Magnetic Resonance Spectroscopy Parameters Research Articles

Central nervous system involvement in chronic inflammatory demyelinating polyradiculoneuropathy—MRS and DTI study

ObjectiveThe current research aimed to analyze the alterations within the motor cortex and pyramidal pathways and their association with the degree of damage within the peripheral nerve fibers in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). To achieve that goal, we investigated the microstructural changes within the pyramidal white matter tracts using diffusion tensor imaging (DTI) parameters, evaluated metabolic alterations in both precentral gyri using magnetic resonance spectroscopy (MRS) ratios, and correlated them with the neurographic findings in patients with CIDP.MethodsThe spectroscopic ratios of NAA/Cr, Cho/Cr, and mI/Cr from both precentral gyri and the values of fractional anisotropy (FA), axial diffusivity (AD), and mean diffusivity (MD) from both of the corticospinal tracts were correlated with the results of neurological and neurographic findings. The comparison of DTI parameters between the patients and controls was performed using Student’s t-test or the Mann–Whitney U test. Due to the lack of normal distribution of most variables, Spearman’s Rho rank coefficient was used to test all correlations. All analyses were performed at a significant level of alpha = 0.05 using STATISTICA 13.3.ResultsCompared to the control group (CG), the patient group showed significantly lower ratios of NAA/Cr (1.66 ± 0.11 vs. 1.61 ± 0.15; p = 0.022), higher ratios of ml/Cr in the right precentral gyrus (0.57 ± 0.15 vs. 0.61 ± 0.08; p = 0.005), and higher levels of Cho/Cr within the left precentral gyrus (0.83 ± 0.09 vs. 0.88 ± 0.14, p = 0.012). The DTI parameters of MD from the right CST and AD from the right and left CSTs showed a strong positive correlation (0.52–0.53) with the sural sensory nerve action potential (SNAP) latency of the right sural nerve. There were no other significant correlations between other DTI and MRS parameters and neurographic results.SignificanceIn our study, significant metabolic alterations were found in the precentral gyri in patients with CIDP without clinical symptoms of central nervous system involvement. The revealed changes reflected neuronal loss or dysfunction, myelin degradation, and increased gliosis. Our results suggest coexisting CNS damage in these patients and may provide a new insight into the still unknown pathomechanism of CIDP.

Magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics study may differentiate pre-eclampsia from gestational hypertension.

To investigate the findings of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and serum metabolomics for differentiating pre-eclampsia (PE) from gestational hypertension (GH). This prospective study enrolled 176 subjects including a primary cohort with healthy non-pregnant women (HN, n = 35), healthy pregnant women (HP, n = 20), GH (n = 27), and PE (n = 39) and a validation cohort with HP (n = 22), GH (n = 22), and PE (n = 11). T1 signal intensity index (T1SI), apparent diffusion coefficient (ADC) value, and the metabolites on MRS were compared. The differentiating performances of single and combined MRI and MRS parameters for PE were evaluated. Serum liquid chromatography-mass spectrometry (LC-MS) metabolomics was investigated by sparse projection to latent structures discriminant analysis. Increased T1SI, lactate/creatine (Lac/Cr), and glutamine and glutamate (Glx)/Cr and decreased ADC value and myo-inositol (mI)/Cr in basal ganglia were found in PE patients. T1SI, ADC, Lac/Cr, Glx/Cr, and mI/Cr yielded an area under the curves (AUC) of 0.90, 0.80, 0.94, 0.96, and 0.94 in the primary cohort, and of 0.87, 0.81, 0.91, 0.84, and 0.83 in the validation cohort, respectively. A combination of Lac/Cr, Glx/Cr, and mI/Cr yielded the highest AUC of 0.98 in the primary cohort and 0.97 in the validation cohort. Serum metabolomics analysis showed 12 differential metabolites, which are involved in pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism. MRS is expected to be a noninvasive and effective tool for monitoring GH patients to avoid the development of PE. • Increased T1SI and decreased ADC value in the basal ganglia were found in PE patients than in GH patients. • Increased Lac/Cr and Glx/Cr, and decreased mI/Cr in the basal ganglia were found in PE patients than in GH patients. • LC-MS metabolomics showed that the major differential metabolic pathways between PE and GH were pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism.

Radiological Prediction of Isocitrate Dehydrogenase (IDH) Mutational Status and Pathological Verification for Lower-Grade Astrocytomas

Background and objectiveThe isocitrate dehydrogenase (IDH) status of patients with World Health Organization (WHO) grade II or III astrocytoma is essential for understanding its biological features and determining therapeutic strategies. This study aimed to use radiological analysis to predict the IDH status of patients with lower-grade astrocytomas and to verify the pathological implications.MethodsIn this study, 47 patients with grade II (17 cases) or III astrocytomas (30 cases), based on 2016 WHO Classification, underwent methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) on the same day between January 2013 and June 2020. The patients were retrospectively assessed. Immunohistochemistry showed 23 cases of IDH-mutant and 24 of IDH-wildtype. Based on fluid-attenuated recovery inversion (FLAIR)/T2 imaging, three doctors blinded to clinical data independently allocated 18 patients to the clear boundary group between the tumor and the normal brain and 29 to the unclear boundary group. The peak ratios of N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and Cho/NAA and the tumor-to-normal region (T/N) ratio for maximum accumulation in MET-PET were calculated. For statistical analysis, Fisher’s exact test was used to assess associations between two variables, and the Mann-Whitney U test to compare the values between the IDH-wildtype and IDH-mutant groups. The optimal cut-off values of MET T/N ratio and MRS parameters for discriminating IDH-wildtype from IDH-mutant were obtained using receiver operating characteristics curves.ResultsThe unclear boundary group had significantly more IDH-wildtype cases than the clear boundary group (P<0.001). The IDH-wildtype group had significantly lower Cho/Cr (<1.84) and Cho/NAA (<1.62) ratios (P=0.02 and P=0.047, respectively) and a higher MET T/N ratio (>1.44, P=0.02) than the IDH-mutant group. The odds for the IDH-wildtype were 0.22 for patients who fulfilled none of the four criteria, including boundary status and three ratios, and 0.9 for all four criteria.ConclusionsThese results suggest that the combination of MRI, MRS, and MET-PET examination could be helpful for the prediction of IDH status in WHO grade II/III gliomas.

Radiological hints for differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia

Differentiation cerebellar multiple systemic atrophy (MSA-C) from spinocerebellar ataxia (SCA) is important. The “hot cross bun” sign (HCBS) at pons and magnetic resonance spectroscopy (MRS) are helpful. However, the prevalence of HCBS and the alteration of cerebellar MRS parameters are evolving with disease progression. We hypothesized that since the HCBS and MRS are evolving with time, different parameters for differentiation of MSA-C and SCA are required at different disease stages. The aim of this study was to evaluate the HCBS and MRS changes in patients with MSA-C and SCA at different disease stages. A total of 398 patients with molecularly confirmed SCA (SCA1, 2, 3, 6, 17) and 286 patients diagnosed with probable MSA-C (without mutations in SCA1, 2, 3, 6, 17 genes), who had received brain magnetic resonance imaging (MRI) and MRS from January 2000 to January 2020, were recruited. Twenty-five patients were molecularly identified as having SCA1, 68 as SCA2, 253 as SCA3, 34 as SCA6, and 18 as SCA17. We compared their clinical parameters and neuroimaging features at different disease stages. The presence of HCBS was assessed using an axial T2 fast spin-echo or FLAIR sequence. Proton MRS was recorded with voxel of interest focusing on cerebellar hemispheres and cerebellar vermis and avoiding cerebrospinal fluid spaces space using a single-voxel stimulated echo acquisition mode sequence. We found that patients with MSA-C tend to have a higher prevalence of pontine HCBS, worse Scale for the Assessment and Rating of Ataxia scores, lower cerebellar N-acetyl aspartate (NAA)/creatinine (Cr), and choline (Cho)/Cr, compared to patients with SCA at corresponding disease stages. In MSA-C patients with a disease duration < 1 year and without pontine HCBS, a cerebellar NAA/Cr ≤ 0.79 is a good indicator of the possibility of MSA-C. By using the pontine HCBS and cerebellar MRS, discerning MSA-C from SCA became possible. This study provides cutoff values of MRS to serve as clues in differentiating MSA-C from SCAs.

Brain metabolite alterations related to alcohol use: a meta-analysis of proton magnetic resonance spectroscopy studies.

Alcohol misuse and alcohol use disorder (AlUD) have neurobiological consequences. This meta-analysis of proton magnetic resonance spectroscopy (MRS) studies aimed to assess the differences in brain metabolite levels in alcohol misuse and AUD relative to controls (PROSPERO registration: CRD42020209890). Hedge's g with random-effects modeling was used. Sub-group and meta-regression techniques explored potential sources of demographic and MRS parameter heterogeneity. A comprehensive literature review identified 43 studies, resulting in 69 models across gray and white matter (GM, WM). Lower N-acetylaspartate levels were found in frontal, anterior cingulate cortex (ACC), hippocampal, and cerebellar GM, and frontal and parietal WM, suggesting decreased neuronal and axonal viability. Lower choline-containing metabolite levels (all metabolites contributing to choline peak) were found in frontal, temporal, thalamic, and cerebellar GM, and frontal and parietal WM, suggesting membrane alterations related to alcohol misuse. Lower creatine-containing metabolite levels (Cr; all metabolites contributing to Cr peak) were found in temporal and occipital cortical GM, while higher levels were noted in midbrain/brainstem GM; this finding may have implications for using Cr as an internal reference. The lack of significant group differences in glutamate-related levels is possibly related to biological and methodological complexities. The few studies reporting on GABA found lower levels restricted to the ACC. Confounding variables were age, abstinence duration, treatment status, and MRS parameters (echo time, quantification type, data quality). This first meta-analysis of proton MRS studies consolidates the numerous individual studies to identify neurometabolite alterations within alcohol misuse and AUD. Future studies can leverage this new formalized information to investigate treatments that might effectively target the observed disturbances.

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.

NI-6 Preoperative differential diagnosis of grade II and grade III in cases with astrocytoma, IDH mutant

Purpose: We attempted to differentiate between IDH-mutant astrocytoma Grade II and grade III by using methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Subjects and Methods: We retrospectively analyzed 41 adult supratentorial glioma cases with confirmed histological diagnosis and IDH status from June 2015 to June 2020. These included 21 males, with an average age of 38.5 years (19–59 years), including seven astrocytoma grade II (A-II) and 34 grade III (A-III) cases. We determined the accumulation value rate of the maximum tumor to normal cortex accumulation value (T/N ratio) in MET-PET. We obtained the peak ratios of N-acetyl aspartate (NAA)/ creatine (Cr), choline (Cho)/Cr, and Cho/NAA. We investigated the correlation between the T/N ratios and MRS parameters and examined the contrast effects on MRI. Results: There were no significant differences in the T/N ratio and MRS parameters between A-IIs and A-IIIs. Only Cho/NAA ratios were significantly correlated with the T/N ratios (r = 0.443, P = 0.0037). We divided the distribution map into four areas with the highest T/N ratio of AII (1.59) and the highest Cho/NAA ratio (3.66). That is, 1) T/N ratio ≤ 1.59 & Cho/NAA ≤ 3.66, 2) >1.59 & ≤ 3.66, 3) ≤1.59 & > 3.66, 4) > 1.59 & > 3.66. The diagnostic rates for A-III were 1) 61.1% (11/18), 2) 100% (7/7), 3) 100% (9/9), and 4) 100% (7/7). We found the contrast effects in only 7 cases (20.6%) of A-III, which were distributed in areas 2) to 4). Conclusion: A-IIs and A-IIIs distributed in area 1) were difficult to distinguish, and they need careful observation as a step before the transition to areas 2)-4). Meanwhile, A-IIIs reaching widespread distribution to areas 2)-4) because of their wide range of malignancies require clinically aggressive treatment. The method might be beneficial in grade analysis of IDH-mutant astrocytomas.

Diagnostic Performance of Proton Magnetic Resonance Spectroscopy and 18F-Fluorocholine PET to Differentiate Benign From Malignant Breast Lesions.

The aim of this study was to evaluate the diagnostic performance of the proton magnetic resonance spectroscopy (MRS) and 18F-fluorocholine (FCH) PET for suspicious breast findings on conventional imaging (mammography and breast ultrasound). From September 2012 to December 2015, 37 women with 39 breast lesions on conventional imaging were enrolled and underwent proton MRS and FCH PET. The MRS parameters of choline signal-to-noise ratio (SNR), choline integral (I(cho)), and the PET parameters including SUVmax in the prone (SUV1) and supine (SUV2) positions were analyzed. Receiver operating characteristic curves with the area under the curve, sensitivity, and specificity under the optimal cutoff points for the different parameters were determined. Twenty-three lesions (59%) were malignant, and 16 (41.0%) were benign. The malignant lesions tended to show significantly higher MRS and PET parameters than benign lesions (choline SNR, P = 0.007; I(cho), P = 0.003; SUV1 and SUV2, P < 0.0001). Fair to moderate correlations were noted between the choline SNR and PET parameters (SUV1, Spearman rank correlation coefficient, ρ = 0.477; SUV2, ρ = 0.483), as well as I(cho) and PET parameters (SUV1, ρ = 0.493; SUV2, ρ = 0.549). The SUV2 showed the highest diagnostic performance (area under the curve, 0.918). Using 2.5 as the optimal cutoff point, the SUV2 yields 89.5% sensitivity and 87.5% specificity for differentiating malignant from benign lesions. The MRS parameters were fairly to moderately correlated with FCH PET parameters, and both could differentiate malignant from benign breast lesions with SUV2 showing best diagnostic performance.

Magnetic resonance spectroscopy - its added value in brain glioma multiparametric assessment.

In this study, we analysed the results of magnetic resonance spectroscopy (MRS) in the patients with gliomas, including the error rate, MRS parameters variability, correlations with gene mutations and overall usefulness for clinical practice. Eighty patients with glial tumours were examined by multiparametric MRI completed with single voxel MRS, as one group, then as two separate groups according to progression of the disease after the initial surgery. The error rate between the groups, MRS parameters variability, hazard ratios and correlations between metabolites, genetic markers and tumour grade were all analysed. Variability in Cho/Cr(h) was significantly higher in the group with a disease progression (p = 0.044). In the patients with a stable disease, strong significant negative correlations between Cho/Cr and Cho/NAA with p53 mutation (-0.945 and -0.812 respectively, p < 0.05) and between Cho/Cr and IDH1, 2 mutation (-0.796, p < 0.05) were found. In the patients with tumour progression, a significant positive correlation of NAA/Cr with 1p19q codeletion (0.486, p < 0.05) and of Cho/Cr and Cho/NAA values with p53 mutation (0.477 and 0.416, p < 0.05) were identified. Tumour grade positively correlated with Cho/Cr values (0.304, p = 0.02) in the whole patient group. MRS brings an added value to multiparametric MRI evaluation of brain tumours in the patient follow-up after an initial surgery, especially in ambiguous findings (Tab. 5, Fig. 2, Ref. 29).

Magnetic resonance spectroscopy of the normal appearing grey matter in the posterior cingulate gyrus in the prognosis and monitoring of disease activity in MS patients treated with interferon-β in a 3-year follow-up

Several predictors of non-response to interferon-β (IFN-β) treatment have been proposed. The aim of the study was to identify metabolite changes in the normal-appearing cortex of the posterior cingulate gyrus (PCG) using MRS (magnetic resonance spectroscopy) and to investigate their usefulness in prognosis of NEDA (no evidence of disease activity) in the 3-year follow-up and in monitoring treatment effects during IFN-β therapy in the parallel period of time in multiple sclerosis (MS) patients.Forty-one relapsing-remitting MS patients and 41 sex- and age-matched healthy subjects underwent routine MRI protocol with MRS sequence with the use of a 1.5 T magnet. A single voxel size of 2x2x2cm was inserted in the cortex of PCG region. Associations between baseline metabolic ratios, conventional MRI findings, demographic and clinical factors, and NEDA status were evaluated using logistic, Cox, and multinomial logistic regression models.MS patients in the initial scan showed a statistically significant decline in NAA/Cr ratio (p < 0.0001) and an increase in Cho/Cr ratio (p = 0.016) compared to the control group. None of the MRS parameters predicted NEDA maintenance or the time to loss of NEDA. In treatment monitoring only an improvement in the combination of NAA/Cr + Cho/Cr ratio between the 1st and 2nd year of treatment was connected with a 6.27-fold chance (p = 0.025) of having simultaneous NEDA maintenance.To conclude, metabolite alterations in the PCG region did not predict NEDA maintenance, but they seem to be useful in treatment monitoring.

Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy for Differentiating Between Enhanced Gliomas and Malignant Lymphomas

Although the treatment strategies for malignant lymphomas and gliomas differ, it is usually difficult to preoperatively distinguish between them. Magnetic resonance spectroscopy (MRS) was recently reported to be useful for preoperative diagnoses; however, MRS data analysis using LCModel, which is a quantitative and objective method, was performed in only a few of the existing reports. The clinical characteristics, conventional magnetic resonance imaging findings, and MRS parameters using LCModel were evaluated to identify the factors that can help distinguish between malignant lymphomas and enhanced gliomas. In total, 59 cases were evaluated, including 13 cases of malignant lymphoma, 1 case of pilocytic astrocytoma, 5 cases of grade Ⅱ glioma, 5 cases of grade Ⅲ glioma, and 35 cases of glioblastoma. There was no correlation between clinical characteristics (sex and age) and diagnosis. Neither T1- nor T2-weighted image was useful for differentiation between the 2 forms of tumors, but the apparent diffusion coefficient minimum value was useful for distinguishing malignant lymphomas from gliomas, with an area under the curve (AUC) value of 0.852. MRS analysis using LCModel revealed differences in glutamate (Glu), N-acetylaspartate (NAA)+ N-acetylaspartylglutamate (NAAG), Glu+ glutamine, and Lipid (Lip) 13a+ Lip13b between malignant lymphomas and gliomas. The largest AUC was 0.904, which was obtained for the Glu level, followed by 0.883 and 0.866 for NAA+ NAAG and Lip13a+ Lip13b, respectively. Quantitative analysis of proton-MRS using LCModel is considered to be a valuable method for distinguishing between gliomas and malignant lymphomas.

Multiparametric MRI in differentiating solitary brain metastasis from high-grade glioma: diagnostic value of the combined use of diffusion-weighted imaging, dynamic susceptibility contrast imaging, and magnetic resonance spectroscopy parameters.

The purpose of this study was to determine whether the combined use of diffusion weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and dynamic susceptibility contrast imaging (DSCI) parameters could provide a more accurate diagnosis in the differentiation of high-grade glioma (HGG) from solitary brain metastasis (SBM) in the enhancing tumour and in the peritumoural region. Fifty-six patients who received DWI, DSCI, and MRS before surgery were assessed. In differentiating SBM from HGG, the cutoff values of the DWI-apparent diffusion coefficient (ADCmin, ADCmax, and ADCmean), DSCI-relative cerebral blood volume (rCBV), and MRS-Cho/Cr, Cho/NAA, and NAA/Cr parameters for the peritumoural region were determined with ROC. The combined ROC curve was used for the different combinations of the peritumoural region DWI, DSCI, and MRS parameters in differentiating between the two tumours, and the best model combination was formed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. This study was approved by the Institutional Review Board at our institutes. In the enhancing tumour, all the parameters except NAA/Cr (P = 0.024) exhibited no statistical difference in differentiating between these two groups (P > 0.05). AUC values for ADCmin, ADCmax, ADCmean, rADCmin, rADCmax, rADCmean, rCBV, Cho/Cr, Cho/NAA, and NAA/Cr parameters in the peritumoural region in differentiating SBM from HGG were 0.860, 0.822, 0.848, 0.822, 0.801, 0.822, 0.906, 0.851, 0.903, and 0.784, respectively. In differentiating HGG from SBM, the best model consisted of the combination of peritumoural ADCmin, rCBV, and Cho/NAA parameters. AUC values were 0.970. The combination of peritumoural region ADCmin, rCBV, and Cho/NAA parameters can help in differentiating SBM from HGG, with a diagnostic accuracy of 97%.

Targeting phosphocreatine metabolism in relapsing-remitting multiple sclerosis: evaluation with brain MRI, 1H and 31P MRS, and clinical and cognitive testing.

Fluoxetine and prucalopride might change phosphocreatine (PCr) levels via the cAMP-PKA pathway, an interesting target in the neurodegenerative mechanisms of MS. We conducted a two-center double-blind, placebo-controlled, randomized trial including 48 relapsing-remitting MS patients. Patients were randomized to receive placebo (n = 13), fluoxetine (n = 15), or prucalopride (n = 14) for 6 weeks. Proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were evaluated at weeks 0 and 6. No significant changes were observed for both 31P and 1H MRS indices. We found a significant effect on white matter volume and a trend towards an increase in grey matter and whole brain volume in the fluoxetine group at week 2; however, these effects were not sustained at week 6 for white matter and whole brain volume. Fluoxetine and prucalopride showed a positive effect on 9-HPT, depression, and fatigue scores. Both fluoxetine and prucalopride had a symptomatic effect on upper limb function, fatigue, and depression, but this should be interpreted with caution. No effect of treatment was found on 31P and 1H MRS parameters, suggesting that these molecules do not influence the PCr metabolism.

Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas.

Somatostatin analogs (SSAs) are considered one of the most effective medical treatments for patients with growth hormone-secreting pituitary adenomas (GH-PAs). The postoperative electron microscopy (EM) pathological subtype and SSTR2 expression in the tumor are the most established predictors of patient response to SSA therapy. The aim of this study was to evaluate how will magnetic resonance spectroscopy (MRS) measurements before surgery predict the EM pathological subtypes and SSTR2 expression of tumors, and thereby serve as an indicator for the therapeutic sensitivity to SSAs of patients with GH-PAs. Eighteen patients with GH pituitary macroadenomas who underwent transsphenoidal surgery were included in this retrospective study. The preoperative MRS data and T2 signal intensity were obtained from patients by 1.5 T MR spectroscopy of the sellar mass. The EM pathological subtypes of tumors were determined after surgery through examination of cell granulations. The expressions of somatostatin receptor 2 (SSTR2), SSTR5, P21, P27, and Ki-67 were evaluated by immunohistochemistry. The MRS parameters that were found to significantly predict the EM pathological subtypes of tumors, as calculated by the receiver operating characteristic curve, were the choline (Ch) value at 3140.5 MR units (sensitivity 69.2%, specificity 100%) and the choline/creatine (Ch/Cr) ratio at 1.27 (sensitivity 92.3%, specificity 100%). Further, the Ch/Cr ratio, but not other MRS data, was shown to negatively correlate with the expression of SSTR2 (P = 0.02). The Ch/Cr ratio was also found to positively correlate with the Ki-67 value (P < 0.05) and T2 signal (P < 0.05), but not with other factors that were examined in this study. Moreover, the Ch/Cr ratio could predict the EM pathological subtypes of tumors with an accuracy of 83.3% (5/6) for patients with an isointense T2 signal. The Ch/Cr ratio by MRS could effectively predict the tumor subtype and was significantly correlated with the expression of SSTR2, which was consistent with other predictors. It was also able to distinguish the patients with isointense T2 signals. Our results provide a potentially new and non-invasive method to predict the response to SSAs in patients with GH pituitary macroadenomas.

Correlation of Serum Biomarkers and Magnetic Resonance Spectroscopy in Monitoring Disease Progression in Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Due to mtDNA A3243G Mutation.

Background: Analysis of serum biomarkers and magnetic resonance spectroscopy (MRS) are useful for monitoring disease progression in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). We evaluated the correlation of serum biomarkers and MRS parameters during changes associated with stroke-like episodes.Methods: In 13 symptomatic MELAS patients carrying the A3243G mutation, we retrospectively obtained 207 voxels from 41 MRS studies, which were divided into three groups according to the temporal association with stroke-like episodes. The MRS NAA/Cr, Cho/Cr, NAA/Cho ratios, the presence of a lactate peak, serum biomarkers, serum lactate level and the pyruvate (Lac/Pyr) ratio were determined.Results: In regions with acute infarcts, the severity of serum Lac/Pyr and that of the MRS lactate peak (P = 0.0007) correlated; serum lactate (P = 0.02), severity of elevated serum lactate (P = 0.04), and serum Lac/Pyr (P = 0.02) correlated weakly. In previously infarcted regions, the severity of the MRS lactate peak and serum Lac/Pyr (P = 0.03), as well as the severity of serum Lac/Pyr (P = 0.02) were weakly correlated. In structurally normal regions, we found a weak to moderate negative correlation between serum lactate and MRS NAA/Cr (P = 0.008), and between the severity of elevated serum lactate and MRS NAA/Cr (P = 0.002) as well as MRS NAA/Cho (P = 0.02).Conclusions: MRS parameters correlate with specific serum biomarkers, and are useful for monitoring changes in brain metabolites, particularly as related to stroke-like episodes.

Anti-MAG associated cerebellar ataxia and response to rituximab.

Myelin-associated glycoprotein (MAG) is a glycoprotein specific to Schwann cells. Schwann cells produce myelin for nerve cells in the peripheral nervous system. MAG also plays a role in the central nervous system (CNS) by maintaining myelin integrity and inhibiting axonal regeneration from cerebellar neurons. There is a well-established link between distal demyelinating neuropathy and anti-MAG antibodies in patients with monoclonal gammopathy of unknown significance. We describe a series of five patients with anti-MAG antibodies with evidence of cerebellar rather than just sensory ataxia and our experience of treatment with rituximab. Cerebellar ataxia was clinically suspected and confirmed using magnetic resonance spectroscopy (MRS) of the cerebellum. All patients underwent detailed nerve conduction studies. Four patients were males. The ages ranged from 64 to 82years. All patients were anti-MAG positive and also had IgM monoclonal gammopathy. Four patients had neuropathy, whilst one had no evidence of neuropathy. All patients were treated with rituximab and showed improvement in the MRS parameters of the cerebellum. Anti-MAG antibodies might be involved in the pathogenesis of idiopathic sporadic ataxias, even in the absence of peripheral neuropathy. Rituximab seems to be a promising therapeutic intervention for those cases.

Invivo MR spectroscopy predicts high tumor grade in endometrial cancer.

Background Invivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue ( P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors ( P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. Invivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer.

Brain imaging in myotonic dystrophy type 1: A systematic review.

To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1). We searched Embase (index period 1974-2016) and MEDLINE (index period 1946-2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias. Results were summarized and pooled prevalence of imaging abnormalities was calculated, where possible. In DM1, various imaging changes are widely dispersed throughout the brain, with apparently little anatomical specificity. We found general atrophy and widespread gray matter volume reductions in all 4 cortical lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter hyperintensities is 70% (95% CI 64-77), compared with 6% (95% CI 3-12) in unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and reduced fractional anisotropy in virtually all major association, projection, and commissural white matter tracts. Functional studies demonstrate reduced glucose uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and abnormal fMRI connectivity patterns that correlate with personality traits. There is significant between-study heterogeneity in terms of imaging methods, which together with the established clinical variability of DM1 may explain divergent results. Longitudinal studies are remarkably scarce. DM1 brains show widespread white and gray matter involvement throughout the brain, which is supported by abnormal resting-state network, PET/SPECT, and MRS parameters. Longitudinal studies evaluating spatiotemporal imaging changes are essential.

Efficacy of 1H-MRSI and DWI for Non-invasive Grading of Brain Gliomas

Background: Distinguishing low-grade from high-grade gliomas can aid in optimal treatment planning and prognostication. Diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) have been applied in several studies for non-invasive glioma grading. However, these studies focused on limited aspects of these imaging techniques and used different study setups, resulting in occasionally inconsistent and incomparable conclusions in the literature. Objectives: This study was designed to introduce the optimal imaging setup and the most reliable and applicable imaging parameters in glioma grading, using DWI and MRS. Patients and Methods: During this prospective study, using a 3T-MR scanner, 55 glioma patients underwent brain MRS with short, intermediate, and long echo times (TEs), as well as DWI using low, intermediate, and high b-values. Postoperatively, all of the specimens were graded pathologically using light microscopy. Results: We found that Max (Chol/Cr)/ Min (NAA/Cr) ((maximum choline to creatine ratio)/(minimum N-acetyl aspartate to creatine ratio)), followed by Max (Chol/ Cr), both in long-TE, were the most reliable metabolite ratios on MRS for accurate glioma grading. These had values for area under the curve (AUC) of 0.92 (P < 0.05) and 0.89 (P = 0.001), respectively, compared to conventional MR imaging (cMRI), which had an AUC of 0.83 (P < 0.05). DWI at maximal accuracy showed an AUC of 0.80 (P < 0.05). Conclusion: Max (Chol/Cr)/Min (NAA/Cr) in long-TE was the most reliable of all of the MRS parameters studied, while DWI showed no superiority over cMRI in glioma grading. No significant differences existed among the various b-values applied, or between the minimum and mean tumor apparent diffusion coefficient values used in DWI-based glioma grading.

Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson's Disease.

Parkinson's disease (PD) is the most second common neurodegenerative movement disorder. Neuroinflammation due to systemic inflammation and elevated oxidative stress is considered a major factor promoting the pathogenesis of PD, but the relationship of structural brain imaging parameters to clinical inflammatory markers has not been well studied. Our aim was to evaluate the association of magnetic resonance spectroscopy (MRS) measures with inflammatory markers. Blood samples were collected from 33 patients with newly diagnosed PD and 30 healthy volunteers. MRS data including levels of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) were measured in the bilateral basal ganglia and cerebellum. Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes were significantly different between PD patients and normal healthy volunteers. Significant positive correlations were noted between MRS measures and inflammatory marker levels. In conclusion, patients with PD seem to have abnormal levels of inflammatory markers in the peripheral circulation and deficits in MRS measures in the dominant basal ganglion and cerebellum.