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Tamura K, Ito K, Kishimoto R, Yoshida K, Kishimoto T, Obata T, Yamaguchi T. The Effect of Steatosis on Shear-Wave Velocity and Viscoelastic Properties Related to Liver Fibrosis Progression in Rat Models. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:592-599. [PMID: 38238201 DOI: 10.1016/j.ultrasmedbio.2024.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 12/26/2023] [Accepted: 01/01/2024] [Indexed: 02/17/2024]
Abstract
OBJECTIVE Hepatic fibrosis has recently been evaluated using ultrasonography or magnetic resonance elastography. Although the shear wave velocity (SWV) obtained using point shear wave elastography (pSWE) provides a valuable measure of fibrosis, underlying steatosis may affect its measurement. METHODS Using hepatic fibrosis samples, this study evaluated the effect of steatosis on the shear wave velocity of pSWE (Vs) and viscoelastic properties (assessed by dynamic mechanical analysis) of rat liver. Fifty rats with various grades of steatosis and fibrosis underwent open abdominal in vivo Vs measurements using a commercial ultrasound scanner. The mechanical properties of hepatic tissue were also characterized under ex vivo conditions using dynamic mechanical analysis and the Zener model of viscoelasticity. RESULTS Fibrosis and steatosis progression influenced Vs and elasticity. The SWV computed using the Zener model and Vs showed a substantial correlation (r > 0.8). Fibrosis progression increased SWV. Steatosis was also related to SWV. Steatosis progression obscured the SWV change associated with fibrosis progression. CONCLUSION We conclude that steatosis progression affects the evaluation of fibrosis progression. This finding could aid discrimination of non-alcoholic steatohepatitis from non-alcoholic fatty liver disease using SWV.
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Affiliation(s)
- Kazuki Tamura
- Preeminent Medical Photonics Education & Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
| | - Kazuyo Ito
- Institute of Engineering, Tokyo University of Agriculture and Technology, Koganei-shi, Tokyo 184-8588 Japan
| | - Riwa Kishimoto
- Applied MRI Research, Department of Molecular Imaging and Theranostics, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-0024, Japan
| | - Kenji Yoshida
- Center for Frontier Medical Engineering, Chiba University, Inage-ku, Chiba 263-8522, Japan
| | - Takashi Kishimoto
- Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
| | - Takayuki Obata
- Applied MRI Research, Department of Molecular Imaging and Theranostics, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-0024, Japan
| | - Tadashi Yamaguchi
- Center for Frontier Medical Engineering, Chiba University, Inage-ku, Chiba 263-8522, Japan
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Song Y, Li WB, Saleem N, Tian G, Ruan L, Zhang H. Viscoelastic Characteristics in Mouse Model of Hepatic Steatosis With Inflammation by Kelvin-Voigt Fractional Derivative Modeling. ULTRASOUND IN MEDICINE & BIOLOGY 2023; 49:1811-1816. [PMID: 37225609 DOI: 10.1016/j.ultrasmedbio.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 05/26/2023]
Abstract
OBJECTIVE The aim of the work described here was to measure the characteristics of viscoelasticity and fluidity in a mouse model of hepatic steatosis and inflammation using a nano-indentation test and the Kelvin-Voigt fractional derivative (KVFD) model and to explore the viscoelasticity and fluidity characteristics in mice with different degrees of hepatic steatosis with inflammation. METHODS Twenty-five ApoE mice were randomly divided into an experimental high-fat diet group (n = 15) and an ordinary-food control group (n = 10), then subdivided into four subgroups based on pathological degree of hepatic steatosis: S0 (normal), S1 (mild), S2 (moderate) and S3 (severe). The 25 liver specimens from these mice were evaluated by a slope-keeping relaxation nano-indentation test. RESULTS Elasticity (E0) was significantly higher in the S3 group than in the S1 and S2 groups, while fluidity (α) and viscosity (τ) were significantly lower in S3 than in S1 and S2 (all p values < 0.05). The following cutoff values for the diagnosis of hepatic steatosis >33% with inflammation were also determined: E0 > 85.01 Pa (area under the curve [AUC]: 0.917, 95% confidence interval [CI]: 0.735-0.989), α ≤ 0.38 (AUC: 0.885, 95% CI: 0.695-0.977),\ and τ ≤ 3.92 (AUC: 0.813, 95% CI: 0.607-0.939). CONCLUSION Increases in the degree of hepatic steatosis with inflammation in mice paralleled gradual increases in the stiffness of the liver and gradual decreases in the fluidity and viscosity of the liver.
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Affiliation(s)
- Yan Song
- Department of Ultrasound, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Wen-Bin Li
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Nimra Saleem
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Gang Tian
- Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Litao Ruan
- Department of Ultrasound, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hongmei Zhang
- Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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Czernuszewicz TJ, Aji AM, Moore CJ, Montgomery SA, Velasco B, Torres G, Anand KS, Johnson KA, Deal AM, Zukić D, McCormick M, Schnabl B, Gallippi CM, Dayton PA, Gessner RC. Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models. Hepatol Commun 2022; 6:1827-1839. [PMID: 35202510 PMCID: PMC9234684 DOI: 10.1002/hep4.1912] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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.
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Affiliation(s)
- Tomasz J Czernuszewicz
- SonoVol, Inc.DurhamNCUSA.,Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
| | | | | | - Stephanie A Montgomery
- Department of Pathology and Laboratory MedicineUniversity of North CarolinaChapel HillNCUSA
| | - Brian Velasco
- Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
| | - Gabriela Torres
- Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
| | - Keerthi S Anand
- Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
| | - Kennita A Johnson
- Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
| | - Allison M Deal
- Biostatistics CoreLineberger Cancer CenterUniversity of North CarolinaChapel HillNCUSA
| | | | | | - Bernd Schnabl
- 19979Department of MedicineUniversity of California San DiegoLa JollaCAUSA.,19979Department of MedicineVA San Diego Healthcare SystemSan DiegoCAUSA
| | - Caterina M Gallippi
- Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
| | - Paul A Dayton
- Joint Department of Biomedical EngineeringUniversity of North Carolina and North Carolina State UniversityChapel HillNCUSA
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Destrempes F, Gesnik M, Chayer B, Roy-Cardinal MH, Olivié D, Giard JM, Sebastiani G, Nguyen BN, Cloutier G, Tang A. Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease. PLoS One 2022; 17:e0262291. [PMID: 35085294 PMCID: PMC8794185 DOI: 10.1371/journal.pone.0262291] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
Objective To develop a quantitative ultrasound (QUS)- and elastography-based model to improve classification of steatosis grade, inflammation grade, and fibrosis stage in patients with chronic liver disease in comparison with shear wave elastography alone, using histopathology as the reference standard. Methods This ancillary study to a prospective institutional review-board approved study included 82 patients with non-alcoholic fatty liver disease, chronic hepatitis B or C virus, or autoimmune hepatitis. Elastography measurements, homodyned K-distribution parametric maps, and total attenuation coefficient slope were recorded. Random forests classification and bootstrapping were used to identify combinations of parameters that provided the highest diagnostic accuracy. Receiver operating characteristic (ROC) curves were computed. Results For classification of steatosis grade S0 vs. S1-3, S0-1 vs. S2-3, S0-2 vs. S3, area under the receiver operating characteristic curve (AUC) were respectively 0.60, 0.63, and 0.62 with elasticity alone, and 0.90, 0.81, and 0.78 with the best tested model combining QUS and elastography features. For classification of inflammation grade A0 vs. A1-3, A0-1 vs. A2-3, A0-2 vs. A3, AUCs were respectively 0.56, 0.62, and 0.64 with elasticity alone, and 0.75, 0.68, and 0.69 with the best model. For classification of liver fibrosis stage F0 vs. F1-4, F0-1 vs. F2-4, F0-2 vs. F3-4, F0-3 vs. F4, AUCs were respectively 0.66, 0.77, 0.72, and 0.74 with elasticity alone, and 0.72, 0.77, 0.77, and 0.75 with the best model. Conclusion Random forest models incorporating QUS and shear wave elastography increased the classification accuracy of liver steatosis, inflammation, and fibrosis when compared to shear wave elastography alone.
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Affiliation(s)
- François Destrempes
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Marc Gesnik
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Boris Chayer
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Marie-Hélène Roy-Cardinal
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Damien Olivié
- Department of Radiology, Radiation oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
- Department of Radiology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
| | - Jeanne-Marie Giard
- Department of Medicine, Division of Hepatology and Liver Transplantation, Université de Montréal, Montréal, Québec, Canada
| | - Giada Sebastiani
- Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre (MUHC), Montréal, Québec, Canada
| | - Bich N. Nguyen
- Department of Pathology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
- Department of Pathology and Cellular Biology, Université de Montréal, Montréal, Québec, Canada
| | - Guy Cloutier
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
- Department of Radiology, Radiation oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
- Institute of Biomedical Engineering, University of Montreal, Montréal, Québec, Canada
- * E-mail: (GC); (AT)
| | - An Tang
- Department of Radiology, Radiation oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
- Department of Radiology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
- Laboratory of Medical Image Analysis, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada
- * E-mail: (GC); (AT)
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Basavarajappa L, Baek J, Reddy S, Song J, Tai H, Rijal G, Parker KJ, Hoyt K. Multiparametric ultrasound imaging for the assessment of normal versus steatotic livers. Sci Rep 2021; 11:2655. [PMID: 33514796 PMCID: PMC7846566 DOI: 10.1038/s41598-021-82153-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 01/15/2021] [Indexed: 12/13/2022] Open
Abstract
Liver disease is increasing in prevalence across the globe. We present here a multiparametric ultrasound (mpUS) imaging approach for assessing nonalcoholic fatty liver disease (NALFD). This study was performed using rats (N = 21) that were fed either a control or methionine and choline deficient (MCD) diet. A mpUS imaging approach that includes H-scan ultrasound (US), shear wave elastography, and contrast-enhanced US measurements were then performed at 0 (baseline), 2, and 6 weeks. Thereafter, animals were euthanized and livers excised for histological processing. A support vector machine (SVM) was used to find a decision plane that classifies normal and fatty liver conditions. In vivo mpUS results from control and MCD diet fed animals reveal that all mpUS measures were different at week 6 (P < 0.05). Principal component analysis (PCA) showed that the H-scan US data contributed the highest percentage to the classification among the mpUS measurements. The SVM resulted in 100% accuracy for classification of normal and high fat livers and 92% accuracy for classification of normal, low fat, and high fat livers. Histology findings found considerable steatosis in the MCD diet fed animals. This study suggests that mpUS examinations have the potential to provide a comprehensive estimation of the main components of early stage NAFLD.
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Affiliation(s)
- Lokesh Basavarajappa
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Jihye Baek
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
| | - Shreya Reddy
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Jane Song
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA
| | - Haowei Tai
- Department of Electrical and Computer Engineering, University of Texas at Dallas, Richardson, TX, USA
| | - Girdhari Rijal
- Department of Medical Laboratory Sciences, Tarleton State University, Forth Worth, TX, USA
| | - Kevin J Parker
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, BSB 13.929, 800 W Campbell Rd, Richardson, TX, 75080, USA. .,Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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6
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Gesnik M, Bhatt M, Roy Cardinal MH, Destrempes F, Allard L, Nguyen BN, Alquier T, Giroux JF, Tang A, Cloutier G. In vivo Ultrafast Quantitative Ultrasound and Shear Wave Elastography Imaging on Farm-Raised Duck Livers during Force Feeding. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:1715-1726. [PMID: 32381381 DOI: 10.1016/j.ultrasmedbio.2020.03.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 02/05/2020] [Accepted: 03/10/2020] [Indexed: 06/11/2023]
Abstract
Shear wave elastography (speed and dispersion), local attenuation coefficient slope and homodyned-K parametric imaging were used for liver steatosis grading. These ultrasound biomarkers rely on physical interactions between shear and compression waves with tissues at both macroscopic and microscopic scales. These techniques were applied in a context not yet studied with ultrasound imaging, that is, monitoring steatosis of force-fed duck livers from pre-force-fed to foie gras stages. Each estimated feature presented a statistically significant trend along the feeding process (p values <10-3). However, whereas a monotonic increase in the shear wave speed was observed along the process, most quantitative ultrasound features exhibited an absolute maximum value halfway through the process. As the liver fat fraction in foie gras is much higher than that seen clinically, we hypothesized that a change in the ultrasound scattering regime is encountered for high-fat fractions, and consequently, care has to be taken when applying ultrasound biomarkers to grading of severe states of steatosis.
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Affiliation(s)
- Marc Gesnik
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada
| | - Manish Bhatt
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada
| | - Marie-Hélène Roy Cardinal
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada
| | - François Destrempes
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada
| | - Louise Allard
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada
| | - Bich N Nguyen
- Service of Pathology, University of Montreal Hospital (CHUM), Montréal, QC, Canada
| | - Thierry Alquier
- CRCHUM and Montreal Diabetes Research Center, Montréal, QC, Canada; Department of Medicine, University of Montreal, Montréal, QC, Canada
| | - Jean-François Giroux
- Department of Biological Sciences, University of Quebec in Montreal, Montréal, QC, Canada
| | - An Tang
- Service of Radiology, University of Montreal Hospital (CHUM), Montréal, QC, Canada; Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Montréal, QC, Canada; Laboratory of Medical Image Analysis, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada; Institute of Biomedical Engineering, University of Montreal, Montréal, QC, Canada
| | - Guy Cloutier
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, QC, Canada; Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Montréal, QC, Canada; Institute of Biomedical Engineering, University of Montreal, Montréal, QC, Canada.
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7
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Lefebvre T, Wartelle-Bladou C, Wong P, Sebastiani G, Giard JM, Castel H, Murphy-Lavallée J, Olivié D, Ilinca A, Sylvestre MP, Gilbert G, Gao ZH, Nguyen BN, Cloutier G, Tang A. Prospective comparison of transient, point shear wave, and magnetic resonance elastography for staging liver fibrosis. Eur Radiol 2019; 29:6477-6488. [PMID: 31278577 DOI: 10.1007/s00330-019-06331-4] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 05/16/2019] [Accepted: 06/13/2019] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To perform head-to-head comparisons of the feasibility and diagnostic performance of transient elastography (TE), point shear-wave elastography (pSWE), and magnetic resonance elastography (MRE). METHODS This prospective, cross-sectional, dual-center imaging study included 100 patients with known or suspected chronic liver disease caused by hepatitis B or C virus, nonalcoholic fatty liver disease, or autoimmune hepatitis identified between 2014 and 2018. Liver stiffness measured with the three elastographic techniques was obtained within 6 weeks of a liver biopsy. Confounding effects of inflammation and steatosis on association between fibrosis and liver stiffness were assessed. Obuchowski scores and AUCs for staging fibrosis were evaluated and the latter were compared using the DeLong method. RESULTS TE, pSWE, and MRE were technically feasible and reliable in 92%, 79%, and 91% subjects, respectively. At univariate analysis, liver stiffness measured by all techniques increased with fibrosis stages and inflammation and decreased with steatosis. For classification of dichotomized fibrosis stages, the AUCs were significantly higher for distinguishing stages F0 vs. ≥ F1 with MRE than with TE (0.88 vs. 0.71; p < 0.05) or pSWE (0.88 vs. 0.73; p < 0.05), and for distinguishing stages ≤ F1 vs. ≥ F2 with MRE than with TE (0.85 vs. 0.75; p < 0.05). TE, pSWE, and MRE Obuchowski scores for staging fibrosis stages were respectively 0.89 (95% CI 0.85-0.93), 0.90 (95% CI 0.85-0.94), and 0.94 (95% CI 0.91-0.96). CONCLUSION MRE provided a higher diagnostic performance than TE and pSWE for staging early stages of liver fibrosis. TRIAL REGISTRATION NCT02044523 KEY POINTS: • The technical failure rate was similar between MRE and US-based elastography techniques. • Liver stiffness measured by MRE and US-based elastography techniques increased with fibrosis stages and inflammation and decreased with steatosis. • MRE provided a diagnostic accuracy higher than US-based elastography techniques for staging of early stages of histology-determined liver fibrosis.
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Affiliation(s)
- Thierry Lefebvre
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada.,Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.,Medical Physics Unit, McGill University, Montreal, Canada
| | - Claire Wartelle-Bladou
- Department of Medicine, Division of Hepatology and Liver Transplantation, Université de Montréal, Montreal, Canada
| | - Philip Wong
- Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre (MUHC), Montreal, Canada
| | - Giada Sebastiani
- Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre (MUHC), Montreal, Canada
| | - Jeanne-Marie Giard
- Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.,Department of Medicine, Division of Hepatology and Liver Transplantation, Université de Montréal, Montreal, Canada
| | - Hélène Castel
- Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.,Department of Medicine, Division of Hepatology and Liver Transplantation, Université de Montréal, Montreal, Canada
| | - Jessica Murphy-Lavallée
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada
| | - Damien Olivié
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada
| | - André Ilinca
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada.,Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada
| | - Marie-Pierre Sylvestre
- Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.,Department of Social and Preventive Medicine, École de santé publique de l'Université de Montréal (ESPUM), Montreal, Canada
| | - Guillaume Gilbert
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada.,MR Clinical Science, Philips Healthcare Canada, Markham, Canada
| | - Zu-Hua Gao
- Department of Pathology, McGill University, Montreal, Canada
| | - Bich N Nguyen
- Service of Pathology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Canada
| | - Guy Cloutier
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada.,Institute of Biomedical Engineering, Université de Montréal, Montreal, Canada.,Laboratory of Biorheology and Medical Ultrasonics (LBUM), Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada
| | - An Tang
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Canada. .,Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada. .,Institute of Biomedical Engineering, Université de Montréal, Montreal, Canada.
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8
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Carbonell G, Berná-Serna JDD, Oltra L, Martínez CM, Garcia-Carrillo N, Guzmán-Aroca F, Salazar FJ, Tudela J, Berná-Mestre JDD. Evaluation of rat liver with ARFI elastography: In vivo and ex vivo study. PLoS One 2019; 14:e0217297. [PMID: 31120974 PMCID: PMC6532896 DOI: 10.1371/journal.pone.0217297] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 05/08/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE The aim of this study was to compare in vivo vs ex vivo liver stiffness in rats with acoustic radiation force impulse (ARFI) elastography using the histological findings as the gold standard. METHODS Eighteen male Wistar rats aged 16-18 months were divided into a control group (n = 6) and obese group (n = 12). Liver stiffness was measured with shear wave velocity (SWV) using the ARFI technique both in vivo and ex vivo. The degree of fibrosis, steatosis and liver inflammation was evaluated in the histological findings. Pearson's correlation coefficient was applied to relate the SWV values to the histological parameters. RESULTS The SWV values acquired in the ex vivo study were significantly lower than those obtained in vivo (P < 0.004). A significantly higher correlation value between the degree of liver fibrosis and the ARFI elastography assessment was observed in the ex vivo study (r = 0.706, P < 0.002), than the in vivo study (r = 0.623, P < 0.05). CONCLUSION Assessment of liver stiffness using ARFI elastography yielded a significant correlation between SWV and liver fibrosis in both the in vivo and ex vivo experiments. We consider that by minimising the influence of possible sources of artefact we could improve the accuracy of the measurements acquired with ARFI.
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Affiliation(s)
- Guillermo Carbonell
- Department of Radiology, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- * E-mail:
| | - Juan de Dios Berná-Serna
- Department of Radiology, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Lidia Oltra
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Department of Physiology, School of Medicine, University of Murcia, Murcia, Spain
| | - Carlos M. Martínez
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Nuria Garcia-Carrillo
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Preclinical Imaging Unit, Laboratory Animal Service, University of Murcia, Murcia, Spain
| | - Florentina Guzmán-Aroca
- Department of Radiology, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
| | - Francisco Javier Salazar
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Department of Physiology, School of Medicine, University of Murcia, Murcia, Spain
| | - José Tudela
- GENZ-Group of Research on Enzymology, Department of Biochemistry and Molecular Biology-A, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, Murcia, Spain
| | - Juan de Dios Berná-Mestre
- Department of Radiology, Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
- Institute of Biomedical Research (IMIB), Virgen de la Arrixaca University Clinical Hospital, University of Murcia, Murcia, Spain
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Tang A, Destrempes F, Kazemirad S, Garcia-Duitama J, Nguyen BN, Cloutier G. Quantitative ultrasound and machine learning for assessment of steatohepatitis in a rat model. Eur Radiol 2018; 29:2175-2184. [PMID: 30560362 DOI: 10.1007/s00330-018-5915-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/29/2018] [Accepted: 11/23/2018] [Indexed: 12/13/2022]
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Parker KJ, Ormachea J, Drage MG, Kim H, Hah Z. The biomechanics of simple steatosis and steatohepatitis. ACTA ACUST UNITED AC 2018; 63:105013. [DOI: 10.1088/1361-6560/aac09a] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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11
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Petitclerc L, Sebastiani G, Gilbert G, Cloutier G, Tang A. Liver fibrosis: Review of current imaging and MRI quantification techniques. J Magn Reson Imaging 2016; 45:1276-1295. [PMID: 27981751 DOI: 10.1002/jmri.25550] [Citation(s) in RCA: 151] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 10/27/2016] [Indexed: 12/13/2022] Open
Abstract
Liver fibrosis is characterized by the accumulation of extracellular matrix proteins such as collagen in the liver interstitial space. All causes of chronic liver disease may lead to fibrosis and cirrhosis. The severity of liver fibrosis influences the decision to treat or the need to monitor hepatic or extrahepatic complications. The traditional reference standard for diagnosis of liver fibrosis is liver biopsy. However, this technique is invasive, associated with a risk of sampling error, and has low patient acceptance. Imaging techniques offer the potential for noninvasive diagnosis, staging, and monitoring of liver fibrosis. Recently, several of these have been implemented on ultrasound (US), computed tomography, or magnetic resonance imaging (MRI). Techniques that assess changes in liver morphology, texture, or perfusion that accompany liver fibrosis have been implemented on all three imaging modalities. Elastography, which measures changes in mechanical properties associated with liver fibrosis-such as strain, stiffness, or viscoelasticity-is available on US and MRI. Some techniques assessing liver shear stiffness have been adopted clinically, whereas others assessing strain or viscoelasticity remain investigational. Further, some techniques are only available on MRI-such as spin-lattice relaxation time in the rotating frame (T1 ρ), diffusion of water molecules, and hepatocellular function based on the uptake of a liver-specific contrast agent-remain investigational in the setting of liver fibrosis staging. In this review, we summarize the key concepts, advantages and limitations, and diagnostic performance of each technique. The use of multiparametric MRI techniques offers the potential for comprehensive assessment of chronic liver disease severity. LEVEL OF EVIDENCE 5 J. MAGN. RESON. IMAGING 2017;45:1276-1295.
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Affiliation(s)
- Léonie Petitclerc
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Quebec, Canada.,Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada
| | - Giada Sebastiani
- Department of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Guillaume Gilbert
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Quebec, Canada.,MR Clinical Science, Philips Healthcare Canada, Markham, Ontario, Canada
| | - Guy Cloutier
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Quebec, Canada.,Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.,Institute of Biomedical Engineering, Université de Montréal, CP 6128, Succursale Centre-ville, Montréal, Québec, Canada.,Laboratory of Biorheology and Medical Ultrasonics, CRCHUM, 900 Saint-Denis, Montréal, Québec, Canada
| | - An Tang
- Department of Radiology, Radio-Oncology and Nuclear Medicine, Université de Montréal, Montreal, Quebec, Canada.,Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.,Institute of Biomedical Engineering, Université de Montréal, CP 6128, Succursale Centre-ville, Montréal, Québec, Canada
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Wang MJ, Ling WW, Wang H, Meng LW, Cai H, Peng B. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl 4-induced liver fibrosis. World J Gastroenterol 2016; 22:10166-10179. [PMID: 28028365 PMCID: PMC5155176 DOI: 10.3748/wjg.v22.i46.10166] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Revised: 09/03/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.
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