Metabolic Changes in Different Stages of Liver Fibrosis: In vivo Hyperpolarized 13C MR Spectroscopy and Metabolic Imaging

2019 ◽  
Vol 21 (5) ◽  
pp. 842-851 ◽  
Author(s):  
Chung-Man Moon ◽  
Sang-Soo Shin ◽  
Suk-Hee Heo ◽  
Hyo-Soon Lim ◽  
Myeong-Ju Moon ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mr Spectroscopy ◽  
Metabolic Changes ◽  
Metabolic Imaging ◽  
Hyperpolarized 13C

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.

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 In vivo application of sub-second spiral chemical shift imaging (CSI) to hyperpolarized 13C metabolic imaging: Comparison with phase-encoded CSI

2010 ◽  
Vol 204 (2) ◽  
pp. 340-345 ◽  
Author(s):  
Dirk Mayer ◽  
Yi-Fen Yen ◽  
Yakir S. Levin ◽  
James Tropp ◽  
Adolf Pfefferbaum ◽  
...  
Keyword(s):  
Chemical Shift ◽  
Chemical Shift Imaging ◽  
Metabolic Imaging ◽  
Hyperpolarized 13C

scholarly journals Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis

2006 ◽  
Vol 66 (22) ◽  
pp. 10855-10860 ◽  
Author(s):  
Klaes Golman ◽  
René in't Zandt ◽  
Mathilde Lerche ◽  
Rikard Pehrson ◽  
Jan Henrik Ardenkjaer-Larsen
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Tumor Diagnosis ◽  
Metabolic Imaging ◽  
Resonance Imaging ◽  
Hyperpolarized 13C

scholarly journals Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS

2019 ◽  
Vol 242 (3) ◽  
pp. 251-260
Author(s):  
Kasper Faarkrog Høyer ◽  
Christoffer Laustsen ◽  
Steffen Ringgaard ◽  
Haiyun Qi ◽  
Christian Østergaard Mariager ◽  
...  
Keyword(s):  
Real Time ◽  
Mr Spectroscopy ◽  
High Sensitivity ◽  
High Specificity ◽  
Metabolic Imaging ◽  
Pyruvate Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Constant Rate ◽  
Real Time Tracking

Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with other metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism during a hyperinsulinemic–isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/[1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/[1-13C]pyruvate (169%) all increased significantly during insulin stimulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in specific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.

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

2021 ◽  
Vol 118 (12) ◽  
pp. e2014631118
Author(s):  
Friederike Hesse ◽  
Vencel Somai ◽  
Felix Kreis ◽  
Flaviu Bulat ◽  
Alan J. Wright ◽  
...  
Keyword(s):  
Cell Death ◽  
Magnetic Resonance ◽  
Drug Treatment ◽  
Tumor Cell ◽  
Mr Spectroscopy ◽  
Spectroscopic Imaging ◽  
Metabolic Imaging ◽  
Resonance Spectroscopy ◽  
Tumor Cell Death

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.

In vivo Detection of Radiation-induced Tissue Alterations by Hyperpolarized 13C Metabolic Imaging

2009 ◽  
Vol 75 (3) ◽  
pp. S48-S49
Author(s):  
L. Senadheera ◽  
D. Mayer ◽  
M.M. Darpolor ◽  
Y. Yen ◽  
D.M. Spielman ◽  
...  
Keyword(s):  
Metabolic Imaging ◽  
Hyperpolarized 13C ◽  
In Vivo Detection ◽  
Radiation Induced ◽  
Tissue Alterations

An intact small animal model of myocardial ischemia-reperfusion: Characterization of metabolic changes by hyperpolarized 13C MR spectroscopy

2015 ◽  
Vol 309 (12) ◽  
pp. H2058-H2066 ◽  
Author(s):  
Hikari A. I. Yoshihara ◽  
Jessica A. M. Bastiaansen ◽  
Corinne Berthonneche ◽  
Arnaud Comment ◽  
Juerg Schwitter
Keyword(s):  
Myocardial Ischemia ◽  
Rat Model ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Metabolic Changes ◽  
Metabolic Imaging ◽  
In Vivo Model ◽  
Small Animals ◽  
Myocardial Ischemia Reperfusion

Hyperpolarized carbon-13 magnetic resonance spectroscopy (13C MRS) enables the sensitive and noninvasive assessment of the metabolic changes occurring during myocardial ischemia-reperfusion. Ischemia-reperfusion models using hyperpolarized 13C MRS are established in heart preparations ex vivo and in large animals in vivo, but an in vivo model in small animals would be advantageous to allow the study of reperfusion metabolism with neuroendocrine and inflammatory responses intact with the option to perform a greater number of experiments. A novel intact rat model of ischemia-reperfusion is presented that incorporates hyperpolarized 13C MRS to characterize reperfusion metabolism. Typically, in an in vivo model, a tissue input function (TIF) is required to account for apparent changes in the metabolism of injected hyperpolarized [1-13C]pyruvate resulting from changes in perfusion. Whereas the measurement of a TIF by metabolic imaging is particularly challenging in small animals, the ratios of downstream metabolites can be used as an alternative. The ratio of [13C]bicarbonate:[1-13C]lactate (RatioBic/Lac) measured within 1–2 min after coronary release decreased vs. baseline in ischemic rats ( n = 10, 15-min occlusion, controls: n = 10; P = 0.017 for interaction, 2-way ANOVA). The decrease in oxidative pyruvate metabolism [RatioBic/Lac(Ischemia)/RatioBic/Lac(Baseline)] modestly correlated with area at risk ( r = 0.66; P = 0.002). Hyperpolarized 13C MRS was also used to examine alanine production during ischemia, which is observed in ex vivo models, but no significant change was noted; metrics incorporating [1-13C]alanine did not substantially improve the discrimination of ischemic-reperfused myocardium from nonischemic myocardium. This intact rat model, which mimics the human situation of reperfused myocardial infarction, could be highly valuable for the testing of new drugs to treat reperfusion injury, thereby facilitating translational research.

TAMI-40. PEDIATRIC H3K27M MUTANT GLIOMAS UNDERGO METABOLIC REPROGRAMMING THAT CAN BE LEVERAGED FOR NON-INVASIVE METABOLIC IMAGING

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi206-vi207
Author(s):  
Meryssa Tran ◽  
Georgios Batsios ◽  
Céline Taglang ◽  
Anne Marie Gillespie ◽  
Javad Nazarian ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Phospholipid Metabolism ◽  
Metabolic Reprogramming ◽  
Metabolic Imaging ◽  
Resonance Spectroscopy ◽  
1H Mrs ◽  
Hyperpolarized 13C ◽  
Non Invasive ◽  
13C Mrs

Abstract Diffuse midline gliomas (DMGs) are a universally lethal form of childhood cancer. The infiltrative nature of DMGs makes them difficult to visualize by conventional magnetic resonance imaging. Genomics studies indicate that DMGs are driven by unique histone H3K27M mutations that result in broad epigenetic dysregulation. Many of the resulting changes in gene expression have the potential to induce metabolic reprogramming, which has been identified as a hallmark of cancer. The goal of this study was to dissect metabolic reprogramming in preclinical DMG models in order to identify novel magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers that can be exploited for non-invasive imaging. First, we used 1H-MRS, which reports on steady-state metabolism, to examine H3K27M mutant SF7761 cells and H3 wild-type normal human astrocytes (NHA). Lactate, glutathione and phosphocholine, which are involved in glycolysis, redox and phospholipid metabolism respectively, were elevated in SF7761 cells relative to NHAs. Mechanistically, these metabolic alterations were associated with upregulation of key enzymes including hexokinase 2, glutamate cysteine ligase and choline kinase a. Importantly, in vivo 1H-MRS showed elevated lactate, glutathione and total choline (combined signal from choline, phosphocholine and glycerophosphocholine) in mice bearing orthotopic SF7761 tumors relative to tumor-free controls. We then examined alterations in dynamic metabolic pathways in our models. Using thermally-polarized 13C-MRS, we identified elevated production of [2-13C]-lactate from [2-13C]-glucose in SF7761 cells relative to NHAs. Hyperpolarized 13C-MRS is a method of enhancing the 13C-MR signal such that metabolic fluxes can be interrogated with high sensitivity. Hyperpolarized [1-13C]-pyruvate flux to [1-13C]-lactate non-invasively monitors glycolysis and is in clinical trials in adult glioma patients. Importantly, hyperpolarized [1-13C]-pyruvate metabolism to lactate was elevated in SF7761 cells relative to NHAs. Collectively, our studies suggest that H3K27M mutant DMGs undergo reprogramming of glucose, redox and phospholipid metabolism that can be leveraged for non-invasive 1H- and hyperpolarized 13C-MRS-based imaging.

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