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Background: Fat infiltration in skeletal muscle is related to declining muscle strength, whereas excess subcutaneous fat is implicated in the development of metabolic diseases. Methods: Using multi-slice axial T2-weighted (T2w) MR images, this retrospective study characterized muscle fat infiltration (MFI) and fat distribution in the lower extremity of 107 subjects (64M/43F, age 11–79 years) with diverse ethnicities (including White, Black, Latino, and Asian subjects). Results: MRI data analysis shows that MFI, evaluated by the relative intensities of the pixel histogram profile in the calf muscle, tends to increase with both age and BMI. However, statistical significance was found only for the age correlation in women (p < 0.002), and the BMI correlation in men (p = 0.04). Sex disparities were also seen in the fat distribution, which was assessed according to subcutaneous fat thickness (SFT) and the fibula bone marrow cross-sectional area (BMA). SFT tends to decrease with age in men (p < 0.01), whereas SFT tends to increase with BMI only in women (p < 0.01). In contrast, BMA tends to increase with age in women (p < 0.01) and with BMI in men (p = 0.04). Additionally, MFI is positively correlated with BMA but not with SFT, suggesting that compromised bone structure may contribute to fat infiltration in the surrounding skeletal muscle. Conclusions: The findings of this study highlight a sex factor affecting MFI and fat distribution, which may offer valuable insights into effective strategies to prevent and treat MFI in women versus men. [ABSTRACT FROM AUTHOR]

[Objectives] Solid Oxide Fuel Cell-Micro Gas Turbine(SOFC-MGT) hybrid power generation system will help to improve the endurance and stealth of conventionally powered submarines. So in order to analyze the performance characteristics of this system in different operating modes,[Methods] the fuel cell AIP system improved by Matlab/Simulink is combined with Micro Gas Turbine(MGT)to form a top-level cyclic hybrid power generation system in this paper. And the dual-mode is proposed according to the sailing state of the submarine. The simulation model of SOFC-MGT hybrid power generation system and exhaust treatment system is established to analyze the performance indicators under design conditions, as well as the influences of current,water-carbon ratio,CH4 flow rate,air component and other factors on the system performance.[Results] The simulation results verify the validity and feasibility of the model; in these two modes,the power generation efficiency is 59.48% and 61.61%,and the maximum power is 217 kW and 223 kW,where the system net power in the mode 2 is higher. The submarine dual-mode SOFC-MGT hybrid power system can maintain stable output power and high power generation efficiency under different working conditions of the submarine,achieving obviously better performance than other AIP systems.[Conclusions] This study results can provide theoretical support for the application of SOFC-MGT hybrid power generation system to conventional submarines.

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle. [ABSTRACT FROM AUTHOR]

Introduction: Mitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer's disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study's first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups. Methods: Forty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH]. Results: Thirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD. Conclusion: To our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD. [ABSTRACT FROM AUTHOR]

Background: The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of β-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are providing new avenues to measure BEM accurately using 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7-Tesla. This study investigates whether a methodology using partial volume-coil 31P MRS at 7T over parieto-occipital lobes can accurately quantify high-energy phosphate and membrane phospholipid metabolites in aMCI. A secondary objective was to explore BEM and membrane phospholipid indices' correspondence with cognitive performance in domains of executive function (EF), memory, attention, and visuospatial skills in aMCI, a heterogeneous population. Methods: 19 aMCI participants enrolled in the study completed cognitive assessment and 31P MRS scan. BEM indices were measured using three energy indicators: energy reserve (PCr/t-ATP), energy consumption (intracellular_Pi/t-ATP), and metabolic state (PCr/intracellular_Pi) along with regulatory co-factors of BEM-intracellular Mg2 + and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs) – membrane phospholipid indicator. Results: 31P MRS scan showed thirteen well-resolved peaks with precise quantification of the phosphorus metabolites at UHF. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p = 0.004), (metabolic state indicator: CVLT p = 0.007)], executive function [(metabolic state indicator: TOSL (p = 0.044)], and attention [(pH: selective auditory task, p = 0.044)]. The finding of an inverse relationship observed in the parieto-occipital lobes suggests an association between neuronal energy markers with cognition in aMCI. Conclusion: The significant contribution of this preliminary research was to establish the feasibility of utilizing a methodology at UHF to accurately measure high-energy phosphate and membrane phospholipid metabolites in a population with heterogeneous outcomes. This work offers a novel approach for future work to further elucidate early dementia biomarkers or precursors to the downstream accumulation of amyloid and tau using the combination of MRS-PET imaging modalities in AD. [ABSTRACT FROM AUTHOR]

Carbon-13 magnetic resonance spectroscopy (13C MRS) offers a noninvasive method to assess glycogen levels in skeletal muscle and to identify excess glycogen accumulation in patients with glycogen storage disease (GSD). Despite the clinical potential of the method, it is currently not widely used for diagnosis or for follow-up of treatment. While it is possible to perform acceptable 13C MRS at lower fields, the low natural abundance of 13C and the inherently low signal-to-noise ratio of 13C MRS makes it desirable to utilize the advantage of increased signal strength offered by ultra-high fields for more accurate measurements. Concomitant with this advantage, however, ultra-high fields present unique technical challenges that need to be addressed when studying glycogen. In particular, the question of measurement reproducibility needs to be answered so as to give investigators insight into meaningful inter-subject glycogen differences. We measured muscle glycogen levels in vivo in the calf muscle in three patients with McArdle disease (MD), one patient with phosphofructokinase deficiency (PFKD) and four healthy controls by performing 13C MRS at 7T. Absolute quantification of the MRS signal was achieved by using a reference phantom with known concentration of metabolites. Muscle glycogen concentration was increased in GSD patients (31.5±2.9 g/kg w. w.) compared with controls (12.4±2.2 g/kg w. w.). In three GSD patients glycogen was also determined biochemically in muscle homogenates from needle biopsies and showed a similar 2.5-fold increase in muscle glycogen concentration in GSD patients compared with controls. Repeated inter-subject glycogen measurements yield a coefficient of variability of 5.18%, while repeated phantom measurements yield a lower 3.2% system variability. We conclude that noninvasive ultra-high field 13C MRS provides a valuable, highly reproducible tool for quantitative assessment of glycogen levels in health and disease. [ABSTRACT FROM AUTHOR]

Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation- and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few in vivo human studies have been performed. Here, non-invasive in vivo magnetic resonance spectroscopy ( 1 H and 31 P) was applied to test scan feasibility and assess neurotransmitter balance and energy metabolism in Lafora disease towards a better understanding of pathogenesis. Macromolecule-suppressed gamma-aminobutyric acid (GABA)-edited 1 H magnetic resonance spectroscopy and 31 P magnetic resonance spectroscopy at 3 and 7 tesla, respectively, were performed in 4 Lafora disease patients and a total of 21 healthy controls (12 for the 1 H magnetic resonance spectroscopy and 9 for the 31 PMRS). Spectra were processed using in-house software and fit to extract metabolite concentrations. From the 1 H spectra, we found 33% lower GABA concentrations ( P = 0.013), 34% higher glutamate + glutamine concentrations ( P = 0.011) and 24% lower N -acetylaspartate concentrations ( P = 0.0043) in Lafora disease patients compared with controls. From the 31 P spectra, we found 34% higher phosphoethanolamine concentrations ( P = 0.016), 23% lower nicotinamide adenine dinucleotide concentrations ( P = 0.003), 50% higher uridine diphosphate glucose concentrations ( P = 0.004) and 225% higher glucose 6-phosphate concentrations in Lafora disease patients versus controls ( P = 0.004). Uridine diphosphate glucose is the substrate of glycogen synthase, and glucose 6-phosphate is its extremely potent allosteric activator. The observed elevated uridine diphosphate glucose and glucose 6-phosphate levels are expected to hyperactivate glycogen synthase and may underlie the generation of polyglucosans in Lafora disease. The increased glutamate + glutamine and reduced GABA indicate altered neurotransmission and energy metabolism, which may contribute to the disease's intractable epilepsy. These results suggest a possible basis of polyglucosan formation and potential contributions to the epilepsy of Lafora disease. If confirmed in larger human and animal model studies, measurements of the dysregulated metabolites by magnetic resonance spectroscopy could be developed into non-invasive biomarkers for clinical trials., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Mitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer's disease (AD). Advanced imaging technologies, such as 31 phosphorus magnetic resonance spectroscopy ( 31 P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study's first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31 P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups., Methods: Forty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular&#95;Pi/t-ATP), metabolic state indicator (intracellular&#95;Pi/PCr), and regulatory co-factors [magnesium (Mg 2+ ) and intracellular pH]., Results: Thirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption ( p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator ( p = 0.007) and lower Mg 2+ ( p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg 2+ and cognitive performance of memory ( p = 0.013), EF ( p = 0.023), and attention ( p = 0.0003) in CN but not in aMCI or AD., Conclusion: To our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Das, Ren, Spence and Chapman.)

Background: The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of β-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are providing new avenues to measure BEM accurately using 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7-Tesla. This study investigates whether a methodology using partial volume-coil 31P MRS at 7T over parieto-occipital lobes can accurately quantify high-energy phosphate and membrane phospholipid metabolites in aMCI. A secondary objective was to explore BEM and membrane phospholipid indices' correspondence with cognitive performance in domains of executive function (EF), memory, attention, and visuospatial skills in aMCI, a heterogeneous population., Methods: 19 aMCI participants enrolled in the study completed cognitive assessment and 31P MRS scan. BEM indices were measured using three energy indicators: energy reserve (PCr/t-ATP), energy consumption (intracellular&#95;Pi/t-ATP), and metabolic state (PCr/intracellular&#95;Pi) along with regulatory co-factors of BEM-intracellular Mg 2 + and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs) - membrane phospholipid indicator., Results: 31P MRS scan showed thirteen well-resolved peaks with precise quantification of the phosphorus metabolites at UHF. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p = 0.004), (metabolic state indicator: CVLT p = 0.007)], executive function [(metabolic state indicator: TOSL ( p = 0.044)], and attention [(pH: selective auditory task, p = 0.044)]. The finding of an inverse relationship observed in the parieto-occipital lobes suggests an association between neuronal energy markers with cognition in aMCI., Conclusion: The significant contribution of this preliminary research was to establish the feasibility of utilizing a methodology at UHF to accurately measure high-energy phosphate and membrane phospholipid metabolites in a population with heterogeneous outcomes. This work offers a novel approach for future work to further elucidate early dementia biomarkers or precursors to the downstream accumulation of amyloid and tau using the combination of MRS-PET imaging modalities in AD., (Copyright © 2020 Das, Ren, Spence, Rackley and Chapman.)

Magnetic resonance imaging is a powerful clinical imaging technique that allows for noninvasive tomographic visualization of anatomic structures with high spatial resolution and soft tissue contrast. However, its application in molecular imaging of cancer has been limited by the lack of sensitivity and detection accuracy in depicting the biochemical expression of these diseases. Here, we combine an ultrasensitive design of superparamagnetic polymeric micelles (SPPM) and an off-resonance saturation (ORS) method to enhance the imaging efficacy of tumor biomarkers in vivo. SPPM nanoparticles encoded with cyclic(RGDfK) were able to target the alpha(v)beta(3)-expressing microvasculature in A549 non-small cell lung tumor xenografts in mice. ORS greatly improved tumor detection accuracy over the conventional T(2)*-weighted method by its ability to turn "ON" the contrast of SPPM. This combination of ORS imaging with a tumor vasculature-targeted, ultrasensitive SPPM design offers new opportunities in molecular imaging of cancer.