This study evaluated quantitative ultrasound features for assessing hepatic fibrosis in a rat model of cirrhosis induced by diethylnitrosamine (DEN). Rats received DEN (n=12) or served as controls (n=4). Ultrasound images were analyzed for echo-intensity and heterogeneity at 0, 10, and 13 weeks. Both features increased significantly with time in DEN rats compared to controls. Histological analysis found DEN rats developed METAVIR grades F2-F4 fibrosis while controls were F0. Echo-intensity and heterogeneity correlated strongly with METAVIR grade. Ultrasound could non-invasively track fibrotic changes and distinguish fibrosis grades, suggesting potential for assessing liver fibrosis.
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Monitoring liver fibrosis with quantitaive B-Mode ultrasound
1. Quantitative Assessment of
Diethylnitrosamine-induced Hepatic Fibrosis
by
Non-Invasive Ultrasound
Laith R Sultan MD, Julia C DSouza BSE, Susan M Schultz RDMS, Tong Wu PhD,
Terrence Gade MD PhD,Sean D Carlin PhD, Stephen J Hunt MD PhD,
Chandra M Sehgal PhD
3. Cirrhosis: Diagnosis
Cirrhosis and liver disease represent
the 12th leading cause of death
overall, and 5th leading cause of
death for 45 - 54 year olds in US
Liver biopsy is the gold standard for
assessing fibrosis and cirrhosis
Shortcomings of liver biopsy:
Invasive
Sampling error:
Complications
4. Objective
To evaluate fibrotic changes in a preclinical model using
B-mode ultrasound
Approach:
Quantitative, computer-extracted features
Diethylnitrosamine (DEN)-induced rat model
6. Materials & Methods
Image and Statistical Analysis
Sampling: 6 image acquisitions throughout liver
4 - 6 ROIs/image
Echo-intensity = mean brightness of ROIs
Heterogeneity = variance of 1st order histogram
Intragroup (temporal progression): ANOVA with
subsequent t-tests between three timepoints
Intergroup (DEN vs control): Two-sided t-tests
at each timepoint
7. Preparation of H&E and trichrome stains
METAVIR grading by veterinary pathologist
Spearman correlation between sonographic
parameters and METAVIR score
Materials & Methods
Pathologic Validation
10. DEN rats: METAVIR grades F2-F4
Control rats: F0
F3 F4F2
Results
Histology
11. Results
Correlation of 13w sonographic data with METAVIR
score
Echointensity vs. Fibrosis grade Heterogeneity vs. Fibrosis grade
Rho = 0.8242
p = 0.0003
Rho = 0.8287
p = 0.0002
12. Different grades of fibrosis show separate populations based on echointensity and heterogeneity
Results
Population grouping of METAVIR grades by sonographic measures
F
4
F
0
F
2
F
3
13. Limitations
Limited data for intermediate stages of fibrosis Image
and sacrifice at earlier time points
Similarities in characterization of F2/F3 lesions
Further characterization with additional computerized
features
14. Conclusion
B-mode US tracks fibrotic changes in a rat model.
Sonographic features correlate to histology.
Potential role for B-mode US for the non-invasive
measurement of liver fibrosis.
15. Future Directions
Preclinical correlation of sonographic features to HCC
development
Rat model comparison to fibroscan results
Comparison of biopsy-proven METAVIR fibrosis scoring with
clinical ultrasound measurements
#4: The most common serious complication of liver biopsy is intraperitoneal hemorrhage, although hematoma and hemobilia can also occur. Other potential complications of liver biopsy include right upper abdominal pain, right shoulder pain, bile peritonitis or pneumothorax.
lobar difference between METAVIR grades in up to 24.2% of cases1
#7:
Intragroup (temporal progression): ANOVA
Intergroup (DEN vs control): Two-sided t-tests at each timepoint
#8: Collaboration with colleagues in the vet school certified veterinary pathologist blinded to the imaging results graded the histology
#9: Echo-intensity:
Mean liver echo-intensity increased from 42.9 at baseline to 56.4 at 10 weeks (p = 0.0013) reaching the level of 59.9 at 13 weeks (p = 0.0002) from DEN starting time.
#10: Echo-intensity:
Mean liver echo-intensity increased from 42.9 at baseline to 56.4 at 10 weeks (p = 0.0013) reaching the level of 59.9 at 13 weeks (p = 0.0002) from DEN starting time.
#14: Have an animal model that is useful for studying fibrosis US can be used to track changes
Quantitative texturized computer analysis captures the fibrotic changes in an animal model
#15: Have an animal model that is useful for studying fibrosis US can be used to track changes
Quantitative texturized computer analysis captures the fibrotic changes in an animal model
#16: Have an animal model that is useful for studying fibrosis US can be used to track changes
Quantitative texturized computer analysis captures the fibrotic changes in an animal model