Multivoxel Spectroscopy Research Articles

PO22ELEVATED GLUTAMATE, USING MAGNETIC RESONANCE SPECTROSCOPY, IS ASSOCIATED WITH SEIZURES IN PATIENTS WITH GLIOBLASTOMAS

INTRODUCTION: Seizures are common in patients with a Glioblastoma. Although the epileptogenic mechanism remains unclear, it is suggested to be dependent upon peritumoural changes. Histological analysis of human intratumoural and peritumoural glioma tissue demonstrated that glutamate concentrations in tissue from both sites were increased in patients with seizures when compared to those without. It would be advantageous to have a non-invasive method for predicting which patients are most likely to be affected by seizures. METHOD: 80 patients with a Glioblastoma were imaged pre-operatively at 3T with sequences including anatomical and multivoxel spectroscopy. Regions of interest (ROIs) were selected in a circumferential consecutive pattern from the border of the T1-weighted enhancing region to normal appearing brain. Glutamate parameters (Glu + Gln/Cr) were calculated per voxel and expressed as a ratio to normal brain. Clinical variables were analysed in relation to tumour progression and survival. RESULTS: The mean Glu + Gln/Cr concentration remained more than 1.5 times higher compared to normal brain at a 3 cm radial distance from the T1-weighted enhancing margin in the seizure group. At this distance, the mean Glu + Gln/Cr concentration ratio had returned to 1 in the non-seizure group (Seizures 1.56 ± 0.1 vs. non-seizures 0.92 ± 0.06, p < 0.001). The presence of seizures was associated with a shorter time to progression on multivariate analysis (HR = 7.55; p = 0.01). CONCLUSION: We demonstrate that the presence of seizures is associated with elevated tumour and peritumoural glutamate concentrations and a shortened time to tumour progression in Glioblastomas. Glutamate may play a role in the pathogenesis of seizures and represent a potential biomarker for tumour progression.

OP51METABOLIC ACTIVITY OF THE INVASIVE MICROENVIRONMENT OF GLIOBLASTOMAS DETERMINES TIME PROGRESSION: A MULITOMODAL MRI STUDY

INTRODUCTION: Virtually all glioblastoma (GBM) patients will die from progressive disease adjacent to the tumour resection cavity. Our previous work has shown that we can identify the invasive margin with diffusion tensor MR (DTI) and that we can use multimodal MRI to study the microenvironment of this region. This study aims to understand how the microenvironment influences progression and response to therapy. METHOD: 50 patients with GBM were recruited prospectively and imaged pre-operatively at 3 Tesla. Imaging involved conventional imaging, DTI, dynamic susceptibility perfusion imaging (to provide rCBV) and multivoxel short echo spectroscopy. Regions of interest from the invasive margin were identified on the DTI and perfusion and metabolite analysis performed. All patients subsequently underwent a 5-ALA guided resection followed by chemoradiotherapy. The progression free survival interval (PFS) was noted for all patients. ROC curves were produced to assess different parameters ability to predict PFS >1 year. Survival was assessed with Kaplan-Meier survival curves and a multivariate Cox regression model used to assess impact of imaging parameters with clinical parameters. RESULTS: 30% of patients had PFS > 1 year. The best predictor of this was the NAA/Cho ratio (AUC 0.73) - a marker of cellular proliferation. A cut-off of 0.6 differentiated between PFS > 1 year and PFS 0.6 PFS = 497 days (P = 0.01). CONCLUSION: Our data suggests that more metabolically active tumour margin is associated with better outcome. One hypothesis is that areas with low Cho/NAA have less proliferative activity and are less likely to respond to cytotoxic therapy.

Abstract 1498: Feasibility of 2-hydroxyglutarate 1H-MR spectroscopy for routine clinical glioma imaging

Abstract The metabolic genes isocitrate dehydrogenase 1 (IDH1) or IDH2 are mutated in 70-80% of WHO grade II and III glioma. The mutant IDH enzyme gains a new function producing D-2-hydroxyglutarate (2-HG). 2-HG is a small molecule that accumulates in IDH mutant gliomas as high as 5 to 35 mM and is considered the principal effector of IDH mutation in cancers. Proton magnetic resonance spectroscopy (MRS) is an approved method in brain tumors to identify and quantify metabolites within brain lesions by using signals emitted by proton nuclei (1H). The 2-HG molecule has five nonexchangeable scalar-coupled protons that give rise to multiplet resonances in MR spectra. First attempts to measure 2-HG in IDH mutant glioma have been promising but were limited to scanners dedicated to research MRIs, long scanning times, and large tumors. The goal of this study was to explore the feasibility of performing 2HG-MRS as part of standard glioma imaging. We developed single and multivoxel spectroscopy techniques using unique alterations of pulse sequence parameters and software routines on clinical 3Tesla MRI scanners. We added those sequences to our clinical MRI protocol. All metabolites, including 2-HG, were estimated by linear combination of model (LC Model). 107 consecutive glioma patients were evaluated, including 48 (45%) WHO grade II glioma, 40 (37%) grade III glioma and 19(18%) grade IV glioma. 80/107 (75%) patients had IDH mutant gliomas. At the time of MRS, 42(39%) patients were on active treatment with radiation or chemotherapy, 19(18%) had received such treatment in the past, and 46(43%) had never received radiation or chemotherapy. MRI tumor volume was &amp;lt;8cc in 38 (36%) patients and ≥8cc in 69 (64%) patients. 2-HG MRS was negative in all patients with IDH-wild type tumors and in all IDH-mutant gliomas with a tumor volume &amp;lt;8cc. In the group of IDH-mutant tumors with a tumor volume ≥8cc, 2-HG MRS was positive in approximately 35% of the untreated patients and in approximately 30% of the treated patients. For a subset of patients we measured dynamic changes in 2-HG over time (multiple times MRS). A drop in 2HG-MRS signal was associated with treatment response. 2-HG MRS in the clinical setting is feasible. Specificity was 100%. Sensitivity appears, at least in part, dependent on tumor volume with higher sensitivity in larger tumors. In patients with a detectable 2-HG peak, 2HG-MRS represents a promising non-invasive biomarker to monitor tumor growth and treatment response. Final results for the entire cohort will be presented at the meeting. Citation Format: Macarena I. de la Fuente, Robert Young, Jennifer Rubel, Jamie Tisnado, Samuel Briggs, Andrei I. Holodny, Joseph Deasy, Lisa M. DeAngelis, Justin Cross, Ingo K. Mellinghoff, Sunitha Thakur. Feasibility of 2-hydroxyglutarate 1H-MR spectroscopy for routine clinical glioma imaging. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1498. doi:10.1158/1538-7445.AM2015-1498

Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas.

PurposeTo use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)‐defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions.Materials and MethodsIn all, 50 GBM patients were imaged preoperatively at 3T with anatomic sequences, DTI, dynamic susceptibility perfusion MR (DSCI), and multivoxel spectroscopy. The DTI and DSCI data were coregistered to the spectroscopy data and regions of interest (ROIs) were made in the invasive (determined by DTI), noninvasive regions, and normal brain. Values of relative cerebral blood volume (rCBV), N‐acetyl aspartate (NAA), myoinositol (mI), total choline (Cho), and glutamate + glutamine (Glx) normalized to creatine (Cr) and Cho/NAA were measured at each ROI.ResultsInvasive regions showed significant increases in rCBV, suggesting angiogenesis (invasive rCBV 1.64 [95% confidence interval, CI: 1.5–1.76] vs. noninvasive 1.14 [1.09–1.18]; P < 0.001), Cho/Cr (invasive 0.42 [0.38–0.46] vs. noninvasive 0.35 [0.31–0.38]; P = 0.02) and Cho/NAA (invasive 0.54 [0.41–0.68] vs. noninvasive 0.37 [0.29–0.45]; P = < 0.03), suggesting proliferation, and Glx/Cr (invasive 1.54 [1.27–1.82] vs. noninvasive 1.3 [1.13–1.47]; P = 0.028), suggesting glutamate release; and a significantly reduced NAA/Cr (invasive 0.95 [0.85–1.05] vs. noninvasive 1.19 [1.06–1.31]; P = 0.008). The mI/Cr was not different between the three ROIs (invasive 1.2 [0.99–1.41] vs. noninvasive 1.3 [1.14–1.46]; P = 0.68). In the noninvasive regions, the values were not different from normal brain.ConclusionCombining DTI to identify the invasive region with perfusion and spectroscopy, we can identify changes in invasive regions not seen in noninvasive regions. J. Magn. Reson. Imaging 2016;43:487–494.

NI-02 * ELEVATED MYOINOSITOL IN DIFFUSE ASTROCYTOMA; A MARKER OF ANAPLASTIC PHENOTYPE, AND NOT ATTRIBUTABLE TO MICROGLIAL INFILTRATION

PURPOSE: Although in vivo MRS has been extensively applied to gliomas, the relevance of myoinositol (Myo) to malignant phenotype and the cell types that contribute signal are poorly understood. Microglial infiltration is associated with Myo elevation in inflammatory and neurodegenerative diseases, and has been implicated in neoangiogenesis in transforming gliomas. The aim of this study was to examine the relationship between Myo and Cho imaging biomarkers and enzymatic tissue markers of Myo synthesis and microglial cell type in grade II and III astrocytomas. SUBJECTS AND METHODS: 28 patients with diffuse astrocytoma (14 diffuse LGG, WHO grade II; 14 anaplastic, WHO grade III; 13 stereotactic biopsies, 15 surgical specimens) underwent multivoxel spectroscopy at 1.5 T or 3T (TE = 30ms, TR = 1500ms, 8x8 grid; Siemens Avanto/Verio, Erlangen, De). Metabolite ratios were estimated using proprietary software. Tissue immunostains with rabbit polyclonal antibodies directed against human inositol monophosphatase (IMPA1; Sigma – dilution 1:400; 25 cases) and Iba1 (Wako – dilution 1:750; 21 cases), were assessed semi-quantitatively. Myo/Cr and Cho/Cr ratios were compared (Kruskal-Wallis) and compared with Iba-1 and IMPA1 levels (Wilcoxon rank-sum), and metabolite ratios with Iba1 (Spearman's rank test). Co-localisation of highest Myo/Cr and Cho/Cr was also measured (Fisher's exact test). RESULTS: Myo/Cr was significantly lower in grade II compared with grade III tumours (p < 0.01). Highest Myo/Cr co-localised with highest Cho/Cr voxels in 72%. IMPA1 scores were significantly higher in grade III compared to grade II lesions (p < 0.01). There was no correlation between semi-quantitative microglial analysis using Iba1 antibody and Myo/Cr or tumour grade. CONCLUSION: Higher Myo in grade III than grade II astrocytomas suggests that it is not a marker of indolent tumour phenotype, as has been previously suggested, and may reflect increased de novo synthesis relating to p53 mutations. Our data do not suggest that microglia account for raised Myo levels in gliomas.

Apparent diffusion coefficient and Magnetic resonance spectroscopy in grading of malignant brain neoplasms

AimThis work aims to study the role of combined apparent diffusion coefficient (ADC) and Magnetic resonance spectroscopy (MRS) in grading malignant brain neoplasms. MethodsA prospective study included 40 patients who were evaluated by standard contrast enhanced MRI, diffusion weighted imaging and multivoxel spectroscopy. ResultsStatistically significant difference was found between tumoral ADC values in low grade versus high grade tumors and metastasis and also between the peritumoral ADC values in metastasis versus low and high grade tumors. Statistically significant difference is noticed between tumoral Cho/Cr ratio values in low grade versus high grade tumors and metastasis, and also peritumoral Cho/Cr ratio values in low grade and metastasis versus high grade tumors. Statistically significant difference between tumoral Cho/NAA ratio in low grade versus high grade tumors and metastasis and lastly between peritumoral Cho/NAA ratio in low grade and metastasis versus high grade tumors was found. Lipid and lactate peaks were found frequently in high grade tumors and metastasis. ConclusionThe combination of calculated ADC values and MR spectroscopy is useful in grading of malignant brain tumors and were more useful together than each on its own.

In vivo evidence of glutamate toxicity in multiple sclerosis.

There is increasing evidence that altered glutamate (Glu) homeostasis is involved in the pathophysiology of multiple sclerosis (MS). The aim of this study was to evaluate the in vivo effects of excess brain Glu on neuroaxonal integrity measured by N-acetylaspartate (NAA), brain volume, and clinical outcomes in a large, prospectively followed cohort of MS subjects. We used multivoxel spectroscopy at 3T to longitudinally estimate Glu and NAA concentrations from large areas of normal-appearing white and gray matter (NAWM and GM) in MS patients (n = 343) with a mean follow-up time of 5 years. Using linear mixed-effects models, Glu was examined as a predictor of NAA decline, annualized percentage brain volume change, and evolution of clinical outcomes (Multiple Sclerosis Functional Composite [MSFC], Paced Auditory Serial Addition Test-3 [PASAT], and Expanded Disability Status Scale). Glu/NAA ratio was tested as a predictor of brain volume loss and clinical outcomes. Baseline Glu[NAWM] was predictive of accelerated longitudinal decline in NAA[GM] (-0.06mM change in NAA[GM] /yr for each unit increase in Glu; p = 0.004). The sustained elevation of Glu[NAWM] was predictive of a loss of 0.28mM/yr in NAA[NAWM] (p < 0.001) and 0.15mM/yr in NAA[GM] (p = 0.056). Each 10% increase in Glu/NAA[NAWM] was associated with a loss of 0.33% brain volume/yr (p = 0.001), 0.009 standard deviations/yr in MSFC z-score (p < 0.001), and 0.17 points/yr on the PASAT (p < 0.001). These results indicate that higher Glu concentrations increase the rate of NAA decline, and higher Glu/NAA[NAWM] ratio increases the rate of decline of brain volume, MSFC, and PASAT. This provides evidence of a relationship between brain Glu and markers of disease progression in MS.

Can magnetic resonance spectroscopy differentiate endometrial cancer?

To investigate whether the choline-containing compounds (Cho) obtained from three-dimensional (1)H magnetic resonance (MR) spectroscopy can differentiate endometrial cancer (ECa) from benign lesions in endometria or in submucosa (BLs-ESm) and is associated with the aggressiveness of ECa. Fifty-seven patients (ECa, 38; BLs-ESm, 19) underwent preoperative multi-voxel MR spectroscopy at 3.0T. The ratio of the sum of the Cho peak integral to the sum of the unsuppressed water peak integral (Cho/water) and the coefficient of variation (CV) used to describe the variability of Cho/water in one lesion were calculated. Mean Cho/water (±standard deviation [SD]) was (3.02 ± 1.43) × 10(-3) for ECa and (1.68 ± 0.33) × 10(-3) for BLs-ESm (p < 0.001). Mean Cho/water was (4.42 ± 1.53) × 10(-3) for type II ECa and (2.65 ± 1.17) × 10(-3) for type I ECa (p = 0.001). There were no significant differences among different stages of ECa (p = 0.107) or different grades of ECa (p = 0.142). The Cho/water was positively correlated with tumour stage (r = 0.386, p = 0.017) and size (r = 0.333, p = 0.041). The CV was also positively correlated with tumour stage (r = 0.537, p = 0.001) and size (r = 0.34, p = 0.037). The Cho/water can differentiate ECa from BLs-ESm and differentiate type II from type I ECa, but cannot differentiate different stages of ECa or different grades of ECa. Cho/water increased with the increase of tumour stage and size. • First report to attempt to assess ECa aggressiveness with magnetic resonance spectroscopy (MRS). • MRS can differentiate type I from type II ECa. • MRS can differentiate ECa from BLs-ESm. • MRS cannot differentiate different stages of ECa or different grades of ECa. • Cho/water increased with the increase of tumour stage and size.

Thalamic metabolic alterations with cognitive dysfunction in idiopathic trigeminal neuralgia: a multivoxel spectroscopy study.

Although abnormalities in metabolite compositions in the thalamus are well described in patients with idiopathic trigeminal neuralgia (ITN), differences in distinct thalamic subregions have not been measured with proton magnetic resonance spectroscopy ((1)H-MRS), and whether there are correlations between thalamic metabolites and cognitive function still remain unknown. Multivoxel MRS was recorded to investigate the metabolic alterations in the thalamic subregions of patients with ITN. The regions of interest were localized in the anterior thalamus (A-Th), intralaminar portion of the thalamus (IL-Th), posterior lateral thalamus (PL-Th), posterior medial thalamus (PM-Th), and medial and lateral pulvinar of the thalamus (PuM-Th and PuL-Th). The N-acetylaspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) ratios were measured in the ITN and control groups. Scores of the visual analogue scale (VAS) and the Montreal Cognitive Assessment (MoCA) were analyzed to correlate with the neuroradiological findings. The NAA/Cr ratio in the affected side of PM-Th and PL-Th in ITN patients was statistically lower than that in the corresponding regions of the thalamus in controls. The NAA/Cr ratio in the affected PM-Th was negatively associated with VAS and disease duration. Furthermore, decreases of NAA/Cr and Cho/Cr were detected in the affected side of IL-Th, and lower Cho/Cr was positively correlated with MoCA values in the ITN group. Our result of low level of NAA/Cr in the affected PM-Th probably serves as a marker of the pain-rating index, and decreased Cho/Cr in IL-Th may be an indicator of cognitive disorder in patients with ITN.

Development of a Low-Cost Phantom to Assess Absolute Quantification in Multi-Voxel MR Spectroscopy

Background: Magnetic resonance spectroscopy (MRS) is a technique to measure chemical shift and can be used to analyze biochemical parameters in a region-of-interest (ROI) of the tissue through a procedure called Quantification. Evaluation of accuracy and robustness of a quantification method is extremely important to help validate it in practice. This is particularly important when the method deals with absolute quantification as there is no consensus regarding absolute values found in different ROIs. Usually, such evaluation procedures are initially tested on simulated signals and then on phantom signals in the next step. Most of MRS phantoms designed so far are not multi-purpose, in that they evaluate either quality assurance and reliability, or absolute quantification results. Objectives: Here, we designed a low-cost MRS phantom with flexibility to contain one single solution for quality assurance and reliability tests, as well as different combinations of metabolites with known concentrations for evaluation of (absolute) quantification algorithms. Patients and Methods: Phantom production: Phantom was designed in cylindrical-shape. Phantom can be filled with water or any other liquid. A detachable circular holder plate was designed for the interior of the cylinder of phantom. The holder contained 55 holes to hold 25 standard 10 mL vials with 15 mm diameters for holes. Another circular plate at the bottom with holes of 5mm diameter was used in order to fix the vials in their place. The cone-shape vials could be filled with pure metabolites or any combination of metabolites with desired concentrations. The resulting cylindrical phantom body had an outer diameter of 21 cm, an inner diameter of 14 cm and a height 15 cm. The body of the phantom was made of acrylic glass with removable top that allowed easy access to the interior chamber. An O-ring was used to watertight the lid of the phantom. All materials, laser-cut and production procedure cost less than 100$.Data acquisition: Proton MRS imaging experiments were performed on a 1.5T Siemens Avanto MRI/MRS system in the room temperature using Point REsolved Spectroscopy (PRESS) pulse sequence with manufactures built-in auto-shimming on the volume-of-interest, CHESS water suppression and 3D imaging parameters as follows: TE/TR = 30/1500 ms, voxel size = 888 mm3, NEX = 2, frequency bandwidth = 2000Hz and number of data points = 1024. Each vial was filled with a pure metabolite with known concentration as exists in human normal brain. All solutions of metabolites were calibrated in chemical laboratory with highly sophisticated instruments. : Processing: Signal quantification, residual water peak removal and phase corrections were carried out with the Java-based MRUI quantification package. Receiver coil inhomogeneity was compensated using, 3D T2-weighted images acquired from the pure water phantom. Results: Position of the voxels on the T1-weighted MR scout image was shown. One sample spectrum of Choline in built-in Siemens Syngo MRS Package was shown. Quantification for all metabolites in different slices of each vial, based on QUEST method in jMRUI software, and after being post-processed with the 3D receive coil inhomogeneity profile was depicted. The result was in linear relationship between volume and concentration. Conclusions: We developed a versatile and low-cost phantom for evaluation purposes in different MR imaging and spectroscopy studies, with special capabilities to be utilized for multi-voxel spectroscopy experiments with the goal of absolute quantification.

Gliomas hemisféricos OMS grado II: revisión del manejo actual

The optimal management of diffuse WHO grade II gliomas (GGII) is still controversial. Some authors propose a long-term radiological follow-up of the tumor, others perform a biopsy and treat only if clinical or radiological signs of progression, finally, others propose an active treatment from diagnosis. There is mounting evidence that suggest that expectant management is no longer optimal, supporting active treatment from diagnosis. In the present work, an extensive review of the recent literature was performed, in order to clarify some of these controversies. Neuroimaging techniques, such as magnetic resonance imaging (MRI), multivoxel spectroscopy or methionine positron emission tomography (PET), give valuable information about the tumor, but lack of sufficient reliability to make a definitive diagnosis of GGII. Stereotactic biopsy leads to misdiagnosis in up to 71% of cases, which has been associated with sampling errors and inter-observer variability due to the small sample obtained. Therefore, it is now considered that a definitive diagnosis of GGII requires a detailed histological analysis of the sample after maximum tumor removal. Despite the lack of class I evidence, there is growing evidence from cohort studies, favoring extensive surgical resection to improve survival and time to tumor degeneration. Surgery is also effective to treat epilepsy, as an improvement in up to 76% of drug-resistant epilepsies has been documented. Consequently, surgery is now considered as a crucial step for diagnosis and treatment of these tumors. Early radiotherapy after surgery lengthens the period without progression but does not affect overall survival, and is related to cognitive disorders that affect quality of life. Hence, this treatment could be deferred until tumor progression.

Clinical applications of imaging biomarkers. Part 2. The neurosurgeon's perspective

Advances in imaging, including multivoxel spectroscopy, tractography, functional MRI and positron emission spectroscopy, are being used by neurosurgeons to target aggressive areas in gliomas, and to help identify tumour boundaries, functional areas and tracts. Neuro-oncological surgeons need to understand these techniques to help maximise tumour resection, while minimising morbidity in an attempt to improve the quality of patient outcome. This article reviews the evidence for the practical use of multimodal imaging in modern glioma surgery.

Evaluation of Normal Appearing White Matter in Multiple Sclerosis

The aim of this study was to determine diffusion magnetic resonance imaging (MRI), magnetization transfer (MT) imaging and multivoxel MR spectroscopy findings in plaques, periplaque white matter and normal appearing white matter (NAWM) regions in multiple sclerosis (MS) and to correlate the findings with the expanded disability status scale (EDSS). A total of 30 patients with MS and 30 healthy control subjects were studied and apparent diffusion coefficient (ADC) values, MT ratio (MTR), N-acetyl-aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratios were measured in plaques, periplaques and NAWM regions and compared with the control subjects. The MTR and NAA/Cr ratio were decreased more in plaques than periplaques and NAWM, in contrast ADC values and Cho/Cr ratios were highest in plaques and higher in periplaques than in NAWM. Decreased MTR and NAA/Cr in NAWM demonstrated moderate inverse correlations (r = - 0.604, p < 0.001 and r = - 0.494, p < 0.001, respectively) while Cho/Cr ratios and ADC of NAWM demonstrated weak linear correlations (r = 0.370, p = 0.004, r = 0.297, p = 0.021 respectively) with EDSS. The MS, MTR and MR spectroscopy findings were found to be useful for detecting subtle abnormalities in NAWM. Although ADC values were significantly altered in plaque and periplaque regions a significance difference was not found in NAWM.

Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma

Patients with diffuse intrinsic pontine glioma (DIPG) face a grim prognosis with limited treatment options. Many patients will enroll on investigational trials though the role of chemotherapy or immunotherapy is unclear. Radiographic changes on conventional MRI are used to evaluate tumor response and progression, but are not predictive of outcome in these patients. More sensitive measures of tumor biology are needed to improve patient management. We evaluated changes in magnetic resonance spectroscopy (MRS) biomarkers in patients with DIPG. Thirty-eight patients were enrolled prospectively on an IRB-approved protocol, which included standard MRI, single voxel spectroscopy (SVS) and multi-slice multi-voxel spectroscopy (MRSI). Scans were performed at multiple time points during each patient's clinical course, with a total of 142 scans. The prognostic values of Choline:N-acetylaspartate (Cho:NAA), Cho:Creatine (Cho:Cr) and the presence of lactate and lipids (+Lac/Lip) were evaluated. Cho:NAA and variance in Cho:NAA values among different voxels within a tumor were each predictive of shorter survival. This prospective study shows that MRS can be used to identify high-risk patients and monitor changes in tumor metabolism, which may reflect changes in tumor behavior.

Quadrature coils for magnetic resonance spectroscopy in the detection of prostate cancer: Single voxel acquisition does not improve the diagnostic accuracy of multivoxel images

ObjectiveTo determine the viability of quadrature coils for detecting prostate cancer using single voxel and multivoxel spectroscopy images. Material and methodsWe used a quadrature coil on a 1.5T MR scanner to evaluate 23 patients with suspected prostate cancer and prostate specific antigen levels greater than 4 ng/ml (mean 12 ± 8 ng/ml), independently of findings at digital rectal examination. We acquired T2-weighted images and MR spectroscopy images. We also acquired single voxel studies in areas in which the T2-weighted images or the multivoxel images were altered. We used a citrate solution to verify the spectroscopic calibration. ResultsUsing spectroscopy images and a (Cho + Cr)/Cit cutoff of 1.40 in single voxel spectroscopy, we achieved a sensitivity of 92%, specificity of 55%, a negative predictive value of 86%, and a positive predictive value of 69%. Using a cutoff of 0.75 decreased specificity slightly (45%). The (Cho + Cr)/Cit ratio calculated for the single volume obtained from the most abnormal area in the T2-weighted images and in the multivoxel spectroscopy slices was not significantly different between cancerous and non-cancerous tissues (ANOVA, p=0.1), although there was a clear trend toward increased coefficients with hyperplasia and neoplastic degeneration. ConclusionThe quadrature coil enables multivoxel and single voxel spectroscopic images of clinically and technically acceptable quality to be obtained. Using single voxel spectroscopy does not improve the diagnostic performance of multivoxel spectroscopy and T2-weighted images.

A 1H magnetic spectroscopy study in the first-episode patients with positive symptoms of schizophrenia

Objective To identify the possible alterations of brain function in prefrontal lobes and hippocampus in the first-episode patients with positive symptoms of schizophrenia using magnetic resonance spectroscopy. Methods 20 patients were selected to perform MRI and HMRS examination. Proton multi-voxel spectroscopy imaging(1 H-MRSI)was obtained from two sides of the hippocampus and frontal lobes regions. The metabolites included N-acetylaspartate (NAA), and choline-containing compounds (Cho), creatine and phosphocreatine (Cr).The ratios of NAA/Cr, Cho/Cr and NAA/Cho were determined. Results (1)The Cho/Cr ratio was significantly reduced in left frontal white matter of patients compared to right(1. 178 ± 0.210 vs 1.437 ± 0. 337). (2) There was no statistically significant difference in metabolite levels in between left anterior cingulate gray matter and right (N AA. Cr: 1. 339 ± 0.452 vs 1. 748 ± 0. 147;Cho/Cr: 1. 406 ± 0. 394 vs 1. 761 ± 0.362) (P ＜ 0.05). (3) The NAA/Cr, Cho/Cr were significantly reduced in left hippocampus of patients compared to right. Conclusion The results implicate that the metabolic abnormalities might exist in the left hippocampus and frontal lobe of schizophrenic patients with positive symptoms. Key words: Schizophrenia; Frontal lobes; Hippocampus; Magnetic resonance spectroscopy

Complementariedad de la espectroscopía univóxel y la imágen de espectroscopía multivóxel obtenidas mediante bobina de cuadratura para la detección del carcinoma de próstata

Objective To determine the viability of quadrature coils for detecting prostate cancer using single voxel and multivoxel spectroscopy images. Material and methods We used a quadrature coil on a 1.5 T MR scanner to evaluate 23 patients with suspected prostate cancer and prostate specific antigen levels greater than 4 ng/ml (mean 12±8 ng/ml), independently of findings at digital rectal examination. We acquired T2-weighted images and MR spectroscopy images. We also acquired single voxel studies in areas in which the T2-weighted images or the multivoxel images were altered. We used a citrate solution to verify the spectroscopic calibration. Results Using spectroscopy images and a (Co+Cr)/Cit cutoff of 1.40 in single voxel spectroscopy, we achieved a sensitivity of 92%, specificity of 55%, a negative predictive value of 86%, and a positive predictive value of 69%. Using a cutoff of 0.75 decreased specificity slightly (45%). The (Co+Cr)/Cit ratio calculated for the single volume obtained from the most abnormal area in the T2-weighted images and in the multivoxel spectroscopy slices was not significantly different between cancerous and non-cancerous tissues (ANOVA, p=0.1), although there was a clear trend toward increased coefficients with hyperplasia and neoplastic degeneration. Conclusion The quadrature coil enables multivoxel and single voxel spectroscopic images of clinically and technically acceptable quality to be obtained. Using single voxel spectroscopy does not improve the diagnostic performance of multivoxel spectroscopy and T2-weighted images.

Three-dimensional multivoxel spectroscopy of the healthy hippocampus—are the metabolic differences related to the location?

The aim of this study was to determine the bilateral distribution of proton metabolites along the long axis of the hippocampus. Forty-one healthy volunteers were examined using a 1.5T magnetic resonance imaging system, using proton three-dimensional spectroscopic imaging (3D CSI) of the left and the right hippocampus separately. Three dominant signals were measured: choline (Cho), total creatine (tCr), and n-acetylaspartate (NAA) and expressed as ratios of Cho:tCr, NAA:tCr, NAA:Cho and NAA:(Cho+tCr). We compared the data from three hippocampal regions: head, body and tail. Lower NAA:tCr ratios were found in head compared with the body (p<0.05) and in the head compared with the tail (p<0.05) bilaterally. Lower NAA:Cho and NAA:(Cho+tCr) ratios were found in the head compared with the body (p<0.05), in the body compared with the tail (p<0.05), and in the head compared with the tail (p<0.05) bilaterally. There was no statistically significant difference between the left and the right hippocampus. Ratios of NAA:tCr, NAA:Cho, and NAA:(Cho+tCr) in hippocampal tissue were significantly higher posteriorly than anteriorly. As the differences are present in healthy volunteers, the appearance in patients related to approximate voxel positioning within hippocampi may result in false-positive results.

Multivoxel 1H MR Spectroscopic Approach to the Diagnosis of Intraventricular Central Neurocytoma

We describe the proton ((1)H) magnetic resonance spectroscopic (MRS) imaging of central neurocytoma (CNC), a rare benign intraventricular neuronal tumor. Multivoxel MR Spectroscopy is a feasible and reproducible non-invasive tool for the specific diagnosis of CNC and to distinguish CNC from other intraventricular tumor types. The detection of glycine and alanine peaks, high choline and lactate and low NAA levels are characteristic of CNC.

Metabolic changes in the normal ageing brain: Consistent findings from short and long echo time proton spectroscopy

Objectives Sixty three healthy subjects were measured to assess dependence of brain metabolites on age using short- and long echo time spectroscopy in different brain regions. Material and methods Younger and elderly humans were measured with long echo time (TE = 135 ms) 3D-MR-spectroscopic imaging (MRSI) (10 subjects) and with ultra-short echo (TE = 11 ms) time 2D-MRSI (7 subjects). In addition, results from single voxel 1H-spectroscopy (TE = 20 ms) of two cohorts of 46 healthy subjects were retrospectively correlated with age. Results 3D-MR SI revealed reduced NAA/Cr in the older group in the frontal lobe (−22%; p < 0.01), parietal lobe (−28%; p < 0.01) and semiovale (−9%; p < 0.01) compared to the younger group. Cho/Cr was elevated in the semiovale (+35%; p < 0.01) and in the n. lentiformis (+42%; p < 0.01) in the older group. NAA/Cho was reduced in all regions measured, except the thalamus, in the older group compared to the younger group (from −21 to −49%; p < 0.01). 2D-MRSI revealed decreased total NAA (−3.1% per decade; p < 0.01) and NAA/Cr (−3.8% per decade; p < 0.01), increased total Cho (+3.6% per decade; p < 0.01) and Cho/Cr (+4.6% per decade; p < 0.01) and increased total myo-Inositol (mI, +4.7% per decade; p < 0.01) and mI/Cr (+5.4% per decade; p < 0.01) and decreased NAA/Cho (−8% per decade; p < 0.01) in semiovale WM. Results from single voxel spectroscopy revealed a significantly negative correlation of NAA/Cho in frontal (−13% per decade; p < 0.01) and in temporal lobe (−7.4% per decade; p < 0.01) as well as increased total Cr (10% per decade; p < 0.01) in frontal lobe. Other results from single voxel measurements were not significant, but trends were comparable to that from multivoxel spectroscopy. Conclusion Age-related changes measured with long echo time and short echo time 1H-MRS were comparable and cannot, therefore, be caused by different T2 relaxation times in young and old subjects, as suggested previously.