In Vivo Lipid Profiling Using Proton Magnetic Resonance Spectroscopy in an Experimental Liver Fibrosis Model

Cheung, J. T.; Fan, Shu Juan; Gao, Darwin S.; Chow, April M.; Yang, Jian; Man, Kwan; Wu, Ed X.

doi:10.1016/j.acra.2010.10.012

Cited by 19 publications

(25 citation statements)

References 45 publications

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“…Typically, spectra obtained from in vivo 1 H MRS of liver tissue show various lipid peaks as well as choline-containing compounds from the range of 0.9-5.3 ppm (Cheung et al, 2011;Ramamonjisoa et al, 2013). It has been suggested that these possess the characteristics and can be associated with specific lipid resonances (CH 3, 0.9 ppm; (CH 2 ) n, 1.3 ppm; CH 2 C¼CCH 2 , 2.1 ppm; ¼CCH 2 C¼, 2.8 ppm;CH¼CH, 5.3 ppm) (Lim et al, 2003;Gentile and Pagliassotti, 2008;Corbin et al, 2009;Cheung et al, 2011;Yahya et al, 2011;Gajdošík et al, 2014).…”

Section: Introductionmentioning

confidence: 98%

In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons

Song

Baek

Lee

et al. 2015

Chemistry and Physics of Lipids

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Section: Introductionmentioning

confidence: 98%

In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons

Song

Baek

Lee

et al. 2015

Chemistry and Physics of Lipids

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“…This could be interpreted as a greater amount of SFA compared with the group of mice fed a standard diet although GC reports an increase of SFA only for the control mice fed a HF/HS diet and rather a decrease for the mouse model. In other studies, the TUBI was reported to be higher in animal models of fi brosis ( 25 ) or steatohepatitis ( 14 ) than baseline controls. Here L-G6pc Ϫ / Ϫ mice did not show any fi brosis marker ( 5 ).…”

Section: H-mrs Of Mice With Genetically Induced Steatosis (L-g6pcmentioning

confidence: 99%

“…At high magnetic fi elds [ у 3 Tesla (T)], which allows a better spectral dispersion, 1 H-MRS has also been used to characterize lipid accumulation and lipid composition in a rat model of liver fi brosis ( 25 ), or to evaluate fat content in diabetic obese rats ( 26 ) and mice ( 22 ). Recently, this technique was correlated with histology and TG level ( 21 ) in order to compare these techniques for fat quantifi cation in mice.…”

Section: Mr Experimental Conditionsmentioning

confidence: 99%

In vivo hepatic lipid quantification using MRS at 7 Tesla in a mouse model of glycogen storage disease type 1a

Ramamonjisoa

Ratiney

Mutel

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org Glycogen storage disease type 1 (GSD 1) is an autosomal recessive metabolic disorder resulting in severe impairment of glucose production and large accumulation of lipids within hepatocytes (steatosis) ( 1, 2 ). The phenotype of GSD 1 results from a defect in the glucose-6 phosphatase (G6Pase) complex, leading to severe hypoglycemia due to the loss of endogenous glucose production. Despite a strict diet, patients with GSD 1 develop hepatomegaly and steatosis and may develop, with age, hepatocellular adenoma that can ultimately evolve into hepatocellular carcinoma ( 3, 4 ). Recently, a viable mouse model of GSD 1a with a liverspecifi c deletion of G6Pase catalytic subunit (L-G6pc Ϫ / Ϫ ) has been generated and validated ( 5 ). GSD 1a mice exhibit hepatic pathological features very similar to those observed in GSD 1a patients.The accumulation of lipids in the liver relates to the buildup of neutral lipids, such as triglycerides (TGs) and cholesterol esters, stored as lipid droplets in hepatocytes and leading to hepatic steatosis. This fat accumulation may originate from a ) peripheral fat stored in adipose tissue that fl ows to the liver as plasma nonesterifi ed fatty acids, b ) fatty acids newly made within the liver through de novo lipogenesis, and c ) dietary fatty acids ( 6, 7 ).Steatosis is highly linked to the development of metabolic diseases such as obesity or type 2 diabetes, but it can also result from genetic disorders impacting lipid and glucose metabolism such as in GSD 1a, ␣ 1-antitrypsin defi ciency, Abstract The assessment of liver lipid content and composition is needed in preclinical research to investigate steatosis and steatosis-related disorders. The purpose of this study was to quantify in vivo hepatic fatty acid content and composition using a method based on short echo time proton magnetic resonance spectroscopy (MRS) at 7 Tesla. A mouse model of glycogen storage disease type 1a with inducible liver-specifi c deletion of the glucose-6-phosphatase gene (L-G6pc ؊ / ؊ ) mice and control mice were fed a standard diet or a high-fat/high-sucrose (HF/HS) diet for 9 months. In control mice, hepatic lipid content was found signifi cantly higher with the HF/HS diet than with the standard diet. As expected, hepatic lipid content was already elevated in L-G6pc ؊ / ؊ mice fed a standard diet compared with control mice. L-G6pc ؊ / ؊ mice rapidly developed steatosis which was not modifi ed by the HF/HS diet. On the standard diet, estimated amplitudes from olefi nic protons were found signifi cantly higher in L-G6pc ؊ / ؊ mice compared with that in control mice. L-G6pc ؊ / ؊ mice showed no noticeable polyunsaturation from diallylic protons. Total unsaturated fatty acid indexes measured by gas chromatography were in agreement with MRS measurements. These results showed the great potential of high magnetic fi eld MRS to follow the diet impact and lipid alterations in mouse liver.

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“…2. Liver fibrosis was induced in fibrosis group by subcutaneous injection of 1:3 mixture of carbon tetrachloride (CCl 4 ) in olive oil at a dose of 4 μL/g of body weight twice a week for 8 weeks (24,26,44). Intermittent administration of CCl 4 has been widely used to experimentally induce liver fibrosis in rodents by evoking a marked infiltration of inflammatory cells, thus mimicking the changes in chronic viral hepatitis-associated fibrosis in many ways (45,46).…”

Section: Methodsmentioning

confidence: 99%

“…Changes in both ADC and other diffusion properties were observed during the progression of liver fibrosis using diffusion tensor imaging and intravoxel incoherent motion analysis (24) (25). Proton magnetic resonance spectroscopy was also demonstrated to provide a sensitive means to assess liver fibrosis through characterizing metabolic changes without the use of contrast agents (26). More recently, longitudinal and transverse relaxation times, as well as spin-lattice relaxation time in the rotating frame ( T 1ρ ), were shown to alter in fibrotic livers (27–29(30).…”

Section: Introductionmentioning

confidence: 99%

Molecular MRI of Liver Fibrosis by a Peptide-Targeted Contrast Agent in an Experimental Mouse Model

Chow

Tan

Gao

et al. 2013

Investigative Radiology

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Liver fibrosis is a common response to chronic liver injury that is associated with high morbidity and mortality. Clinical utility of conventional and advanced MRI techniques for staging liver fibrosis has yet to be established. Study on molecular MRI of liver fibrosis is limited mainly due to difficulty in searching for a specific biomarker and synthesizing corresponding molecular probe. Liver fibrosis is characterized by an increased amount of extracellular matrix consisting of fibril-forming collagens, and matrix glycoconjugates such as fibronectin, which may serve as a specific molecular target for contrast-enhanced molecular MRI. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4) intoxication mimicking hepatic fibrosis and cirrhosis after 4 and 8 weeks. The feasibility of CGLIIQKNEC (CLT1) peptide-targeted nanoglobular contrast agent (Gd-P) for detection of liver fibrosis through molecular imaging of fibronectin was investigated at 7 T. Differential enhancements were observed and characterized between normal and fibrotic livers using Gd-P at 0.03 mmol/kg, comparing to non-targeted controls (Gd-CP and Gd-C). For Gd-P injection, both the peak and steady-state ΔR1 of normal livers was significantly lower than those after 4-week and 8-week of CCl4 dosing. Liver fibrogenesis with increased amount of fibronectin in the extracellular space in insulted livers were confirmed by histological observations. These results indicate that Gd-P binds to fibrin-fibronectin complexes in livers, demonstrating the possibility of staging and characterizing liver fibrosis by probing the accumulation of fibronectin in fibrotic livers with molecular MRI.

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In Vivo Lipid Profiling Using Proton Magnetic Resonance Spectroscopy in an Experimental Liver Fibrosis Model

Cited by 19 publications

References 45 publications

In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons

In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons

In vivo hepatic lipid quantification using MRS at 7 Tesla in a mouse model of glycogen storage disease type 1a

Molecular MRI of Liver Fibrosis by a Peptide-Targeted Contrast Agent in an Experimental Mouse Model

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