Intraperitoneal Injections as an Alternative Method for Micro-CT Contrast Enhanced Detection of Murine Liver Tumors

Sweeney, Nathan W.; Marchant, Stephen; Martinez, Jesse D.

doi:10.2144/btn-2018-0162

Cited by 6 publications

(6 citation statements)

References 12 publications

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“…However, long-term follow-up was not performed, unlike in our study. Considering these previous successful longitudinal imaging studies and the results of our own study, 2,24 -26 longitudinal imaging using nanoparticle contrast agents and microCT may offer an effective tool for the follow-up of liver cancer mouse models.…”

Section: Discussionmentioning

confidence: 67%

“…In this study, the smallest liver cancer nodule that could be identified on microCT imaging was 0.60 mm, as compared with the minimum discernible size of 0.30 mm in a previous study. 2 Recently, there was a report of an injection of hepatocellular-specific contrast agent (Fenestra LC, MediLumine Inc., Montreal, Canada) into the abdominal cavity to obtain a contrast-enhanced image of the hepatic parenchyma without requiring initial injection through the lateral tail vein 24 ; however, serial imaging required multiple injections of contrast media into the abdominal cavity. Furthermore, images need to be obtained 16 h after contrast agent injection to obtain the best image, and the contrast enhancement intensity was lower than that obtained with the ExiTron nano 12000 used in our experiment.…”

Section: Discussionmentioning

confidence: 99%

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Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model

Yang

Kim

et al. 2021

Technol Cancer Res Treat

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Introduction: Micro-computed tomography with nanoparticle contrast agents may be a suitable tool for monitoring the time course of the development and progression of tumors. Here, we suggest a practical and convenient experimental method for generating and longitudinally imaging murine liver cancer models. Methods: Liver cancer was induced in 6 experimental mice by injecting clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 plasmids causing mutations in genes expressed by hepatocytes. Nanoparticle agents are captured by Kupffer cells and detected by micro-computed tomography, thereby enabling longitudinal imaging. A total of 9 mice were used for the experiment. Six mice were injected with both plasmids and contrast, 2 injected with contrast alone, and one not injected with either agent. Micro-computed tomography images were acquired every 2- up to 14-weeks after cancer induction. Results: Liver cancer was first detected by micro-computed tomography at 8 weeks. The mean value of hepatic parenchymal attenuation remained almost unchanged over time, although the standard deviation of attenuation, reflecting heterogeneous contrast enhancement of the hepatic parenchyma, increased slowly over time in all mice. Histopathologically, heterogeneous distribution and aggregation of Kupffer cells was more prominent in the experimental group than in the control group. Heterogeneous enhancement of hepatic parenchyma, which could cause image quality deterioration and image misinterpretation, was observed and could be due to variation in Kupffer cells distribution. Conclusion: Micro-computed tomography with nanoparticle contrast is useful in evaluating the induction and characteristics of liver cancer, determining appropriate size of liver cancer for testing, and confirming therapeutic response.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model

Yang

Kim

et al. 2021

Technol Cancer Res Treat

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“…15 With tissue or vascular specific contrast agents, CT has become a powerful tool to monitor tumor growth in animal livers. 16 CECT is able to grasp the "fast-in and out" feature of HCC lesions and exhibit the blood flow in the tumor. 17 A normal liver derives 80% of its blood from the portal vein and the other 20% from the hepatic artery.…”

Section: Discussionmentioning

confidence: 99%

Clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in liver

Liu¹,

Dong²,

Xu³

et al. 2021

Pak J Med Sci

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Objectives: To explore the clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in the liver and investigate the association between such small nodular lesions and the degree of tumor differentiation. Methods: Combined imaging modalities were performed on 120 patients who were admitted by Linyi Maternal and Child Health hospital from December 2018 to December 2020 and diagnosed with hepatic nodular lesions. The CT scans were interpreted by two senior imageologists while the ultrasound scans were analyzed by two senior sonographers. A comparative analysis was carried out on different scan modes and the postoperative or post-puncture pathological results using the t-test, the χ2 test, and the Pearson’s correlation analysis. Results: Compared to the pathological results, definite diagnoses of 55 malignant cases were made using CECT alone, with the coincidence rate of 78.6%; CECT combined with CEUS formed correct diagnoses in 64 cases, and the coincidence rate was up to 91.4%. The difference between the two scan modes was statistically significant (p= 0.03). Based on pathological diagnosis, seventy out of the 120 cases of small nodular lesions were identified as malignant, while the other 50 cases were benign. The single imaging modality diagnosed 63 malignant and 57 benign nodules, whereas the combined modalities identified 68 malignancies and 52 benign conditions. Compared to CECT as a single imaging modality, the combined modalities showed a higher degree of sensitivity and accuracy, and the difference was statistically significant (sensitivity: p= 0.03; accuracy: p= 0.02); in the malignant cases, the magnitudes of contrast enhancement of CT and ultrasound imaging decreased with an increase in the degree of differentiation, indicating a negative correlation between these factors. Conclusions: CECT combined with CEUS has a higher coincidence rate, greater sensitivity, and better diagnostic accuracy when being used for characterization and diagnosis of small nodular lesions in the liver. A higher degree of tumor differentiation means a decreased magnitude of contrast enhancement and a blurrier boundary, which indicates that CECT and CEUS are complementary to each other in classifying malignant liver nodules. The use of the combined imaging modalities shows clinical value for characterizing small liver nodules and predicting the degree of malignancy. doi: https://doi.org/10.12669/pjms.37.7.4306 How to cite this:Liu J, Bao D, Xu Z, Zhuge X. Clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in liver. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4306 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…Among those modalities, X-ray micro-CT has gained significant traction for several reasons, including its noninvasive 3D imaging capability, isotropic spatial resolution (∼ 10 – 100 μm), good balance between resolution and field of view, fast speed, easy processing, and relatively low cost compared to MRI (Clark and Badea 2021). Since tumors generally have similar density to their surrounding tissues, contrast material is needed for improved tumor visibility when using micro-CT. For example, Fenestra LC is one of the most used nanoparticle (NP)-based contrast agents for liver and spleen micro-CT imaging (Bakan et al 2000, Sweeney et al 2019) as they can be taken up by phagocytic cells and accumulate in functioning liver or spleen regions. Several NP-based blood stream contrast agents have been used to monitor the development of liver and spleen tumors in a longitudinal manner (Almajdub et al 2007, Kim et al 2008, Boll et al 2011, Sweeney et al 2019, Cassol et al 2019, Liu et al 2019), via volume extraction (Cassol et al 2019), and vascularity (Sulheim et al 2018) measurements.…”

Section: Introductionmentioning

confidence: 99%

“…Since tumors generally have similar density to their surrounding tissues, contrast material is needed for improved tumor visibility when using micro-CT. For example, Fenestra LC is one of the most used nanoparticle (NP)-based contrast agents for liver and spleen micro-CT imaging (Bakan et al 2000, Sweeney et al 2019) as they can be taken up by phagocytic cells and accumulate in functioning liver or spleen regions. Several NP-based blood stream contrast agents have been used to monitor the development of liver and spleen tumors in a longitudinal manner (Almajdub et al 2007, Kim et al 2008, Boll et al 2011, Sweeney et al 2019, Cassol et al 2019, Liu et al 2019), via volume extraction (Cassol et al 2019), and vascularity (Sulheim et al 2018) measurements. However, compared with liver/spleen tumors, breast tumor imaging is more challenging, since NPs can accumulate in liver and spleen tissues, forming a negative contrast for tumors and enabling a clear discrimination between tumors and surrounding tissues.…”

Section: Introductionmentioning

confidence: 99%

Contrast-enhanced photon-counting micro-CT of tumor xenograft models

Li,

Guo,

Verma

et al. 2024

Preprint

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Photon-counting micro computed tomography (micro-CT) offers new potential in preclinical imaging, particularly in distinguishing materials. It becomes especially helpful when combined with contrast agents, enabling the differentiation of tumors from surrounding tissues. There are mainly two types of contrast agents in the market for micro-CT: small molecule-based and nanoparticle-based. However, despite their widespread use in liver tumor studies, there is a notable gap in research on the application of these commercially available agents for photon-counting micro-CT in breast and ovarian tumors. Herein, we explored the effectiveness of these agents in differentiating tumor xenografts from various origins (AU565, MDA-MB-231, and SKOV-3) in nude mice, using photon-counting micro-CT. Specifically, ISOVUE-370 (a small molecule-based agent) and Exitrone Nano 12000 (a nanoparticle-based agent) were investigated in this context. To improve tumor visualization, we proposed a novel color visualization method for photon-counting micro-CT, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Our in vivo experiments confirm its effectiveness, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggested that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 gives more comprehensive tumor enhancement but with a significant variance between scans due to its short blood half-time. This variability leads to high sensitivity to timing and individual differences among mice. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemistry. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor development and response to treatments.

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Intraperitoneal Injections as an Alternative Method for Micro-CT Contrast Enhanced Detection of Murine Liver Tumors

Cited by 6 publications

References 12 publications

Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model

Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model

Clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in liver

Contrast-enhanced photon-counting micro-CT of tumor xenograft models

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