Dataset Information

Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment.

ABSTRACT: Carnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alternative to quantify carnosine in human skeletal muscle. However, carnosine quantification by 1H-MRS has some potential limitations that warrant a thorough experimental examination of its validity. The present investigation examined the reliability, accuracy and sensitivity for the determination of muscle carnosine in humans using in vitro and in vivo experiments and comparing it to reference method for carnosine quantification (high-performance liquid chromatography - HPLC). We used in vitro 1H-MRS to verify signal linearity and possible noise sources. Carnosine was determined in the m. gastrocnemius by 1H-MRS and HPLC to compare signal quality and convergent validity. 1H-MRS showed adequate discriminant validity, but limited reliability and poor agreement with a reference method. Low signal amplitude, low signal-to-noise ratio, and voxel repositioning are major sources of error.

SUBMITTER: da Eira Silva V

PROVIDER: S-EPMC7078313 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment.

da Eira Silva Vinicius V Painelli Vitor de Salles VS Shinjo Samuel Katsuyuki SK Ribeiro Pereira Wagner W Cilli Eduardo Maffud EM Sale Craig C Gualano Bruno B Otaduy Maria Concepción MC Artioli Guilherme Giannini GG

Scientific reports 20200317 1

Carnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alter ...[more]

PMID: 32184463

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Project description:Mitochondrial efficiency is a critical metabolic parameter with far-reaching implications for tissue homeostasis. However, the direct measurement of oxygen consumption (VO2) and ATP production from a large tissue sample in vivo remains challenging. Using phosphorus (31P) and proton (1H) magnetic resonance spectroscopy (MRS), this study aimed to non-invasively quantify the skeletal muscle ATP synthesis rate and VO2 to determine mitochondrial efficiency at rest and during muscle contraction in humans. We assessed mitochondrial efficiency in the plantar flexor muscles of 12 healthy adults (21 ± 1 years) using 31P and 1H MRS within a 3T MR system. MRS data were acquired at rest and during constant workloads to quantify oxidative ATP synthesis (ATPox) rate and myoglobin-derived oxygen consumption (Mb-derived VO2). At rest, ATPox was 0.85 ± 0.24 mm min-1, and Mb-derived VO2 was 0.46 ± 0.11 mm min-1, resulting in a P/O ratio of 1.95 ± 0.68. During graded exercise, end-exercise PCr concentration decreased from 29 ± 5.7 mm to 18 ± 4.8 mm, and end-exercise Mb oxygenation declined linearly to 47 ± 11%. ATPox synthesis rate increased linearly with exercise workload (r = 0.65 ± 0.31), whereas there was no significant change in Mb-derived VO2 (r = -0.19 ± 0.60), leading to non-physiological P/O values during exercise (>3). The results indicate that combined 31P/1H-MRS at rest offers a promising approach for non-invasively quantifying mitochondrial efficiency in large muscle samples, suggesting its potential as a clinical endpoint of mitochondrial function. However, further refinement is needed for use during exercise. KEY POINTS: Mitochondrial efficiency, converting chemical energy from carbon fuels into ATP, is a vital metabolic parameter for tissue homeostasis, but measuring oxygen consumption (VO2) and ATP production in vivo has been challenging. This study used phosphorus (31P) and proton (1H) magnetic resonance spectroscopy (MRS) to non-invasively quantify the skeletal muscle ATP synthesis rate and VO2 at rest and during muscle contraction in humans. At rest, the oxidative ATP synthesis (ATPox) and myoglobin-derived VO2 (Mb-derived VO2) were measured, resulting in a P/O ratio of 1.95 in the plantar flexor muscles. During exercise, the ATPox rate increased with workload, but Mb-derived VO2 did not change significantly, leading to non-physiological P/O ratios. The findings suggest that 31P/1H-MRS at rest is a promising method for assessing mitochondrial efficiency and could be used as a clinical endpoint for mitochondrial function in vivo, although further refinement is needed for exercise conditions.

Project description:BackgroundNatural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31 P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients.MethodsQuantitative MRI/31 P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Fat fraction (FF), contractile cross-sectional area (cCSA), and muscle water T2 in both global leg and thigh segments and individual muscles and 31 P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31 P MRS markers and functional markers.ResultsPosterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T2 values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T2 values were found in the anterior part of thigh and leg. Almost all 31 P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pHw , and remained, similar as to water T2 , abnormal for the whole study duration. Global thigh water T2 at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = -0.55, P = 0.010).ConclusionsThis multi-centre study has shown that quantitative MRI/31 P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb-girdle muscular dystrophy subtypes.

Project description:Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adult. Based on transcriptome profile MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate Dehydrogenase-1 (IDH1) mutations have been described in several tumours, including gliomas, while in MB are exceptionally reported and not routinely investigated. By mean of magnetic resonance spectroscopy (MRS) we unequivocally assessed the presence the oncometabolite D-2-Hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutation, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also exceptionally described in MB. To our knowledge this is the first reported case of MB harboring both mutations together. Of note, tumour exhibited a heterogeneous phenotype with a tumour component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting coexistence of two different major tumour clones. These findings draw attention to the need of a deeper genetic characterization of MB in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, reported data underling the importance of performing MRS for the identification of IDH mutations in non-glial tumours. The use of throughput molecular profiling analysis and advanced medical imaging technology will certainly increase the frequency with which rare tumour entities will be identified. Whether they have any particular therapeutic implications or prognostic relevance requires further investigations.

Project description:Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor-provided MRS protocols are increasingly recognized, especially when used at high fields (≥3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25-30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion-corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections.

Project description:Background. Generally, males display greater strength and muscle capacity than females while performing a task. Muscle biopsy is regarded as the reference method of evaluating muscle functions; however, it is invasive and has sampling errors, and is not practical for longitudinal studies and dynamic measurement during excise. In this study, we built an in-house force control and gauge system for quantitatively applying force to quadriceps while the subjects underwent (31)P Magnetic Resonance Spectroscopy ((31)P-MRS); our aim was to investigate if there is a sex difference of phosphate metabolite change in working muscles in young heathy Chinese volunteers. Methods. Volunteers performed knee-extending excises using a force control and gauge system while lying prone in a Philips 3T Magnetic Resonance (MR) scanner. The (31)P-MRS coil was firmly placed under the middle of the quadriceps . (31)P-MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) were acquired from quadriceps while subjects were in a state of pre-, during- and post-exercise. The PCr, Pi, PCr/Pi, PCr/ATP, pH, work/energy cost ratio (WE), kPCr and oxidative capacity were compared between males and females. Results. A total of 17 volunteers underwent the study. Males: N = 10, age = 23.30 ± 1.25years; females: N = 7, age = 23.57 ± 0.79 years. In this study, males had significantly greater WE (16.33 ± 6.46 vs. 7.82 ± 2.16, p = 0.002) than females. Among PCr, Pi, PCr/Pi, PCr/ATP, pH, kPCr and oxidative capacity at different exercise status, only PCr/Pi (during-exercise, males = 5.630 ± 1.647, females = 4.014 ± 1.298, p = 0.047), PCr/ATP (during-exercise, males =1.273 ± 0.219, females = 1.523 ± 0.167, p = 0.025), and ATP (post-exercise, males = 24.469 ± 3.911 mmol/kg, females = 18.353 ± 4.818 mmol/kg, p = 0.035) had significant sex differences. Males had significantly greater PCr/Pi, but less PCr/ATP than females during exercise, suggesting males had higher energy transfer efficiency than females. At the post-exercise status, the recovery of PCr did not show sex difference. Conclusions. Our in-house force control and gauge system quantitatively applied force during the exercise for (31)P-MRS experiments, and a sex difference of higher energy transfer efficiency and WE was detected in males with mild loaded exercising quadriceps. This noninvasive technology allows us to further study and understand the sex difference of high energy phosphate metabolism in the future.

Project description:ObjectivesDespite improved survival due to new treatments, the 10-year survival rate in patients with breast cancer is approximately 75%. Lymphovascular invasion (LVI), a prognostic marker independent from histological grade and stage, can only be fully determined at final histological examination. Lipid composition is deregulated in tumour via de novo lipogenesis, with alteration in lipogenic genes in LVI. We hypothesise alteration in lipid composition derived from novel non-invasive spectroscopy method is associated with LVI positivity.MethodsThirty female patients (age 39-78) with invasive ductal carcinoma were enrolled, with 13 LVI negative and 17 LVI positive. Saturated, monounsaturated, polyunsaturated fatty acids and triglycerides (SFA, MUFA, PUFA and TRG) were quantified from ex vivo breast tumours freshly excised from patients on a 3 T clinical MRI scanner, and proliferative activity marker Ki-67 and serotonin derived histologically.ResultsThere were significantly lower MUFA (p = 0.0189) in LVI positive (median: 0.37, interquartile range (IQR): 0.25-0.64) than negative (0.63, 0.49-0.96). There were significantly lower TRG (p = 0.0226) in LVI positive (1.32, 0.95-2.43) than negative (2.5, 1.92-4.15). There was no significant difference in SFA (p = 0.6009) or PUFA (p = 0.1641). There was no significant correlation between lipid composition against Ki-67 or serotonin, apart from a borderline negative correlation between PUFA and serotonin (r = - 0.3616, p = 0.0496).ConclusionLipid composition might provide a biomarker to study lymphovascular invasion in breast cancer.Key points• Monounsaturated fatty acids in lymphovascular invasion (LVI) positive invasive breast carcinoma were significantly lower than that in LVI negative. • Triglycerides in LVI positive invasive breast carcinoma were significantly lower than that in LVI negative. • Lipid composition from MR spectroscopy reflects the rate of de novo lipogenesis and provides a potential biomarker independent from histological grade and stage.

Dataset Information

Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment.

Publications

Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment.

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