Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy.
Ontology highlight
ABSTRACT:
SUBMITTER: Beloueche-Babari M
PROVIDER: S-EPMC2813738 | biostudies-other | 2010 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Quantitative assessment of cerebral glucose consumption rate (CMRglc) and tricarboxylic acid cycle flux (VTCA) is crucial for understanding neuroenergetics under physiopathological conditions. In this study, we report a novel in vivo Deuterium (2H) MRS (DMRS) approach for simultaneously measuring and quantifying CMRglc and VTCA in rat brains at 16.4 Tesla. Following a brief infusion of deuterated glucose, dynamic changes of isotope-labeled glucose, glutamate/glutamine (Glx) and water contents in the brain can be robustly monitored from their well-resolved 2H resonances. Dynamic DMRS glucose and Glx data were employed to determine CMRglc and VTCA concurrently. To test the sensitivity of this method in response to altered glucose metabolism, two brain conditions with different anesthetics were investigated. Increased CMRglc (0.46 vs. 0.28 µmol/g/min) and VTCA (0.96 vs. 0.6 µmol/g/min) were found in rats under morphine as compared to deeper anesthesia using 2% isoflurane. This study demonstrates the feasibility and new utility of the in vivo DMRS approach to assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an alternative MRS tool for in vivo study of metabolic coupling relationship between aerobic and anaerobic glucose metabolisms in brain under physiopathological states.
| S-EPMC5669347 | biostudies-literature
Project description:Despite maximally-safe resection of the MRI-defined contrast-enhanced (CE) central tumor area and chemo-radiotherapy, most glioblastoma patients relapse within one year in peritumor FLAIR regions. Spectroscopic MRI (MRSI) can discriminate metabolic tumor areas with higher recurrence potential as CNI+ regions (Choline/N-acetyl-aspartate Index>2) can predict relapse sites. As relapses are mainly imputed to glioblastoma stem-like cells (GSC), CNI+ areas might be GSC-enriched. We conducted a prospective trial in 16 GBM patients subjected to preoperative MRSI/MRI and surgery/chemo-radiotherapy to investigate GSC content in CNI+ versus CNI- biopsies from CE/FLAIR. Biopsy characterization by RNAseq revealed that FLAIR/CNI+ areas were enriched in stem-related gene signature, but also in pathways related to DNA repair, adhesion/migration and mitochondrial bioenergetics.
2023-11-03 | GSE239379 | GEO
Project description:In the past decades, new methods for tumor staging, restaging, treatment response monitoring, and recurrence detection of a variety of cancers have emerged in conjunction with the state-of-the-art positron emission tomography with 18F-fluorodeoxyglucose ([18F]-FDG PET). 13C magnetic resonance spectroscopic imaging (13CMRSI) is a minimally invasive imaging method that enables the monitoring of metabolism in vivo and in real time. As with any other method based on 13C nuclear magnetic resonance (NMR), it faces the challenge of low thermal polarization and a subsequent low signal-to-noise ratio due to the relatively low gyromagnetic ratio of 13C and its low natural abundance in biological samples. By overcoming these limitations, dynamic nuclear polarization (DNP) with subsequent sample dissolution has recently enabled commonly used NMR and magnetic resonance imaging (MRI) systems to measure, study, and image key metabolic pathways in various biological systems. A particularly interesting and promising molecule used in 13CMRSI is [1-13C]pyruvate, which, in the last ten years, has been widely used for in vitro, preclinical, and, more recently, clinical studies to investigate the cellular energy metabolism in cancer and other diseases. In this article, we outline the technique of dissolution DNP using a 3.35 T preclinical DNP hyperpolarizer and demonstrate its usage in in vitro studies. A similar protocol for hyperpolarization may be applied for the most part in in vivo studies as well. To do so, we used lactate dehydrogenase (LDH) and catalyzed the metabolic reaction of [1-13C]pyruvate to [1-13C]lactate in a prostate carcinoma cell line, PC3, in vitro using 13CMRSI.
| S-EPMC5226623 | biostudies-literature
Project description:BackgroundPrecision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.MethodsThirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.ResultsThere was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = -0.3734, p = 0.0421).ConclusionOur results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.
| S-EPMC7374160 | biostudies-literature
Project description:AimsMaternal metabolic disorders place the mother at risk for negative pregnancy outcomes with potentially long-term health impacts for the child. Metabolic syndrome, a cluster of features associated with increased risk of metabolic disorders, such as cardiovascular disease, diabetes and stroke, affects roughly one in five Canadians. Metabolomics is a relatively new technique that may be a useful tool to identify women at risk of metabolic disorders. This study set out to characterize urinary metabolic biomarkers of pregnant women with obesity and of pregnant women who later developed gestational diabetes mellitus (pre-GDM), compared to controls.Methods and materialsSecond trimester urine samples were collected through the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort and examined with 1H nuclear magnetic resonance (NMR) spectroscopy. Multivariate analysis was used to examine group differences, and machine learning feature selection tools identified the metabolites contributing to separation.ResultsObesity and pre-GDM metabolomes were distinct from controls and from each other. In each comparison, the glycine, serine and threonine pathways were the most impacted. Pantothenate, formic acid and glycine were downregulated by obesity, while formic acid, dimethylamine and galactose were downregulated in pre-GDM. The three most impacted metabolites for the comparison of obesity versus pre-GDM groups were upregulated creatine/caffeine, downregulated sarcosine/dimethylamine and upregulated maltose/sucrose in individuals who later developed GDM.ConclusionThese findings suggest a role for urinary metabolomics in the prediction of GDM and metabolic marker identification for potential diagnostics and prognostics in women at risk.
| S-EPMC7831222 | biostudies-literature
Project description:Despite huge efforts in development of drugs targeting oncogenic signalling, the number of such drugs entering clinical practice to date remains limited. Rational use of biomarkers for drug candidate selection and early monitoring of response to therapy may accelerate this process. Magnetic resonance spectroscopy (MRS) can be used to assess metabolic effects of drug treatment both in vivo and in vitro, and technological advances are continuously increasing the utility of this non-invasive method. In this review, we summarise the use of MRS for monitoring the effect of targeted anticancer drugs, and discuss the potential role of MRS in the context of personalised cancer treatment.
| S-EPMC5528296 | biostudies-other
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.
2023-04-25 | GSE225302 | GEO
Project description:BackgroundTemperatures below the freezing point of water and the ensuing ice crystal formation pose serious challenges to cell structure and function. Consequently, species living in seasonally cold environments have evolved a multitude of strategies to reorganize their cellular architecture and metabolism, and the underlying mechanisms are crucial to our understanding of life. In multicellular organisms, and poikilotherm animals in particular, our knowledge about these processes is almost exclusively due to invasive studies, thereby limiting the range of conclusions that can be drawn about intact living systems.MethodologyGiven that non-destructive techniques like (1)H Magnetic Resonance (MR) imaging and spectroscopy have proven useful for in vivo investigations of a wide range of biological systems, we aimed at evaluating their potential to observe cold adaptations in living insect larvae. Specifically, we chose two cold-hardy insect species that frequently serve as cryobiological model systems--the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis.ResultsIn vivo MR images were acquired from autumn-collected larvae at temperatures between 0 degrees C and about -70 degrees C and at spatial resolutions down to 27 microm. These images revealed three-dimensional (3D) larval anatomy at a level of detail currently not in reach of other in vivo techniques. Furthermore, they allowed visualization of the 3D distribution of the remaining liquid water and of the endogenous cryoprotectants at subzero temperatures, and temperature-weighted images of these distributions could be derived. Finally, individual fat body cells and their nuclei could be identified in intact frozen Eurosta larvae.ConclusionsThese findings suggest that high resolution MR techniques provide for interesting methodological options in comparative cryobiological investigations, especially in vivo.
| S-EPMC2586655 | biostudies-literature
Project description:Metabolic reprogramming is an important hallmark of cancer. Alterations in many metabolic pathways support the requirement for cellular building blocks that are essential for cancer cell proliferation. This metabolic reprogramming can be imaged using magnetic resonance spectroscopy (MRS). H MRS can inform on alterations in the steady-state levels of cellular metabolites, but the emergence of hyperpolarized C MRS has now also enabled imaging of metabolic fluxes in real-time, providing a new method for tumor detection and monitoring of therapeutic response. In the case of glioma, preclinical cell and animal studies have shown that the hyperpolarized C MRS metabolic imaging signature is specific to tumor type and can distinguish between mutant IDH1 glioma and primary glioblastoma. Here, we review these findings, first describing the main metabolic pathways that are altered in the different glioma subtypes, and then reporting on the use of hyperpolarized C MRS and MR spectroscopic imaging (MRSI) to probe these pathways. We show that the future translation of this hyperpolarized C MRS molecular metabolic imaging method to the clinic promises to improve the noninvasive detection, characterization, and response-monitoring of brain tumors resulting in improved patient diagnosis and clinical management.
| S-EPMC5082749 | biostudies-literature
Project description:Demyelination and axonal degeneration caused by multiple sclerosis (MS) exist in the white matter and not only in the lesion area. Magnetic resonance spectroscopy (MRS) could provide a unique insight into metabolic changes in the normal appearing white matter (NAWM). To evaluate the subtle axonal degeneration and delineate the spatial distribution of metabolite abnormalities in the NAWM in patients with MS. A total of 17 clinically definite relapsing-remitting MS (RRMS) patients and 21 healthy controls were enrolled in this study. 2D 1H magnetic resonance spectroscopic imaging (MRSI) performed at 3 Tesla was used to measure metabolite concentrations in the frontal-parietal-occipital NAWM. Ratios of N-acetyl-aspartate (NAA) and choline (Cho) to creatine (Cr) and Cho to NAA were calculated in each voxel. MS patients showed decreased NAA/Cr and increased Cho/NAA ratios in the NAWM compared to healthy controls. In the parietal NAWM, the extent of NAA/Cr decrease was significantly higher than that in the frontal and parietal-occipital NAWM. Decreased NAA in the NAWM would provide useful metabolic information for evaluation of disease progression in MS. The high extent of NAA decrease in the parietal NAWM helps improve the accuracy of the prediction.
| S-EPMC5411203 | biostudies-literature