A Quantitative Comparison of 31P Magnetic Resonance Spectroscopy RF Coil Sensitivity and SNR between 7T and 10.5T Human MRI Scanners Using a Loop-Dipole 31P-1H Probe.

In vivo phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) imaging (MRSI) is an important non-invasive imaging tool for studying cerebral energy metabolism, intracellular nicotinamide adenine dinucleotide (NAD) and redox ratio, and mitochondrial function. However, it is challenging to achieve high signal-to-noise ratio (SNR) 31P MRS/MRSI results owing to low phosphorus metabolites concentration and low phosphorous gyromagnetic ratio (γ). Many works have demonstrated that ultrahigh field (UHF) could significantly improve the 31P-MRS SNR. However, there is a lack of studies of the 31P MRSI SNR in the 10.5 Tesla (T) human scanner. In this study, we designed and constructed a novel 31P-1H dual-frequency loop-dipole probe that can operate at both 7T and 10.5T for a quantitative comparison of 31P MRSI SNR between the two magnetic fields, taking into account the RF coil B1 fields (RF coil receive and transmit fields) and relaxation times. We found that the SNR of the 31P MRS signal is 1.5 times higher at 10.5T as compared to 7T, and the power dependence of SNR on magnetic field strength (B0) is 1.9.

Alteration of skeletal muscle energy metabolism assessed by 31 P MRS in clinical routine: Part 2. Clinical application.

In this second part of a two-part paper, we intend to demonstrate the impact of the previously proposed advanced quality control pipeline. To understand its benefit and challenge the proposed methodology in a real scenario, we chose to compare the outcome when applying it to the analysis of two patient populations with significant but highly different types of fatigue: COVID-19 and multiple sclerosis (MS). 31 P-MRS was performed on a 3 T clinical MRI, in 19 COVID-19 patients, 38 MS patients, and 40 matched healthy controls. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Long and short TR acquisitions were also made at rest for T1 correction. The advanced data quality control pipeline presented in Part 1 is applied to the selected patient cohorts to investigate its impact on clinical outcomes. We first used power and sample size analysis to estimate objectively the impact of adding the quality control score (QCS). Then, comparisons between patients and healthy control groups using the validated QCS were performed using unpaired t tests or Mann-Whitney tests (p < 0.05). The application of the QCS resulted in increased statistical power, changed the values of several outcome measures, and reduced variability (standard deviation). A significant difference was found between the T1PCr and T1Pi values of MS patients and healthy controls. Furthermore, the use of a fixed correction factor led to systematically higher estimated concentrations of PCr and Pi than when using individually corrected factors. We observed significant differences between the two patient populations and healthy controls for resting [PCr]-MS only, [Pi ], [ADP], [H2 PO4 - ], and pH-COVID-19 only, and post-exercise [PCr], [Pi ], and [H2 PO4 - ]-MS only. The dynamic indicators τPCr , τPi , ViPCr , and Vmax were reduced for COVID-19 and MS patients compared with controls. Our results show that QCS in dynamic 31 P-MRS studies results in smaller data variability and therefore impacts study sample size and power. Although QCS resulted in discarded data and therefore reduced the acceptable data and subject numbers, this rigorous and unbiased approach allowed for proper assessment of muscle metabolites and metabolism in patient populations. The outcomes include an increased metabolite T1 , which directly affects the T1 correction factor applied to the amplitudes of the metabolite, and a prolonged τPCr , indicating reduced muscle oxidative capacity for patients with MS and COVID-19.

Alteration of skeletal muscle energy metabolism assessed by phosphorus-31 magnetic resonance spectroscopy in clinical routine, part 1: Advanced quality control pipeline.

Implementing a standardized phosphorus-31 magnetic resonance spectroscopy (31 P-MRS) dynamic acquisition protocol to evaluate skeletal muscle energy metabolism and monitor muscle fatigability, while being compatible with various longitudinal clinical studies on diversified patient cohorts, requires a high level of technicality and expertise. Furthermore, processing data to obtain reliable results also demands a great degree of expertise from the operator. In this two-part article, we present an advanced quality control approach for data acquired using a dynamic 31 P-MRS protocol. The aim is to provide decision support to the operator to assist in data processing and obtain reliable results based on objective criteria. We present here, in part 1, an advanced data quality control (QC) approach of a dynamic 31 P-MRS protocol. Part 2 is an impact study that will demonstrate the added value of the QC approach to explore data derived from two clinical populations that experience significant fatigue, patients with coronavirus disease 2019 and multiple sclerosis. In part 1, 31 P-MRS was performed using 3-T clinical MRI in 175 subjects from clinical and healthy control populations conducted in a University Hospital. An advanced data QC score (QCS) was developed using multiple objective criteria. The criteria were based on current recommendations from the literature enriched by new proposals based on clinical experience. The QCS was designed to indicate valid and corrupt data and guide necessary objective data editing to extract as much valid physiological data as possible. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Using QCS enabled rapid identification of subjects with data anomalies, allowing the user to correct the data series or reject them partially or entirely, as well as identify fully valid datasets. Overall, the use of the QCS resulted in the automatic classification of 45% of the subjects, including 58 participants who had data with no criterion violation and 21 participants with violations that resulted in the rejection of all dynamic data. The remaining datasets were inspected manually with guidance, allowing acceptance of full datasets from an additional 80 participants and recovery phase data from an additional 16 subjects. Overall, more anomalies occurred with patient data (35% of datasets) compared with healthy controls (15% of datasets). In conclusion, the QCS ensures a standardized data rejection procedure and rigorous objective analysis of dynamic 31 P-MRS data obtained from patients. This methodology contributes to efforts made to standardize 31 P-MRS practices that have been underway for a decade, with the goal of making it an empowered tool for clinical research.

Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse nuclear magnetic resonance spectroscopy.

Favipiravir (brand name Avigan), a widely known anti-influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA-dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir-ribofuranosyl-5'-monophosphate (favipiravir-RMP), by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate-determining step in the generation of the active metabolite, quantitative and real-time monitoring of the HGPRT-catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established. 19 F- or 31 P-based nuclear magnetic resonance (NMR) are powerful techniques for observation of intermolecular interactions, chemical reactions, and metabolism of molecules of interest, given that NMR signals of the heteronuclei sensitively reflect changes in the chemical environment of these moieties. Here, we demonstrated direct, sensitive, target-selective, nondestructive, and real-time observation of HGPRT-catalyzed conversion of favipiravir to favipiravir-RMP by performing time-lapse 19 F-NMR monitoring of the fluorine atom of favipiravir. In addition, we showed that 31 P-NMR can be used for real-time observation of the identical reaction by monitoring phosphorus atoms of the phosphoribosyl group of favipiravir-RMP and of the pyrophosphate product of that reaction. Furthermore, we demonstrated that NMR approaches permit the determination of general parameters of enzymatic activity such as Vmax and Km . This method not only can be widely employed in enzyme assays, but also may be of use in the screening and development of new favipiravir-analog antiviral prodrugs that can be phosphoribosylated more efficiently by HGPRT, which would increase the intracellular concentration of the drug's active form. The techniques demonstrated in this study would allow more detailed investigation of the pharmacokinetics of fluorinated drugs, and might significantly contribute to opening new avenues for widespread pharmaceutical studies.

Characterization and correction of center-frequency effects in X-nuclear eddy current compensations on a clinical MR system.

PURPOSE: The aim of the study was to investigate whether incorrectly compensated eddy currents are the source of persistent X-nuclear spectroscopy and imaging artifacts, as well as methods to correct this. METHODS: Pulse-acquire spectra were collected for 1 H and X-nuclei (23 Na or 31 P) using the minimum TR permitted on a 3T clinical MRI system. Data were collected in 3 orientations (axial, sagittal, and coronal) with the spoiler gradient at the end of the TR applied along the slice direction for each. Modifications to system calibration files to tailor eddy current compensation for each X-nucleus were developed and applied, and data were compared with and without these corrections for: slice-selective MRS (for 23 Na and 31 P), 2D spiral trajectories (for 13 C), and 3D cones trajectories (for 23 Na). RESULTS: Line-shape distortions characteristic of eddy currents were demonstrated for X-nuclei, which were not seen for 1 H. The severity of these correlated with the amplitude of the eddy current frequency compensation term applied by the system along the axis of the applied spoiler gradient. A proposed correction to eddy current compensation, taking account of the gyromagnetic ratio, was shown to dramatically reduce these distortions. The same correction was also shown to improve data quality of non-Cartesian imaging (2D spiral and 3D cones trajectories). CONCLUSION: A simple adaptation of the default compensation for eddy currents was shown to eliminate a range of artifacts detected on X-nuclear spectroscopy and imaging.

Effects of contrast agents on relaxation properties of 31P metabolites.

PURPOSE: Phosphorous MR spectroscopy (31P-MRS) forms a powerful, non-invasive research tool to quantify the energetics of the heart in diverse patient populations. 31P-MRS is frequently applied alongside other radiological examinations, many of which use various contrast agents that shorten relaxation times of water in conventional proton MR, for a better characterisation of cardiac function, or following prior computed tomography (CT). It is, however, unknown whether these agents confound 31P-MRS signals, for example, 2,3-diphosphoglycerate (2,3-DPG). METHODS: In this work, we quantitatively assess the impact of non-ionic, low osmolar iodinated CT contrast agent (iopamidol/Niopam), gadolinium chelates (linear gadopentetic acid dimeglumine/Magnevist and macrocyclic gadoterate meglumine/Dotarem) and superparamagnetic iron oxide nanoparticles (ferumoxytol/Feraheme) on the nuclear T1 and T2 of 31P metabolites (ie, 2,3-DPG), and 1H in water in live human blood and saline phantoms at 11.7 T. RESULTS: Addition of all contrast agents led to significant shortening of all relaxation times in both 1H and 31P saline phantoms. On the contrary, the T1 relaxation time of 2,3-DPG in blood was significantly shortened only by Magnevist (P = .03). Similarly, the only contrast agent that influenced the T2 relaxation times of 2,3-DPG in blood samples was ferumoxytol (P = .02). CONCLUSION: Our results show that, unlike conventional proton MR, phosphorus MRS is unconfounded in patients who have had prior CT with contrast, not all gadolinium-based contrast agents influence 31P-MRS data in vivo, and that ferumoxytol is a promising contrast agent for the reduction in 31P-MRS blood-pool signal.

SCFit: Software for single-crystal NMR analysis. Free vs constrained fitting.

The design and implementation of a software package for the analysis of single-crystal NMR data is presented. The SCFit software can treat spectra arising from various interactions: (i) chemical shift tensor only; (ii) chemical shift tensor and quadrupolar coupling tensor; (iii) dipolar and indirect nuclear spin-spin coupling tensors; (iv) all four interactions. The software is demonstrated on recently reported 17O and 31P single-crystal NMR data for triphenylphosphine oxide and for two of its halogen-bonded cocrystals. The 17O single-crystal NMR data represent a case where all four above-mentioned interactions simultaneously affect the spectra. SCFit can fit the chemical shift and quadrupolar coupling in two ways: (i) through an unconstrained fitting process where all tensor parameters are freely optimized or (ii) through a constrained fitting process where the principal components of the tensors may be fixed to values known previously with high precision via the analysis of powder samples. The second strategy is explored in an effort to reduce the number of unknowns in the fitting process; an improvement in the precision of the resulting tensor orientations is noted in some cases.

Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study.

Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = -0.63, P < 0.01) and fasting plasma glucose ( r = -0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = -0.43, P = 0.03) and M/I ( r = -0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.

Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vaso-occlusive crisis in exercising muscle of a sickle cell mouse.

While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest - exercise - recovery at two different intensities in ten SCD mice. Among these mice, one single mouse presented divergent responses. A statistical analysis (based on confidence intervals) revealed that this single mouse presented slower phosphocreatine resynthesis and inorganic phosphate disappearance during the post-stimulation recovery of one of the protocols, what could suggest an ischemia. This study described, for the first time in a sickle cell mouse in vivo, exacerbated metabolic changes triggered by an exercise session that would be suggestive of a live observation of a muscular VOC. However, no evidence of a direct cause-effect relationship between exercise and VOC has been put forth.

MRI assessment of regional differences in phosphorus-31 metabolism and morphological abnormalities of the foot muscles in diabetes.

PURPOSE: To assess differences in the phosphorus-31 (31 P) metabolism and morphology in multiple muscle regions in the forefoot of diabetic patients and normal subjects. MATERIALS AND METHODS: Fifteen diabetic patients and 15 normal subjects were assessed for muscle atrophy by 1 H magnetic resonance imaging (MRI) at 3T to grade the flexor hallucis, adductor hallucis, interosseous regions, and entire foot cross-section. Each region and the entire foot were also quantitatively evaluated for metabolic function using 31 P imaging for spatial mapping of the inorganic phosphate (Pi) to phosphocreatine (PCr) ratio (Pi/PCr). The ratio of viable muscle area to the predefined region areas (31 P/1 H) was calculated. The variability of each method was assessed by its coefficient of variation (CV). RESULTS: Muscle atrophy was significantly more severe in diabetic compared to normal subjects in all regions (P < 0.01). The 31 P/1 H area ratio was significantly larger in the adductor hallucis than in the other two regions (P < 0.05). The Pi/PCr ratio was significantly different between the two groups in the flexor hallucis and interosseous regions (P < 0.05) but not adductor hallucis region. The CV for Pi/PCr ranged from 10.13 to 55.84, while it ranged from 73.40 to 263.90 for qualitative grading. CONCLUSION: Changes in atrophy and metabolism appear to occur unequally between different regions of the forefoot in diabetes. The adductor hallucis region appears more capable of maintaining structural and metabolic integrity than the flexor hallucis or interosseous regions. The CV analysis suggests that the quantitative 31 P methods have less variability than the qualitative grading. J. Magn. Reson. Imaging 2016;44:1132-1142.

Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression.

Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health's experimental medicine initiative, we conducted a placebo-controlled dose-ranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment (31)P-MRS scans were used to measure frontal lobe PCr, to assess CM's target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted.

Impact of age on exercise-induced ATP supply during supramaximal plantar flexion in humans.

Currently, the physiological factors responsible for exercise intolerance and bioenergetic alterations with age are poorly understood due, at least in art, to the confounding effect of reduced physical activity in the elderly. Thus, in 40 healthy young (22 ± 2 yr) and old (74 ± 8 yr) activity-matched subjects, we assessed the impact of age on: 1) the relative contribution of the three major pathways of ATP synthesis (oxidative ATP synthesis, glycolysis, and the creatine kinase reaction) and 2) the ATP cost of contraction during high-intensity exercise. Specifically, during supramaximal plantar flexion (120% of maximal aerobic power), to stress the functional limits of the skeletal muscle energy systems, we used (31)P-labeled magnetic resonance spectroscopy to assess metabolism. Although glycolytic activation was delayed in the old, ATP synthesis from the main energy pathways was not significantly different between groups. Similarly, the inferred peak rate of mitochondrial ATP synthesis was not significantly different between the young (25 ± 8 mM/min) and old (24 ± 6 mM/min). In contrast, the ATP cost of contraction was significantly elevated in the old compared with the young (5.1 ± 2.0 and 3.7 ± 1.7 mM·min(-1)·W(-1), respectively; P < 0.05). Overall, these findings suggest that, when young and old subjects are activity matched, there is no evidence of age-related mitochondrial and glycolytic dysfunction. However, this study does confirm an abnormal elevation in exercise-induced skeletal muscle metabolic demand in the old that may contribute to the decline in exercise capacity with advancing age.

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Introduction: Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging. Methods: In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method. Results: The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age. Discussion: These results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

Fuel from within: Can suspended phosphorus maintain algal blooms in Lake Dianchi.

Extensive algal bloom in the surface water is a pressing issue in Lake Dianchi that causes lake restoration to be difficult owing to complex and variable phosphorus (P) sources in the water column. P released from algae, suspended particles (SS), and sediment can provide sustainable P sources for algal blooms. However, little is known regarding the dynamic of P speciation in these substances from different sources. In this study, solution 31P nuclear magnetic resonance (31P NMR) and chemical sequential extraction were employed to identify P speciation in algae, SS, and sediment during different periods. Results showed that dissolved inorganic P (Pi) directly accumulated in algae in the form of orthophosphate (ortho-P) and pyrophosphate (pyro-P). Algae preferentially utilized Pi, followed by organic P (Po) in the water column when the Pi was insufficient during growth and reproduction. The 31P NMR spectra demonstrated that ortho-P, orthophosphate monoesters (mono-P), orthophosphate diesters (diester-P), and pyro-P dominated the P compounds across the samples tested. Increasing remineralization of SS mono-P driven by intense alkaline phosphatase activities was caused by increasing P needs of algae and pressure of P supply in the water column. The higher ratios of diester-P to mono-P in sediment (mean 0.55) than those in algae (mean 0.07) and SS (mean 0.11 in surface water, 0.14 in bottom water) suggested that the degradation and regeneration occurred within these P compounds during or after sedimentation. Pi content in algae during growth and reproduction was controlled by its P absorption and utilization strategies. Results of this study provide insights into the dynamic cycling of P in algae, SS, and sediment, explaining the reason for algal blooms in the surface water with low concentrations of dissolved P.

Milk Phospholipid Profiling Among Japanese Women with Differing Docosahexaenoic Acid Levels.

To characterize the milk phospholipids (PLs) profile using phosphorus-31 nuclear magnetic resonance (31P-NMR) and to investigate the effect of elevated milk docosahexaenoic acid (DHA) levels on PLs profiles in Japanese mothers. Methods: Milk samples from eligible patients with high and low DHA from a former cross-sectional study (n = 20; n = 10 for each group) were included. Fifteen milk PLs were analyzed using 31P-NMR, and the profiles were compared group-wise using Mann-Whitney U-test. The P value of <0.05 was considered statistically significant. Results: The median DHA content in milk was 1.13% and 0.29% for the high and low milk DHA groups, respectively. Twelve PLs, excluding lysophosphatidylserine, cardiolipin, and phosphatidylglycerol, were detected in all participants with 100% positive results. The median concentrations and proportions of total PLs, sphingophospholipids, and glycerophospholipids were comparable between groups. The proportions of choline-containing glycerophospholipid were significantly higher in the high milk DHA group than that in the low milk DHA group (24.09% [median, interquartile range: 23.08%-26.38%] and 21.41% [20.74%-22.84%], P = 0.019). Although the proportions of phosphatidylinositol were significantly lower in the high milk DHA group than that in the low milk DHA group (6.62% [5.75%-6.72%] versus 7.63% [7.11%-8.16%], P = 0.002), while that of phosphatidylcholine (21.90% [18.51%-23.22%] versus 19.78% [18.17%-20.26%], P = 0.059) and alkyl-acyl phosphatidylcholine (0.60% [0.40%-0.74%] versus 0.33% [0.14%-0.51%], P = 0.059) were higher in the former than that in the latter. Conclusions: Our results were comparable to that of the previous literature. Large variations in the milk DHA might affect the composition of choline-containing glycerophospholipids in Japanese mothers. However, possible confounders were not excluded in the study populations.

In vivo magnetic resonance spectrometry imaging demonstrates comparable adaptation of brain energy metabolism to metabolic stress induced by 72 h of fasting in depressed patients and healthy volunteers.

Major depressive disorder (MDD) is characterized by dysregulation of stress systems and by abnormalities in cerebral energy metabolism. Stress induction has been shown to impact neurometabolism in healthy individuals. Contrarily, neurometabolic changes in response to stress are insufficiently investigated in MDD patients. Metabolic stress was induced in MDD patients (MDD, N = 24) and in healthy individuals (CTRL, N = 22) by application of an established fasting protocol in which calorie intake was omitted for 72 h. Both study groups were comparable regarding age, gender distribution, and body mass index (BMI). Fasting-induced effects on brain high-energy phosphate levels and membrane phospholipid metabolism were assessed using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Two-way repeated measures ANOVAs did not reveal significant interaction effects (group x fasting) or group differences in adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), phosphodiesters (PDE), or pH levels between MDD and CTRL. Fasting, independent of group, significantly increased ATP and decreased Pi levels and an overall increase in PME/PDE ratio as marker for membrane turnover was observed. Overall these results indicate reactive changes in cerebral energetics and in membrane phospholipid metabolism in response to fasting. The observed effects did not significantly differ between CTRL and MDD, indicating that neurometabolic adaptation to metabolic stress is preserved in MDD patients.

Dynamics of phosphorus composition in suspended particulate matter from a turbid eutrophic shallow lake (Lake Chaohu, China): Implications for phosphorus cycling and management.

Particulate phosphorus (P) dominates the total P (TP) content in lacustrine water columns and is a primary source of dissolved P in turbid eutrophic shallow lakes. However, the spatiotemporal variability of P compositions in suspended particulate matter (SPM) remains poorly understood. In this study, we applied chemical extraction and solution 31P nuclear magnetic resonance (31P NMR) to assess the seasonal variations of SPM P compositions from a shallow turbid lake (Lake Chaohu, China) and its main river tributaries. P fractionation analysis indicated that mobile P (the sum of labile-P, iron-bound P, and organic P) accounted for >60% of the TP in SPM and showed high spatiotemporal variability throughout the year-long field investigation. In most seasons, riverine SPM (in urban rivers or rivers with high flow) contained a higher mobile P content than that of the lake and was therefore a dominant source of lacustrine mobile particulate P. Solution 31P NMR identified five types of P compounds in SPM, with highest contributions from orthophosphate. Organic P components and concentrations showed high seasonal variability, and elevated p values occurred during the summer algal bloom. The correlation analysis between organic and inorganic P fractions inferred the possible degradation of organic P into reactive inorganic components of SPM. Consequently, biological or chemical processes would further transform the labile inorganic P into soluble reactive phosphorus, which is readily utilized by lacustrine algae. Our results suggest that the labile forms of P in SPM were highly dynamic and significantly contributed to the eutrophication of the turbid shallow lake.

Failing Homeostasis of Quadriceps Muscle Energy- and pH Balance During Bicycling in a Young Patient With a Fontan Circulation.

Aims: Patients with a congenital heart condition palliated with a Fontan circulation generally present with decreased exercise capacity due to impaired cardiopulmonary function. Recently, a study in patients with a Fontan circulation reported evidence for abnormal vascular endothelial function in leg muscle. We investigated if abnormal skeletal muscle hemodynamics during exercise play a role in the limited exercise tolerance of Fontan patients. If so, abnormalities in intramuscular energy metabolism would be expected both during exercise as well as during post-exercise metabolic recovery. Methods: In a young patient with a Fontan circulation and his healthy twin brother we studied the in vivo dynamics of energy- and pH-balance in quadriceps muscle during and after a maximal in-magnet bicycling exercise challenge using 31-phosphorus magnetic resonance spectroscopy. An unrelated age-matched boy was also included as independent control. Results: Quadriceps phosphocreatine (PCr) depletion during progressive exercise was more extensive in the Fontan patient than in both controls (95% vs. 80%, respectively). Importantly, it failed to reach an intermittent plateau phase observed in both controls. Quadriceps pH during exercise in the Fontan patient fell 0.3 units at low to moderate workloads, dropping to pH 6.6 at exhaustion. In both controls quadriceps acidification during exercise was absent but for the maximal workload in the twin brother (pH 6.8). Post-exercise, the rate of metabolic recovery in the Fontan patient and both controls was identical (time constant of PCr recovery 32 ± 4, 31 ± 2, and 28 ± 4 s, respectively). Conclusion: Homeostasis of quadriceps energy- and pH-balance during a maximal exercise test failed in the Fontan patient in comparison to his healthy twin brother and an age-matched independent control. Post-exercise metabolic recovery was normal which does not support the contribution of significant endothelial dysfunction affecting adequate delivery of oxidative substrates to the muscle to the lower exercise capacity in this particular Fontan patient. These results suggest that mitochondrial ATP synthetic capacity of the quadriceps muscle was intact but cardiac output to the leg muscles during exercise was insufficient to meet the muscular demand for oxygen. Therefore, improving cardiac output remains the main therapeutic target to improve exercise capacity in patients with a Fontan circulation.

Short-term evaluation of cardiac morphology, function, metabolism and structure following diagnosis of adult-onset growth hormone deficiency.

OBJECTIVE: The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR). DESIGN: Cardiac magnetic resonance (CMR) techniques, including cardiac 31P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls. RESULTS: In GH deficient patients LV systolic function (EF%: 61 ±â€¯1.7 vs 62.1 ±â€¯0.8; p = .44) was not different in spite of a lower LV mass (83.2 ±â€¯5.3 vs 145.3 ±â€¯11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ±â€¯0.2 vs 2.1 ±â€¯0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ±â€¯0.8 vs 2.3 ±â€¯0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ±â€¯9 vs 147.9 ±â€¯7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients. CONCLUSIONS: GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated.

Human Cardiac 31P-MR Spectroscopy at 3 Tesla Cannot Detect Failing Myocardial Energy Homeostasis during Exercise.

Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) is a unique non-invasive imaging modality for probing in vivo high-energy phosphate metabolism in the human heart. We investigated whether current 31P-MRS methodology would allow for clinical applications to detect exercise-induced changes in (patho-)physiological myocardial energy metabolism. Hereto, measurement variability and repeatability of three commonly used localized 31P-MRS methods [3D image-selected in vivo spectroscopy (ISIS) and 1D ISIS with 1D chemical shift imaging (CSI) oriented either perpendicular or parallel to the surface coil] to quantify the myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio in healthy humans (n = 8) at rest were determined on a clinical 3 Tesla MR system. Numerical simulations of myocardial energy homeostasis in response to increased cardiac work rates were performed using a biophysical model of myocardial oxidative metabolism. Hypertrophic cardiomyopathy was modeled by either inefficient sarcomere ATP utilization or decreased mitochondrial ATP synthesis. The effect of creatine depletion on myocardial energy homeostasis was explored for both conditions. The mean in vivo myocardial PCr/ATP ratio measured with 3D ISIS was 1.57 ± 0.17 with a large repeatability coefficient of 40.4%. For 1D CSI in a 1D ISIS-selected slice perpendicular to the surface coil, the PCr/ATP ratio was 2.78 ± 0.50 (repeatability 42.5%). With 1D CSI in a 1D ISIS-selected slice parallel to the surface coil, the PCr/ATP ratio was 1.70 ± 0.56 (repeatability 43.7%). The model predicted a PCr/ATP ratio reduction of only 10% at the maximal cardiac work rate in normal myocardium. Hypertrophic cardiomyopathy led to lower PCr/ATP ratios for high cardiac work rates, which was exacerbated by creatine depletion. Simulations illustrated that when conducting cardiac 31P-MRS exercise stress testing with large measurement error margins, results obtained under pathophysiologic conditions may still lie well within the 95% confidence interval of normal myocardial PCr/ATP dynamics. Current measurement precision of localized 31P-MRS for quantification of the myocardial PCr/ATP ratio precludes the detection of the changes predicted by computational modeling. This hampers clinical employment of 31P-MRS for diagnostic testing and risk stratification, and warrants developments in cardiac 31P-MRS exercise stress testing methodology.