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Feasibility of deuterium magnetic resonance spectroscopy of 3-O-Methylglucose at 7 Tesla.

ABSTRACT: Deuterium Magnetic Resonance Spectroscopy (DMRS) is a non-invasive technique that allows the detection of deuterated compounds in vivo. DMRS has a large potential to analyze uptake, perfusion, washout or metabolism, since deuterium is a stable isotope and therefore does not decay during biologic processing of a deuterium labelled substance. Moreover, DMRS allows the distinction between different deuterated substances. In this work, we performed DMRS of deuterated 3-O-Methylglucose (OMG). OMG is a non-metabolizable glucose analog which is transported similar to D-glucose. DMRS of OMG was performed in phantom and in vivo measurements using a preclinical 7 Tesla MRI system. The chemical shift (3.51 ± 0.1 ppm) and relaxation times were determined. OMG was injected intravenously and spectra were acquired over a period of one hour to monitor the time evolution of the deuterium signal in tumor-bearing rats. The increase and washout of OMG could be observed. Three different exponential functions were compared in terms of how well they describe the OMG washout. A mono-exponential model with offset seems to describe the observed time course best with a time constant of 1910 ± 770 s and an offset of 2.5 ± 1.2 mmol/l (mean ± std, N = 3). Chemical shift imaging could be performed with a voxel size of 7.1 mm x 7.1 mm x 7.9 mm. The feasibility of DMRS with deuterium labelled OMG could be demonstrated. These data might serve as basis for future studies that aim to characterize glucose transport using DMRS.

SUBMITTER: Hartmann B

PROVIDER: S-EPMC8184010 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Human cardiac 31P magnetic resonance spectroscopy at 7 Tesla.

Project description:PurposePhosphorus magnetic resonance spectroscopy ((31)P-MRS) affords unique insight into cardiac energetics but has a low intrinsic signal-to-noise ratio (SNR) in humans. Theory predicts an increased (31)P-MRS SNR at 7T, offering exciting possibilities to better investigate cardiac metabolism. We therefore compare the performance of human cardiac (31)P-MRS at 7T to 3T, and measure T1s for (31)P metabolites at 7T.MethodsMatched (31)P-MRS data were acquired at 3T and 7T, on nine normal volunteers. A novel Look-Locker CSI acquisition and fitting approach was used to measure T1s on six normal volunteers.ResultsT1s in the heart at 7T were: phosphocreatine (PCr) 3.05 ± 0.41s, γ-ATP 1.82 ± 0.09s, α-ATP 1.39 ± 0.09s, β-ATP 1.02 ± 0.17s and 2,3-DPG (2,3-diphosphoglycerate) 3.05 ± 0.41s (N = 6). In the field comparison (N = 9), PCr SNR increased 2.8× at 7T relative to 3T, the Cramer-Ráo uncertainty (CRLB) in PCr concentration decreased 2.4×, the mean CRLB in PCr/ATP decreased 2.7× and the PCr/ATP SD decreased 2×.ConclusionCardiac (31)P-MRS at 7T has higher SNR and the spectra can be quantified more precisely than at 3T. Cardiac (31)P T1s are shorter at 7T than at 3T. We predict that 7T will become the field strength of choice for cardiac (31)P-MRS.

| S-EPMC4106879 | biostudies-literature

Cerebral phosphoester signals measured by 31P magnetic resonance spectroscopy at 3 and 7 Tesla.

Project description:Abnormal cell membrane metabolism is associated with many neuropsychiatric disorders. Free phosphomonoesters and phosphodiesters, which can be detected by in vivo 31P magnetic resonance spectroscopy (MRS), are important cell membrane building blocks. However, the quantification of phosphoesters has been highly controversial even in healthy individuals due to overlapping signals from macromolecule membrane phospholipids (MP). In this study, high signal-to-noise ratio (SNR) cerebral 31P MRS spectra were acquired from healthy volunteers at both 3 and 7 Tesla. Our results indicated that, with minimal spectral interference from MP, the [phosphocreatine (PCr)]/[phosphocholine (PC) + glycerophosphocholine (GPC)] ratio measured at 7 Tesla agreed with its value expected from biochemical constraints. In contrast, the 3 Tesla [PCr]/[PC+GPC] ratio obtained using standard spectral fitting procedures was markedly smaller than the 7 Tesla ratio and than the expected value. The analysis suggests that the commonly used spectral model for MP may fail to capture its complex spectral features at 3 Tesla, and that additional prior knowledge is necessary to reliably quantify the phosphoester signals at low magnetic field strengths when spectral overlapping is significant.

| S-EPMC7971532 | biostudies-literature

The STEMRI trial: magnetic resonance spectroscopy imaging can define tumor areas enriched in glioblastoma-stem-like cells

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

Quantitative assessment of brain glucose metabolic rates using in vivo deuterium magnetic resonance spectroscopy.

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

Magnetic Resonance Microscopy at Cellular Resolution and Localised Spectroscopy of Medicago truncatula at 22.3 Tesla.

Project description:Interactions between plants and the soil's microbial & fungal flora are crucial for the health of soil ecosystems and food production. Microbe-plant interactions are difficult to investigate in situ due to their intertwined relationship involving morphology and metabolism. Here, we describe an approach to overcome this challenge by elucidating morphology and the metabolic profile of Medicago truncatula root nodules using Magnetic Resonance (MR) Microscopy, at the highest magnetic field strength (22.3?T) currently available for imaging. A home-built solenoid RF coil with an inner diameter of 1.5?mm was used to study individual root nodules. A 3D imaging sequence with an isotropic resolution of (7 ?m)3 was able to resolve individual cells, and distinguish between cells infected with rhizobia and uninfected cells. Furthermore, we studied the metabolic profile of cells in different sections of the root nodule using localised MR spectroscopy and showed that several metabolites, including betaine, asparagine/aspartate and choline, have different concentrations across nodule zones. The metabolite spatial distribution was visualised using chemical shift imaging. Finally, we describe the technical challenges and outlook towards future in vivo MR microscopy of nodules and the plant root system.

| S-EPMC6976659 | biostudies-literature

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla.

Project description:RationaleChronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.MethodsWe studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference.ResultsCompared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants.ConclusionsThe changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample.

| S-EPMC8770374 | biostudies-literature

Brain glutamate in anorexia nervosa: a magnetic resonance spectroscopy case control study at 7 Tesla.

Project description:RationaleAnorexia nervosa (AN) is a serious psychiatric disorder with high morbidity and mortality. There are no established pharmacological treatments and the neurobiology of the condition is poorly understood. Previous studies using magnetic resonance spectroscopy (MRS) have shown that AN may be associated with reductions in indices of brain glutamate; however, at conventional field strengths (≤3 T), it is difficult to separate glutamate from its precursor and metabolite, glutamine.ObjectivesThe objective of the present study was to use high field (7 T) MRS to measure concentrations of glutamate, in three separate brain voxels, in women with AN.MethodsWe studied 13 female participants with AN and 12 healthy female controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen. Neurometabolites were calculated using the unsuppressed water signal as a reference and corrected for individual cerebrospinal fluid concentration in the voxel.ResultsWe found that participants with AN had significantly lower concentrations of glutamate in all three voxels (mean reduction 8%, p = 0.002) but glutamine levels were not altered. Concentrations of N-acetylaspartate, creatine, GABA and glutathione were also unchanged. However, inositol was lower in AN participants in anterior cingulate (p = 0.022) and occipital cortex (p = 0.002).ConclusionsWomen with AN apparently have widespread reductions in brain glutamate. Further work will be needed to assess if this change has pathophysiological relevance or whether it is a consequence of the many physical changes produced in AN by food restriction.

| S-EPMC5225214 | biostudies-literature

Interictal pontine metabolism in migraine without aura patients: A 3 Tesla proton magnetic resonance spectroscopy study.

Project description:In the pons, glutamatergic mechanisms are involved in regulating inhibitory descending pain modulation, serotoninergic neurotransmission as well as modulating the sensory transmission of the trigeminovascular system. Migraine involves altered pontine activation and structural changes, while biochemical, genetic and clinical evidence suggests that altered interictal pontine glutamate levels may be an important pathophysiological feature of migraine abetting to attack initiation. Migraine without aura patients were scanned outside attacks using a proton magnetic resonance spectroscopy protocol optimized for the pons at 3 Tesla. The measurements were performed on two separate days to increase accuracy and compared to similar repeated measurements in healthy controls. We found that interictal glutamate (i.e. Glx) levels in the pons of migraine patients (n = 33) were not different from healthy controls (n = 16) (p = 0.098), while total creatine levels were markedly increased in patients (9%, p = 0.009). There was no correlation of glutamate or total creatine levels to migraine frequency, days since the last attack, usual pain intensity of attacks or disease duration. In conclusion, migraine is not associated with altered interictal pontine glutamate levels. However, the novel finding of increased total creatine levels suggests that disequilibrium in the pontine energy metabolism could be an important feature of migraine pathophysiology.

| S-EPMC8498457 | biostudies-literature

Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.

Project description:2H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-2H2]malate, following injection of [2,3-2H2]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized 2H MR spectroscopy at 7 T. Malate production was also imaged in EL4 tumors using a fast 2H chemical shift imaging sequence. The malate/fumarate ratio increased from 0.016 ± 0.02 to 0.16 ± 0.14 in EL4 tumors 48 h after drug treatment (P = 0.0024, n = 3), and from 0.019 ± 0.03 to 0.25 ± 0.23 in MDA-MB-231 tumors (P = 0.0001, n = 5) and from 0.016 ± 0.04 to 0.28 ± 0.26 in Colo205 tumors (P = 0.0002, n = 5) 24 h after drug treatment. These increases were correlated with increased levels of cell death measured in excised tumor sections obtained immediately after imaging. 2H MR measurements of [2,3-2H2]malate production from [2,3-2H2]fumarate provide a potentially less expensive and more sensitive method for detecting cell death in vivo than 13C MR measurements of hyperpolarized [1,4-13C2]fumarate metabolism, which have been used previously for this purpose.

| S-EPMC8000230 | biostudies-literature

Assessment of bone marrow fat by 3-Tesla magnetic resonance spectroscopy in patients with chronic kidney disease.

Project description:Proton magnetic resonance spectroscopy (1H MRS) is an imaging method for quantification of bone marrow fat. It has been used for evaluation of bone marrow changes in patients with chronic disorders, such as chronic kidney disease (CKD). In these patients, there is a high turnover state, with an excessive amount of non-mineralized component of bone, leading to skeletal fragility and subsequent increased fracture risk. Thirty CKD patients underwent magnetic resonance spectroscopy (MRS) and quantitative computed tomography (QCT), and eight healthy controls underwent MRS at lumbar spine. Proton density fat fraction (PDFF) and volumetric bone mineral density (vBMD) of L1-L3 were determined from MRS and QCT respectively. CKD patients were divided into three groups according to glomerular filtration rate (GFR); for each patient, blood levels of parathyroid hormone (PTH) were also reported. Paired t-tests, Pearson's correlation coefficients and analysis of variance were applied. The mean age of patients was 59.6±11.5 years, mean GFR value was 21.5±8.8 mL/min and mean PTH value was 149.2±53.1 pg/mL. PDFF at L1-L3 levels was significantly higher in CKD patients compared to controls (71.4±8.7 vs. 55.5±7.6; P<0.001) and showed an inverse correlation with vBMD (r=-0.71; P<0.001). PDFF significantly increased from CKD group 1 to CKD group 3 (P=0.002) and was inversely correlated with GFR (r=-0.53; P=0.003). There was no significant association between PDFF and PTH values (P>0.05). In CKD patients, PDFF assessed by MRS at lumbar spine is higher than in healthy population, correlates with bone loss assessed by QCT and significantly increases with the worsening of renal function. MRS is a reliable and highly repeatable tool for PDFF quantification in CKD patients.

| S-EPMC10644130 | biostudies-literature

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