Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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
_version_ 1784736136681226240
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
work_keys_str_mv AT czernuszewicztomaszj developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT ajiadamm developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT moorechristopherj developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT montgomerystephaniea developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT velascobrian developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT torresgabriela developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT anandkeerthis developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT johnsonkennitaa developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT dealallisonm developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT zukicdzenan developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT mccormickmatthew developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT schnablbernd developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT gallippicaterinam developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT daytonpaula developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels
AT gessnerryanc developmentofaroboticshearwaveelastographysystemfornoninvasivestagingofliverdiseaseinmurinemodels