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Clinical and (31)P magnetic resonance spectroscopy characterization of patients with critical limb ischemia before and after autologous cell therapy.
Dubský, M, Šedivý, P, Němcová, A, Drobný, M, Hazdrová, J, Fejfarová, V, Bém, R, Jirkovská, A, Dezortová, M, Hájek, M
Physiological research. 2019;(4):559-566
Abstract
Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ( (31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO(2)). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO(2) as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO(2) increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO(2) on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.
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Nuclear Magnetic Resonance-Based Metabolic Comparative Analysis of Two Apple Varieties with Different Resistances to Apple Scab Attacks.
Sciubba, F, Di Cocco, ME, Gianferri, R, Capuani, G, De Salvador, FR, Fontanari, M, Gorietti, D, Delfini, M
Journal of agricultural and food chemistry. 2015;(37):8339-47
Abstract
Apple scab, caused by the fungus Venturia inaequalis, is the most serious disease of the apple worldwide. Two cultivars (Malus domestica), having different degrees of resistance against fungi attacks, were analyzed by (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy. Aqueous and organic extracts of both apple flesh and skin were studied, and over 30 metabolites, classified as organic acids, amino acids, carbohydrates, phenolic compounds, lipids, sterols, and other metabolites, were quantified by means of one-dimensional (1D) and two-dimensional (2D) NMR experiments. The metabolic profiles of the two apple cultivars were compared, and the differences were correlated with the different degrees of resistance to apple scab by means of univariate analysis. Levels of metabolites with known antifungal activity were observed not only to be higher in the Almagold cultivar but also to show different correlation patterns in comparison to Golden Delicious, implying a difference in the metabolic network involved in their biosynthesis.
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3.
Enhanced axonal metabolism during early natalizumab treatment in relapsing-remitting multiple sclerosis.
Wiebenga, OT, Klauser, AM, Schoonheim, MM, Nagtegaal, GJ, Steenwijk, MD, van Rossum, JA, Polman, CH, Barkhof, F, Pouwels, PJ, Geurts, JJ
AJNR. American journal of neuroradiology. 2015;(6):1116-23
Abstract
BACKGROUND AND PURPOSE The considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging. MATERIALS AND METHODS In this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-β or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter. RESULTS At baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-β/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased. CONCLUSIONS Patients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism.
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Decreased left perisylvian GABA concentration in children with autism and unaffected siblings.
Rojas, DC, Singel, D, Steinmetz, S, Hepburn, S, Brown, MS
NeuroImage. 2014;:28-34
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Abstract
Imbalanced levels of excitation and inhibition (E/I) have been proposed to account for various behavioral and electrophysiological phenotypes in autism. Although proton magnetic resonance spectroscopy ((1)H-MRS) studies have been published on various metabolite levels in autism, including glutamate, the major excitatory neurotransmitter, few (1)H-MRS studies have yet been conducted the major inhibitory neurotransmitter GABA. Seventeen individuals with autism spectrum disorders (ASD) participated in a single-voxel, point resolved spectroscopy (PRESS) study conducted on a 3T magnet. Data were also acquired on 14 unaffected siblings of children with autism, and 17 age- and gender-matched healthy control subjects. GABA concentration was measured along with Creatine (Cr) in a single voxel aligned with the auditory cortex in the perisylvian region of the left hemisphere. The ratio of GABA to Cr was significantly lower in the ASD group than the control subjects. Siblings also exhibited lower GABA/Cr ratios compared to controls. Cr concentration did not differ between groups. The volumes of gray matter, white matter and CSF did not differ between groups in the whole brain or within the spectroscopy voxel. Reduced auditory GABA concentration in ASD is consistent with one previous MRS study of GABA concentration in the frontal lobe in autism, suggesting that multiple neocortical areas may be involved. Lower GABA levels are consistent with theories of ASD as a disorder involving impaired inhibitory neurotransmission and E/I imbalance. The reduction in unaffected siblings suggests that it may be a heritable biomarker, or endophenotype, of autism.
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1H-magnetic resonance spectroscopy in diffuse and focal cervical cord lesions in multiple sclerosis.
Bellenberg, B, Busch, M, Trampe, N, Gold, R, Chan, A, Lukas, C
European radiology. 2013;(12):3379-92
Abstract
OBJECTIVES To investigate differences between focal and diffuse cervical lesions in multiple sclerosis (MS) by proton magnetic resonance spectroscopy ((1)H-MRS) at 1.5 T in comparison to quantitative MR imaging of the upper cervical cord area and T2 relaxometry at baseline and follow-up. METHODS Including 22 MS patients with persistent spinal cord symptoms by either diffuse or focal lesions and 17 controls, we acquired MRS, the mean cord area and the water T2 relaxation time and disability at baseline and follow-up. Cross-sectional analyses included group-level comparisons and correlation studies. Follow-up studies covered assessment of reproducibility and progression of the baseline results. RESULTS Compared with focal lesions, diffuse lesions were attended by more cord atrophy, longer T2, elevated levels of creatine (Cre) and reduced N-acetyl aspartate (NAA)/Cre (focal/diffuse: 83 ± 9/73 ± 15 mm(2), 121 ± 21/104 ± 13 ms, 3.6 ± 1.1/5.1 ± 2.4 mM, 2.4 ± 1.1/2.0 ± 0.9). NAA/Cre at baseline was associated significantly with cord atrophy and with clinical progression during follow-up. Baseline MRS results were not significantly correlated to the clinical disability parameters. The reproducibility of MRS was 0.17-0.30. Longitudinal changes of the MRS results were not statistically significant. CONCLUSIONS MRS indicated differences in demyelination and gliosis between diffuse and focal cervical lesions in MS. Although longitudinal spectral and clinical changes were sparse, NAA/Cre turned out to be the most sensitive spectral parameter.
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Prostate cancer: 1HMRS-DCEMR at 3T versus [(18)F]choline PET/CT in the detection of local prostate cancer recurrence in men with biochemical progression after radical retropubic prostatectomy (RRP).
Panebianco, V, Sciarra, A, Lisi, D, Galati, F, Buonocore, V, Catalano, C, Gentile, V, Laghi, A, Passariello, R
European journal of radiology. 2012;(4):700-8
Abstract
OBJECTIVES This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3T magnet versus [(18)F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrence in patients with biochemical progression after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS 84 consecutive patients at high risk of local recurrence underwent combined 1HMRSI-DCEMR and 18-Fcholine- PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weighted sequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging (CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate; dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence. The population was divided into two groups. Group A included 28 patients with a lesion size ranging between 5.00mm and 7.2mm and PSA reduction following radiation therapy. Group B included 56 patients with a lesion size between 7.6mm and 19.4mm. Sensitivity, specificity, positive predictive value (PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed. RESULTS In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75% (PPV 96%) while PET-CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) in identifying local recurrence. The accuracy of MRI was 89% while PET-CT showed an accuracy of 60%. Areas under the ROC curve (AUC) values for MR and PET-CT were 0.833 and 0.562, respectively. In Group B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) with accuracy of 94%. PET-CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%. The AUCs for MR and PET-CT values were 0.971 and 0.837, respectively. CONCLUSION The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify local prostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2-2ng/mL).
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Comparative determination of energy production rates and mitochondrial function using different 31P MRS quantitative methods in sedentary and trained subjects.
Layec, G, Bringard, A, Le Fur, Y, Vilmen, C, Micallef, JP, Perrey, S, Cozzone, PJ, Bendahan, D
NMR in biomedicine. 2011;(4):425-38
Abstract
Muscle energetics has been largely and quantitatively investigated using (31)P MRS. Various methods have been used to estimate the corresponding rate of oxidative ATP synthesis (ATP(ox)); however, potential differences among methods have not been investigated. In this study, we aimed to compare the rates of ATP production and energy cost in two groups of subjects with different training status using four different methods: indirect method (method 1), ADP control model (method 2) and phosphate potential control model (method 3). Method 4 was a modified version of method 3 with the introduction of a correction factor allowing for similar values to be obtained for the end-exercise oxidative ATP synthesis rate inferred from exercise measurements and the initial recovery phosphocreatine resynthesis rate. Seven sedentary and seven endurance-trained subjects performed a dynamic standardised rest-exercise-recovery protocol. We quantified the rates of ATP(ox) and anaerobic ATP synthesis (ATP(ana)) using (31)P MRS data recorded at 1.5 T. The rates of ATP(ox) over the entire exercise session were independent of the method used, except for method 4 which provided significantly higher values in both groups (p < 0.01). In addition, methods 1-3 were cross-correlated, thereby confirming their statistical agreement. The rate of ATP(ana) was significantly higher with method 1 (p < 0.01) and lower with method 4 (p < 0.01). As a result of the higher rate of ATP(ox), EC (method 4) calculated over the entire exercise session was higher and initial EC (method 1) was lower in both groups compared with the other methods. We showed in this study that the rate of ATP(ox) was independent of the calculation method, as long as no corrections (method 4) were performed. In contrast, results related to the rates of ATP(ana) were strongly affected by the calculation method and, more exactly, by the estimation of protons generated by ATP(ox). Although the absolute EC values differed between the methods, within- or between-subject comparisons are still valid given the tight relationships between them.
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Multivoxel MRS: right frontal parafalcine cortex - area of neurobiochemical gender differentiation?
Ostojic, J, Kozic, D, Lucic, M, Konstantinovic, J, Covickovic-Sternic, N, Pavlovic, A, Bogdanovic-Stojanovic, D, Semnic, R
Neuro endocrinology letters. 2011;(5):683-7
Abstract
OBJECTIVE To determine the presence of gender neurometabolic differences in healthy men and women by multivoxel magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS We performed multivoxel magnetic resonance imaging and spectroscopy in 50 healthy volunteers (27 women and 23 men) using 1.5T scanner. Spectra from 12 different voxels were obtained, covering frontal, paracentral, and parietal white and gray matter. Three dominant signals were analyzed: NAA, tCr and Cho, and expressed as ratios of Cho/tCr, NAA/tCr, NAA/Cho. RESULTS There was statistically significant gender difference between Cho/Cr and NAA/Cr metabolites ratio in only one location - the right frontal parafalcine cortex. There was no statistically significant difference in NAA/Cho ratio between men and women. CONCLUSION Our study suggests that right frontal parafalcine cortex is a sexually dysmorphic area and supports the value of multivoxel MRS as a method able to define spatial biochemical heterogeneity of the cerebral tissue.
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Comparisons of apolipoprotein B levels estimated by immunoassay, nuclear magnetic resonance, vertical auto profile, and non-high-density lipoprotein cholesterol in subjects with hypertriglyceridemia (SAFARI Trial).
Grundy, SM, Vega, GL, Tomassini, JE, Tershakovec, AM
The American journal of cardiology. 2011;(1):40-6
Abstract
Low-density lipoprotein (LDL) cholesterol and triglyceride-rich lipoproteins constitute non-high-density lipoprotein (non-HDL) cholesterol. These are atherogenic lipoproteins and non-HDL cholesterol is a secondary target of treatment beyond LDL cholesterol in patients with hypertriglyceridemia. Some investigators favor total apolipoprotein B over non-HDL cholesterol as the secondary target of treatment. This is based on publications suggesting that total apolipoprotein B is more predictive of cardiovascular events than non-HDL cholesterol. Several methods are available for estimating total apolipoprotein B. This study compared total apolipoprotein estimated by immunonephelometric assay (INA), vertical auto profile (VAP), nuclear magnetic resonance (NMR), and non-HDL cholesterol levels in patients with hypertriglyceridemia from the previously reported Simvastatin plus Fenofibrate for Combined Hyperlipidemia (SAFARI) trial. Total apolipoprotein B levels were found to be highest by INA, intermediate by NMR and non-HDL cholesterol, and lowest by VAP. Concordance for non-HDL cholesterol levels among the INA, VAP, and NMR methods was better than that for total apolipoprotein B levels; the correlation between non-HDL cholesterol and apolipoprotein B by INA was strongest (0.929). In patients with a low triglyceride/HDL cholesterol ratio (<3.5), total apolipoprotein B determined by INA was higher than that estimated from non-HDL cholesterol levels, whereas in patients with a high triglyceride/HDL C ratio (≥3.5), apolipoprotein B predicted using non-HDL cholesterol was in better agreement with INA-determined apolipoprotein B levels. Similar trends were observed with VAP using equations specific for LDL particle size. In conclusion, more work is needed to improve agreement of apolipoprotein B measurements among methods employed clinically. Non-HDL cholesterol is also useful to predict total apolipoprotein B and some improvement may be attained by taking into account the ratio of triglyceride/HDL cholesterol as a measurement of LDL particle size.
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Nuclear magnetic resonance-based metabolomics enable detection of the effects of a whole grain rye and rye bran diet on the metabolic profile of plasma in prostate cancer patients.
Moazzami, AA, Zhang, JX, Kamal-Eldin, A, Aman, P, Hallmans, G, Johansson, JE, Andersson, SO
The Journal of nutrition. 2011;(12):2126-32
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Abstract
Prostate cancer (PC) is the most common cancer in the Western world and the second most important cancer causing male deaths, after lung cancer, in the United States and Britain. Lifestyle and dietary changes are recommended for men diagnosed with early-stage PC. It has been shown that a diet rich in whole grain (WG) rye reduces the progression of early-stage PC, but the underlying mechanism is not clear. This study sought to identify changes in the metabolic signature of plasma in patients with early-stage PC following intervention with a diet rich in WG rye and rye bran product (RP) compared with refined white wheat product (WP) as a tool for mechanistic investigation of the beneficial health effects of RP on PC progression. Seventeen PC patients received 485 g RP or WP in a randomized, controlled, crossover design during a period of 6 wk with a 2-wk washout period. At the end of each intervention period, plasma was collected after fasting and used for (1)H NMR-based metabolomics. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. A metabolomics analysis of plasma showed an increase in 5 metabolites, including 3-hydroxybutyric acid, acetone, betaine, N,N-dimethylglycine, and dimethyl sulfone, after RP. To understand these metabolic changes, fasting plasma homocysteine, leptin, adiponectin, and glucagon were measured separately. The plasma homocysteine concentration was lower (P = 0.017) and that of leptin tended to be lower (P = 0.07) after RP intake compared to WP intake. The increase in plasma 3-hydroxybutyric acid and acetone after RP suggests a shift in energy metabolism from anabolic to catabolic status, which could explain some of the beneficial health effects of WG rye, i.e., reduction in prostate-specific antigen and reduced 24-h insulin secretion. In addition, the increase in betaine and N,N-dimethylglycine and the decrease in homocysteine show a favorable shift in homocysteine metabolism after RP intake.