Combined Magnetic Resonance Spectroscopy Research Articles

Impact of race-independent equations on estimating glomerular filtration rate for the assessment of kidney dysfunction in liver disease

BackgroundAltered hemodynamics in liver disease often results in overestimation of glomerular filtration rate (GFR) by creatinine-based GFR estimating (eGFR) equations. Recently, we have validated a novel eGFR equation based on serum myo-inositol, valine, and creatinine quantified by nuclear magnetic resonance spectroscopy in combination with cystatin C, age and sex (GFRNMR). We hypothesized that GFRNMR could improve chronic kidney disease (CKD) classification in the setting of liver disease.ResultsWe conducted a retrospective multicenter study in 205 patients with chronic liver disease (CLD), comparing the performance of GFRNMR to that of validated CKD-EPI eGFR equations, including eGFRcr (based on creatinine) and eGFRcr-cys (based on both creatinine and cystatin C), using measured GFR as reference standard. GFRNMR outperformed all other equations with a low overall median bias (-1 vs. -6 to 4 ml/min/1.73 m2 for the other equations; p < 0.05) and the lowest difference in bias between reduced and preserved liver function (-3 vs. -16 to -8 ml/min/1.73 m2 for other equations). Concordant classification by CKD stage was highest for GFRNMR (59% vs. 48% to 53%) and less biased in estimating CKD severity compared to the other equations. GFRNMR P30 accuracy (83%) was higher than that of eGFRcr (75%; p = 0.019) and comparable to that of eGFRcr-cys (86%; p = 0.578).ConclusionsAddition of myo-inositol and valine to creatinine and cystatin C in GFRNMR further improved GFR estimation in CLD patients and accurately stratified liver disease patients into CKD stages.

Magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics study may differentiate pre-eclampsia from gestational hypertension.

To investigate the findings of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and serum metabolomics for differentiating pre-eclampsia (PE) from gestational hypertension (GH). This prospective study enrolled 176 subjects including a primary cohort with healthy non-pregnant women (HN, n = 35), healthy pregnant women (HP, n = 20), GH (n = 27), and PE (n = 39) and a validation cohort with HP (n = 22), GH (n = 22), and PE (n = 11). T1 signal intensity index (T1SI), apparent diffusion coefficient (ADC) value, and the metabolites on MRS were compared. The differentiating performances of single and combined MRI and MRS parameters for PE were evaluated. Serum liquid chromatography-mass spectrometry (LC-MS) metabolomics was investigated by sparse projection to latent structures discriminant analysis. Increased T1SI, lactate/creatine (Lac/Cr), and glutamine and glutamate (Glx)/Cr and decreased ADC value and myo-inositol (mI)/Cr in basal ganglia were found in PE patients. T1SI, ADC, Lac/Cr, Glx/Cr, and mI/Cr yielded an area under the curves (AUC) of 0.90, 0.80, 0.94, 0.96, and 0.94 in the primary cohort, and of 0.87, 0.81, 0.91, 0.84, and 0.83 in the validation cohort, respectively. A combination of Lac/Cr, Glx/Cr, and mI/Cr yielded the highest AUC of 0.98 in the primary cohort and 0.97 in the validation cohort. Serum metabolomics analysis showed 12 differential metabolites, which are involved in pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism. MRS is expected to be a noninvasive and effective tool for monitoring GH patients to avoid the development of PE. • Increased T1SI and decreased ADC value in the basal ganglia were found in PE patients than in GH patients. • Increased Lac/Cr and Glx/Cr, and decreased mI/Cr in the basal ganglia were found in PE patients than in GH patients. • LC-MS metabolomics showed that the major differential metabolic pathways between PE and GH were pyruvate metabolism, alanine metabolism, glycolysis, gluconeogenesis, and glutamate metabolism.

Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment.

Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models. Using 1H MRS in combination with chemometrics identified several metabolic alterations in temozolomide-treated cells, including a significant increase in steady-state glutamate levels. This was confirmed in vivo, where the observed 1H MRS increase in glutamate/glutamine occurred prior to tumor shrinkage. Cells labeled with [1-13C]glucose and [3-13C]glutamine, the principal sources of cellular glutamate, showed that flux to glutamate both from glucose via the tricarboxylic acid cycle and from glutamine were increased following temozolomide treatment. In line with these results, hyperpolarized [5-13C]glutamate produced from [2-13C]pyruvate and hyperpolarized [1-13C]glutamate produced from [1-13C]α-ketoglutarate were significantly higher in temozolomide-treated cells compared with controls. Collectively, our findings identify 1H MRS-detectable elevation of glutamate and hyperpolarized 13C MRS-detectable glutamate production from either pyruvate or α-ketoglutarate as potential translatable metabolic biomarkers of response to temozolomide treatment in mutant IDH1 glioma. SIGNIFICANCE: These findings show that glutamate can be used as a noninvasive, imageable metabolic marker for early assessment of tumor response to temozolomide, with the potential to improve treatment strategies for mutant IDH1 patients.

Three concomitant C-C dissociation pathways during the mechanical activation of an N-heterocyclic carbene precursor.

Chemical reactions usually proceed through a radical, concerted or ionic mechanism; transformations in which all three mechanisms occur are rare. In polymer mechanochemistry, a mechanical force, transduced along polymer chains, is used to activate covalent bonds in mechanosensitive molecules (mechanophores). Cleavage of a C-C bond often follows a homolytic pathway, but some mechanophores have also been designed that react in a concerted or, more rarely, a heterolytic manner. Here, using 1H- and 19F-nuclear magnetic resonance spectroscopy in combination with deuterium labelling, we show that the dissociation of a mechanophore built around an N-heterocyclic carbene precursor proceeds with the rupture of a C-C bond through concomitant heterolytic, concerted and homolytic pathways. The distribution of products probably arises from a post-transition-state bifurcation in the reaction pathway, and their relative proportion is dictated by the polarization of the scissile C-C bond.

Endometriosis phenotypes are associated with specific serum metabolic profiles determined by proton-nuclear magnetic resonance

Research questionWhat is the correlation between serum metabolic profile and endometriosis phenotype? DesignA pilot study nestled in a prospective cohort study at a university hospital, including 46 patients with painful endometriosis who underwent surgery and 21 controls who did not have macroscopic endometriotic lesions. Endometriosis was strictly classified into two groups of 23 patients each: endometrioma (OMA) and deep infiltrating endometriosis (DIE). Serum samples were collected before surgery for metabolomic profiling based on proton-nuclear magnetic resonance spectroscopy in combination with statistical approaches. Comparative identification of the metabolites in the serum from endometriosis patients and from controls was carried out, including an analysis according to endometriosis phenotype. ResultsThe serum metabolic profiles of the endometriosis patients revealed significantly lower concentrations of several amino acids compared with the controls, whereas the concentrations of free fatty acids and ketone bodies were significantly higher. The OMA and the DIE phenotypes each had a specific metabolic profile, with higher concentrations of two ketone bodies in the OMA group, and higher concentrations of free fatty acids and lipids in the DIE group. ConclusionProton-nuclear magnetic resonance-based metabolomics of serum samples were found to have ample potential for identifying metabolic changes associated with endometriosis phenotypes. This information may improve our understanding of the pathogenesis of endometriosis.

Determination of chlorogenic acid in traditional Chinese prescription Shuanghuanglian capsule using quantitative nuclear magnetic resonance spectroscopy in combination with solid phase extraction

Determination of chlorogenic acid in traditional Chinese prescription Shuanghuanglian capsule using quantitative nuclear magnetic resonance spectroscopy in combination with solid phase extraction

Isolation, Identification, and Decomposition of Antibacterial Dialkylresorcinols from a Chinese Pseudomonas aurantiaca Strain.

A chemical investigation of a Chinese Pseudomonas aurantiaca strain has yielded a new benzoquinone (4) and furanone (5), in addition to the known dialkylresorcinols 1 and 2. Extensive decomposition studies on the major metabolite 1 produced an additional furanone derivative (6), a hydroxyquinone (7), and two unusual resorcinol and hydroxyquinone dimers (8 and 9). Structures were elucidated by nuclear magnetic resonance spectroscopy in combination with tandem mass spectrometry analysis. These studies illustrate the potential of artifacts as a source of additional chemical diversity. Compounds 1 and 2 showed moderate antibacterial activity against a panel of Gram-positive pathogens, while the antibacterial activities of the artifacts (4-9) were reduced.

Electric field gradients in 2H–NbSe2: 93Nb NMR measurements and first-principles calculations

Accurate atomic scale structure is of importance for revealing the still mysterious electronic phase transitions in a famous 2D metal, 2H–NbSe2. In this work, the electric field gradients (EFGs) of 2H–NbSe2 at Nb sites in the normal state were investigated by 93Nb nuclear magnetic resonance spectroscopy in combination with first-principles computations. The previous T 3/2 and linear T models for describing the temperature dependent EFGs were tested and discussed according to our measured and theoretically computed EFG data in this two-dimensional metal.

Diurnal changes in human brain glutamate + glutamine levels in the course of development and their relationship to sleep

Sleep slow waves during non-rapid eye movement (NREM) sleep play a crucial role in maintaining cortical plasticity, a process that is especially important in the developing brain. Children show a considerably larger overnight decrease in slow wave activity (SWA; the power in the EEG frequency band between 1 and 4.5 ​Hz during NREM sleep), which constitutes the primary electrophysiological marker for the restorative function of sleep. We previously demonstrated in adults that this marker correlates with the overnight reduction in cortical glutamate ​+ ​glutamine (GLX) levels assessed by magnetic resonance spectroscopy (MRS), proposing GLX as a promising biomarker for the interplay between cortical plasticity and SWA. Here, we used a multimodal imaging approach of combined MRS and high-density EEG in a cross-sectional cohort of 46 subjects from 8 to 24 years of age in order to examine age-related changes in GLX and its relation to SWA. Gray matter volume, GLX levels and SWA showed the expected age-dependent decrease. Unexpectedly, the overnight changes in GLX followed opposite directions when comparing children to adults. These age-related changes could neither be explained by the overnight decrease in SWA nor by circadian factors.

Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways.

There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.

Cerebral metabolism in patients with cognitive disorders: a combined MRS and PET study

Magnetic resonance spectroscopy (MRS) allows studying the content of many metabolites in neural tissue in vivo. There are numerous studies devoted to the MRS data analysis in Alzheimer's disease (AD), but their results are contradictory. Thus, it is rational to compare the data obtained with MRS and positron emission tomography (PET) with fluorodeoxyglucose (FDG), which allows evaluating the brain functional state. In this paper, the authors compared MRS data in AD and mild cognitive impairment (MCI) with the cerebral glucose metabolism changes according to FDG PET. Multivoxel proton MRS of the supraventricular area was performed in patients with AD (n=16) and MCI (n=14). The following metabolites ratios were evaluated: NAA/Cr, Cho/Cr, NAA/Cho (NAA - N-acetylaspartate, Cr - creatine, Cho - choline). All patients underwent neurological examination, assessment of cognitive status and PET with FDG. A decrease in NAA/Cr and Cho/Cr ratios in the supraventricular white matter and medial cortex in both hemispheres was observed in AD patients. In the MCI group, NAA/Cr ratio were decreased only in left white matter adjusting to the parietal cortex. Positive correlations of NAA/Cr and Cho/Cr ratios with cognitive status, as well as the cerebral glucose metabolism rate according to the PET data in frontal, parietal, temporal and cingulate cortex were revealed. The decrease in the NAA/Cr ratio in the supraventricular white matter and the medial cortex in AD and the correlation of this index with the results of cognitive tests and cerebral glucose metabolism suggest that it can be of diagnostic significance, reflecting the severity of cognitive impairment. In this case, the NAA/Cr ratio should be evaluated taking into account the changes in concentrations of both metabolites (NAA and Cr) in dementia.

Application of MRS- and ASL-guided navigation for biopsy of intracranial tumors.

The diagnosis of a tumor depends on accurate identification of the target area for biopsy. However, tumor heterogeneity and the inability of conventional structural data for identifying the most malignant areas can reduce this accuracy. To evaluate the feasibility and practicality of magnetic resonance spectroscopy (MRS)- and arterial spin labeling (ASL)-guided MRI navigation for needle biopsy of intracranial tumors. Thirty patients with intracranial tumors who underwent intraoperative stereotactic biopsy were retrospectively analyzed. Contrast-enhanced 3D-BRAVO or 3D-T2FLAIR structural data, combined with MRS and ASL data, were used to identify the target area for biopsy. High-choline or high-perfusion sites were chosen preferentially, and then the puncture trajectory was optimized to obtain specimens for histopathologic examination. Twenty-two specimens were collected from 20 glioma patients (two specimens each were collected from two patients) and ten specimens were collected from ten lymphoma patients. The diagnosis rate after the biopsy was 93.3% (28/30). Two gliomas were initially diagnosed as gliosis and subsequently diagnosed correctly after the collection of a second biopsy specimen. Combined MRS and ASL helped target selection in 23 cases (76.7%), including three cases each of low-enhancing and non-enhancing gliomas. In two cases, the target selection decision was changed because the areas initially chosen on the basis of positron emission tomography data did not match the high-perfusion areas identified with ASL. Compared with conventional MRI, combined MRS and ASL improved the accuracy of target selection for the stereotactic biopsy of intracranial tumors.

Magnetic resonance spectroscopy of fiber tracts in children with traumatic brain injury: A combined MRS - Diffusion MRI study.

Traumatic brain injury can cause extensive damage to the white matter (WM) of the brain. These disruptions can be especially damaging in children, whose brains are still maturing. Diffusion magnetic resonance imaging (dMRI) is the most commonly used method to assess WM organization, but it has limited resolution to differentiate causes of WM disruption. Magnetic resonance spectroscopy (MRS) yields spectra showing the levels of neurometabolites that can indicate neuronal/axonal health, inflammation, membrane proliferation/turnover, and other cellular processes that are on-going post-injury. Previous analyses on this dataset revealed a significant division within the msTBI patient group, based on interhemispheric transfer time (IHTT); one subgroup of patients (TBI-normal) showed evidence of recovery over time, while the other showed continuing degeneration (TBI-slow). We combined dMRI with MRS to better understand WM disruptions in children with moderate-severe traumatic brain injury (msTBI). Tracts with poorer WM organization, as shown by lower FA and higher MD and RD, also showed lower N-acetylaspartate (NAA), a marker of neuronal and axonal health and myelination. We did not find lower NAA in tracts with normal WM organization. Choline, a marker of inflammation, membrane turnover, or gliosis, did not show such associations. We further show that multi-modal imaging can improve outcome prediction over a single modality, as well as over earlier cognitive function measures. Our results suggest that demyelination plays an important role in WM disruption post-injury in a subgroup of msTBI children and indicate the utility of multi-modal imaging.

Combined apparent diffusion coefficient value (ADC) and 1H magnetic resonance spectroscopy (MRS) in breast lesions: Benefits and limitations

ObjectiveThis study aimed to assess the diagnostic value of a combined imaging protocol of diffusion-weighted MRI, apparent diffusion coefficient (ADC) values, and MR spectroscopy(MRS) in discriminating benign and malignant breast lesions. Patients and methodstwenty-six female patients complaining from breast lesions were included in this study. Diffusion weighted images, apparent diffusion coefficients value, and magnetic resonance spectroscopy were obtained to all patients. ResultsCombined ADC value and MRS in discriminating benign breast lesions from malignant tumors were false-positive in 3 patients , true-positive in 14 patients, false-negative in 1 patient and true-negative in 8 patients with specificity of 72.7%, sensitivity of 93.3%, NPV of 88.9%, PPV of 82.4% and accuracy of 84.6%. ConclusionA great advantage of ADC value is the significant difference between benign and malignant lesions, because of this it plays an important role in characterization of breast lesions. MRS is the only in vivo technique which can detect tissue metabolites. In our study combined MRS with ADC value increased sensitivity in detecting lesions, while the specificity remained at lower level than that of the ADC value alone.

GABA concentrations in the anterior temporal lobe predict human semantic processing

There is now considerable convergent evidence from multiple methodologies and clinical studies that the human anterior temporal lobe (ATL) is a semantic representational hub. However, the neurochemical nature of the ATL in the semantic processing remains unclear. The current study investigated the neurochemical mechanism underlying semantic processing in the ATL. We combined functional magnetic resonance imaging (fMRI) with resting-state magnetic resonance spectroscopy (MRS) to measure task-related blood-oxygen level-dependent (BOLD) signal changes during sematic processing and resting-state GABA concentrations in the ATL. Our combined fMRI and MRS investigation showed that the stronger ATL BOLD response induced by the semantic task, the lower GABA concentration in the same region. Moreover, individuals with higher GABA concentration in the ATL showed better semantic performance and stronger BOLD-related fluctuations in the semantic network. Our data demonstrated that the resting-state GABA concentration predicts neural changes in the human ATL and task performance during semantic processing. Our findings indicate that individuals with higher GABA may have a more efficient semantic processing leading to better task performance and imply that GABAergic neurochemical processes are potentially crucial to the neurobiological contribution of the ATL to semantic cognition.

Authentication of butter from lard adulteration using high-resolution of nuclear magnetic resonance spectroscopy and high-performance liquid chromatography

ABSTRACTFood authentication is an interesting issue for all parties in the food industry, including the fats and oils industry. Some unethical players try to blend high-quality foods, such as butter, with lower ones like lard, therefore, the analytical methods capable of analyzing the adulteration practices must be developed. This study used proton nuclear magnetic resonance spectroscopy in combination with high-performance liquid chromatography for the authentication of butter from lard adulteration. The identification of triacylglycerol composition of lard as a chemical marker for halal authentication is analyzed using high-performance liquid chromatography and high resolution nuclear magnetic resonance spectroscopy. The suitability of proton nuclear magnetic resonance provides a high-performance approach for determination butter adulterated with lard in their entirety of all proton bearing components. Peaks in the region of 2.60–2.84 ppm show special characteristics only present in lard. Only lard has its own unique characteristics which only polyunsaturated fatty acids would give signals 7 at δ 2.63, that corresponded to the chemical shift of the double-allylic methylene protons. In the same way, the intensity of signal at 2.63 ppm, due to methylenic protons in a position α to two double bonds, that is to say, due to the linoleic group. Furthermore, we also correlate some signals between 1H and 13C-NMR spectra for the confirmation of signals.

Metabolomic analysis of urine with Nuclear Magnetic Resonance spectroscopy in patients with idiopathic sudden sensorineural hearing loss: A preliminary study

ObjectiveIdiopathic sudden sensorineural hearing loss is a frequent emergency, with unknown aetiology and usually treated with empiric therapy. Steroids represent the only validated treatment but prognosis is unpredictable and the possibility to select the patients who will not respond to steroids could avoid unnecessary treatments. Metabolomic profiling of the biofluids target the analysis of the final product of genic expression and enzymatic activity, defining the biochemical phenotype of a whole biologic system. MethodsWe studied the metabolomics of the urine of a cohort of patients with idiopathic sudden sensorineural hearing loss, correlating the metabolic profiles with the clinical outcomes. Metabolomic profiling of urine samples was performed by 1H Nuclear Magnetic Resonance spectroscopy in combination with multivariate statistical approaches. Results26 patients were included in the study: 5 healthy controls, 13 patients who did not recover after treatment at 6 months while the remaining 8 patients recovered from the hearing loss. The orthogonal partial least square-discriminant analysis score plot showed a significant separation between the two groups, responders and non-responders after steroid therapy, R2Y of 0.83, Q2 of 0.38 and p value <0.05. The resulting metabolic profiles were characterized by higher levels of urinary B-Alanine, 3-hydroxybutyrate and Trimethylamine N-oxide, and lower levels of Citrate and Creatinine in patients with worst outcome. ConclusionIdiopathic sudden sensorineural hearing loss is a specific disease with unclear systemic changes, but our data suggest that there are different types of this disorder or patients predisposed to effective action of steroids allowing the recover after treatment.

Refined Analysis of Brain Energy Metabolism Using In Vivo Dynamic Enrichment of 13C Multiplets.

Carbon-13 nuclear magnetic resonance spectroscopy in combination with the infusion of 13C-labeled precursors is a unique approach to study in vivo brain energy metabolism. Incorporating the maximum information available from in vivo localized 13C spectra is of importance to get broader knowledge on cerebral metabolic pathways. Metabolic rates can be quantitatively determined from the rate of 13C incorporation into amino acid neurotransmitters such as glutamate and glutamine using suitable mathematical models. The time course of multiplets arising from 13C-13C coupling between adjacent carbon atoms was expected to provide additional information for metabolic modeling leading to potential improvements in the estimation of metabolic parameters.The aim of the present study was to extend two-compartment neuronal/glial modeling to include dynamics of 13C isotopomers available from fine structure multiplets in 13C spectra of glutamate and glutamine measured in vivo in rats brain at 14.1 T, termed bonded cumomer approach. Incorporating the labeling time courses of 13C multiplets of glutamate and glutamine resulted in elevated precision of the estimated fluxes in rat brain as well as reduced correlations between them.

Metabolic changes may precede proteostatic dysfunction in a Drosophila model of amyloid beta peptide toxicity

Amyloid beta (Aβ) peptide aggregation is linked to the initiation of Alzheimer's disease; accordingly, aggregation-prone isoforms of Aβ, expressed in the brain, shorten the lifespan of Drosophila melanogaster. However, the lethal effects of Aβ are not apparent until after day 15. We used shibireTS flies that exhibit a temperature-sensitive paralysis phenotype as a reporter of proteostatic robustness. In this model, we found that increasing age but not Aβ expression lowered the flies' permissive temperature, suggesting that Aβ did not exert its lethal effects by proteostatic disruption. Instead, we observed that chemical challenges, in particular oxidative stressors, discriminated clearly between young (robust) and old (sensitive) flies. Using nuclear magnetic resonance spectroscopy in combination with multivariate analysis, we compared water-soluble metabolite profiles at various ages in flies expressing Aβ in their brains. We observed 2 genotype-linked metabolomic signals, the first reported the presence of any Aβ isoform and the second the effects of the lethal Arctic Aβ. Lethality was specifically associated with signs of oxidative respiration dysfunction and oxidative stress.

ATPS-14KETOGENIC DIET-INDUCED INCREASE IN MCT1 FACILITATES KETONE BODY OXIDATION IN RAT GLIOMAS

The dependence of brain tumor cells on glucose is the target of the ketogenic diet (KD), which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of KDs as therapy has been of particular interest for brain tumors because they reportedly cannot oxidize ketone bodies and therefore would be starved. However, in vivo studies assessing the ability of tumors to oxidize ketone bodies are lacking. We investigated ketone body oxidation in vitro and vivo using 13C magnetic resonance spectroscopy in combination with infusion of the 13C-labeled ketone body, beta-hydroxybutyrate (BHB) in two rodent glioma models (9L & RG2). The detection of 13C in glutamate following the infusion of [2,4-13C]-BHB was the primary outcome parameter and proof of oxidative 13C-BHB metabolism in the rat gliomas. Steady-state metabolic modeling was applied to further characterize the 13C-BHB metabolism. The level of glutamate 13C-labeling and 13C-BHB oxidation in 9L and RG2 rat gliomas was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a KD, immunohistochemistry showed that the ketone body transporter MCT1 was upregulated, facilitating uptake and doubling oxidation of ketone bodies in gliomas. These results demonstrate that rat gliomas can easily oxidize ketone bodies and indicate an adaptation through upregulation of ketone body transport when fed a KD. These data are not supporting the hypothesis that brain tumors are metabolically inflexible. Furthermore, there are indications that KDs in humans could also induce an increase in MCT1. MCT1 is a drug target for which an inhibitor is currently investigated in a clinical trial. Overall, these results indicate that the use of KDs as therapy targeting brain tumor metabolism and the effect of such diets on MCT1 needs further investigation, particularly in patients.