31P Magnetic Resonance Spectroscopy Research Articles

Qualitative and quantitative analysis of Brønsted and Lewis acid sites in zeolites: A combined probe-assisted 1H MAS NMR and NH3-TPD investigation

Zeolite is one of the most important heterogeneous catalysts in acid catalytic reactions. Considering that the catalytic behaviors of zeolites are mostly related to their acidic characteristics, extensive attention has been attracted to the measurements of acid type, strength and concentration in zeolites. Numerous techniques including Fourier-transform infrared spectroscopy (FTIR), probe-assisted 1H, 13C and 31P magic angle spinning nuclear magnetic resonance spectroscopy (MAS NMR) as well as temperature programmed desorption of ammonia (NH3-TPD) have been developed for determining the acid sites. Nevertheless, a single approach is defective to characterize the acid sites comprehensively. Herein, combining the probe-assisted (e.g., NH3 and CD3CN) 1H MAS NMR and NH3-TPD, the acid sites in different zeolites including the acid type, density and strength were determined. The commonly utilized NH3-TPD to determine the acid strength of zeolite samples with different topologies should be rigorously considered owing to zeolite confinement effect. Controlling the desorption temperature of NH3 probe molecules, the acid type (i.e., Brønsted acid sites (BAS) and Lewis acid sites (LAS)) and the corresponding density could be determined by NH3 probe-assisted 1H MAS NMR spectroscopy, while the acid strength could be investigated via CD3CN probe-assisted 1H MAS NMR spectroscopy.

Muscular stress is equal when resistance exercise with blood flow restriction is matched in total work volume: A cross-sectional, cross-over study.

We compared muscular metabolic stress during exercise performed at multiple intensities, from very low to moderate, with blood flow restriction (BFR) adjusted by the same work volume. Twenty-five healthy young adults performed unilateral plantar flexion at 1 repetition/2 s in a magnetic resonance system. The BFR exercise protocols were as follows: (A) exercise with 10% of one repetition maximum (1-RM) for 360 s, (B) 15% 1-RM for 240 s, (C) 20% 1-RM for 180 s, (D) 30% 1-RM for 120 s, and (E) 40% 1-RM for 90 s. All protocols had the same total work volume (load × repetitions = 1800). A high-intensity protocol at 65% 1-RM without BFR (60 s) was also performed for comparison. We used 31 P-magnetic resonance spectroscopy to evaluate the muscular metabolic stress in the subjects' calf muscle, defined as decreases in phosphocreatine and intramuscular pH. The phosphocreatine depletion (A: 15.6 ± 0.7, B: 14.8 ± 0.8, C: 15.2 ± 0.6, D: 14.3 ± 0.6, E: 10.9 ± 0.5 mM; no significant difference [ns]) and the intramuscular pH decrease (A: 6.82 ± 0.02, B: 6.84 ± 0.01, C: 6.83 ± 0.02, D: 6.83 ± 0.02, E: 6.77 ± 0.02; ns) at the end of each exercise were similar and greater than those produced by the 65% 1-RM without BFR. If the total work volumes are equal, the metabolic stress in exercising muscle may reach similar levels at the end of exercise with BFR and could provide similar successful training effects.

Frontal-temporal regional differences in brain energy metabolism and mitochondrial function using 31P MRS in older adults.

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer's disease (AD). The aim of the current study was to investigate mitochondrial function over frontal and temporal regions in a sample of 70 cognitively normal older adults with subjective memory complaints and a first-degree family history of AD. We hypothesized cerebral mitochondrial function and energy metabolism would be greater in temporal as compared to frontal regions based on the high energy consumption in the temporal lobes (i.e., hippocampus). To test this hypothesis, we used phosphorous (31P) magnetic resonance spectroscopy (MRS) which is a non-invasive and powerful method for investigating in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. We used a single voxel method (left temporal and bilateral prefrontal) to achieve optimal sensitivity. Results of separate repeated measures analyses of variance showed 31P MRS ratios of static energy, energy reserve, energy consumption, energy demand, and phospholipid membrane metabolism were greater in the left temporal than bilateral prefrontal voxels. Our findings that all 31P MRS ratios were greater in temporal than bifrontal regions support our hypothesis. Future studies are needed to determine whether findings are related to cognition in older adults.

The Association of Skeletal Muscle Energetics With Recurrent Falls in Older Adults Within the Study of Muscle, Mobility and Aging.

Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated. In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for number of falls (total), recurrent falls (2+), and fall-related injuries over the past 12 months at baseline and again after 1 year. Skeletal muscle energetics were assessed at baseline in vivo using 31P Magnetic Resonance Spectroscopy for the maximal rate of adenosine triphosphate recovery (ATPmax)after an acute bout of exercise, and ex vivo by High-Resolution Respirometry for the maximal rate of complex I and II supported oxygen consumption (MaxOXPHOS) in permeabilized muscle fibers from the vastus lateralis. At least 1 fall was reported in 28.7% of SOMMA participants in the first year of the study, with 12% of older adults reporting recurrent falls (2+). Individuals who experienced recurrent falls had a slower 400-m walk gait speed (1.0±0.2 vs 1.1±0.2, p < .001), reported fewer alcoholic drinks per week in the past year (2.4±4.3 vs 2.8±4.4, p = .054), and took a significantly greater number of medication in the 30 days before their baseline visit (5.6±4.4 vs 4.2±3.4, p < .05). A history of falls was reported in 63% of individuals who experienced recurrent falls in the first year of the study compared to 22.8% who experienced 1 or fewer falls. MaxOXPHOS was significantly lower in those who reported recurrent falls (p = .008) compared to those with 1 or fewer falls, but there was no significant difference in ATPmax (p = .369). Neither muscle energetics measure was significantly associated with total number of falls or injurious falls, but recurrent falls were significantly higher with lower MaxOXPHOS (risk ratio = 1.33, 95% confidence interval = 1.02-1.73, p = .033). However, covariates accounted for the increased risk. Mitochondrial energetics were largely unrelated to fall risk in older adults when accounting for variables, suggesting that the complex etiology of falls may not be related to a single "hallmark of aging" biological pathway.

Chemical kinetics of silver diammine fluoride in demineralization and remineralization solutions-an in vitro study.

Silver Diammine Fluoride (SDF) is a clinical minimal intervention to manage dentin caries. Its chemistry in demineralization conditions has been investigated widely, but far less in remineralization conditions. The aim was to investigate and compare the chemical reactions when SDF is added to remineralization and demineralization solutions. 0.01 ml SDF (Riva Star) was added to deionized water (DW); demineralization (DS = pH4) and remineralization (RS = pH7.0) solutions. The time sequence of concentrations of NH4+, F-, and Ag+ were measured using ion selective electrodes (ISEs) every 2 min. The pH was also measured. Precipitates were characterized using x-ray Diffraction (XRD) and, 31P and 19F nuclear magnetic resonance spectroscopy (NMR). The concentrations of NH4+ and Ag+ showed decreasing trends in DW (-0.12 and -0.08 mM/h respectively), and in DS (-1.06 and -0.5 mM/h respectively); with corresponding increase in F- concentration (0.04 and 0.7 mM/h respectively). However, in RS, NH4+ concentration showed little change (0.001 mM/h), and Ag+ and F- concentrations were negligible. XRD results showed that precipitates (in RS only) contained AgCl, and metallic Ag. NMR showed that fluorapatite/carbonated fluorapatite (FAP/CFAP) were formed. The pH increased after SDF addition in all three solutions. SDF dissolved to release NH4+, F- and Ag + . In DW and DS, NH4+ combined with Ag+ to form diamminesilver, causing an increase of F- and pH. In RS, F- reacted with Ca2+ and (PO)43- to form FAP/CFAP, and Ag+ reacted with Cl- to form AgCl/Ag. These suggests why SDF is effective in managing dentin caries.

SKELETAL MUSCLE ENERGETICS ARE ASSOCIATED WITH PERFORMANCE FATIGABILITY

Abstract Performance fatigability manifests as insufficient energy to complete daily physical tasks and worsens with aging, exacerbating vulnerability to disability. Skeletal muscle energetics also declines with aging. Thus, we hypothesized muscle energetics may be an important contributor to performance fatigability. In the Study of Muscle, Mobility and Aging (SOMMA), participants completed a usual-paced 400m walk while wearing a wrist-worn ActiGraph, from which raw data were used to derive the Pittsburgh Performance Fatigability Index (PPFI, higher=more severe fatigability) that quantifies percent decline in the entire individual cadence-versus-time trajectory. Maximal oxidative phosphorylation (maxOXPHOS) in skeletal muscle mitochondria was quantified in vitro using high-resolution respirometry in permeabilized fiber bundles from vastus lateralis muscle biopsies. Maximal adenosine triphosphate production (ATPmax) was assessed in vivo by 31P magnetic resonance spectroscopy. We conducted separate tobit regressions to examine associations of maxOXPHOS and ATPmax with PPFI, adjusting for technician/site, age, sex, race, height, weight, and mins/day moderate-to-vigorous physical activity measured by ActiGraph in free-living, in N=795 participants with complete PPFI scores and &amp;gt;1 energetics measure (70-94 yrs, 58% women). Median PPFI scores were 1.4% [IQR: 0-2.9%]. After adjustment, each SD (18.4 pmol/(s*mg)) lower maxOXPHOS was associated with 0.55% (95% CI: 0.26, 0.85) higher PPFI scores, while each SD (0.2 mM/sec) lower ATPmax was associated with 0.54% (95% CI: 0.27, 0.81) higher PPFI scores. Our results indicate that lower skeletal muscle energetics were associated with more severe performance fatigability. This suggests that therapeutics targeting muscle energetics may thereby potentially mitigate fatigability and lessen susceptibility to disability among older adults.

ASSOCIATION OF DIABETES WITH BODY COMPOSITION, CARDIORESPIRATORY FITNESS, AND MITOCHONDRIAL ENERGETICS

Abstract We investigated the association of diabetes with cardiorespiratory fitness and skeletal muscle mitochondrial energetics in older adults (N=876, mean age ± SD: 76.3 ± 5.0 yrs.; 59% females) from the Study of Muscle, Mobility and Aging (SOMMA). Participants were grouped by self-reported diabetes status (N=131, with diabetes). Cardiorespiratory fitness (modified Balke protocol), mitochondrial energetics (31P magnetic resonance spectroscopy [31P-MRS] and high resolution respirometry from skeletal muscle biopsy), physical activity (wearable accelerometer) and body composition (magnetic resonance imaging) were measured. Generalized linear regression models were used to calculate means adjusted by age, race, gender, BMI, and co-morbidities. Thigh fat-free muscle volume (p=0.12) and abdominal subcutaneous adipose tissue depot (p=0.15) were similar between those with and without diabetes. However, visceral (18.84%, p&amp;gt;0.01) and intramuscular adipose tissue (6.57%, p=0.02) were higher in older adults with diabetes. VO2peak (-4.79%, p&amp;gt;0.01), and mitochondria energetics measured by ATPmax (-5.10%, p=0.04), maximum complex I+II carbohydrate (maxOXPHOSCHO) (-6.67%, p=0.02) and fatty acid (maxOXPHOSFAO) (-8.70%, p=0.01) stimulated respiration were lower in those with diabetes compared to those without. Following further adjustments for both physical activity and visceral adiposity, revealed that only VO2peak (-4.65%, p&amp;gt;0.01) and maxOXPHOSFAO (-7.38%, p=0.02) remained significantly lower in older adults with diabetes. Overall, our data suggests that cardiorespiratory fitness and skeletal muscle mitochondria energetics are reduced in older adults with diabetes, independent of visceral adiposity and physical activity.

MITOCHONDRIAL ENERGETICS AND PERCEIVED PHYSICAL FATIGABILITY SEVERITY IN OLDER ADULTS

Abstract It has been hypothesized that lower skeletal muscle energetics may contribute to onset of age-related perceived fatigability. Consistent with this idea, previous research found that maximal ATP production (ATPmax) was associated with higher perceived exertion (i.e., fatigability) measured in older adults with the Borg Scale at the end of a slow walking task. We extend this work to SOMMA examining skeletal muscle energetics (ATPmax and maximal complex I&amp;II supported oxidative phosphorylation [maxOXPHOS]) with perceived physical fatigability using the Pittsburgh Fatigability Scale (PFS, range 0-50, higher=greater). PFS captures fatigue perception anchored to activities of varying intensity and duration. We assessed ATPmax in vivo by 31P magnetic resonance spectroscopy following an acute knee extensor exercise bout. maxOXPHOS was quantified ex vivo in permeabilized fiber bundles by high-resolution spectroscopy. Participants (N=721 with PFS and ≥1 energetics measure) were aged 76.4±5.0 years, 56.7% women, 86.7% White. Lower ATPmax (r=-0.21) and maxOXPHOS (r=-0.29) correlated with higher PFS scores (both p&amp;lt;0.001). Linear regressions adjusted for age, sex, technician, and total daily accelerometry-derived physical activity revealed that each one SD lower ATPmax (0.15 mM/sec) was associated with 1.15 (95% CI: 0.50, 1.79) higher PFS scores; each one SD lower maxOXPHOS (18.5 pmol/(sec*mg)) was associated with 1.79 (95% CI: 1.14, 2.45) higher PFS scores. Impaired skeletal muscle energetics may be implicated in the etiologic pathway of age-related fatigability. Next steps will examine the longitudinal association between changes in skeletal muscle energetics and age-related fatigability.

CARDIORESPIRATORY FITNESS AND MITOCHONDRIAL ENERGETICS IN THE OLDEST OLD: THE STUDY OF MUSCLE, MOBILITY AND AGING

Abstract Cardiorespiratory fitness (CRF) and mitochondrial energetics are known to decrease with aging, albeit with a great degree of heterogeneity. Studies reporting these declines typically include individuals younger than 85 years of age. We investigated CRF and mitochondrial energetics in a cohort of old (O: 70-84yrs.; n=698) and oldest old (OO: 85+yrs.; n=70) adults enrolled in SOMMA. Cardiorespiratory fitness (VO2peak) was measured by modified Balke treadmill protocol, and mitochondrial energetics was assessed by 31P Magnetic Resonance Spectroscopy (ATPmax) and high-resolution respirometry of myofibers (oxidative phosphorylation, OXPHOS). Bivariate associations and group differences were assessed using unadjusted and adjusted regression models with clinical site/technician, gender, race, body mass index and physical activity (steps per day) as covariates. Old and oldest old groups showed an association between VO2peak and OXPHOS (R2=0.282, p&amp;lt;0.001; R2=0279, p=0.0083; respectively, adjusted for site/technician), but only the old group showed associations between VO2peak and ATPmax (R2=0.201, p&amp;lt;0.001; R2=0.017, p=0.609; respectively, adjusted for site/technician). Group comparison adjusted for clinical site, gender, and race, showed lower VO2peak (p &amp;lt; 0.001), OXPHOS (p=0.026), and ATPmax (p=0.0014) in the OO compared to O group. However, no group differences in OXPHOS (p=0.08) and ATPmax (p=0.09) are observed when adjusting for body composition and physical activity, factors known to affect mitochondria. In conclusion, CRF associates with different measures of mitochondrial energetics in older adults, but only with mitochondrial respiration in oldest old. Additionally, we suggest that decreases in mitochondrial energetics observed in the oldest old are related to age, changes in body composition and physical activity.

DECONSTRUCTING MULTIMORBIDITY AND MUSCLE MITOCHONDRIAL RESPIRATION AND ENERGETICS IN OLDER ADULTS

Abstract Lower cardiorespiratory fitness among older adults is associated with greater multimorbidity burden, including cardiovascular disease, cancer, and dementia. Those with poorer muscle mitochondrial energetics also have lower cardiorespiratory fitness. We have previously shown lower mitochondrial respiration and energetics (OXPHOS and ATPmax) have higher morbidity burden using a summary measure, but the associations among specific conditions have not been examined. We leverage data from the SOMMA cohort (N=856, 76.4yrs, 59% women, 85.5% white); participants self-reported physician diagnosis of 11 age-related conditions (i.e., cancer, cardiac arrhythmia, chronic kidney disease (CKD), chronic obstructive pulmonary disease, coronary heart disease (CHD), depression, diabetes). Mitochondrial respiration was assessed by high-resolution respirometry of vastus lateralis using permeabilized fiber bundles. 31P magnetic resonance spectroscopy of the quadriceps measured ATPmax. In adjusted logistic models with beta-coefficients reported per SD decrement in each mitochondrial measure, fatty-acid-supported Leak respiration was associated with CKD (OR: 2.3(95%CI=1.2,4.3)), fatty acid and complex I&amp;II supported oxidative phosphorylation (OXPHOS) with depression (OR: 1.8(95%CI=1.1,2.7)). Many respirometry measures and ATPmax associated with diabetes, with maximal electron transport system (ETS) capacity having the highest odds (OR: 1.5(95%CI=1.1,2.0)). No other associations were statistically significant for conditions listed above. These results indicate that mitochondrial respiration and energetics are more impaired in depression, kidney disease, and diabetes. This raises new questions about the role of mitochondrial respiration and energetics as cause or consequences of these conditions. Overall, our analyses suggest compromised mitochondrial function may have implications for specific aging-related conditions, and global measures of morbidity burden may not reflect these distinctions.

Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH.

In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH). This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function. Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks ("peak") and 4 weeks ("trough") after the third dose of burosumab. All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal. The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.

The effect of contact/collision sport participation without concussion on neurometabolites: A systematic review and meta-analysis of magnetic resonance spectroscopy studies.

The aim of this study was to systematically review prior research investigating the effects of contact/collision sport participation on neurometabolite levels in the absence of concussion. Four online databases were searched to identify studies that measured neurometabolite levels in contact/collision sport athletes (without concussion) using proton (1 H) or phosphorus (31 P) magnetic resonance spectroscopy (MRS). All study designs were acceptable for inclusion. Meta-analytic procedures were used to quantify the effect of contact/collision sport participation on neurometabolite levels and explore the impact of specific moderating factors (where sufficient data were available). Narrative synthesis was used to describe outcomes that could not be meta-analysed. Nine observational studies involving 300 contact/collision sport athletes were identified. Six studies (providing 112 effect estimates) employed longitudinal (cohort) designs and three (that could not be meta-analysed) employed case-control designs. N-acetylaspartate (NAA; g = -0.331, p = 0.013) and total creatine (tCr; creatine + phosphocreatine; g = -0.524, p = 0.029), but not glutamate-glutamine (Glx), myo-inositol (mI) or total choline (tCho; choline-containing compounds; p's > 0.05), decreased between the pre-season and mid-/post-season period. Several moderators were statistically significant, including: sex (Glx: 6 female/23 male, g = -0.549, p = 0.013), sport played (Glx: 22 American football/4 association football [soccer], g = 0.724, p = 0.031), brain region (mI: 2 corpus callosum/9 motor cortex, g = -0.804, p = 0.015), and the MRS quantification approach (mI: 18 absolute/3 tCr-referenced, g = 0.619, p = 0.003; andtCho: 18 absolute/3 tCr-referenced, g = 0.554, p = 0.005). In case-control studies, contact/collision sport athletes had higher levels of mI, but not NAA or tCr compared to non-contact sport athletes and non-athlete controls. Overall, this review suggests that contact/collision sport participation has the potential to alter neurometabolites measured via 1 H MRS in the absence of concussion. However, further research employing more rigorous and consistent methodologies (e.g. interventional studies with consistent 1 H MRS pulse sequences and quantifications) is required to confirm and better understand the clinical relevance of observed effects.

Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.

Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m2, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. URL: https://www. gov; Unique identifier: NCT04467411.

Impact of cannabis use on brain metabolism using 31P and 1H magnetic resonance spectroscopy

PurposeThis prospective cross-sectional study investigated the influence of regular cannabis use on brain metabolism in young cannabis users by using combined proton and phosphorus magnetic resonance spectroscopy.MethodsThe study was performed in 45 young cannabis users aged 18–30, who had been using cannabis on a regular basis over a period of at least 2 years and in 47 age-matched controls. We acquired 31P MRS data in different brain regions at 3T with a double-resonant 1H/31P head coil, anatomic images, and 1H MRS data with a standard 20-channel 1H head coil. Absolute concentration values of proton metabolites were obtained via calibration from tissue water as an internal reference, whereas a standard solution of 75 mmol/l KH2PO4 was used as an external reference for the calibration of phosphorus signals.ResultsWe found an overall but not statistically significant lower concentration level of several proton and phosphorus metabolites in cannabis users compared to non-users. In particular, energy-related phosphates such as adenosine triphosphate (ATP) and inorganic phosphate (Pi) were reduced in all regions under investigation. Phosphocreatine (PCr) showed lowered values mainly in the left basal ganglia and the left frontal white matter.ConclusionThe results suggest that the increased risk of functional brain disorders observed in long-term cannabis users could be caused by an impairment of the energy metabolism of the brain, but this needs to be verified in future studies.

P17 The Beneficial Effect of Oral Cr Supplementation in an Early Childhood Rat Model of Chronic Hepatic Encephalopathy: In Vivo Longitudinal 1H and 31P Magnetic Resonance Spectroscopy Study

P17 The Beneficial Effect of Oral Cr Supplementation in an Early Childhood Rat Model of Chronic Hepatic Encephalopathy: In Vivo Longitudinal 1H and 31P Magnetic Resonance Spectroscopy Study

PCr/ATP ratios and mitochondrial function in the heart. A comparative study in humans

Cardiac energy status, measured as phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio with 31P-Magnetic Resonance Spectroscopy (31P-MRS) in vivo, is a prognostic factor in heart failure and is lowered in cardiometabolic disease. It has been suggested that, as oxidative phosphorylation is the major contributor to ATP synthesis, PCr/ATP ratio might be a reflection of cardiac mitochondrial function. The objective of the study was to investigate whether PCr/ATP ratios can be used as in vivo marker for cardiac mitochondrial function. We enrolled thirty-eight patients scheduled for open-heart surgery in this study. Cardiac 31P-MRS was performed before surgery. Tissue from the right atrial appendage was obtained during surgery for high-resolution respirometry for the assessment of mitochondrial function. There was no correlation between the PCr/ATP ratio and ADP-stimulated respiration rates (octanoylcarnitine R2 < 0.005, p = 0.74; pyruvate R2 < 0.025, p = 0.41) nor with maximally uncoupled respiration (octanoylcarnitine R2 = 0.005, p = 0.71; pyruvate R2 = 0.040, p = 0.26). PCr/ATP ratio did correlate with indexed LV end systolic mass. As no direct correlation between cardiac energy status (PCr/ATP) and mitochondrial function in the heart was found, the study suggests that mitochondrial function might not the only determinant of cardiac energy status. Interpretation should be done in the right context in cardiac metabolic studies.

Resveratrol supplementation or diet intervention effects on heart-liver axis in prediabetic female rats submitted to high-fat-high-sucrose diet

NAFLD and type 2 diabetes (T2D) share a bidirectional relationship and cardiovascular diseases (CVD) as leading death cause, but this relationship in prediabetes is still poorly known, especially for women which exhibit an exacerbated CVD risk. Here, we evaluated the effects of resveratrol supplementation (RSV) or diet intervention on the heart-liver axis of prediabetic female rats submitted to high-fat-high-sucrose diet (HFS). Forty Female Wistar rats were divided into 4 groups fed for 5 months with: a standard diet (CTRL), HFS diet (HFS), HFS diet supplemented for the last 2 months with RSV (1 mg/kg/day in water) (RSV) or HFS diet for 3 months followed by 2 months of standard diet (RSD). In vivo Magnetic Resonance Imaging was performed to study cardiac morphology/function. Then, tolerance to ischemia-reperfusion injury was investigated ex vivo by simultaneous measurement of cardiac function (RPP, EDP) and energy metabolism by 31P Magnetic Resonance Spectroscopy. Hepatic total lipid and triglycerides (TG) contents along expression of genes involved in lipid metabolism/inflammation were studied. HFS induced glucose intolerance (P < 0.01), increased diastolic left ventricular volume and thickness (P < 0.05) and heart weight to tibia length ratio (HTLR) (P < 0.01). HFS diet also altered myocardial tolerance to IR, with impaired RPP and EDP (P < 0.001) and PCr during reperfusion (P < 0.05). Both treatments improved glucose tolerance (P < 0.05). Importantly, despite maintained HFS diet, RSV restored the elevated diastolic volume and thickness in vivo (P < 0.01 CTRL, RSV vs. HFS, RSD) and HTLR level (P < 0.001 CTRL, RSV vs. HFS, RSD), conversely to RSD. Both treatments improved the tolerance to IR, with increased RPP (P < 0.05 vs. HFS) along with PCr during reperfusion (P < 0.001, P < 0.01 vs. HFS respectively). Only RSV decreased EDP during IR injury (P < 0.05). In the liver HFS diet induced total lipid and TG accumulation (P < 0.01) as well as elevated expression of lipid oxidation/peroxidation genes without effect on lipogenesis and inflammation cytokines genes. Both treatments normalized hepatic total lipid levels. RSD restored TG levels along elevated lipid metabolism gene expressions (P < 0.01) whereas RSV partially reduced the increase (P < 0.05). Despite maintained HFS and moderate hepatic lipid metabolism effects, RSV exhibited better cardioprotection than RSD, suggesting its potential to protect against early cardiac alterations associated with prediabetes and NAFLD, especially for women.

X-nuclear MRS and MRI on a standard clinical proton-only MRI scanner

In light of the growing interest in-vivo deuterium metabolic imaging, hyperpolarized 13C, 15N, 3He, and 129Xe imaging, as well as 31P spectroscopy and imaging in large animals on clinical MR scanners, we demonstrate the use of a (radio)frequency converter system to allow X-nuclear MR spectroscopy (MRS) and MR imaging (MRI) on standard clinical MRI scanners without multinuclear capability. This is not only an economical alternative to the multinuclear system (MNS) provided by the scanner vendors, but also overcomes the frequency bandwidth problem of some vendor-provided MNSs that prohibit users from applications with X-nuclei of low magnetogyric ratio, such as deuterium (6.536 MHz/Tesla) and 15N (-4.316 MHz/Tesla). Here we illustrate the design of the frequency converter system and demonstrate its feasibility for 31P (17.235 MHz/Tesla), 13C (10.708 MHz/Tesla), and 15N MRS and MRI on a clinical MRI scanner without vendor-provided multinuclear hardware.

Structure of amorphous materials in the NASICON system NaTi2Si x PO12

The structure of glasses in the sodium (Na) super-ionic conductor (NASICON) system NaTi2Si x PO12 with x = 0.8 and x = 1.0 was explored by combining neutron and high-energy x-ray diffraction with 29Si, 31P and 23Na solid-state nuclear magnetic resonance (NMR) spectroscopy. The 29Si magic angle spinning (MAS) NMR spectra reveal that the silica component remains fully polymerized in the form of Si4 units, i.e. the silicon atoms are bound to four bridging oxygen atoms. The 31P{23Na} rotational echo adiabatic passage double resonance (REAPDOR) NMR data suggest that the 31P MAS NMR line shape originates from four-coordinated P n units, where n = 1, 2 or 3 is the number of bridging oxygen atoms per phosphorus atom. These sites differ in their 31P-23Na dipolar coupling strengths. The results support an intermediate range order scenario of a phosphosilicate mixed network-former glass in which the phosphate groups selectively attract the Na+ modifier ions. Titanium takes a sub-octahedral coordination environment with a mean Ti–O coordination number of 5.17(4) for x = 0.8 and 4.86(4) for x = 1.0. A mismatch between the P–O and Si–O bond lengths of 8% is likely to inhibit the incorporation of silicon into the phosphorus sites of the NASICON crystal structure.

Impaired Physical Performance in X-linked Hypophosphatemia Is not Caused by Depleted Muscular Phosphate Stores.

X-linked hypophosphatemia (XLH) is a rare genetic disease, characterized by renal phosphate wasting and complex musculoskeletal manifestations including decreased physical performance. To characterize muscular deficits in patients with XLH and investigate phosphate stores in muscles. Case-control study (Muscle fatigability in X-linked Hypophosphatemia [MuXLiH]) with a 1-time assessment at the German Aerospace Center (DLR), Cologne, from May to December 2019, including patients with XLH cared for at the Osteology Department, University of Wuerzburg. Thirteen patients with XLH and 13 age/sex/body weight-matched controls aged 18-65 years were included. The main outcome measure was 31P-magnetic resonance spectroscopy (31P-MRS)-based assessment of phosphate metabolites in the soleus muscle at rest. Further analyses included magnetic resonance imaging-based muscle volume measurement, laboratory testing, isokinetic maximum voluntary contraction (MVC), fatigue testing, and jumping mechanography. By means of 31P-MRS, no significant differences were observed between XLH and controls regarding phosphate metabolites except for a slightly increased phosphocreatine to inorganic phosphate (PCr/Pi) ratio (XLH: 13.44 ± 3.22, control: 11.01 ± 2.62, P = .023). Quadriceps muscle volume was reduced in XLH (XLH: 812.1 ± 309.0 mL, control: 1391.1 ± 306.2 mv, P < .001). No significant differences were observed regarding isokinetic maximum torque (MVC) adjusted to quadriceps muscle volume. Jumping peak power and jump height were significantly reduced in XLH vs controls (both P < .001). The content of phosphoric compounds within the musculature of patients with XLH was not observed to be different from controls. Volume-adjusted muscle strength and fatiguability were not different either. Reduced physical performance in patients with XLH may result from long-term adaptation to reduced physical activity due to skeletal impairment.