Characterisation of paediatric brain tumours by their MRS metabolite profiles.

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.

Interhemispheric reactivity of the subthalamic nucleus sustains progressive dopamine neuron loss in asymmetrical parkinsonism.

Parkinson's disease (PD) is characterized by the progressive and asymmetrical degeneration of the nigrostriatal dopamine neurons and the unilateral presentation of the motor symptoms at onset, contralateral to the most impaired hemisphere. We previously developed a rat PD model that mimics these typical features, based on unilateral injection of a substrate inhibitor of excitatory amino acid transporters, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), in the substantia nigra (SN). Here, we used this progressive model in a multilevel study (behavioral testing, in vivo 1H-magnetic resonance spectroscopy, slice electrophysiology, immunocytochemistry and in situ hybridization) to characterize the functional changes occurring in the cortico-basal ganglia-cortical network in an evolving asymmetrical neurodegeneration context and their possible contribution to the cell death progression. We focused on the corticostriatal input and the subthalamic nucleus (STN), two glutamate components with major implications in PD pathophysiology. In the striatum, glutamate and glutamine levels increased from presymptomatic stages in the PDC-injected hemisphere only, which also showed enhanced glutamatergic transmission and loss of plasticity at corticostriatal synapses assessed at symptomatic stage. Surprisingly, the contralateral STN showed earlier and stronger reactivity than the ipsilateral side (increased intraneuronal cytochrome oxidase subunit I mRNA levels; enhanced glutamate and glutamine concentrations). Moreover, its lesion at early presymptomatic stage halted the ongoing neurodegeneration in the PDC-injected SN and prevented the expression of motor asymmetry. These findings reveal the existence of endogenous interhemispheric processes linking the primary injured SN and the contralateral STN that could sustain progressive dopamine neuron loss, opening new perspectives for disease-modifying treatment of PD.

Comparative study of bilateral putamen for patients with severe Parkinson's disease detected by 1H magnetic resonance spectroscopy.

Background: The diagnosis of Parkinson's disease (PD) is challenging because the clinical symptoms overlap with other neurodegenerative diseases. The discovery of reliable biomarkers is highly expected to facilitate clinical diagnosis. Through the analysis of the 1H magnetic resonance spectroscopy (1H-MRS) in the putamen, the purpose of the study was to discuss the possibility of the difference in metabolite concentrations between the left and right putamen as biomarkers for patients with severe PD. Methods: We collected 1H-MRS of unilateral or bilateral putamen from 41 patients and used the independent sample t-test and paired t-test to analyze 4 metabolite concentrations, including choline (Cho), total N-acetyl aspartate (tNAA), total creatine (tCr), and combined glutamate and glutamine; Bonferroni correction was used to correct P values for multiple comparisons. We designed 4 controlled experiments as follows: (I) PD patients versus healthy controls (HCs) in the left putamen; (II) PD patients versus HCs in the right putamen; (III) the left putamen versus the right putamen for PD patients; and (IV) the left putamen versus the right putamen for HCs. Results: No statistically significant differences (P>0.05) were detected among 4 metabolites in the ipsilateral and bilateral putamen for the PD and HCs groups, except for tCr in the left putamen (PD 6.426±0.557, HCs 6.026±0.460, P=0.046) for ipsilateral comparisons. Conclusions: In the bilateral putamen of severe PD patients, there was no statistically significant difference in the 4 metabolites. The difference (P<0.05) in tCr in the left putamen might be a potential biomarker to distinguish HCs from severe patients in clinic. This might provide a reference for the clinical diagnosis and acquisition strategy of 1H-MRS in severe PD.

Comparison of 1H-magnetic resonance spectroscopy and blood biochemistry as methods for monitoring non-diffuse hepatic steatosis in a rat model.

No method of monitoring drug-induced hepatic steatosis has been established, which is a concern in drug development. Hepatic steatosis is divided into diffuse and non-diffuse forms according to the pattern of fat deposition. Diffuse hepatic steatosis was reported as evaluable by 1H-magnetic resonance spectroscopy (1H-MRS), which is used as an adjunct to the MRI examination. Blood biomarkers for hepatic steatosis have been also actively investigated. However, there are few reports to conduct 1H-MRS or blood test in human or animal non-diffuse hepatic steatosis with reference to histopathology. Therefore, to investigate whether non-diffuse hepatic steatosis can be monitored by 1H-MRS and/or blood samples, we compared histopathology to 1H-MRS and blood biochemistry in a non-diffuse hepatic steatosis rat model. Non-diffuse hepatic steatosis was induced by feeding rats the methionine choline deficient diet (MCDD) for 15 days. The evaluation sites of 1H-MRS and histopathological examination were three hepatic lobes in each animal. The hepatic fat fraction (HFF) and the hepatic fat area ratio (HFAR) were calculated from 1H-MRS spectra and digital histopathological images, respectively. Blood biochemistry analyses included triglycerides, total cholesterol, alanine aminotransferase, and aspartate aminotransferase. A strong correlation was found between HFFs and HFARs in each hepatic lobe (r = 0.78, p < 0.0001) in rats fed the MCDD. On the other hand, no correlation was found between blood biochemistry values and HFARs. This study showed that 1H-MRS parameters correlated with histopathological changes but blood biochemistry parameters didn't, so that it is suggested that 1H-MRS has the potential to be a monitoring method for non-diffuse hepatic steatosis in rats fed the MCDD. Given that 1H-MRS is commonly used in preclinical and clinical studies, 1H-MRS should be considered a candidate method for monitoring drug-induced hepatic steatosis.

Macromolecular-Suppressed GABA-Edited MR Spectroscopy in the Posterior Cingulate Cortex of Patients With Acute Mild Traumatic Brain Injury.

BACKGROUND: Mild traumatic brain injury (mTBI) causes a number of molecular and cellular alterations. There is evidence of an imbalance between the main excitatory (glutamate, Glu) and the main inhibitory (gamma-aminobutyric acid [GABA]) neurotransmitters following mTBI. In vivo human GABA-Glu balance studies following mTBI are sparse. PURPOSE: To investigate the effect of acute mTBI on the GABA concentration measured in the posterior cingulate cortex (PCC) of pediatric patients by using the macromolecular (MM)-suppressed GABA J-editing technique. STUDY TYPE: Prospective patient and phantom. PARTICIPANTS: A total of 14 pediatric patients (mean age 16.0 ± 1.7) with acute mTBI (<3 days after trauma; Glasgow Coma Scale 15) and 16 healthy volunteers (mean age 16.9 ± 2.8). Phantom: 524 cm3 sphere containing 10 mM glycine, 10 mM GABA. FIELD STRENGTH/SEQUENCE: A 3 T, MEGA-PRESS pulse sequence. ASSESSMENT: GABA spectra were processed in Gannet software. MM-suppressed GABA editing efficiency was derived from the phantom study. Absolute GABA and glutamate + glutamine (Glx) concentrations were quantified using different types of correction and compared between groups. N-acetyl aspartate (NAA) and choline (Cho) levels relative to tCr were also compared. STATISTICAL TESTS: Shapiro-Wilk test, Mann-Whitney U test, Student t-test, Pearson or Spearman correlations. P < 0.01 was considered statistically significant. RESULTS: The MM-suppressed GABA editing efficiency was 0.63. GABA signal fit error was <16% for all participants. The GABA concentration in the PCC of the mTBI group was significantly different from that in healthy controls: GABA/tCr was higher by 27%, absolute GABA concentration with different types of correction was higher by ≈17%. No significant differences were observed in Glx concentrations (P ≥ 0.32) or in Glx/tCr (P ≥ 0.1), NAA/tCr (P = 0.55), and Cho/tCr levels (P = 0.85). DATA CONCLUSION: We report an increase in the GABA concentration in the PCC region in acute mTBI pediatric patients. This may suggest activation of GABA synthesis and impairment of the GABAergic system after acute mTBI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

How to select the quantitative magnetic resonance technique for subjects with fatty liver: A systematic review.

BACKGROUND: Early quantitative assessment of liver fat content is essential for patients with fatty liver disease. Mounting evidence has shown that magnetic resonance (MR) technique has high accuracy in the quantitative analysis of fatty liver, and is suitable for monitoring the therapeutic effect on fatty liver. However, many packaging methods and postprocessing functions have puzzled radiologists in clinical applications. Therefore, selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging. AIM: To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver. METHODS: We completed a systematic literature review of quantitative MR techniques for detecting fatty liver, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Studies were retrieved from PubMed, Embase, and Cochrane Library databases, and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria. The Reference Citation Analysis database (https:// www.referencecitationanalysis.com) was used to analyze citation of articles which were included in this review. RESULTS: Forty studies were included for spectroscopy, two-point Dixon imaging, and multiple-point Dixon imaging comparing liver biopsy to other imaging methods. The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed. CONCLUSION: The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.

Magnetic Resonance Imaging and Spectroscopy Analysis in a Pelizaeus-Merzbacher Disease Rat Model.

Pelizaeus−Merzbacher disease (PMD) is an X-linked recessive disorder of the central nervous system. We performed 7 Tesla magnetic resonance imaging of the brain in Tama rats, a rodent PMD model, and control rats, as well as evaluated the diagnostic values. In the white matter of the Tama rats, the T2 values were prolonged, which is similar to that observed in patients with PMD (60.7 ± 1.8 ms vs. 51.6 ± 1.3 ms, p < 0.0001). The apparent diffusion coefficient values in the white matter of the Tama rats were higher than those of the control rats (0.68 ± 0.03 × 10−3 mm2/s vs. 0.64 ± 0.03 × 10−3 mm2/s, p < 0.05). In proton magnetic resonance spectroscopy, the N-acetylaspartate (6.97 ± 0.12 mM vs. 5.98 ± 0.25 mM, p < 0.01) and N-acetylaspartate + N-acetylaspartylglutamate values of the Tama rats were higher (8.22 ± 0.17 mM vs. 7.14 ± 0.35 mM, p < 0.01) than those of the control rats. The glycerophosphocholine + phosphocholine values of the Tama rats were lower than those of the control rats (1.04 ± 0.09 mM vs. 1.45 ± 0.04 mM, p < 0.001). By using Luxol fast blue staining, we confirmed dysmyelination in the Tama rats. These results are similar to those of patients with PMD and other PMD animal models.

[Correlation of Lipin gene expression with hepatic fat content in rats with intrauterine growth retardation]. / LipinåŸºå› è¡¨è¾¾ä¸Žå®«å† å‘è‚²è¿Ÿç¼“å¤§é¼ è‚è„è„‚è‚ªå«é‡çš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR). METHODS: Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T 1H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content. RESULTS: The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05). CONCLUSIONS: Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.

Glutamate cycle changes in the putamen of patients with de novo Parkinson's disease using 1H MRS.

INTRODUCTION: To investigate glutamatergic metabolism changes in the putamen of patients with de novo Parkinson's Disease (PD) and test the hypothesis that glutamate (Glu) levels are abnormally elevated in the putamen contralateral to where the motor clinical signs predominate as expected from observations in animal models. METHODS: 1H NMR spectra from 17 healthy control volunteers were compared with spectra from 17 de novo PD patients of who 14 were evaluated again after 2-3 years of disease progression. Statistical analysis used random-effects models. RESULTS: The only significant difference between PD patients and controls was a higher glutamine (Gln) concentration in the putamen ipsilateral to the hemibody with predominant motor signs (Visit 1: 6.0 ± 0.4 mM vs. 5.2 ± 0.2 mM, p < 0.05; Visit 2: 6.2 ± 0.3 mM vs. 5.2 ± 0.2 mM, p < 0.05). At Visit 1, PD patients had higher Glu and Gln levels in the putamen ipsilateral versus contralateral to dominant clinical signs (Glu: 12.2 ± 0.6 mM vs. 10.4 ± 0.6 mM, p < 0.05; Gln: 6.0 ± 0.4 mM vs. 4.8 ± 0.4 mM, p < 0.05; Glu and Gln pool (Glx): 17.9 ± 0.8 mM vs. 14.7 ± 1.1 mM, p < 0.05). At Visit 2, the sum of the two metabolites remained significantly higher in the ipsilateral versus contralateral putamen (Glx: 18.3 ± 0.6 mM vs. 16.1 ± 0.9 mM, p < 0.05). CONCLUSION: In de novo PD patients, the putamen ipsilateral to the more affected hemibody showed elevated Gln versus controls and elevated Glu and Gln concentrations versus the contralateral side. Abnormalities in Glu metabolism therefore occur early in PD but unexpectedly in the putamen contralateral to the more damaged hemisphere, suggesting they are not dependent solely on dopamine loss.

Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency.

BACKGROUND: Pantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency. A reliable technique to identify the neurometabolic effects of PANK dysfunction and to monitor therapeutic responses is needed. METHODS: We applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671. RESULTS: 1H MRS reliably quantified changes in cerebral metabolites, including glutamate/glutamine, lactate, and N-acetyl aspartate in a neuronal Pank1 and Pank2 double-knockout (SynCre+ Pank1,2 dKO) mouse model of brain CoA deficiency. The neuronal SynCre+ Pank1,2 dKO mice had distinct decreases in Glx/tCr, NAA/tCr, and lactate/tCr ratios compared to the wildtype matched control mice that increased in response to BBP-671 treatment. CONCLUSIONS: BBP-671 treatment completely restored glutamate/glutamine levels in the brains of the mouse model, suggesting that these metabolites are promising clinically translatable biomarkers for future therapeutic trials.

Added value of magnetic resonance spectroscopy for diagnosing childhood cerebellar tumours.

1 H-magnetic resonance spectroscopy (MRS) provides noninvasive metabolite profiles with the potential to aid the diagnosis of brain tumours. Prospective studies of diagnostic accuracy and comparisons with conventional MRI are lacking. The aim of the current study was to evaluate, prospectively, the diagnostic accuracy of a previously established classifier for diagnosing the three major childhood cerebellar tumours, and to determine added value compared with standard reporting of conventional imaging. Single-voxel MRS (1.5 T, PRESS, TE 30 ms, TR 1500 ms, spectral resolution 1 Hz/point) was acquired prospectively on 39 consecutive cerebellar tumours with histopathological diagnoses of pilocytic astrocytoma, ependymoma or medulloblastoma. Spectra were analysed with LCModel and predefined quality control criteria were applied, leaving 33 cases in the analysis. The MRS diagnostic classifier was applied to this dataset. A retrospective analysis was subsequently undertaken by three radiologists, blind to histopathological diagnosis, to determine the change in diagnostic certainty when sequentially viewing conventional imaging, MRS and a decision support tool, based on the classifier. The overall classifier accuracy, evaluated prospectively, was 91%. Incorrectly classified cases, two anaplastic ependymomas, and a rare histological variant of medulloblastoma, were not well represented in the original training set. On retrospective review of conventional MRI, MRS and the classifier result, all radiologists showed a significant increase (Wilcoxon signed rank test, p < 0.001) in their certainty of the correct diagnosis, between viewing the conventional imaging and MRS with the decision support system. It was concluded that MRS can aid the noninvasive diagnosis of posterior fossa tumours in children, and that a decision support classifier helps in MRS interpretation.

Correlation of Lipin gene expression with hepatic fat content in rats with intrauterine growth retardation / 中国当代儿科杂志

OBJECTIVES@#To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR).@*METHODS@#Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T 1H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content.@*RESULTS@#The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05).@*CONCLUSIONS@#Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.

[Comparison of 1H-MRS, Dixon fat-water separation and Z-spectral imaging for quantification of brown adipose tissue in rats].

OBJECTIVE: To evaluate the performance of 1H-magnetic resonance spectroscopy (1H-MRS), Dixon fat-water separation and Z-spectral magnetic resonance imaging (ZS-MRI) for quantification of fat content in phantoms and brown adipose tissues in rats. OBJECTIVE: First, six water-oil mixture phantoms with different fat fractions (0, 20%, 40%, 60%, 80% and 100%) were prepared and placed in a 50-mL centrifuge tube. ZS-MRI, 1H-MRS and Dixon's method were used to quantitatively evaluate the fat content of the phantom, and the results were compared against the actual fat fractions. Then, ZS-MRI and Dixon's method were used to collect the data in the interscapular region of 6 rats, the fat-water distribution map was calculated, and the results were compared with 1H-MRS. OBJECTIVE: ZS-MRI accurately quantified fat contents in the phantoms (Y=0.95*X+1.48). ZS-MRI was capable of distinguishing brown adipose tissue from white adipose tissue and defining the spatial distribution of the adipose tissue, and the results were highly consistent with those obtained by Dixon's method. No significant differences were found in the results derived by ZS-MRI and 1H-MRS for quantification of brown adipose tissue (P=0.35). OBJECTIVE: ZS-MRI can generate an artifact-free fat distribution map for quantitative measurement of the content and distribution of brown adipose tissues in rats.

Effect of electromyostimulation on intramyocellular lipids of the vastus lateralis in older adults: a randomized controlled trial.

BACKGROUND: Excessive intramyocellular lipid (IMCL) accumulation is a primary cause of skeletal muscle insulin resistance, especially in older adults, and interventions that reduce IMCL contents are important to improve insulin sensitivity. Electromyostimulation (EMS)-induced changes in IMCL content in older adults remain unknown. The purpose of this study was to clarify the effects of a single bout of EMS on the IMCL content of the vastus lateralis muscle in older adults. METHODS: Twenty-two physically active, non-obese older men and women were randomly assigned to an EMS intervention group (69.0 ± 5.2 years, n = 12) or a control group (68.4 ± 3.5 years, n = 10). EMS was applied to the vastus lateralis (7 s on and 7 s off) for 30 min; control participants sat quietly for 30 min. IMCL content within the vastus lateralis was quantified with 1H-magnetic resonance spectroscopy (n = 7 per group). Fasting plasma glucose and insulin values were determined from blood samples collected before and after the EMS intervention. RESULTS: EMS induced a significant reduction in plasma glucose (93.1 ± 9.6 to 89.5 ± 9.1 mg/dL, p < 0.01), but not IMCL content (15.7 ± 15.7 to 15.8 ± 13.1 mmol/kg wet weight, p = 0.49) or insulin (5.4 ± 2.4 to 4.7 ± 2.7 µIU/mL, p = 0.18). In the control group, no changes in IMCL content in the vastus lateralis was observed after prolonged quiet sitting. CONCLUSION: EMS intervention for 30 min induces changes in plasma glucose, but no changes in IMCL content in older adults. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center ID: UMIN000020126 . Retrospectively registered on December 222,015. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023242.

GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients.

Background: Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered in patients responsive to either anticonvulsants or ß-adrenergic blockers. Methods: In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using 1H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls. Results: There were no group differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. There was no correlation with tremor severity. Discussion: Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.

3T MEGA-PRESS study of N-acetyl aspartyl glutamate and N-acetyl aspartate in activated visual cortex.

OBJECTIVE: To measure N-acetyl aspartyl glutamate (NAAG) and N-acetyl aspartate (NAA) concentrations in visual cortex activated by a continuous stimulation in a 3 T field. METHODS: NAAG and NAA spectra were obtained with MEGA-PRESS pulse sequence (TE/TR = 140/2000 ms; δONNAAG/δOFFNAAG = 4.61/4.15 ppm; δONNAA/δOFFNAA = 4.84/4.38 ppm) in 14 healthy volunteers at rest and upon stimulation by a radial checkerboard flickering at a frequency of 8 Hz. Spectra of all subjects were frequency and phase aligned and then averaged. Additionally, to obtain the time-dependency data, spectra were divided into time sections of 64 s each. The intensities of NAA, NAAG and lactate + macromolecular (Lac + MM) signals were defined by integration of the real part of spectra. The heights of the central resonance of NAAG and NAA signals were measured. RESULTS: The NAAG and NAA concentrations, measured with 2.5% and 0.5% error, respectively, were unaffected by visual activation. A significant increase in the Lac + MM signal by ~ 12% is clearly observed. No stimulation-induced time dependency was found for NAAG or NAA, while the increase in Lac + MM was gradual. The concentration values in visual cortex are in good agreement with the 7 T MRS measurements: [NAAG] = 1.55 mM, [NAA] = 11.95 mM. CONCLUSION: The MEGA-PRESS pulse sequence together with the spectral preprocessing techniques allowed to demonstrate that the concentrations of NAAG and NAA in the visual cortex remain constant during continuous visual stimulation within the margin of error. An increase in the lactate signal intensity signifies the activation of the anaerobic glycolysis in activated visual cortex.

Neurochemical Differences in Spinocerebellar Ataxia Type 14 and 1.

Autosomal-dominant spinocerebellar ataxias (SCA) are neurodegenerative diseases characterized by progressive ataxia. Here, we report on neurometabolic alterations in spinocerebellar ataxia type 1 (SCA1; SCA-ATXN1) and 14 (SCA14; SCA-PRKCG) assessed by non-invasive 1H magnetic resonance spectroscopy. Three Tesla 1H magnetic resonance spectroscopy was performed in 17 SCA14, 14 SCA1 patients, and in 31 healthy volunteers. We assessed metabolites in the cerebellar vermis, right cerebellar hemisphere, pons, prefrontal, and motor cortex. Additionally, clinical characteristics were obtained for each patient to correlate them with metabolites. In SCA14, metabolic changes were restricted to the cerebellar vermis compared with widespread neurochemical alterations in SCA1. In SCA14, total N-acetylaspartate (tNAA) was reduced in the vermis by 34%. In SCA1, tNAA was reduced in the vermis (24%), cerebellar hemisphere (26%), and pons (25%). SCA14 patients showed 24% lower glutamate+glutamine (Glx) and 46% lower γ-aminobutyric acid (GABA) in the vermis, while SCA1 patients showed no alterations in Glx and GABA. SCA1 revealed a decrease of aspartate (Asp) in the vermis (62%) and an elevation in the prefrontal cortex (130%) as well as an elevation of myo-inositol (Ins) in the cerebellar hemisphere (51%) and pons (46%). No changes of Asp and Ins were detected in SCA14. Beyond, glucose (Glc) was increased in the vermis of both SCA14 (155%) and SCA1 (247%). 1H magnetic resonance spectroscopy revealed differing neurochemical profiles in SCA1 and SCA14 and confirmed metabolic changes that may be indicative for neuronal loss and dysfunctional energy metabolism. Therefore, 1H magnetic resonance spectroscopy represents a helpful tool for in-vivo tracking of disease-specific pathophysiology.

Abnormalities in Brain and Muscle Microstructure and Neurochemistry of the DMD Rat Measured by in vivo Diffusion Tensor Imaging and High Resolution Localized 1H MRS.

Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by the lack of dystrophin with progressive degeneration of skeletal muscles. Most studies regarding DMD understandably focus on muscle, but dystrophin is also expressed in the central nervous system, potentially resulting in cognitive and behavioral changes. Animal models are being used for developing more comprehensive neuromonitoring protocols and clinical image acquisition procedures. The recently developed DMD rat is an animal model that parallels the progressive muscle wasting seen in DMD. Here, we studied the brain and temporalis muscle structure and neurochemistry of wild type (WT) and dystrophic (DMD) rats using magnetic resonance imaging and spectroscopy. Both structural and neurochemistry alterations were observed in the DMD rat brain and the temporalis muscle. There was a decrease in absolute brain volume (WT = 1579 mm3; DMD = 1501 mm3; p = 0.039, Cohen's d = 1.867), but not normalized (WT = 4.27; DMD = 4.02; p = 0.306) brain volume. Diffusion tensor imaging (DTI) revealed structural alterations in the DMD temporalis muscle, with increased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). In the DMD rat thalamus, DTI revealed an increase in fractional anisotropy (FA) and a decrease in RD. Smaller normalized brain volume correlated to severity of muscle dystrophy (r = -0.975). Neurochemical changes in the DMD rat brain included increased GABA and NAA in the prefrontal cortex, and GABA in the hippocampus. Such findings could indicate disturbed motor and sensory signaling, resulting in a dysfunctional GABAergic neurotransmission, and an unstable osmoregulation in the dystrophin-null brain.

Magnetic Resonance Spectroscopy of the Head and Neck: Principles, Applications, and Challenges.

Several investigations have revealed the utility of magnetic resonance spectroscopy (MRS) as an adjunct in the evaluation of lesions of the head and neck. This technique remains a challenge in the head and neck because of its low signal-to-noise ratio and long acquisition times. In this review article, the basics of image acquisition technique and reported clinical utilities of head and neck MRS are presented.

Metabolic syndrome and myocardium steatosis in subclinical type 2 diabetes mellitus: a 1H-magnetic resonance spectroscopy study.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that collectively cause an increased risk of type 2 diabetes mellitus (T2DM) and nonatherosclerotic cardiovascular disease. This study aimed to evaluate the role of myocardial steatosis in T2DM patients with or without MetS, as well as the relationship between subclinical left ventricular (LV) myocardial dysfunction and myocardial steatosis. METHODS AND MATERIALS: We recruited 53 T2DM patients and 20 healthy controls underwent cardiac magnetic resonance examination. All T2DM patients were subdivide into two group: MetS group and non-MetS. LV deformation, perfusion parameters and myocardial triglyceride (TG) content were measured and compared among these three groups. Pearson's and Spearman analysis were performed to investigate the correlation between LV cardiac parameters and myocardial steatosis. The receiver operating characteristic curve (ROC) was performed to illustrate the relationship between myocardial steatosis and LV subclinical myocardial dysfunction. RESULTS: An increase in myocardial TG content was found in the MetS group compared with that in the other groups (MetS vs. non-MetS: 1.54 ± 0.63% vs. 1.16 ± 0.45%; MetS vs. normal: 1.54 ± 0.63% vs. 0.61 ± 0.22%; all p < 0.001). Furthermore, reduced LV deformation [reduced longitudinal and radial peak strain (PS); all p < 0.017] and microvascular dysfunction [increased time to maximum signal intensity (TTM) and reduced Upslope; all p < 0.017)] was found in the MetS group. Myocardial TG content was positively associated with MetS (r = 0.314, p < 0.001), and it was independently associated with TTM (ß = 0.441, p < 0.001) and LV longitudinal PS (ß = 0.323, p = 0.021). ROC analysis exhibited that myocardial TG content might predict the risk of decreased LV longitudinal myocardial deformation (AUC = 0.74) and perfusion function (AUC = 0.71). CONCLUSION: Myocardial TG content increased in T2DM patients with concurrent MetS. Myocardial steatosis was positively associated with decreased myocardial deformation and perfusion dysfunction, which may be an indicator for predicting diabetic cardiomyopathy.