High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Non-Alcoholic Fatty Liver Disease Progression in Mice

Fernández-Domínguez, Itziar; Gómez, Nieves; Luka, Zigmund; Wagner, Conrad; Lu, Shelly C.; Mato, José M.; Martínez‐Chantar, María Luz; Rodríguez-Cuesta, Juan

doi:10.1016/j.ultrasmedbio.2011.04.012

Cited by 17 publications

(11 citation statements)

References 26 publications

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“…On week 8, 2 mice were randomly chosen from each group and high-frequency ultrasound imaging was performed using the Vevo 2100 Imaging System (VisualSonics Inc., Toronto, Ontario, Canada) to determine the development/extent of liver steatosis and fibrosis (Fernandez-Dominguez et al 2011). During imaging sessions, mice were kept under anesthesia using 1.5% isoflurane in oxygen and restrained on a heated stage.…”

Section: Methodsmentioning

confidence: 99%

A compromised liver alters polychlorinated biphenyl-mediated toxicity

et al. 2017

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Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the PCB mixture, Arcolor1260 (20 mg/kg) and analyzed for inflammatory, calorimetry and metabolic parameters. Consistent with the literature, MCD diet-fed mice demonstrated steatosis, indicative of a compromised liver. Mice fed the MCD-diet and subsequently exposed to PCB126 showed observable wasting syndrome leading to mortality. PCB126 and Aroclor1260 exposure worsened hepatic fibrosis exhibited by the MCD groups. Interestingly, PCB126 but not Aroclor1260 induced steatosis and inflammation in CD-fed mice. Mice with liver injury and subsequently exposed to PCBs also manifested metabolic disturbances due to alterations in hepatic gene expression. Furthermore, PCB exposure in MCD-fed mice led to extra-hepatic toxicity such as upregulated circulating inflammatory biomarkers, implicating endothelial cell dysfunction. Taken together, these results indicate that environmental pollution can exacerbate toxicity caused by diet-induced liver injury which may be partially due to dysfunctional energy homeostasis. This is relevant to PCB-exposed human cohorts who suffer from alcohol or diet-induced fatty liver diseases.

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Section: Methodsmentioning

confidence: 99%

A compromised liver alters polychlorinated biphenyl-mediated toxicity

et al. 2017

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“…High-resolution ultrasonography is a recently available technology, which has now become applicable for studies with mice [ 11 , 12 ]. As a non-invasive approach, it is possible to conduct continuous observations of disease progress in the same mouse using high-resolution ultrasonography [ 13 , 14 ]. There is no direct evidence that the clinicopathological changes observed in a mouse model are comparable to those in human infection; however, the pathophysiology of schistosomiasis in humans seems to be similar to findings in the murine model.…”

Section: Introductionmentioning

confidence: 99%

Real-time observation of pathophysiological processes during murine experimental Schistosoma japonicum infection using high-resolution ultrasound imaging

Maezawa

Furushima-Shimogawara

Yasukawa

et al. 2018

Trop Med Health

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BackgroundHepatosplenic lesion formation is one of the typical clinical symptoms of schistosomiasis japonica. Although it is established that circum-oval granuloma formation mediated by T lymphocytes is the key event triggering the formation of hepatic lesions, the time-course kinetics of disease progression remains to be fully elucidated.MethodsThe real-time process of the pathophysiology of schistosomiasis japonica from the early to late clinical phase was non-invasively observed in a murine experimental infection model using high-resolution ultrasonography. Together with clinical parameters, including body weight and the levels of serum markers of hepatic damage or fibrosis, ultrasonography was used to assess changes in the liver parenchyma and diameter of the portal vein and portal blood flow velocity. In parallel, parasitological parameters were observed, including egg number in the feces and maturation of parasites.ResultsAbnormal high-echo spot patterns in the liver parenchyma, reflecting hepatic fibrosis in ultrasonography, appeared in the liver at 4 weeks post-infection and the pattern became more enlarged and severe over time. This finding was concordant with parasite maturation and initial egg excretion. The serum M2BPGi level markedly increased from 8 weeks post-infection, suggesting sharp deterioration of hepatic fibrosis. At the same time, the diameter of the portal vein, reflecting portal hypertension, became enlarged and reached the peak level at 8 weeks post-infection. Ascites were apparent around the spleen at 9 weeks post-infection, and dilatation of the splenic vein was noted at 10 weeks post-infection. Live adult worms seemed to be detected in the portal vein at 4 weeks post-infection by ultrasonography.ConclusionsWe obtained real-time imaging of the development of hepatosplenic lesions of schistosomiasis japonica in mice. The time-course kinetics of the onset, development, and modulation of each symptom was uncovered. These results are expected to provide new clues for understanding the pathophysiology of human schistosomiasis japonica.

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“…Most of these models are used for longitudinal monitoring of the disease process and to assess the effectiveness of novel therapeutic approaches. Methods that allow non-invasive longitudinal liver imaging include micro-computed tomography (micro-CT) [14] , [15] , magnetic resonance imaging (MRI) [16] , ultrasound [17] , as well as more sensitive techniques with lower resolutions, such as positron emission tomography (PET) [18] , [19] , [20] and fluorescence imaging [18] . The increased availability of high-resolution imaging modalities allow researchers the opportunity (and sometimes the need) to identify with precision the pathological processes at work, making knowledge of the macroscopic anatomical situation of the murine liver essential.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional In Vivo Imaging of the Murine Liver: A Micro-Computed Tomography-Based Anatomical Study

et al. 2012

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Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.

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High-Frequency Ultrasound Imaging for Longitudinal Evaluation of Non-Alcoholic Fatty Liver Disease Progression in Mice

Cited by 17 publications

References 26 publications

A compromised liver alters polychlorinated biphenyl-mediated toxicity

A compromised liver alters polychlorinated biphenyl-mediated toxicity

Real-time observation of pathophysiological processes during murine experimental Schistosoma japonicum infection using high-resolution ultrasound imaging

Three-Dimensional In Vivo Imaging of the Murine Liver: A Micro-Computed Tomography-Based Anatomical Study

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