Title
Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models
Date Issued
01 July 2022
Access level
open access
Resource Type
journal article
Author(s)
Czernuszewicz T.J.
Aji A.M.
Moore C.J.
Montgomery S.A.
Velasco B.
Anand K.S.
Johnson K.A.
Deal A.M.
Zukić D.
McCormick M.
Schnabl B.
Gallippi C.M.
Dayton P.A.
Gessner R.C.
University of North Carolina
Publisher(s)
John Wiley and Sons Inc
Abstract
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 (R2 = 0.891) and fibrosis (R2 = 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.
Start page
1827
End page
1839
Volume
6
Issue
7
Language
English
OCDE Knowledge area
Gastroenterología, Hepatología Robótica, Control automático Ingeniería médica
Scopus EID
2-s2.0-85125133420
PubMed ID
Source
Hepatology Communications
ISSN of the container
2471254X
Sponsor(s)
Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R44DK112492 and P30DK120515). National Institute on Alcohol Abuse and Alcoholism - R37AA020703. National Heart, Lung, and Blood Institute - T32HL069768.
Sources of information: Directorio de Producción Científica Scopus