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Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models
Shear wave elastography (SWE) is an ultrasound‐based stiffness quantification technology that is used for noninvasive liver fibrosis assessment. However, despite widescale clinical adoption, SWE is largely unused by preclinical researchers and drug developers for studies of liver disease progression...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234684/ https://www.ncbi.nlm.nih.gov/pubmed/35202510 http://dx.doi.org/10.1002/hep4.1912 |
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author | Czernuszewicz, Tomasz J. Aji, Adam M. Moore, Christopher J. Montgomery, Stephanie A. Velasco, Brian Torres, Gabriela Anand, Keerthi S. Johnson, Kennita A. Deal, Allison M. Zukić, Dženan McCormick, Matthew Schnabl, Bernd Gallippi, Caterina M. Dayton, Paul A. Gessner, Ryan C. |
author_facet | Czernuszewicz, Tomasz J. Aji, Adam M. Moore, Christopher J. Montgomery, Stephanie A. Velasco, Brian Torres, Gabriela Anand, Keerthi S. Johnson, Kennita A. Deal, Allison M. Zukić, Dženan McCormick, Matthew Schnabl, Bernd Gallippi, Caterina M. Dayton, Paul A. Gessner, Ryan C. |
author_sort | Czernuszewicz, Tomasz J. |
collection | PubMed |
description | Shear wave elastography (SWE) is an ultrasound‐based stiffness quantification technology that is used for noninvasive liver fibrosis assessment. However, despite widescale clinical adoption, SWE is largely unused by preclinical researchers and drug developers for studies of liver disease progression in small animal models due to significant experimental, technical, and reproducibility challenges. Therefore, the aim of this work was to develop a tool designed specifically for assessing liver stiffness and echogenicity in small animals to better enable longitudinal preclinical studies. A high‐frequency linear array transducer (12‐24 MHz) was integrated into a robotic small animal ultrasound system (Vega; SonoVol, Inc., Durham, NC) to perform liver stiffness and echogenicity measurements in three dimensions. The instrument was validated with tissue‐mimicking phantoms and a mouse model of nonalcoholic steatohepatitis. Female C57BL/6J mice (n = 40) were placed on choline‐deficient, L‐amino acid‐defined, high‐fat diet and imaged longitudinally for 15 weeks. A subset was sacrificed after each imaging timepoint (n = 5) for histological validation, and analyses of receiver operating characteristic (ROC) curves were performed. Results demonstrated that robotic measurements of echogenicity and stiffness were most strongly correlated with macrovesicular steatosis (R(2) = 0.891) and fibrosis (R(2) = 0.839), respectively. For diagnostic classification of fibrosis (Ishak score), areas under ROC (AUROCs) curves were 0.969 for ≥Ishak1, 0.984 for ≥Ishak2, 0.980 for ≥Ishak3, and 0.969 for ≥Ishak4. For classification of macrovesicular steatosis (S‐score), AUROCs were 1.00 for ≥S2 and 0.997 for ≥S3. Average scanning and analysis time was <5 minutes/liver. Conclusion: Robotic SWE in small animals is feasible and sensitive to small changes in liver disease state, facilitating in vivo staging of rodent liver disease with minimal sonographic expertise. |
format | Online Article Text |
id | pubmed-9234684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92346842022-06-30 Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models Czernuszewicz, Tomasz J. Aji, Adam M. Moore, Christopher J. Montgomery, Stephanie A. Velasco, Brian Torres, Gabriela Anand, Keerthi S. Johnson, Kennita A. Deal, Allison M. Zukić, Dženan McCormick, Matthew Schnabl, Bernd Gallippi, Caterina M. Dayton, Paul A. Gessner, Ryan C. Hepatol Commun Original Articles Shear wave elastography (SWE) is an ultrasound‐based stiffness quantification technology that is used for noninvasive liver fibrosis assessment. However, despite widescale clinical adoption, SWE is largely unused by preclinical researchers and drug developers for studies of liver disease progression in small animal models due to significant experimental, technical, and reproducibility challenges. Therefore, the aim of this work was to develop a tool designed specifically for assessing liver stiffness and echogenicity in small animals to better enable longitudinal preclinical studies. A high‐frequency linear array transducer (12‐24 MHz) was integrated into a robotic small animal ultrasound system (Vega; SonoVol, Inc., Durham, NC) to perform liver stiffness and echogenicity measurements in three dimensions. The instrument was validated with tissue‐mimicking phantoms and a mouse model of nonalcoholic steatohepatitis. Female C57BL/6J mice (n = 40) were placed on choline‐deficient, L‐amino acid‐defined, high‐fat diet and imaged longitudinally for 15 weeks. A subset was sacrificed after each imaging timepoint (n = 5) for histological validation, and analyses of receiver operating characteristic (ROC) curves were performed. Results demonstrated that robotic measurements of echogenicity and stiffness were most strongly correlated with macrovesicular steatosis (R(2) = 0.891) and fibrosis (R(2) = 0.839), respectively. For diagnostic classification of fibrosis (Ishak score), areas under ROC (AUROCs) curves were 0.969 for ≥Ishak1, 0.984 for ≥Ishak2, 0.980 for ≥Ishak3, and 0.969 for ≥Ishak4. For classification of macrovesicular steatosis (S‐score), AUROCs were 1.00 for ≥S2 and 0.997 for ≥S3. Average scanning and analysis time was <5 minutes/liver. Conclusion: Robotic SWE in small animals is feasible and sensitive to small changes in liver disease state, facilitating in vivo staging of rodent liver disease with minimal sonographic expertise. John Wiley and Sons Inc. 2022-02-24 /pmc/articles/PMC9234684/ /pubmed/35202510 http://dx.doi.org/10.1002/hep4.1912 Text en © 2022 SonoVol, Inc and University of North Carolina. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Czernuszewicz, Tomasz J. Aji, Adam M. Moore, Christopher J. Montgomery, Stephanie A. Velasco, Brian Torres, Gabriela Anand, Keerthi S. Johnson, Kennita A. Deal, Allison M. Zukić, Dženan McCormick, Matthew Schnabl, Bernd Gallippi, Caterina M. Dayton, Paul A. Gessner, Ryan C. Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models |
title | Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models |
title_full | Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models |
title_fullStr | Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models |
title_full_unstemmed | Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models |
title_short | Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models |
title_sort | development of a robotic shear wave elastography system for noninvasive staging of liver disease in murine models |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234684/ https://www.ncbi.nlm.nih.gov/pubmed/35202510 http://dx.doi.org/10.1002/hep4.1912 |
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