choline/N-acetylaspartate Research Articles

Role of Advanced Magnetic Resonance Imaging in Differentiating among Glioma Subtypes and Predicting Tumor-Proliferative Behavior

Abstract Objective Gliomas are a devastating and heterogeneous group of primary brain tumors. Previously, the source of glioma was undetermined. Recent literature indicates that neural stem cells, or progenitors, are proposed to be the source of glioma. The prognosis of different types of gliomas differs due to their various biological tissue types. Besides the histological grade, the two useful immunohistochemistry markers that show the tumor's biological behavior are isocitrate dehydrogenase (IDH) labeling and the Ki-67 labeling index. We sought to determine the magnetic resonance imaging (MRI) characteristics associated with IDH mutational status and ascertain whether MRI combined with IDH mutational status, can better predict the clinical outcomes of gliomas. Materials and Methods This period study was conducted in the Department of Radiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India for 5 years (May 2016–May 2021). The study cohort included 30 patients diagnosed with gliomas who underwent preoperative MRI followed by surgical resection and histopathological examination. Preoperative MRI images were done to assess qualitative tumor characteristics such as location, margin of tumor, extent, cortical involvement, cystic component, mineralization or hemorrhage, and contrast enhancement. Discussion Differences in MRI features between IDH-mutant (MT) and IDH-wild-type (WT) groups were analyzed using the chi-square test for categorical variables and the Mann–Whitney U test for continuous variables. Statistical analysis was conducted using SPSS software. Results Among the 30 patients evaluated, 18 had IDH-WT and 12 had IDH-MT type gliomas. Male predominance (73.33%) was noted in our study. Brainstem location, indistinct borders (83.33%), less cortical involvement (72.22%), less cystic changes (88.89%), more area of necrotic component (44.44%), significantly increased choline/creatine (Cho/Cr) ratio, and choline/N-acetyl aspartate (Cho/NAA) ratio favors IDH-WT tumors. Positive T2-fluid-attenuated inversion recovery mismatch sign is more frequently seen in IDH-MT (7/12; 58.33%) tumors than in IDH-WT (4/18; 22.22%) tumors. Whereas well-defined contours (66.67%), more cortical involvement (83.33%), more cystic changes (58.33%), and less area of necrotic component favor IDH-MT type tumors. Conclusion MRI is a very promising and valuable tool for differentiating among glioma subtypes and predicting tumor-proliferative behavior in glioma cases. The combination of MRI characteristics with IDH mutation status enhances the predictive accuracy for clinical outcomes in glioma patients. This approach could potentially guide treatment planning and improve prognostic assessments.

Magnetic Resonance Spectroscopy of Intra-axial Gliomas With Histopathological Correlation in a Tertiary Care Center of Eastern Nepal.

Background and objective Magnetic resonance spectroscopy (MRS) is a magnetic resonance imaging technique used to identify in vivo metabolites non-invasively within the tissue of interest. It plays an important role in diagnosing brain lesions, particularly tumors and infections. There are certain metabolites whose levels are increased or decreased in brain tumors, the ratios of which can also be used to grade the tumors as high- or low-grade. This study aimed to assess the spectrum of different metabolites in intraaxial gliomas using magnetic resonance spectroscopy and to assess the usefulness of their ratios for grading gliomas into high-grade and low-grade. Methods This descriptive cross-sectional study was performed in the radiology department of Nobel Medical College and Teaching Hospital, Biratnagar, Nepal over one year (September 2019 to September 2020). Thirty-five patients diagnosed as having intra-axial tumors were enrolled. After taking informed consent the examination findings were recorded in structured proforma. Siemens' 3 Tesla open magnet MAGNETOM Skyra (Siemens Healthineers AG, Munich, Germany) MR scanner was used to evaluate each patient. Data was analyzed using the software Statistical Package for Social Sciences (SPSS), version 26.0 (IBM Corp., Armonk, NY). Results Out of 35 patients scanned, 18 had high-grade glioma and 17 had low-grade glioma. High-grade glioma had a choline/creatine (Cho/Cr) ratio of 2.44 ± 0.78 and a choline/N-acetyl-aspartate (Cho/NAA) ratio of 2.05 ± 0.84. Low-grade glioma had a Cho/Cr ratio of 1.48 ± 0.50 and a Cho/NAA ratio of 1.41 ± 0.19. Fourteen out of eighteen high-grade gliomas had raised lipid/lactate peaks. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy for diagnosing high-grade glioma with a Cho/Cr ratio cut-off of 1.5 was 83.3 %, 82.4%, 83.3%,82.4 %, and 82.85% respectively. Conclusion MRS metabolite ratios can be used to diagnose and grade gliomas. Cho/Cr, Cho/NAA, and the presence or absence of lipid/lactate peak can significantly improve the sensitivity, specificity, predictive values, and accuracy of preoperative glioma grading when used in conjunction with conventional MRI.

The role of 3-Tesla magnetic resonance perfusion and spectroscopy in distinguishing glioblastoma from solitary brain metastasis.

This study aimed to assess the value of magnetic resonance perfusion (MR perfusion) and magnetic resonance spectroscopy (MR spectroscopy) in 3.0-Tesla magnetic resonanceimaging (MRI) for differential diagnosis of glioblastoma (GBM) and solitary brain metastasis (SBM). This retrospective study involved 36 patients, including 24 cases of GBM and 12 of SBM diagnosed using histopathology. All patients underwent a 3.0-Tesla MRI examination with pre-operative MR perfusion and MR spectroscopy. We assessed the differences in age, sex, cerebral blood volume (CBV), relative CBV (rCBV), and the metabolite ratios of choline/N-acetylaspartate (Cho/NAA) and Cho/creatine between the GBM and SBM groups using the Mann-Whitney U-test and Chi-square test. The cutoff value, area under the curve, sensitivity, specificity, positive predictive value, and negative predictive value of the significantly different parameters between these two groups were determined using the receiver operating characteristic curve. In MR perfusion, the CBV of the peritumoral region (pCBV) had the highest preoperative predictive value in discriminating GBM from SBM (cutoff: 1.41; sensitivity: 70.83%; and specificity: 83.33%), followed by the ratio of CBV of the solid tumor component to CBV of normal white matter (rCBVt/n) and the ratio of CBV of the pCBV to CBV of normal white matter (rCBVp/n). In MR spectroscopy, the Cho/NAA ratio of the pCBV (pCho/NAA; cutoff: 1.02; sensitivity: 87.50%; and specificity: 75%) and the Cho/NAA ratio of the solid tumor component (tCho/NAA; cutoff: 2.11; sensitivity: 87.50%; and specificity: 66.67%) were significantly different between groups. Moreover, combining these remarkably different parameters increased their diagnostic utility for distinguishing between GBM and SBM. pCBV, rCBVt/n, rCBVp/n, pCho/NAA, and tCho/NAA are useful indices for differentiating between GBM and SBM. Combining these indices can improve diagnostic performance in distinguishing between these two tumors.

Pseudoprogression in GBM versus true progression in patients with glioblastoma: A multiapproach analysis

Background and purposeTo investigate the feasibility of using a multiapproach analysis combining clinical data, diffusion- and perfusion-weighted imaging, and 3D magnetic resonance spectroscopic imaging to distinguish true tumor progression (TP) from pseudoprogression (PSP) in patients with glioblastoma. Materials and methodsProgression was suspected within 6 months of radiotherapy in 46 of the 180 patients included in the Phase-III SpectroGlio trial (NCT01507506). Choline/creatine (Cho/Cr), choline/N-acetyl aspartate (Cho/NAA) and lactate/N-acetyl aspartate (Lac/NAA) ratios were extracted. Apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps were calculated. ADC, relative CBV values and tumor volume (TV) were collected at relapse. Differences between TP and PSP were evaluated using Mann–Whitney tests, and p values were adjusted with Bonferroni correction. ResultsPatients with suspected progression underwent a new MRI scan 1 month after the first one. Of these, 28 were classified as PSP, and 18 as TP. After a median follow-up of 41 months, median overall survival was higher in PSP than in TP (25.2 vs 20.3 months; p = 0.0092). Lac/NAA and Cho/Cr ratios were higher in TP than in PSP (1.2 vs 0.5; p = 0.006; and 3 vs 2.2; p = 0.021). After multivariate regression analysis, TV was the most significant predictor of TP vs PSP, and the only one retained in the model (p = 0.028). ConclusionThree spectroscopic ratios could be used to differentiate PSP from TP. TV at relapse was the most predictive factor in the multivariate analysis, and overall survival was higher in PSP than in TP.

Brain magnetic resonance spectroscopy to differentiate recurrent neoplasm from radiation necrosis: A systematic review and meta-analysis.

Postradiation treatment necrosis is one of the most serious late sequelae and appears within 6months. The magnetic resonance spectroscopy imaging (MRSI) has been used for the detection of brain tumors. The study aimed to determine the radiological accuracy and efficacy in distinguishing recurrent brain tumor from radiation-induced necrosis by identifying pseudoprogression. The research was performed in accordance with the preferred reporting items for systematic review and meta-analysis guidelines. International electronic databases including 15 English sources were investigated. A total of 4281 papers with 2159 citations from 15 databases from 2011 to 2021 met the search strategies of magnetic resonance (MR) spectroscopy in recurrent brain tumors and postradiation necrosis. Nine studies were enrolled in the meta-analysis with a total of 354 patients (203 male and 151 female) whose average age ranged from 4 to 74years. Anbarloui etal., Elias etal., Nemattalla etal., Smith etal., Zeng etal., and Weybright etal. showed strong evidence of heterogeneity regarding choline/N-acetylaspartate (Cho/NAA) ratio in the evaluation of the nine studies. Elias etal., Nemattalla etal., Bobek-Billewicz etal., and Smith etal. showed a high heterogeneity in Cho/creatine (Cr) ratio. Elias etal., Nemattalla etal., Smith etal., and Weybright etal. revealed high heterogeneity in NAA/Cr ratio estimates. MR spectroscopy is effective in distinguishing recurrent brain tumors from necrosis. Our meta-analysis revealed that Cho/NAA, Cho/Cr, and NAA/Cr ratios were significantly better predictor of detected recurrent tumor. Therefore, the MRSI is an informative tool in the distinction of tumor recurrence versus necrosis.

Clinical and Research MRI Techniques for Assessing Spinal Cord Integrity in Degenerative Cervical Myelopathy-A Scoping Review.

Background: Degenerative cervical myelopathy (DCM) manifests as the primary cause of spinal cord dysfunction and is non-traumatic, chronic and progressive in nature. Decompressive surgery is typically utilised to halt further disability and neurological dysfunction. The limitations of current diagnostic options surrounding assessment and prognostic potential render DCM still largely a clinical diagnosis. Aims: To outline the limitations of current diagnostic techniques, present evidence behind novel quantitative MRI (qMRI) techniques for assessing spinal cord integrity in DCM and suggest future directions. Method: Articles published up to November 2021 were retrieved from Medline, EMBASE and EBM using key search terms: spinal cord, spine, neck, MRI, magnetic resonance imaging, qMRI, T1, T2, T2*, R2*, DTI, diffusion tensor imaging, MT, magnetisation transfer, SWI, susceptibility weighted imaging, BOLD, blood oxygen level dependent, fMRI, functional magnetic resonance imaging, functional MRI, MRS, magnetic resonance spectroscopy. Results: A total of 2057 articles were retrieved with 68 articles included for analysis. The search yielded 2 articles on Quantitative T1 mapping which suggested higher T1 values in spinal cord of moderate-severe DCM; 43 articles on DTI which indicated a strong correlation of fractional anisotropy and modified Japanese Orthopaedic Association scores; 15 articles on fMRI (BOLD) which demonstrated positive correlation of functional connectivity and volume of activation of various connections in the brain with post-surgical recovery; 6 articles on MRS which suggested that Choline/N-acetylaspartate (Cho/NAA) ratio presents the best correlation with DCM severity; and 4 articles on MT which revealed a preliminary negative correlation of magnetisation transfer ratio with DCM severity. Notably, most studies were of low sample size with short timeframes within 6 months. Conclusions: Further longitudinal studies with higher sample sizes and longer time horizons are necessary to determine the full prognostic capacity of qMRI in DCM.

Correlation between functional MRI techniques and early disability in ambulatory patients with relapsing\u2013remitting MS

BackgroundMultiple sclerosis (MS) is a common neurological disorder which can lead to an occasional damage to the central nervous system. Conventional magnetic resonance imaging (cMRI) is an important modality in the diagnosis of MS; however, correlation between cMRI findings and clinical impairment is weak. Non-conventional MRI techniques including apparent diffusion coefficient (ADC) and magnetic resonance spectroscopy (MRS) investigate the metabolic changes over the course of MS and overcome the limits of cMRI.A total of 80 patients with MS and 20 age and sex-matched healthy control subjects were enrolled in this cross-sectional study. Ambulatory patients with relapsing–remitting MS (RRMS) were recruited. Expanded Disability Status Scale (EDSS) was used to assess the disability and the patients were categorized into three groups “no disability”, “minimal disability” and “moderate disability”. All patients underwent cMRI techniques. ADC was measured in MS plaques and in normal appearing white matter (NAWM) adjacent and around the plaque. All metabolites concentrations were expressed as ratios including N-acetyl-aspartate/creatine (NAA/Cr), choline/N-acetyl-aspartate (Cho/NAA) and choline/creatine (Cho/Cr). ADC and metabolite concentrations were measured in the normal white matter of 20 healthy control subjects.ResultsThe study was carried on 80 MS patients [36 males (45%) and 44 females (55%)] and 20 healthy control [8 males (40%) and 12 females (60%)]. The ADC values and MRS parameters in NAWM of patients with MS were significantly different from those of the control group. The number of the plaques on T2 images and black holes were significantly higher at “Minimal disability” group. Most of the enhanced plaques were at the “Moderate disability” group with P value < 0.001. The mean of ADC in the group 1, 2 and 3 of disability was 1.12 ± 0.19, 1.50 ± 0.35, 1.51 ± 0.36, respectively, with P value < 0. 001. In the group 1, 2 and 3 of disability, the mean of NAA/Cr ratio at the plaque was 1.34 ± 0.44, 1.59 ± 0.51 and 1.11 ± 0.15, respectively, with P value equal 0.001.ConclusionThe non-conventional quantitative MRI techniques are useful tools for detection of early disability in MS patients.

3D whole-brain metabolite imaging to improve characterization of low-to-intermediate grade gliomas.

MRI is the standard imaging modality used for diagnosis, treatment planning, and post-treatment management of gliomas. Contrast-enhanced T1-weighted (CE-T1w) MRI is used to plan biopsy and radiation for grade IV gliomas but is less effective for grade II and III gliomas (i.e., low-to-intermediate grade gliomas) which may have minimal or no enhancement. Magnetic resonance spectroscopic imaging (MRSI) is an advanced MRI technique that has been shown, to improve diagnostic yield of biopsy and target delineation for grade IV glioma. The purpose of this study is to determine if MRSI can improve characterization and tissue sampling of low-to-intermediate grade gliomas. Prospective grade II and grade III glioma patients were enrolled to undergo whole brain high-resolution MRSI prior to tissue sampling. Choline/N-acetyl-aspartate (Cho/NAA) maps were overlaid on anatomic imaging and imported into stereotactic biopsy software. Patients were treated with standard-of-care surgery and radiation. Volumes of spectroscopically abnormal tissue were generated and compared with anatomic imaging and areas of enhancing recurrence on follow-up imaging. Ten patients had pathologic diagnosis of grade II (n = 4) or grade III (n = 6) with a median follow-up of 27.3 months. Five patients had recurrence, and regions of recurrence were found to overlap with metabolically abnormal regions on MRSI at the time of diagnosis. MRSI in low-to-intermediate grade glioma patients is predictive of areas of subsequent recurrence. Larger studies are needed to determine if MRSI can be used to guide surgical and radiation treatment planning in these patients.

The impact of magnetic resonance imaging spectroscopy parameters on differentiating between paediatric medulloblastoma and ependymoma.

IntroductionThe distinction of medulloblastomas and ependymomas plays an important role in the care plans and prognosis of children. We aimed to investigate the role of magnetic resonance spectroscopy (MRS) in the differentiation between medulloblastomas and ependymomas in children.Materials and methodsThe institutional review board approved this prospective study. The brain magnetic resonance imaging protocol including axial multivoxel spectroscopy with a TE of 144 ms was assessed in 49 patients, who were divided into 2 groups: 40 patients with medulloblastomas and 9 patients with ependymomas. Receiver operating characteristic (ROC) curve analysis and the Youden index were utilized to determine the best cut-off, sensitivity, specificity, and area under the curve (AUC) values of the independent spectroscopy parameters.ResultsThe choline level (Cho) and the choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA) ratios of medulloblastomas were significantly higher than those of ependymomas (p < 0.05). A Cho/NAA cut-off value of 1.24 to predict the diagnosis of medulloblastoma yielded the highest AUC and sensitivity of 80.3% and 97.5%, respectively, while a Cho cut-off value of 4.64 produced the highest specificity value of 88.9%.ConclusionsOur findings suggest that Cho and Cho/NAA derived from MRS could serve as differential factors between paediatric medulloblastomas and ependymomas. Among those, a Cho/NAA cut-off value of 1.24 to predict the diagnosis of medulloblastoma generated the highest accuracy.

MRI Features of Intracranial Anaplastic Ependymomas: A Comparison of Supratentorial and Infratentorial Lesions.

Background: Several previous reports of anaplastic ependymomas have described their imaging features, and most of these studies were case reports. However, no studies have compared the magnetic resonance imaging (MRI) features between the infratentorial and supratentorial anaplastic ependymomas.Objective: The goal of this study was to explore MRI characteristics for intracranial anaplastic ependymomas.Material and Methods: We retrospectively reviewed the demographics of 165 patients and MRI findings of 60 patients with supratentorial (SAEs) and infratentorial anaplastic ependymomas (IAEs) before surgery. The demographics and MRI features for SAEs and IAEs were compared and evaluated.Results: Among the 60 patients, most SAEs (91.7%) were extraventricular, whereas most IAEs (91.7%) were intraventricular. Of sixty intracranial anaplastic ependymomas, most lesions were well-defined (n = 45) and round-like (n = 36). On T1-weighted imaging, compared with the gray matter, the SAEs exhibited heterogeneous signal intensity, whereas IAEs exhibited iso-hypointense signals. T2 signals exhibited greater associations with hyperintense signals in IAEs; however, SAEs showed hyperintense or hypointense–hyperintense. On diffusion-weighted imaging (DWI), almost all solid tissues of SAEs appeared as hyperintense, whereas IAEs exhibited iso-hypointense signals. Peritumoral edema and intratumoral hemorrhage occurred more frequently in SAEs. Almost all anaplastic ependymomas exhibited heterogeneous enhancement. Cysts or necrosis was associated with 56 anaplastic ependymomas; however, large cysts were more prevalent in SAEs. On magnetic resonance spectroscopy (MRS), the mean choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) ratio of anaplastic ependymomas were (6.58 ± 4.26) and (8.84 ± 6.34), respectively, representing typical high-grade tumors.Conclusion: We demonstrate the conventional and functional MRI features of intracranial anaplastic ependymomas, including DWI and MRS. MRI characteristics, such as location, cyst, diffusion restriction, and peritumoral edema, differed between supratentorial and infratentorial locations. Cho/Cr and Cho/ NAA ratios of anaplastic ependymomas are increased.

Magnetic resonance spectroscopy in pediatric brain tumors: how to make a more confident diagnosis

BackgroundNon-invasive diagnosis of pediatric brain tumors can be challenging due to diverse tumor pathologies and similar imaging appearances. Magnetic resonance spectroscopy (MRS), when combined with high spatial resolution anatomic imaging obtained with conventional magnetic resonance imaging (MRI), provides metabolic information within the lesion as well as the surrounding tissue. The differentiation of neoplastic from non-neoplastic lesions and low-grade from high-grade neoplasms is essential for determining the choice of treatment and the best treatment plan. We aimed to measure specific metabolic ratios and evaluate metabolic profiles of various lesions by MRS to assist in making a more confident diagnosis.ResultsThe choline/creatine (Cho/Cr), choline/N-acetylaspartate (Cho/NAA), and Cho/NAA+Cr ratios all had statistically significant values for the differentiation between neoplastic and non-neoplastic lesions at cutoffs 1.8, 2, and 0.8 respectively. The Cho/NAA, Cho/Cr, Cho/NAA+Cr, and myo-inositol/creatine (mI/Cr) ratios all had statistically significant values for the differentiation of high-grade from low-grade neoplasms at cutoffs 3.3, 3.5, 1.3, and 1.5 respectively. The presence of a lipid lactate peak was only significant for differentiating high-grade from low-grade neoplasms. Medulloblastomas, diffuse pontine gliomas, and choroid plexus carcinoma all showed characteristic metabolic profiles on MRS. Metastasis showed lower Cho/NAA and Cho/Cr ratios outside the tumor margin than high-grade neoplasms.ConclusionThe use of certain metabolite ratios with high sensitivity and specificity to distinguish neoplastic from non-neoplastic lesions and low-grade from high-grade neoplasms while assessing the metabolic profile of the lesion aids in the non-invasive diagnosis of pediatric brain tumors. MRS facilitates earlier treatment planning by determining tumor spatial extent and predicting tumor behavior with potential to solve sampling problems of inaccessible and heterogenous lesions as well as unnecessary sampling of benign lesions.

Three-dimensional echo planar spectroscopic imaging for differentiation of true progression from pseudoprogression in patients with glioblastoma.

Accurate differentiation of true progression (TP) from pseudoprogression (PsP) in patients with glioblastomas (GBMs) is essential for planning adequate treatment and for estimating clinical outcome measures and future prognosis. The purpose of this study was to investigate the utility of three‐dimensional echo planar spectroscopic imaging (3D‐EPSI) in distinguishing TP from PsP in GBM patients. For this institutional review board approved and HIPAA compliant retrospective study, 27 patients with GBM demonstrating enhancing lesions within six months of completion of concurrent chemo‐radiation therapy were included. Of these, 18 were subsequently classified as TP and 9 as PsP based on histological features or follow‐up MRI studies. Parametric maps of choline/creatine (Cho/Cr) and choline/N‐acetylaspartate (Cho/NAA) were computed and co‐registered with post‐contrast T 1‐weighted and FLAIR images. All lesions were segmented into contrast enhancing (CER), immediate peritumoral (IPR), and distal peritumoral (DPR) regions. For each region, Cho/Cr and Cho/NAA ratios were normalized to corresponding metabolite ratios from contralateral normal parenchyma and compared between TP and PsP groups. Logistic regression analyses were performed to obtain the best model to distinguish TP from PsP. Significantly higher Cho/NAA was observed from CER (2.69 ± 1.00 versus 1.56 ± 0.51, p = 0.003), IPR (2.31 ± 0.92 versus 1.53 ± 0.56, p = 0.030), and DPR (1.80 ± 0.68 versus 1.19 ± 0.28, p = 0.035) regions in TP patients compared with those with PsP. Additionally, significantly elevated Cho/Cr (1.74 ± 0.44 versus 1.34 ± 0.26, p = 0.023) from CER was observed in TP compared with PsP. When these parameters were incorporated in multivariate regression analyses, a discriminatory model with a sensitivity of 94% and a specificity of 87% was observed in distinguishing TP from PsP. These results indicate the utility of 3D‐EPSI in differentiating TP from PsP with high sensitivity and specificity.

An optimal spectroscopic feature fusion strategy for MR brain tumor classification using Fisher Criteria and Parameter-Free BAT optimization algorithm

In the present work, a fused metabolite ratio is proposed that integrates the conventional metabolite ratios in a weighted manner to improve the diagnostic accuracy of glioma brain tumor categorization. Each metabolite ratio is weighted by the value generated by the Fisher and the Parameter-Free BAT (PFree BAT) optimization algorithm. Here, feature fusion is formulated as an optimization problem with PFree BAT optimization as its underlying search strategy and Fisher Criterion serving as a fitness function. Experiments were conducted on the magnetic resonance spectroscopy (MRS) data of 50 subjects out of which 27 showed low-grade glioma and rest presented high-grade. The MRS data was analyzed for the peaks. The conventional metabolite ratios, i.e., Choline/N-acetyl aspartate (Cho/NAA), Cho/Creatine (Cho/Cr), were quantitated using peak integration that exhibited difference among the tumor grades. The difference in the conventional metabolite ratios was enhanced by the proposed fused metabolite ratio that was duly validated by metrics of sensitivity, specificity, and the classification accuracy. Typically, the fused metabolite ratio characterized low-grade and high-grade with a sensitivity of 96%, specificity of 91%, and an accuracy of 93.72% when fed to the K-nearest neighbor classifier following a fivefold cross-validation data partitioning scheme. The results are significantly better than that obtained by the conventional metabolites where an accuracy equal to 80%, 87%, and 89% was attained. Prominently, the results using the fused metabolite ratio show a surge of 4.7% in comparison to Cho/Cr+Cho/NAA+NAA/Cr. Moreover, the obtained results are better than the similar works reported in the literature.

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma.

Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique.The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value (18F-FDG SUVmax), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable.18F-FDG SUVmax, Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables.Combined MRI and 18F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB.

Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder

Generalized anxiety disorder (GAD) is associated with brain functional and morphological changes in connected with emotional dysregulation and cognitive deficit. This study dealt with the neural functional deficits and metabolic abnormalities in working memory (WM) task with emotion-inducing distractors in patients with GAD. Fourteen patients with GAD and 14 healthy controls underwent functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) at 3T. In response to the emotional distractors in WM tasks, the patients concurrently showed higher activity in the hippocampus and lower activities in the superior occipital gyrus, superior parietal gyrus, dorsolateral prefrontal cortex (DLPFC) and precentral gyrus compared to the controls. MRS revealed significantly lower choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC. In particular, the Cho ratios were positively correlated with the brain activities based on blood oxygenation level-dependent signal change in the DLPFC. This study provides the first evidence for the association between the metabolic alterations and functional deficit in WM processing with emotion-inducing distractors in GAD. These findings will be helpful to understand the neural dysfunction in connection with WM impairment in GAD.

Optimal differentiation of high- and low-grade glioma and metastasis: a meta-analysis of perfusion, diffusion, and spectroscopy metrics.

To perform a meta-analysis of advanced magnetic resonance imaging (MRI) metrics, including relative cerebral blood volume (rCBV), normalized apparent diffusion coefficient (nADC), and spectroscopy ratios choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA), for the differentiation of high- and low-grade gliomas (HGG, LGG) and metastases (MTS). For systematic review, 83 articles (dated 2000-2013) were selected from the NCBI database. Twenty-four, twenty-two, and eight articles were included respectively for spectroscopy, rCBV, and nADC meta-analysis. In the meta-analysis, we calculated overall means for rCBV, nADC, Cho/Cr (short TE-from 20 to 35 ms, medium-from 135 to 144 ms), and Cho/NAA for the HGG, LGG, and MTS groups. We used random effects model to obtain weighted averages and select thresholds. Overall means (with 95% CI) for rCBV, nADC, Cho/Cr (short and medium echo time, TE), and Cho/NAA were: for HGG 5.47 (4.78-6.15), 1.38 (1.16-1.60), 2.40 (1.67-3.13), 3.27 (2.78-3.77), and 4.71 (3.24-6.19); for LGG 2.00 (1.71-2.28), 1.61 (1.36-1.87), 1.46 (1.20-1.72), 1.71 (1.49-1.93), and 2.36 (1.50-3.23); for MTS 5.06 (3.85-6.27), 1.35 (1.06-1.64), 1.89 (1.72-2.06), 3.14 (1.57-4.72), (Cho/NAA was not available). LGG had significantly lower rCBV, Cho/Cr, and Cho/NAA values than HGG or MTS. No significant differences were found for nADC. Best differentiation between HGG and LGG is obtained from rCBV, Cho/Cr, and Cho/NAA metrics. MTS could not be reliably distinguished from HGG by the methods investigated.

Differentiating Radiation-Induced Necrosis from Recurrent Brain Tumor Using MR Perfusion and Spectroscopy: A Meta-Analysis.

PurposeThis meta-analysis examined roles of several metabolites in differentiating recurrent tumor from necrosis in patients with brain tumors using MR perfusion and spectroscopy.MethodsMedline, Cochrane, EMBASE, and Google Scholar were searched for studies using perfusion MRI and/or MR spectroscopy published up to March 4, 2015 which differentiated between recurrent tumor vs. necrosis in patients with primary brain tumors or brain metastasis. Only two-armed, prospective or retrospective studies were included. A meta-analysis was performed on the difference in relative cerebral blood volume (rCBV), ratios of choline/creatine (Cho/Cr) and/or choline/N-acetyl aspartate (Cho/NAA) between participants undergoing MRI evaluation. A χ2-based test of homogeneity was performed using Cochran’s Q statistic and I2.ResultsOf 397 patients in 13 studies who were analyzed, the majority had tumor recurrence. As there was evidence of heterogeneity among 10 of the studies which used rCBV for evaluation (Q statistic = 31.634, I2 = 97.11%, P < 0.0001) a random-effects analysis was applied. The pooled difference in means (2.18, 95%CI = 0.85 to 3.50) indicated that the average rCBV in a contrast-enhancing lesion was significantly higher in tumor recurrence compared with radiation injury (P = 0.001). Based on a fixed-effect model of analysis encompassing the six studies which used Cho/Cr ratios for evaluation (Q statistic = 8.388, I2 = 40.39%, P = 0.137), the pooled difference in means (0.77, 95%CI = 0.57 to 0.98) of the average Cho/Cr ratio was significantly higher in tumor recurrence than in tumor necrosis (P = 0.001). There was significant difference in ratios of Cho to NAA between recurrent tumor and necrosis (1.02, 95%CI = 0.03 to 2.00, P = 0.044).ConclusionsMR spectroscopy and MR perfusion using Cho/NAA and Cho/Cr ratios and rCBV may increase the accuracy of differentiating necrosis from recurrent tumor in patients with primary brain tumors or metastases.

Brain morphological alterations and cellular metabolic changes in patients with generalized anxiety disorder: A combined DARTEL-based VBM and 1 H-MRS study

Generalized anxiety disorder (GAD) is characterized by emotional dysregulation and cognitive deficit in conjunction with brain morphometric and metabolic alterations. This study assessed the combined neural morphological deficits and metabolic abnormality in patients with GAD. Thirteen patients with GAD and 13 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI and proton magnetic resonance spectroscopy (1H-MRS) at 3Tesla. In this study, the combination of voxel-based morphometry (VBM) and 1H-MRS was used to assess the brain morphometric and metabolic alterations in GAD. The patients showed significantly reduced white matter (WM) volumes in the midbrain (MB), precentral gyrus (PrG), dorsolateral prefrontal cortex (DLPFC) and anterior limb of the internal capsule (ALIC) compared to the controls. In MRS study, the choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC were significantly lower in the patients. Particularly, the WM volume variation of the DLPFC was positively correlated with both of the Cho/Cr and Cho/NAA ratios in patients with GAD. This study provides an evidence for the association between the morphometric deficit and metabolic changes in GAD. This finding would be helpful to understand the neural dysfunction and pathogenesis in connection with cognitive impairments in GAD.

Comparison between magnetic resonance spectroscopy and diffusion weighted imaging in the evaluation of gliomas response after treatment

PurposeTo compare magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) in the assessment of progression and regression of brain tumors in order to assess whether there is correlation between MRS and DWI in the monitoring of patients with primary tumors after therapy. MethodsMagnetic resonance imaging (MRI) has been performed in 80 patients, 48 affected by high grade gliomas (HGG) and 32 affected by low grade gliomas (LGG). The variation of apparent diffusion coefficient (ADC) value and metabolite ratios before and after treatment has been used to test DWI sequences and MRS as predictor to response to therapy. Comparison between post contrast-enhancement sequences, MRS and DWI has been done in terms of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Moreover statistical correlation of ADC deviations with MRS metabolites variations before and after therapy have been studied. ResultsIn the case of HGG, MRS shows better sensitivity, specificity, PPV, NPV and accuracy compared to DWI, especially when considering the Choline/N-acetylaspartate (Cho/NAA) ratio. Regarding the LGG, the technique that better evaluates the response to treatment appears to be the DWI. A moderate correlation between ADC deviations and Cho, Lipide (Lip) and Lactate (Lac) has been found in LGG; while NAA revealed to be weakly correlated to ADC variation. Considering HGG, a weak correlation has been found between ADC deviations and MRS metabolites. ConclusionCombination of DWI and MRS can help to characterize different changes related to treatment and to evaluate brain tumor response to treatment.

Congruency of tumour volume delineated by FET PET and MRSI.

In addition to MR imaging, PET imaging of O-(2-[18F]Fluorethyl)-L-Tyrosine (FET) uptake provides information on brain tumour extent and metabolic activity. Similarly, MRS has been shown to be of value for distinguishing high- from low-grade gliomas. Based on 2D spatially resolved MRSI, an overlap between 18FET uptake and the choline/N-acetyl-aspartate (Cho/NAA) ratio of more than 75 % has been reported.