1H Magnetic Resonance Research Articles

Increased liver fat associates with severe metabolic perturbations in low birth weight men.

Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors. Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD). The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups. Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.

Thalamic Neurometabolite Alterations in Chronic Low Back Pain: A Common Phenomenon across Musculoskeletal Pain Conditions?

A previous study by our group showed that knee osteoarthritis (KOA) patients demonstrate alterations in the thalamic levels of several metabolites, as measured by 1H-magnetic resonance spectroscopy: i.e., higher myo-inositol (mIns), lower N-acetylaspartate (NAA) and lower Choline (Cho), when compared to healthy controls. We sought to replicate these results in a different musculoskeletal pain condition, chronic low back pain (cLBP), and explore whether these metabolites would resolve clinical subtypes of cLBP. Twenty-nine cLBP patients (twenty-two with axial low back pain, cLBPAX, and seven with radicular low back pain, cLBPRAD), and twenty healthy controls were scanned using a conventional PRESS sequence (TE=30ms; TR=1.7s; voxel size=15 × 15 × 15mm) with voxel placement in the left thalamus. Using water-normalized levels, cLBP patients demonstrated higher mIns (p<0.01), lower NAA (p<0.001) and lower Cho (p<0.05) than healthy controls, replicating our prior KOA results in this cLBP cohort. Additionally, NAA was reduced in cLBPAX when compared to cLBPRAD (p<0.05), whereas differences found in Cho and mIns were not statistically significant (p<0.20 and p<0.15, respectively). While pain severity scores were not correlated with metabolite levels, the degree of nociplastic pain, as measured by score on the American College of Rheumatology Fibromyalgia Survey, negatively correlated with NAA. These results suggest that thalamic metabolite changes may be common across spatially different musculoskeletal chronic pain conditions for mIns, a marker of glial dysfunction, NAA, a marker of neuronal integrity, and Cho, a membrane turnover marker. Additionally, the differences between cLBP subtypes suggest that neuronal integrity may have a role to play in the pathophysiology of nociplastic pain. Grant support from 1-R01-NS094306-01A1 (MLL); 1-R01-NS09593701A1 (MLL).

Early Metabolic Changes in 1H-MRSI Predictive for Survival in Patients With Newly Diagnosed High-grade Glioma.

The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy. Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRSI scans provided measures of tumor choline, creatine, and N-acetylaspartate (NAA). Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival. Median follow-up time for patients at risk was 13.4 years. Overall survival (OS) was longer in patients with ≤20% increase (vs. >20%) in normalized choline (p=0.024) or choline/NAA (p=0.024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in patients with ≤40% increase (vs. >40%) in normalized choline (p=0.013). Changes in normalized creatine, choline/creatine, and NAA/creatine from baseline to mid-RT were not associated with OS. From baseline to post-RT, changes in metabolic metrics were not associated with OS or PFS. Threshold values for serial changes in choline metrics on mid-RT MRSI associated with OS and PFS were identified. Metabolic metrics at post-RT did not predict for these survival endpoints. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response and could enable risk-adapted therapy in clinical trial development and clinical practice.

P127. A Preliminary Study on the Association Between Anterior Cingulate Gaba and Trait Boldness

Boldness is a heritable personality trait reflecting low sensitivity to threat. Boldness is negatively associated with symptoms of anxiety disorders and positively associated with the interpersonal and affective deficits observed in psychopathy. Thus, boldness may be an important risk factor for disorders involving abnormal fear processing. Proton (1H) magnetic resonance spectroscopy (MRS) has shown that higher concentrations of prefrontal γ-amino butyric acid (GABA) in the anterior cingulate (ACC) is implicated in the extinction and recovery of conditioned fear. The current study was a preliminary investigation of the link between boldness and GABA concentrations in the ACC.

Imaging biomarkers of TERT or GABPB1 silencing in TERT-positive glioblastoma.

TERT promoter mutations are observed in 80% of wild-type IDH glioblastoma (GBM). Moreover, the upstream TERT transcription factor GABPB1 was recently identified as a cancer-specific therapeutic target for tumors harboring a TERT promoter mutation. In that context, noninvasive imaging biomarkers are needed for the detection of TERT modulation. Multiple GBM models were investigated as cells and in vivo tumors and the impact of TERT silencing, either directly or by targeting GABPB1, was determined using 1H and hyperpolarized 13C magnetic resonance spectroscopy (MRS). Changes in associated metabolic enzymes were also investigated. 1H-MRS revealed that lactate and glutathione (GSH) were the most significantly altered metabolites when either TERT or GABPB1 was silenced, and lactate and GSH levels were correlated with cellular TERT expression. Consistent with the drop in lactate, 13C-MRS showed that hyperpolarized [1-13C]lactate production from [1-13C]pyruvate was also reduced when TERT was silenced. Mechanistically, the reduction in GSH was associated with a reduction in pentose phosphate pathway flux, reduced activity of glucose-6-phosphate dehydrogenase, and reduced NADPH. The drop in lactate and hyperpolarized lactate were associated with reductions in glycolytic flux, NADH, and expression/activity of GLUT1, monocarboxylate transporters, and lactate dehydrogenase A. Our study indicates that MRS-detectable GSH, lactate, and lactate production could serve as metabolic biomarkers of response to emerging TERT-targeted therapies for GBM with activating TERT promoter mutations. Importantly these biomarkers are readily translatable to the clinic, and thus could ultimately improve GBM patient management.

Correlation of Lipin gene expression with hepatic fat content in rats with intrauterine growth retardation

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). 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. 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). 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.

Ethnic and sex differences in hepatic lipid content and related cardiometabolic parameters in lean individuals.

BackgroundNonalcoholic fatty liver affects 25% to 30% of the US and European populations; is associated with insulin resistance (IR), type 2 diabetes, and increased cardiovascular risk; and is defined by hepatic triglyceride (HTG) content greater than 5.56%. However, it is unknown whether HTG content less than 5.56% is associated with cardiometabolic risk factors and whether there are ethnic (Asian Indian, AI, versus non-AI) and/or sex differences in these parameters in lean individuals.MethodsWe prospectively recruited 2331 individuals and measured HTG, using 1H magnetic resonance spectroscopy, and plasma concentrations of triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and uric acid. Insulin sensitivity was assessed using Homeostatic Model Assessment of Insulin Resistance and the Matsuda Insulin Sensitivity Index.ResultsThe 95th percentile for HTG in lean non-AI individuals was 1.85%. Plasma insulin, triglycerides, total cholesterol, LDL-cholesterol, and uric acid concentrations were increased and HDL-cholesterol was decreased in individuals with HTG content > 1.85% and ≤ 5.56% compared with those individuals with HTG content ≤ 1.85%, and these altered parameters were associated with increased IR. Mean HTG was lower in lean non-AI women compared with lean non-AI men, whereas lean AI men and women had a 40% to 100% increase in HTG when compared with non-AI men and women, which was associated with increased cardiometabolic risk factors.ConclusionWe found that the 95th percentile of HTG in lean non-AI individuals was 1.85% and that HTG concentrations above this threshold were associated with IR and cardiovascular risk factors. Premenopausal women were protected from these changes whereas young, lean AI men and women manifested increased HTG content and associated cardiometabolic risk factors.FundingGrants from the United States Department of Health and Human Resources (NIH/National Institute of Diabetes and Digestive and Kidney Diseases): R01 DK113984, P30 DK45735, U24 DK59635, and UL1 RR024139; and the Novo Nordisk Foundation (NNF18CC0034900).

Magnetic Resonance Imaging (MRI) and MR Spectroscopic Methods in Understanding Breast Cancer Biology and Metabolism.

A common malignancy that affects women is breast cancer. It is the second leading cause of cancer-related death among women. Metabolic reprogramming occurs during cancer growth, invasion, and metastases. Functional magnetic resonance (MR) methods comprising an array of techniques have shown potential for illustrating physiological and molecular processes changes before anatomical manifestations on conventional MR imaging. Among these, in vivo proton (1H) MR spectroscopy (MRS) is widely used for differentiating breast malignancy from benign diseases by measuring elevated choline-containing compounds. Further, the use of hyperpolarized 13C and 31P MRS enhanced the understanding of glucose and phospholipid metabolism. The metabolic profiling of an array of biological specimens (intact tissues, tissue extracts, and various biofluids such as blood, urine, nipple aspirates, and fine needle aspirates) can also be investigated through in vitro high-resolution NMR spectroscopy and high-resolution magic angle spectroscopy (HRMAS). Such studies can provide information on more metabolites than what is seen by in vivo MRS, thus providing a deeper insight into cancer biology and metabolism. The analysis of a large number of NMR spectral data sets through multivariate statistical methods classified the tumor sub-types. It showed enormous potential in the development of new therapeutic approaches. Recently, multiparametric MRI approaches were found to be helpful in elucidating the pathophysiology of cancer by quantifying structural, vasculature, diffusion, perfusion, and metabolic abnormalities in vivo. This review focuses on the applications of NMR, MRS, and MRI methods in understanding breast cancer biology and in the diagnosis and therapeutic monitoring of breast cancer.

Electroreduction of Nitrate to Ammonia on Palladium-Cobalt-Oxygen Nanowire Arrays.

Developing high-efficiency electrocatalysts for the selective reduction of nitrate to valuable ammonia is of great significance. Herein, Pd-PdO-modified Co3O4 nanowire arrays on nickel foam (PdCoO/NF) are fabricated by a facile cation-exchange reaction. Pd and PdO can facilitate the generation of adsorbed hydrogen, and abundant oxygen vacancies can promote nitrate activation. Therefore, the PdCoO/NF exhibits a superior nitrate conversion rate (89.3%), Faradaic efficiency (88.6%), and ammonium selectivity (95.3%) at -1.3 V versus a saturated calomel electrode. The source of the produced ammonia is confirmed by 15N isotope labeling experiments and 1H magnetic resonance. This presented synthetic method provides a powerful strategy for the preparation of nanowire arrays with controllable compositions for selective nitrate electroreduction to ammonia.

Alteration of gamma-aminobutyric acid in the left dorsolateral prefrontal cortex of individuals with chronic insomnia: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study

ObjectiveTo investigate changes in the level of gamma-aminobutyric acid (GABA) in the left dorsolateral prefrontal cortex (DLPFC) of patients with chronic insomnia treated with real repetitive transcranial magnetic stimulation (rTMS) as compared to sham-rTMS, as measured with 1H-Magnetic Resonance Spectroscopy (1H-MRS). MethodsForty chronic insomnia participants were randomized to either real or sham rTMS group. The rTMS was administered once per day Continuously for 14 days with the stimulation over the left DLPFC. Left DLPFC GABA level relative to creatine (Cr) was measured by 1H-MRS. Insomnia symptom was evaluated by Insomnia Severity Index (ISI). MRS and ISI were assessed among all participants before and after treatment. This study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100047255). ResultsAfter treatment, the ISI score in real rTMS group was markedly decreased as compared to pre-rTMS (t = −4.25, p < 0.001, Cohen's d = 0.90), whereas no significant change in ISI was observed in the group of sham rTMS. In addition, we observed a significant increase of GABA+/Cr concentration in the real rTMS group after stimulation (0.37 ± 0.11 to 0.40 ± 0.11, p = 0.039), but that of sham did not (0.38 ± 0.10 to 0.39 ± 0.11, p = 0.151). However, there was no significant association between the change of GABA+/Cr in left DLPFC and the changes of ISI scores in the two groups. Conclusion1 Hz rTMS has the potential to increase GABA + level in left DLPFC of patients with chronic insomnia, and warrants further investigation.

Reversibility of brain glucose kinetics in type 2 diabetes mellitus

Aims/hypothesisWe have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA1c normalise intracerebral glucose levels.MethodsEight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m2 and HbA1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent 1H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.ResultsFollowing the intervention, mean ± SD HbA1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA1c (r = 0.71, p=0.048).Conclusion/interpretationThese findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control.Trial registrationClinicalTrials.gov NCT03469492.Graphical abstract

Diffusion Tensor Imaging Revealed Microstructural Changes in Normal-Appearing White Matter Regions in Relapsing-Remitting Multiple Sclerosis.

BackgroundAxons and myelin sheaths are the physical foundation for white matter (WM) to perform normal functions. Our previous study found the metabolite abnormalities in frontal, parietal, and occipital normal-appearing white matter (NAWM) regions in relapsing–remitting multiple sclerosis (RRMS) patients by applying a 2D 1H magnetic resonance spectroscopic imaging method. Since the metabolite changes may associate with the microstructure changes, we used the diffusion tensor imaging (DTI) method to assess the integrity of NAWM in this study.MethodDiffusion tensor imaging scan was performed on 17 clinically definite RRMS patients and 21 age-matched healthy controls on a 3.0-T scanner. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 19 predefined regions of interest (ROIs), which were generated by removing a mask of manually drawn probabilistic lesion map from the Johns Hopkins University white-matter atlas. The mean values of FA, MD, AD, and RD were compared between different groups in the same ROIs.ResultsA probabilistic lesion map was successfully generated, and the lesion regions were eliminated from the WM atlas. We found that the RRMS patients had significantly lower FA in the entire corpus callosum (CC), bilateral of anterior corona radiata, and right posterior thalamic radiation (PTR). At the same time, RRMS patients showed significantly higher MD in the bilateral anterior corona radiata and superior corona radiata. Moreover, all AD values increased, and the bilateral external capsule, PTR, and left tapetum NAWM show statistical significance. What is more, all NAWM tracts showed increasing RD values in RRMS patients, and the bilateral superior corona radiata, the anterior corona radiata, right PTR, and the genu CC reach statistical significance.ConclusionOur study revealed widespread microstructure changes in NAWM in RRMS patients through a ready-made WM atlas and probabilistic lesion map. These findings support the hypothesis of demyelination, accumulation of inflammatory cells, and axonal injury in NAWM for RRMS. The DTI-based metrics could be considered as potential non-invasive biomarkers of disease severity.

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

BackgroundPantothenate 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.MethodsWe applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671.Results1H 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.ConclusionsBBP-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.

Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1T.

Extended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by 1H and 23Na magnetic resonance imaging (MRI) at 21.1T to investigate cellular localization, migration, and recovery over an extended timeframe. MRI provides quantifiable metrics of tissue status through sodium distributions in addition to traditional proton imaging. Quantitative 23Na MRI revealed a significant decrease of sodium concentrations following hMSC aggregate implantation, indicating recovery of homeostasis. This result correlates positively with extended neurological recovery assessed by behavioral analysis and immunohistochemistry. These findings demonstrate the potential of implanted hMSC aggregate therapy to provide extended treatment for ischemic stroke, as well as the robustness of MRI for monitoring such approaches. This method potentially can be translated to a clinical setting for the assessment of extended cell therapy efficacy.

1H-MR spectroscopy in grading of cerebral glioma: A new view point, MRS image quality assessment.

BackgroundNoninvasive preoperative prediction of histological grading is essential for clinical management of cerebral glioma.PurposeThis study aimed to investigate the association between the image quality assessment of 1H magnetic resonance spectroscopy and accurate grading of glioma.Materials and Methods98 glioma patients confirmed by pathology were retrospectively recruited in this single-center study. All patients underwent 1H-MRS examination at 3.0T before surgery. According to WHO standards, all cases were divided into two groups: low-grade glioma (grade I and II, 48 cases) and high-grade glioma (grades III and IV, 50 cases). The metabolite ratios in both grades were calculated before and after image quality assessment. The area under the receiver operating characteristic (ROC) curve was used to evaluate the capacity of each ratio in glioma grading.ResultsThe Cho/Cr, Cho/NAA and NAA/Cr metabolite ratios had certain differences in each glioma group before and after MRS image quality assessment. In the low-grade glioma group, there was a dramatic difference in the Cho/Cr ratio before and after image quality assessment (p = 0.011). After MRS image quality assessment, the accuracy of glioma grading was significantly improved. The Cho/Cr ratio with 83.3% sensitivity and 93.7% specificity is the best index of glioma grading, with the optimal cutoff value of the Cho/Cr ratio being 3.72.ConclusionThe image quality of MRS does affect the metabolite ratios and the results of glioma grading. MRS image quality assessment can observably improve the accuracy rate of glioma grading. The Cho/Cr ratio has the best diagnostic performance in differentiating high-grade from low-grade glioma.

Perfil lipoproteico por espectroscopia nuclear magnética en pacientes con insuficiencia cardiaca crónica comparado con controles emparejados

Introduction and objectivesAdvanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. MethodsThis cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. ResultsThe 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P<.001) and HDL (25.7 vs 27.9μmol/L; P <.001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6μmol/L; P <.001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size. ConclusionsPatients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference.

Glutamic Acid and Total Creatine as Predictive Markers for Epilepsy in Glioblastoma by Using Magnetic Resonance Spectroscopy Before Surgery

Epilepsy in glioblastoma patients significantly reduces their quality of life; however, little is known about the association between predicting epilepsy and metabolites in tumors. In this study, we used 3.0-T magnetic resonance imaging and 1H-magnetic resonance spectroscopy (MRS) to quantify metabolite concentrations in patients with varying epilepsy histories. Fifty-one patients with glioblastoma underwent pretreatment 3.0-T MRI/1H-MRS scanning. Single-voxel (1.5 cm3) MRS, in an enhanced lesion, was acquired using adouble-echo point-resolved spectroscopic sequence with chemical-shift selective water suppression. MRS data were quantified with linear combination model (LC-Model) software. We compared the MRS data between groups withand without epilepsy during the postoperative course(EP). The ratios of glutamate (Glu) and glutamate+ glutamine (Glx) to total creatine (Glu/tCr and Glx/tCr) in the tumor were associated with epilepsy history. The receiver operating characteristic curve analysis showed that a Glu/tCr value of 1.81 was 70% sensitive and 90% specific for the prediction of EP (area under curve: 0.82). In the analysis excluding patients with preoperative epilepsy, a Glu/tCr value of 1.81 was 75% sensitive and 88% specific for the prediction (area under curve: 0.87). Intratumoral metabolite concentrations measured using pretreatment 3.0-T MRI/1H-MRS changed characteristically in the group with EP. Our study suggests that the Glu/tCr ratio in tumors has adequate reliability in predicting EP. Pretreatment MRS is a minimally invasive and simple procedure that can provide useful information on glioblastoma patients.

Crystal structure and DNA cleavage properties of a vanadium complex [NH4][VO(O2)2(pm-im)]⋅3H2O containing 2-(1H-imidazol-2-yl)pyrimidine ligand

A new diperoxovanadium compound, [NH4][VO(O2)2(pm-im)]⋅3H2O (1) (pm-im = 2-(1H-imidazol-2-yl)pyrimidine), has been prepared from aqueous solution and its crystal structure has been determined by single-crystal X-ray diffraction. It belongs to the monoclinic P21/n space group with a = 6.798(4) Å, b = 11.468(6) Å, c = 18.073(9) Å, β = 96.020(6)°, V = 1401.3(13) Å3, and Z = 4. The asymmetric unit of 1 consists of a diperoxovanadium [VO(O2)2(pm-im)]− anion, one free NH4 + counterion, and three lattice water molecules, which are further stacked to form a three-dimensional (3D) supramolecular structure through intra- and intermolecular hydrogen bond interactions. The solution stability of the ion ([VO(O2)2(pm-im)]−) was explored using a combination of multinuclear (1H, 13C, and 51V) magnetic resonance and variable temperature NMR in a 0.15 mol L−1 NaCl/D2O solution that mimics physiological conditions. Additionally, the compound exhibits significant DNA cleavage ability under light, and the electrophoretic result shows that the super helix DNA seems to be directly cleaved into single stranded DNA.

Evidence for distinct neuro-metabolic phenotypes in humans

Advances in magnetic resonance imaging have shown how individual differences in the structure and function of the human brain relate to health and cognition. The relationship between individual differences and the levels of neuro-metabolites, however, remains largely unexplored – despite the potential for the discovery of novel behavioural and disease phenotypes. In this study, we measured 14 metabolite levels, normalised as ratios to total-creatine, with 1H magnetic resonance spectroscopy (MRS) acquired from the bilateral anterior cingulate cortices of six healthy participants, repeatedly over a period of four months. ANOVA tests revealed statistically significant differences of 3 metabolites and 3 commonly used combinations (total-choline, glutamate + glutamine and total-N-acetylaspartate) between the participants, with scyllo-inositol (F=85, p=6e-26) and total-choline (F=39, p=1e-17) having the greatest discriminatory power. This was not attributable to structural differences. When predicting individuals from the repeated MRS measurements, a leave-one-out classification accuracy of 88% was achieved using a support vector machine based on scyllo-inositol and total-choline levels. Accuracy increased to 98% with the addition of total-N-acetylaspartate and myo-inositol – demonstrating the efficacy of combining MRS with machine learning and metabolomic methodology. These results provide evidence for the existence of neuro-metabolic phenotypes, which may be non-invasively measured using widely available 3 Tesla MRS. Establishing these phenotypes in a larger cohort and investigating their connection to brain health and function presents an important area for future study.

Metabolic abnormalities in the basal ganglia and cerebellum in bipolar disorder: A multi-modal MR study

AimsBipolar type I disorder (BD) is characterized by severe mood swings and occurs in about 1% of the population. The mechanisms underlying the disorder remain unknown. Prior studies have suggested abnormalities in brain metabolism using 1H and 31P magnetic resonance spectroscopy (MRS). Supporting altered metabolism, in previous studies we found T1ρ relaxation times in the cerebellum were elevated in participants with BD. In addition, T1ρ relaxation times in the basal ganglia were lower in participants with BD experiencing depressed mood. Based on these findings, this study sought to probe brain metabolism with a focus of extending these assessments to the cerebellum. MethodsThis study collected data from 64 participants with Bipolar type I disorder (BD) and 42 controls. Subjects were scanned at both 3T (anatomical, functional, and T1ρ imaging data) and 7T (31P and 1H spectroscopy). Regions of interest defined by the 1H MRS data were used to explore metabolic and functional changes in the cerebellar vermis and putamen. ResultsElevated concentrations of n-Acetyl-l-aspartate (NAA), glutamate, glutathione, taurine, and creatine were found in the cerebellar vermis along with decreased intra-cellular pH. Similar trends were observed in the right putamen for glutamate, creatine, and pH. We also observed a relationship between T1ρ relaxation times and mood in the putamen. We did not observe a significant effect of medications on these measures. LimitationsThe study was cross sectional in design and employed a naturalistic approach for assessing the impact of medications on the results. ConclusionThis study supports prior findings of reduced pH in mitochondrial dysfunction in BD while also showing that these differences extend to the cerebellum.