Virtual Biopsy with Ultrasound for Liver Fibrosis Staging

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DESCRIPTION (provided by applicant): Liver fibrosis/cirrhosis afflicts hundreds of millions of patients worldwide and 900,000 Americans. Liver biopsy, currently the gold standard for the diagnosis of liver fibrosis, is invasive and may occasionally cause significant complications, which limits the screening of at-risk populations, treatment monitoring, and follow-up. Current serum markers and classic medical imaging such as ultrasound, CT, or MRI do not have sufficient sensitivity/specificity for fibrosis evaluation. Recent studies show that tissue elasticity (i.e. stiffness) may be used for liver fibrosis staging. Herein we propose a novel ultrasound method, Shearwave Ultrasound Dispersion Vibrometry (SDUV), for noninvasive, biopsy-like quantification of elasticity as well as viscosity for liver fibrosis staging. Method: SDUV uses an ultrasound "push" beam within FDA safety limits to stimulate formation of propagating harmonic shear waves in the studied tissue. The propagation speed of induced shear waves is frequency dependent (dispersive) and relates to the tissue's mechanical properties. Shear wave speeds at multiple frequencies (typically hundreds of Hertz) are measured by a separate ultrasound "detect" beam in pulse echo mode and fit with a theoretical dispersion model to inversely solve for tissue elasticity and viscosity. Preliminary studies in tissue-mimicking phantom and striated muscle are very promising. A special pulse sequence has been developed to facilitate a single ultrasound array transducer for both push and detect function, which makes SDUV compatible with current ultrasound scanners. Feasibility of this pulse sequence has been validated with in vivo measurements in normal porcine liver using in-house instrumentation. Aims: 1. Implement SDUV on a commercial ultrasound scanner. 2. Calibrate and optimize the prototype with phantom, in vitro tissue, and in vivo animal experiments. 3. Conduct a clinical research on patients with suspected hepatic fibrosis who are scheduled to have a clinically indicated liver biopsy. Successful completion of this project should result in a new clinical technique, SDUV for noninvasive, fast, economical, and reliable "virtual biopsy" for fibrosis staging. PUBLIC HEALTH RELEVANCE: Successful completion of this project should result in a new ultrasound technique for safe, fast, economical, and reliable staging of liver fibrosis/cirrhosis, which afflicts hundreds of millions of patients worldwide and 900,000 Americans. This technique can be used as a noninvasive alternative to liver biopsy for the screening of at-risk populations, treatment monitoring, and follow-up of patients with chronic liver diseases.