scholarly journals Introduction to in vivo31P magnetic resonance spectroscopy of (human) skeletal muscle

1999 ◽  
Vol 58 (4) ◽  
pp. 861-870 ◽  
Author(s):  
A. Heerschap ◽  
C. Houtman ◽  
H. J. A. in 't Zandt ◽  
A. J. van den Bergh ◽  
B. Wieringa

31P magnetic resonance spectroscopy (MRS) offers a unique non-invasive window on energy metabolism in skeletal muscle, with possibilities for longitudinal studies and of obtaining important bioenergetic data continuously and with sufficient time resolution during muscle exercise. The present paper provides an introductory overview of the current status of in vivo31P MRS of skeletal muscle, focusing on human applications, but with some illustrative examples from studies on transgenic mice. Topics which are described in the present paper are the information content of the 31P magnetic resonance spectrum of skeletal muscle, some practical issues in the performance of this MRS methodology, related muscle biochemistry and the validity of interpreting results in terms of biochemical processes, the possibility of investigating reaction kinetics in vivo and some indications for fibre-type heterogeneity as seen in spectra obtained during exercise.

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  

Abstract Telomere shortening constitutes a natural barrier to uncontrolled proliferation and all tumors must find a mechanism of maintaining telomere length. Most human tumors, including high-grade primary glioblastomas (GBMs) and low-grade oligodendrogliomas (LGOGs) achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. TERT expression is, therefore, a driver of tumor proliferation and, due to this essential role, TERT is also a therapeutic target. However, non-invasive methods of imaging TERT are lacking. The goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression that will enable non-invasive visualization of tumor burden in LGOGs and GBMs. First, we silenced TERT expression by RNA interference in patient-derived LGOG (SF10417, BT88) and GBM (GS2) models. Our results linked TERT silencing to significant reductions in steady-state levels of NADH in all models. NADH is essential for the conversion of pyruvate to lactate, suggesting that measuring pyruvate flux to lactate could be useful for imaging TERT status. Recently, deuterium (2H)-MRS has emerged as a novel, clinically translatable method of monitoring metabolic fluxes in vivo. However, to date, studies have solely examined 2H-glucose and the use of [U-2H]pyruvate for non-invasive 2H-MRS has not been tested. Following intravenous injection of a bolus of [U-2H]pyruvate, lactate production was higher in mice bearing orthotopic LGOG (BT88 and SF10417) and GBM (GS2) tumor xenografts relative to tumor-free mice, suggesting that [U-2H]pyruvate has the potential to monitor TERT expression in vivo. In summary, our study, for the first time, shows the feasibility and utility of [U-2H]pyruvate for in vivo imaging. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental cancer hallmark, i.e. TERT, into glioma patient management.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3406
Author(s):  
Elisabeth Bumes ◽  
Fro-Philip Wirtz ◽  
Claudia Fellner ◽  
Jirka Grosse ◽  
Dirk Hellwig ◽  
...  

Isocitrate dehydrogenase (IDH)-1 mutation is an important prognostic factor and a potential therapeutic target in glioma. Immunohistological and molecular diagnosis of IDH mutation status is invasive. To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, directly in vivo. However, these methods are technically challenging and not broadly available. Therefore, we explored the use of machine learning for the non-invasive, inexpensive and fast diagnosis of IDH status in standard 1H-magnetic resonance spectroscopy (1H-MRS). To this end, 30 of 34 consecutive patients with known or suspected glioma WHO grade II-IV were subjected to metabolic positron emission tomography (PET) imaging with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) for optimized voxel placement in 1H-MRS. Routine 1H-magnetic resonance (1H-MR) spectra of tumor and contralateral healthy brain regions were acquired on a 3 Tesla magnetic resonance (3T-MR) scanner, prior to surgical tumor resection and molecular analysis of IDH status. Since 2-HG spectral signals were too overlapped for reliable discrimination of IDH mutated (IDHmut) and IDH wild-type (IDHwt) glioma, we used a nested cross-validation approach, whereby we trained a linear support vector machine (SVM) on the complete spectral information of the 1H-MRS data to predict IDH status. Using this approach, we predicted IDH status with an accuracy of 88.2%, a sensitivity of 95.5% (95% CI, 77.2–99.9%) and a specificity of 75.0% (95% CI, 42.9–94.5%), respectively. The area under the curve (AUC) amounted to 0.83. Subsequent ex vivo 1H-nuclear magnetic resonance (1H-NMR) measurements performed on metabolite extracts of resected tumor material (eight specimens) revealed myo-inositol (M-ins) and glycine (Gly) to be the major discriminators of IDH status. We conclude that our approach allows a reliable, non-invasive, fast and cost-effective prediction of IDH status in a standard clinical setting.


1998 ◽  
Vol 76 (1) ◽  
pp. 13-26 ◽  
Author(s):  
Judy E Anderson

Regeneration of skeletal muscle tissue includes sequential processes of muscle cell proliferation and commitment, cell fusion, muscle fiber differentiation, and communication between cells of various tissues of origin. Central to the process is the myosatellite cell, a quiescent precursor cell located between the mature muscle fiber and its sheath of external lamina. To form new fibers in a muscle damaged by disease or direct injury, satellite cells must be activated, proliferate, and subsequently fuse into an elongated multinucleated cell. Current investigations in the field concern modulation of the effectiveness of skeletal muscle regeneration, the regeneration-specific role of myogenic regulatory gene expression distinct from expression during development, the impact of growth and scatter factors and their respective receptors in amplifying precursor numbers, and promoting fusion and maturation of new fibers and the ultimate clinical therapeutic applications of such information to alleviate disease. One approach to muscle regeneration integrates observations of muscle gene expression, proliferation, myoblast fusion, and fiber growth in vivo with parallel studies of cell cycling behaviour, endocrine perturbation, and potential biochemical markers of steps in the disease-repair process detected by magnetic resonance spectroscopy techniques. Experiments on muscles from limb, diaphragm, and heart of the mdx dystrophic mouse, made to parallel clinical trials on human Duchenne muscular dystrophy, help to elucidate mechanisms underlying the positive treatment effects of the glucocorticoid drug deflazacort. This review illustrates an effective combination of in vivo and in vitro experiments to integrate the distinctive complexities of post-natal myogenesis in regeneration of skeletal muscle tissue.Key words: satellite cell, cell cycling, HGF/SF, c-met receptor, MyoD, myogenin, magnetic resonance spectroscopy, mdx dystrophic mouse, deflazacort.


2019 ◽  
Author(s):  
Vinicius da Eira Silva ◽  
Vitor de Salles Painelli ◽  
Samuel Katsuyuki Shinjo ◽  
Wagner Ribeiro Pereira ◽  
Eduardo Maffud Cilli ◽  
...  

ABSTRACTCarnosine 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.


2002 ◽  
Vol 36 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Gin S. Malhi ◽  
Michael Valenzuela ◽  
Wei Wen ◽  
Perminder Sachdev

Objective: This paper briefly describes neuroimaging using magnetic resonance spectroscopy (MRS) and provides a systematic review of its application to psychiatric disorders. Method: A literature review ( Index Medicus/ Medline) was carried out, as well as a review of other relevant papers and data known to the authors. Results: Magnetic resonance spectroscopy is a complex and sophisticated neuroimaging technique that allows reliable and reproducible quantification of brain neurochemistry provided its limitations are respected. In some branches of medicine it is already used clinically, for instance, to diagnose tumours and in psychiatry its applications are gradually extending beyond research. Neurochemical changes have been found in a variety of brain regions in dementia, schizophrenia and affective disorders and promising discoveries have also been made in anxiety disorders. Conclusions: Magnetic resonance spectroscopy is a non-invasive investigative technique that has provided useful insights into the biochemical basis of many neuropsychiatric disorders. It allows direct measurement, in vivo, of medication levels within the brain and has made it possible to track the neurochemical changes that occur as a consequence of disease and ageing or in response to treatment. It is an extremely useful advance in neuroimaging technology and one that will undoubtedly have many clinical uses in the near future.


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