scholarly journals Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients

2018 ◽  
Vol 78 (14) ◽  
pp. 3755-3760 ◽  
Author(s):  
Vesselin Z. Miloushev ◽  
Kristin L. Granlund ◽  
Rostislav Boltyanskiy ◽  
Serge K. Lyashchenko ◽  
Lisa M. DeAngelis ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Human Brain ◽  
Lactate Production ◽  
Metabolic Imaging ◽  
Tumor Patients ◽  
Hyperpolarized 13C

scholarly journals In Vivo Assessment of Metabolic Abnormality in Alport Syndrome Using Hyperpolarized [1-13C] Pyruvate MR Spectroscopic Imaging

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 222
Author(s):  
Nguyen-Trong Nguyen ◽  
Eun-Hui Bae ◽  
Luu-Ngoc Do ◽  
Tien-Anh Nguyen ◽  
Ilwoo Park ◽  
...  
Keyword(s):  
Disease Progression ◽  
Alport Syndrome ◽  
Genetic Disorder ◽  
Lactate Production ◽  
Clinical Importance ◽  
Metabolic Imaging ◽  
Renal Metabolism ◽  
Hyperpolarized 13C ◽  
And Control

Alport Syndrome (AS) is a genetic disorder characterized by impaired kidney function. The development of a noninvasive tool for early diagnosis and monitoring of renal function during disease progression is of clinical importance. Hyperpolarized 13C MRI is an emerging technique that enables non-invasive, real-time measurement of in vivo metabolism. This study aimed to investigate the feasibility of using this technique for assessing changes in renal metabolism in the mouse model of AS. Mice with AS demonstrated a significant reduction in the level of lactate from 4- to 7-week-old, while the levels of lactate were unchanged in the control mice over time. This reduction in lactate production in the AS group accompanied a significant increase of PEPCK expression levels, indicating that the disease progression in AS triggered the gluconeogenic pathway and might have resulted in a decreased lactate pool size and a subsequent reduction in pyruvate-to-lactate conversion. Additional metabolic imaging parameters, including the level of lactate and pyruvate, were found to be different between the AS and control groups. These preliminary results suggest that hyperpolarized 13C MRI might provide a potential noninvasive tool for the characterization of disease progression in AS.

scholarly journals Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

2016 ◽  
Vol 18 (9) ◽  
pp. 1209-1218 ◽  
Author(s):  
Amy K. LeBlanc ◽  
Christina Mazcko ◽  
Diane E. Brown ◽  
Jennifer W. Koehler ◽  
Andrew D. Miller ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Human Brain ◽  
Tumor Patients ◽  
Human Brain Tumor ◽  
New Knowledge

NIMG-51. DEUTERIUM METABOLIC IMAGING OF BRAIN TUMOR IMMORTALITY USING 2H-PYRUVATE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi140-vi141
Author(s):  
Georgios Batsios ◽  
Céline Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Sabrina Ronen ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Lactate Production ◽  
Response To Therapy ◽  
Telomere Maintenance ◽  
Metabolic Imaging ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Tumor Proliferation ◽  
Non Invasive ◽  
Tert Expression

Abstract Telomere maintenance is essential for tumor immortality and sustained tumor proliferation. Most tumors, including high-grade glioblastomas and low-grade oligodendrogliomas achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. Due to this essential role, TERT is a therapeutic target and TERT inhibitors such as 6-thio-2’-deoxyguanosine are in clinical trials. Non-invasive methods of imaging TERT, therefore, have the potential to provide a readout of tumor proliferation and response to therapy. We previously showed that TERT expression is associated with elevated levels of NADH in gliomas. Since NADH is essential for the conversion of pyruvate to lactate, measuring pyruvate flux to lactate could be useful for imaging TERT expression. In this context, deuterium magnetic resonance spectroscopy (2H-MRS) recently emerged as a novel, clinically translatable method of monitoring metabolic fluxes. The goal of this study was to assess the potential of [U-2H]pyruvate for non-invasive imaging of TERT status in gliomas. Following intravenous injection of [U-2H]pyruvate, lactate production was significantly higher in mice bearing orthotopic oligodendroglioma (SF10417, BT88) or glioblastoma (GBM1, GBM6) tumors relative to tumor-free controls. 2D chemical shift imaging showed localization of lactate production to tumor vs. contralateral normal brain. Importantly, following treatment of mice bearing orthotopic GBM6 or BT88 tumors with the TERT inhibitor 6-thio-2’-deoxyguanosine, lactate production from [U-2H]pyruvate was significantly reduced at early timepoints when alterations in tumor volume could not be detected by anatomical imaging, pointing to the ability of [U-2H]pyruvate to report on pseudoprogression. Collectively, we have, for the first time, demonstrated the utility of [U-2H]pyruvate for metabolic imaging of brain tumor burden and treatment response in vivo. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental tumor hallmark, i.e. TERT, into glioma patient management.

scholarly journals Genetic variants and cognitive functions in patients with brain tumors

2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Repair ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Cell Cycle Regulation ◽  
Cognitive Outcome ◽  
Cholesterol Transport ◽  
Tumor Patients ◽  
Cycle Regulation

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

scholarly journals Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 504
Author(s):  
Seunggwi Park ◽  
Hashizume Rintaro ◽  
Seul Kee Kim ◽  
Ilwoo Park
Keyword(s):  
Metabolic Imaging ◽  
Metabolic Profiles ◽  
Rodent Models ◽  
In Vivo Metabolism ◽  
Hyperpolarized 13C ◽  
Noninvasive Assessment ◽  
Diffuse Midline Glioma ◽  
Mr Spectroscopic Imaging

The development of hyperpolarized carbon-13 (13C) metabolic MRI has enabled the sensitive and noninvasive assessment of real-time in vivo metabolism in tumors. Although several studies have explored the feasibility of using hyperpolarized 13C metabolic imaging for neuro-oncology applications, most of these studies utilized high-grade enhancing tumors, and little is known about hyperpolarized 13C metabolic features of a non-enhancing tumor. In this study, 13C MR spectroscopic imaging with hyperpolarized [1-13C]pyruvate was applied for the differential characterization of metabolic profiles between enhancing and non-enhancing gliomas using rodent models of glioblastoma and a diffuse midline glioma. Distinct metabolic profiles were found between the enhancing and non-enhancing tumors, as well as their contralateral normal-appearing brain tissues. The preliminary results from this study suggest that the characterization of metabolic patterns from hyperpolarized 13C imaging between non-enhancing and enhancing tumors may be beneficial not only for understanding distinct metabolic features between the two lesions, but also for providing a basis for understanding 13C metabolic processes in ongoing clinical trials with neuro-oncology patients using this technology.

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