scholarly journals Harmonisation of multi-site MRS data with ComBat

2021 ◽  
Author(s):  
Tiffany K Bell ◽  
Kate J Godfrey ◽  
Ashley L Ware ◽  
Keith Owen Yeates ◽  
Ashley DK Harris
Keyword(s):  
Neurological Disorders ◽  
Biological Effects ◽  
Resonance Spectroscopy ◽  
Biological Variability ◽  
Non Invasive ◽  
Standard Press ◽  
Biological Sources ◽  
Using Data ◽  
Data Harmonisation

Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to measure brain chemistry in vivo and has been used to study the healthy brain as well as neuropathology in numerous neurological disorders. The number of multi-site studies using MRS are increasing; however, non-biological variability introduced during data collection across multiple sites, such as differences in scanner vendors and site-specific acquisition implementations for MRS, can obscure detection of biological effects of interest. ComBat is a data harmonisation technique that can remove non-biological sources of variance in multisite studies. It has been validated for use with structural and functional MRI metrics but not for MRS metabolites. This study investigated the validity of using ComBat to harmonize MRS metabolites for vendor and site differences. Analyses were performed using data acquired across 20 sites and included edited MRS for GABA+ (N=218) and macromolecule-suppressed GABA data (N=209), as well as standard PRESS data to quantify NAA, creatine, choline, and glutamate (N=195). ComBat harmonisation successfully mitigated vendor and site differences for all metabolites of interest. Moreover, significant associations were detected between sex and choline levels and between age and glutamate and GABA+ levels that were not detectable prior to harmonisation, confirming the importance of removing site and vendor effects in multi-site data. In conclusion, ComBat harmonisation can be successfully applied to MRS data in multi-site MRS studies.

scholarly journals BIMG-08. DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY USING 2H-PYRUVATE ALLOWS NON-INVASIVE IN VIVO IMAGING OF TERT EXPRESSION IN BRAIN TUMORS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
In Vivo Imaging ◽  
Lactate Production ◽  
Telomere Maintenance ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Non Invasive ◽  
Tert Expression

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.

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
Keyword(s):  
Skeletal Muscle ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Current Status ◽  
Resonance Spectroscopy ◽  
Biochemical Processes ◽  
Non Invasive ◽  
Introductory Overview ◽  
Muscle Biochemistry

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.

scholarly journals Non-Invasive Prediction of IDH Mutation in Patients with Glioma WHO II/III/IV Based on F-18-FET PET-Guided In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3406
Author(s):  
Elisabeth Bumes ◽  
Fro-Philip Wirtz ◽  
Claudia Fellner ◽  
Jirka Grosse ◽  
Dirk Hellwig ◽  
...  
Keyword(s):  
Machine Learning ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Support Vector ◽  
Resonance Spectroscopy ◽  
Idh Mutation ◽  
1H Mrs ◽  
1H Magnetic Resonance Spectroscopy ◽  
Non Invasive

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.

scholarly journals CBMT-41. IMAGING A HALLMARK OF CANCER: HYPERPOLARIZED 13C-MAGNETIC RESONANCE SPECTROSCOPY CAN NON-INVASIVELY MONITOR TERT EXPRESSION IN LOW-GRADE GLIOMAS IN VIVO

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi42-vi42
Author(s):  
Pavithra Viswanath ◽  
Georgios Batsios ◽  
Anne Marie Gillespie ◽  
Russell O Pieper ◽  
Sabrina Ronen
Keyword(s):  
Lactate Production ◽  
Metabolic Imaging ◽  
Imaging Biomarkers ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Normal Brain ◽  
Non Invasive ◽  
Glucose Flux ◽  
Tert Expression

Abstract Telomerase reverse transcriptase (TERT) expression is a hallmark of cancer, including in primary glioblastomas and low-grade oligodendrogliomas. Since TERT is essential for glioma proliferation and is an attractive therapeutic target, metabolic imaging of TERT status can inform on tumor progression and response to therapy. To that end, the goal of this study was to identify non-invasive, translational, hyperpolarized 13C-magnetic resonance spectroscopy-detectable metabolic imaging biomarkers of TERT in low-grade oligodendrogliomas. Unbiased metabolomic analysis of immortalized normal human astrocytes without (NHAcontrol) and with TERT (NHAtert) indicated that TERT induced unique metabolic reprogramming. Notably, TERT increased NADPH and NADH levels. Glucose flux through the pentose phosphate pathway (PPP) is a major producer of NADPH. Non-invasive imaging of PPP flux using hyperpolarized [U-13C,U-2H]-glucose indicated that production of the PPP metabolite 6-phosphogluconate (6-PG) was elevated in NHAtert cells relative to NHAcontrol. Importantly, hyperpolarized [U-13C,U-2H]-glucose flux to 6-PG clearly differentiated tumor from normal brain in orthotopic NHAtert tumor xenografts. Next, we exploited the observation that TERT expression increased NADH, which is essential for the metabolism of hyperpolarized [1-13C]-alanine to lactate. Lactate production from hyperpolarized [1-13C]-alanine was higher in NHAtert cells relative to NHAcontrol. Importantly, hyperpolarized [1-13C]-alanine imaging in orthotopic NHAtert tumors revealed pronounced differences in lactate production between tumor tissue and normal brain. Mechanistically, TERT increased expression of glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme for 6-PG and NADPH production, and of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme for NADH biosynthesis. Silencing TERT reversed G6PDH and NAMPT expression and normalized hyperpolarized [U-13C,U-2H]-glucose and [1-13C]-alanine metabolism, validating our imaging biomarkers. Finally, hyperpolarized [U-13C,U-2H]-glucose and [1-13C]-alanine could monitor TERT status in the clinically relevant, patient-derived BT54 oligodendroglioma model. In summary, we demonstrate, for the first time, non-invasive in vivo imaging of TERT status in gliomas that can enable longitudinal analysis of tumor burden and treatment response in the clinic.

In vivo measurements of mitochondrial function and cell death following hypoxic/ischaemic damage to the new-born brain

1999 ◽  
Vol 66 ◽  
pp. 123-140 ◽  
Author(s):  
Chris E. Cooper
Keyword(s):  
Cell Death ◽  
Magnetic Resonance ◽  
Mitochondrial Function ◽  
Apoptotic Cell ◽  
Cellular Damage ◽  
Resonance Spectroscopy ◽  
Advantages And Disadvantages ◽  
Non Invasive ◽  
The Brain

Critically impaired gas exchange to the brain due to decreased oxygen (hypoxia) or reduced blood flow (ischaemia) is a major cause of brain injury in the perinatal period. There is an accumulating body of evidence suggesting that the irreversible cellular damage in the neonatal brain that occurs subsequent to an hypoxic/ischaemic insult is at the level of the mitochondria. Much of this evidence has been obtained by novel non-invasive measurements of mitochondrial function in vivo. This review focuses on four techniques: near-infrared spectroscopy, magnetic resonance spectroscopy, magnetic resonance imaging and electron paramagnetic resonance spectroscopy. The advantages and disadvantages of these in vivo methods are described in patients and animal models. The picture that emerges is of a slow (1-2 day) energy failure, occurring at the level of the brain mitochondria and leading to a primarily apoptotic cell death. Moderate post-insult hypothermia prevents this damage by an unknown mechanism. It is stressed that isolated cell studies alone are not sufficient to understand the processes occurring at the biochemical and physiological levels. The use of the non-invasive techniques described to understand the biochemistry occurring in vivo is therefore an invaluable aid in integrating cellular and organismal studies of the role of mitochondria in cell death.

Magnetic Resonance Spectroscopy and its Applications in Psychiatry

2002 ◽  
Vol 36 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Gin S. Malhi ◽  
Michael Valenzuela ◽  
Wei Wen ◽  
Perminder Sachdev
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Regions ◽  
Response To Treatment ◽  
Resonance Spectroscopy ◽  
Biochemical Basis ◽  
Non Invasive ◽  
Investigative Technique ◽  
Neurochemical Changes

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.

Non-Invasive In-Vivo Monitoring of 11β-HSD1 Activity Using19F-Magnetic Resonance Spectroscopy.

2010 ◽  
pp. P3-32-P3-32 ◽  
Author(s):  
G Naredo-Gonzalez ◽  
MA Jansen ◽  
GD Merrifield ◽  
OB Sutcliffe ◽  
MK Hansen ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
In Vivo Monitoring ◽  
Non Invasive

scholarly journals Non-invasive Analysis of Human Liver Metabolism by Magnetic Resonance Spectroscopy

2021 ◽  
Author(s):  
John G. Jones
Keyword(s):  
Magnetic Resonance ◽  
Stable Isotope ◽  
Magnetic Resonance Spectroscopy ◽  
Human Liver ◽  
Liver Metabolism ◽  
Resonance Spectroscopy ◽  
Stable Isotope Tracers ◽  
Isotope Tracers ◽  
Non Invasive

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.

scholarly journals Imaging toxin-induced neuroinflammation in mice using hyperpolarized13C magnetic resonance spectroscopy

2019 ◽  
Author(s):  
Lydia M Le Page ◽  
Caroline Guglielmetti ◽  
Chloé Najac ◽  
Brice Tiret ◽  
Myriam M Chaumeil
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Mouse Brain ◽  
Lactate Production ◽  
Contralateral Side ◽  
Resonance Spectroscopy ◽  
Activated Microglia ◽  
Non Invasive ◽  
Induced Changes

AbstractLipopolysaccharide (LPS) is a commonly used agent for induction of neuroinflammation in preclinical studies. Upon injection, LPS causes activation of microglia and astrocytes, whose metabolism alters to favor glycolysis. Assessingin vivoneuroinflammation and its modulation following therapy remains challenging, and new non-invasive methods allowing for longitudinal monitoring would be greatly valuable. Hyperpolarized (HP)13C magnetic resonance spectroscopy (MRS) is a promising technique for assessingin vivometabolism. In addition to applications in oncology, the most commonly used probe of [1-13C] pyruvate has shown potential in assessing neuroinflammation-linked metabolism in mouse models of multiple sclerosis and traumatic brain injury. Here, we wished to investigate LPS-induced neuroinflammatory changes using HP [1-13C] pyruvate and HP13C urea.2D chemical shift imaging following simultaneous intravenous injection of HP [1-13C] pyruvate and HP13C urea was performed at baseline (day 0), day 3 and day 7 post intracranial injection of LPS (n=6) or saline (n=5). Immunofluorescence (IF) analyses were performed for Iba1 (resting and activated microglia/macrophages), GFAP (resting and reactive astrocytes) and CD68 (activated microglia/macrophages).A significant increase in HP [1-13C] lactate production was observed in the injected (ipsilateral) side at 3 and 7 days of the LPS-treated mouse brain, but not in either the contralateral side or saline-injected animals. HP13C lactate/pyruvate ratio, without and with normalization to urea, was also significantly increased in the ipsilateral LPS-injected brain at 7 days compared to baseline. IF analyses showed a significant increase in CD68 and GFAP at 3 days, followed by increased numbers of Iba1 and GFAP positive cells at 7 days post-LPS injection.In conclusion, we can detect LPS-induced changes in the mouse brain using HP13C MRS, in alignment with increased numbers of microglia/macrophages and astrocytes. This study demonstrates that HP13C spectroscopy holds much potential for providing non-invasive information on neuroinflammation.

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