cr values of post-treatment patients were increased significantly compared to that of pre-treatment (p < 0.05).ConclusionThe alteration of ventral prefrontal white matter metabolite levels are likely involved in MDD pathophysiology and imply a crucial role of white matter in MDD.

IM-03 * SERIAL METABOLISM OF DIFFUSE INTRINSIC PONTINE GLIOMA TREATED WITH PEPTIDE BASED VACCINE THERAPY

PURPOSE: Diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis in pediatric neurooncology, with no improvement in outcomes for decades. The goal of this study was to examine myo-inositol (mI)/choline and other metabolites (measured by serial MRS) as predictors of overall survival in (1) a DIPG cohort treated with standard radiochemotherapy and (2) a DIPG cohort treated with radio-therapy followed by peptide-based vaccine therapy. METHODS: 50 MRS studies were performed in 11 patients with DIPG enrolled in a phase 1 clinical trial of peptide based vaccine therapy. 56 MRS studies were performed in 14 patients receiving only radio-chemotherapy. Metabolic profiles were binned into comparable time points after radiation therapy. All spectra were acquired using a single-voxel PRESS sequence (TE = 35ms, TR = 1.5s, 128 averages). Spectra were processed with fully automated LCModel (version 6.3-1c) software. Concentrations of the main metabolites (NAA, Cr, Cho, mI) and metabolite ratios relative to Cho were evaluated. Generalized estimating equations were used to evaluate longitudinal associations between metabolites and/or therapy group and overall survival. RESULTS: The 25 patients survived 6-25 months after diagnosis. Study baseline (post radiotherapy/pre-vaccine, 78-116 days post-diagnosis) mI/choline measures did not predict overall survival, but at subsequent time points higher mI/choline was associated with longer overall survival (p <0.05). A statistical interaction in the model with scans 159-250 days post-diagnosis (p < 0.001) suggested that the association with survival was much greater in the vaccine group (47 days' greater expected survival for each unit higher mI/choline ratio, after ∼2 vaccine doses) than for the non-vaccine group (13 days). DISCUSSION: mI/choline ratio may be a predictive marker for early response to peptide-based vaccine therapy of pediatric DIPG. A larger sample study is needed to further validate that MRS could be used to optimize/adjust peptide based vaccine therapy of DIPG patients.

P16.01 * MAGNETIC RESONANCE SPECTROSCOPY AT 3 T FOR IN VIVO DETECTION OF 2-HYDROXYGLUTARATE IN LOWER GRADE GLIOMAS

Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are detected in up to 75% grade II-III (lower grade) gliomas. IDH1/2 mutations result in the neomorphic synthesis of the oncometabolite 2-hydroxyglutarate (2HG). The detection of 2HG could help for a non-invasive diagnosis, the clinical follow-up, and possibly the screening of patients for targeted, anti IDH1-mutated therapy. 2HG screening is a useful marker to detect the presence of IDH1/2 mutations. A magnetic resonance spectroscopy (MRS) study of 2HG on phantoms has been already performed by our group. AIM: To investigate methods for in vivo detection by MRS of 2HG on glioma patients. METHODS: Spectra from 12 patients with lower grade gliomas were acquired with a 1H-MRS single-voxel PRESS sequence with TE = 30 ms. The subsequent patients were acquired using a tailored PRESS sequence with TE = 97 ms (TE1 = 32 ms, TE2 = 65 ms). Both groups were studied using a clinical MR 3T scanner (Philips Achieva) with a 32 channel head coil. The MR protocol included two MRS acquisition for each subject: a voxel within the tumor and one contralateral. The voxel size was 2x1.5x1.5 cm3 for all the acquisitions for both sequences. Metabolite concentrations were estimated by linear combination analysis and a simulated basis set using LCModel software (version 6.3). After histopathological diagnosis IDH1/2 analysis were performed by immunochemistry and/or PCR. Results from 1H-MRS and immunochemistry or PCR were compared. RESULTS: Our data showed that spectra at TE = 30 ms are not specific: 4 patient carrying wild type gliomas and 8 carrying IDH mutated gliomas resulted in 2 false positive and 5 false negative respectively. The sequence at 97 ms resulted more specific: 4 patient carrying wild type glioma and 2 carrying IDH mutated glioma were correctly identified (0 false positive and 0 false negative, respectively). Moreover the sequence with short TE detected 2HG in the contralateral region in 5 cases, while the sequence with longer TE did not dectect 2HG in contralateral region. DISCUSSION: Our preliminary data suggest that MRS TE =97 ms is specific for 2HG detection. A larger number of samples will be required to confirm the accuracy of the technique.We will also pair the ex vivo detection by MRS with 2HG quantification by HPLC on tumoral samples and other biological fluids.

8.8 Neonatal Encephalopathy in the Cooling Therapy era – Preliminary Cerebral Magnetic Resonance results from the Marble Consortium

BackgroundAlthough cerebral metabolic changes during neonatal encephalopathy (NE) have been well characterised using magnetic resonance spectroscopy (MRS) in single-centre studies, the widespread effect of therapeutic hypothermia is less clear.ObjectiveTo describe...

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

BackgroundDelayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology. Case-control studies utilizing proton-1 magnetic resonance spectroscopy (1H-MRS) have found increased total choline levels in several brain regions in MDD. However, there are no published 1H-MRS reports directly comparing adolescents with MDD and BD. We hypothesized that ACC choline levels would be increased in adolescents with unipolar versus bipolar depression. MethodsWe studied depressed adolescents with MDD (n=28; mean age 17.0±2.1 years) and BD (n=9; 17.3±3.1 years). A Siemens Verio 3-Tesla clinical MRI system was used to acquire scans, using a single-voxel PRESS sequence. The voxel (18.75cm3) was positioned on the ACC in the midsagittal plane. To remove potential gender effects, only female adolescent participants were included. Data were analyzed using the ANOVA and post-hoc Tukey tests. ResultsA significantly increased ACC choline/creatine ratio was observed in participants with MDD (mean=0.253±0.021) compared to BD (mean=0.219±0.020) (p=0.0002). There were no significant differences in the other 1H-MRS metabolites. LimitationsCross sectional design, single gender sample, limited sample size. ConclusionsThe present findings suggest that ACC total choline may have the potential to serve as a diagnostic biomarker in adolescent mood disorders.

Proton magnetic resonance spectroscopy of prefrontal white matter in psychotropic naïve children and adolescents with obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) has a typical onset during childhood or adolescence. Although recent in-vivo proton magnetic resonance spectroscopy (1H-MRS) studies report gray matter metabolite abnormalities in children and adolescents with OCD, there are no existing 1H-MRS studies that measure white matter (WM) metabolite levels in this population. In the present study, we measured metabolite levels in the left and right prefrontal WM (LPFWM and RPFWM, respectively) of psychotropic-naïve children and adolescents with OCD (LPFWM: N=15, mean age 13.3±2.4 years; right RPFWM: N=14, mean age 13.0±2.3 years) and healthy controls (LPFWM: N=17, mean age 11.8±2.7 years; RPFWM: N=18, mean age 12.2±2.8 years). Spectra were acquired using a 3T single voxel PRESS sequence (1.5×2.0×2.0cm3). When age and sex effects were controlled, OCD patients had higher levels of RPFWM choline and N-acetyl-aspartate (NAA). In addition, RPFWM levels of NAA, creatine and myo-inositol were positively and significantly correlated with severity of OCD symptoms. In summary, this is the first published study of WM metabolite levels in children and adolescents with OCD. Our preliminary findings lend further support to the previous findings of WM abnormalities in OCD.

In-vivo metabolic characterization of healthy prostate and orthotopic prostate cancer in rats using proton magnetic resonance spectroscopy at 4.7 T

To assist the development of new anti-cancer drugs, it is important to identify biomarkers of treatment efficacy in the preclinical phases of drug development. In order to improve the predictivity of preclinical experiments, more realistic animal models are needed, for example, tumors xenografted directly on the prostate gland of rodents. To characterize the in-vivo metabolism of healthy rat prostate and of an orthotopic human prostate cancer model using proton magnetic resonance spectroscopy (MRS). The highly metastatic and hormone-independent PC3-MM2 human prostate cancer model was implanted into the ventral prostate lobe of three Nude rats. Healthy Nude (n = 6) and Sprague-Dawley (n = 6) rats were also studied for interspecies comparison of normal prostate metabolism. Magnetic resonance imaging and short echo-time (TE 11.2 ms) single voxel PRESS spectroscopy were performed on dorsal (DP) and ventral (VP) prostate as well as tumor at 4.7 T. The metabolic content and volume of dorsal and ventral lobes were characterized as a function of species and age. Slightly lower total creatine (tCr)/water (11.3 ± 2.6 vs. 15.3 ± 3.0, NS), but significantly higher Inositol (Ins)/water (18.9 ± 1.9 vs. 6.6 ± 3.3, P < 0.003) and total choline (tCho)/water (15.0 ± 2.1 vs. 5.6 ± 1.1, P < 0.00007) were observed within healthy DP lobes with respect to VP lobes. No significant variation in metabolic content was seen in healthy DP and VP lobes of Nude rats as a function of age, and no species dependence was observed in their metabolic content. For the orthotopic PC3-MM2 tumor, implanted in VP, the tCr/water ratio was significantly lower (3.1 ± 0.9) than neighboring DP (12.8 ± 1.8, P < 0.00003) and healthy VP (15.3 ± 3.0, P < 0.00006). For Ins, the metabolite ratio in PC3-MM2 was close to that of healthy VP (4.3 ± 2.8 vs. 6.6 ± 3.3, p = NS), but much lower than in neighboring DP (19.1 ± 1.3, P < 0.00005). A similar trend was also observed for tCho, where metabolite ratios in PC3-MM2, healthy VP and neighboring DP were 3.5 ± 0.9, 5.6 ± 1.1, and 15.9 ± 0.8, respectively. The in-vivo MRS study of healthy prostate and orthotopic prostate cancer is feasible in rats. Such baseline data could be important when following the modifications in metabolism, including during anti-cancer drug development protocols or following radiotherapy.

Magnetic Resonance Spectroscopy of the Normal Cerebellum: What Degree of Variability Can Be Expected?

The objectives of this paper are (a) to establish the reliability of relative metabolite concentrations determined with (1)H-MR spectroscopy of the cerebellum using a method appropriate to the constraints of clinical radiology and (b) to record normal values for metabolites within the cerebellum and to look for differences in metabolite concentrations between the cerebellar hemispheric white matter and the superior vermis. 3-T (1)H-MR spectra were obtained from voxels positioned in the right cerebellar hemispheric white matter and the superior vermis in 55 healthy adults (mean age 41years, range 20 to 77) using a single voxel PRESS sequence (TR/TE = 2,000/144ms). One volunteer (male, age 34years) was examined in six separate sessions over a period of 3weeks. Reliability of intra- and inter-subject metabolite fitted area ratios was determined by evaluating coefficients of variance (%). Inter- and intra-subject coefficients of variance (%) in metabolite ratios were consistently lower in the vermis (4 to 11.6) compared to those of the hemisphere (7.2 to 14.3). Cho/Cr was significantly higher in the vermis (0.83 ± 0.10) compared to the hemisphere (0.76 ± 0.11) and NAA/Cho was significantly lower in the vermis (1.19 ± 0.12) compared to the hemisphere (1.35 ± 0.16). Low inter- and intra-subject variability can be achieved when using a (1)H-MR spectroscopy technique that is appropriate to the time constraints of clinical radiology. The regional variations of Cho/Cr and NAA/Cho within the hemisphere and vermis should be considered when performing studies of diseases, which may preferentially target a particular cerebellar location.

Metabolic differences in the contralateral hippocampus of concordant and discordant mesial temporal sclerosis (MTS) patients: evaluation with proton magnetic resonance spectroscopy (1H-MRS)

PURPOSE: Patients with mesial temporal sclerosis (MTS) are clinically classified as concordant or discordant according to the extent of epileptogenic activity. The aim of this study is to determine whether the metabolic changes in the hippocampus are different in the two groups. MATERIALS AND METHODS: 33 patients diagnosed with MTS, 23 concordant (33±9 years old) and 10 discordant (33±10 years old) and 28 controls (33±10 years old) were evaluated. We obtained magnetic resonance spectroscopy of both hippocampi (ipsilateral and contralateral) on a 3T scanner with single voxel PRESS sequence with TE/TR=135/1500ms. The main metabolites were quantified with LC Model. For comparison between groups statistical tests were performed with a significance level of 0.05. RESULTS: In all patients a reduction of NAAipsi and Cr ipsi was observed, when compared to the contralateral side, but this difference was only significant for the group of concordant patients. In comparison with controls a significant reduction of Cr ipsi and NAAipsi was observed for both groups and for Naa/Cr ipsi in the group of concordant patients while NAA/Cr contra was reduced only in the group of discordant patients. CONCLUSION: Our findings suggest a stronger decline of NAA/Cr ipsi in the group of concordant patients and of NAA/Cr contra in discordant patients, suggesting a slightly different metabolic pattern for both groups. However, we need to increase the sample size to confirm these findings.