Due to limitations of liver biopsy, there is a great need for noninvasive liver fibrosis staging. Ultrasound elastography has shown great promise for noninvasive liver fibrosis staging and may have higher clinical impact than Magnetic Resonance Elastography (MRE) due to its high accessibility and low cost. However, commercial elastography methods based on ultrasound radiation force have high failure rate in obese patients. This is a serious limitation considering the obesity prevalence in the U.S. general population (35.7%) and the increasing number of nonalcoholic steatohepatitis patients who are in need of liver fibrosis staging and are commonly obese. In this project, we will develop and validate a novel ultrasound imaging technology called Random External Vibration Ultrasound Elastography (REVUE) with superior penetration for liver fibrosis staging. REVUE uses external mechanical vibration to produce shear waves that penetrate throughout the liver. Advanced processing algorithms are employed to decompose the complex wave field into simpler unidirectional wave fields for reconstruction of large field-of-view quantitative elastography. The study has 3 aims.
Aim 1 : Implement and Advance REVUE on a traditional ultrasound scanner. We will implement REVUE on a traditional clinical scanner and investigate advanced shear wave generation, detection (by harmonic imaging and coded excitation), and processing methods to facilitate convenient clinical usage and reliable performance in obese patients. We will extend REVUE to 3D imaging for more accurate and comprehensive evaluation of the liver.
Aim 1 includes phantom and preliminary human studies to validate the technologies developed.
Aim 2 : Repeatability and reproducibility study. We will use REVUE prototyped in Aim 1 to study 45 MRE patients. Each patient will have 3 REVUE imaging sessions: each session has 3 independent scans performed by 3 sonographers (a total of 9 scans). The first two sessions will be separated by a 10-minute break and the third performed on a different day. Intraclass correlation coefficients (ICC) will used to evaluate the test-retest repeatability and inter-rater agreement. The overall measurement variance will also be estimated for REVUE.
Aim 3 : In Vivo comparison with MRE. We will use REVUE to study 220 patients and compare results with those of MRE and a state-of-art ultrasound elastography machine (Aixplorer(r)). Data analysis includes measurement success rate, correlation with MRE results, and ROC (receiver operating characteristic) evaluation of performance for separating patients with minimum fibrosis (MRE = 2.9kPa) and patients with advanced fibrosis (MRE = 5.0kPa). Successful completion of this project will lead to a fast and low-cost ultrasound elastography method with deep penetration that meets the vital need for liver fibrosis staging in obese patients. The use of a traditional clinical ultrasound scanner in this proposal provides a clear path to clinical implementation of this technology.

Public Health Relevance

Measurement of liver stiffness by ultrasound can be used as a non-invasive alternative of liver biopsy to stage liver fibrosis, a condition afflicting hundredsof millions of patients worldwide and 900,000 Americans. Current ultrasound measurements of liver stiffness have very high failure rate in obese patients (about 36% of adults in USA are obese). In this study, we will develop and test a new ultrasound technology for liver fibrosis staging that has high measurement success rate in obese patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Burgess-Beusse, Bonnie L
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Mayo Clinic, Rochester
United States
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