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

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...

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Main Authors: Sang Bu An, Kwangmo Yang MD, PhD, Chang Won Kim MD, PhD, Si Ho Choi PhD, Eunji Kim, Sung Dae Kim, Jae Soo Koh
פורמט: Article
שפה:English
יצא לאור: SAGE Publishing 2021-05-01
סדרה:Technology in Cancer Research & Treatment
גישה מקוונת:https://doi.org/10.1177/15330338211016466
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author Sang Bu An
Kwangmo Yang MD, PhD
Chang Won Kim MD, PhD
Si Ho Choi PhD
Eunji Kim
Sung Dae Kim
Jae Soo Koh
author_facet Sang Bu An
Kwangmo Yang MD, PhD
Chang Won Kim MD, PhD
Si Ho Choi PhD
Eunji Kim
Sung Dae Kim
Jae Soo Koh
author_sort Sang Bu An
collection DOAJ
description 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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spelling doaj.art-6beb51bb1b9c43dba97551cd1dd1c03c2022-12-22T00:34:41ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382021-05-012010.1177/15330338211016466Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse ModelSang Bu An0Kwangmo Yang MD, PhD1Chang Won Kim MD, PhD2Si Ho Choi PhD3Eunji Kim4Sung Dae Kim5Jae Soo Koh6 Department of Radiology, , Nowon-gu, Seoul, Korea Department of Radiation Oncology, , Nowon-gu, Seoul, Korea Department of Radiology, School of Medicine and Biomedical Research Institute, , Pusan National University Hospital, Busan, Korea Research Center, , Busan, Korea Department of Radiation Oncology, , Nowon-gu, Seoul, Korea Research Center, , Busan, Korea Department of Pathology, , Nowon-gu, Seoul, KoreaIntroduction: 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.https://doi.org/10.1177/15330338211016466
spellingShingle Sang Bu An
Kwangmo Yang MD, PhD
Chang Won Kim MD, PhD
Si Ho Choi PhD
Eunji Kim
Sung Dae Kim
Jae Soo Koh
Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model
Technology in Cancer Research & Treatment
title Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model
title_full Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model
title_fullStr Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model
title_full_unstemmed Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model
title_short Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model
title_sort longitudinal imaging of liver cancer using microct and nanoparticle contrast agents in crispr cas9 induced liver cancer mouse model
url https://doi.org/10.1177/15330338211016466
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