BIOMED PhD Research Proposal

Title: 
Subharmonic-aided Pressure Estimation (SHAPE) for Portal Hypertension Diagnosis and Management

Speaker:
Hailee Mayer, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisors:
Flemming Forsberg, PhD
Professor
Department of Radiology
Thomas Jefferson University
 
Peter A. Lewin, PhD
Richard B. Beard Distinguished University Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Portal hypertension is characterized by elevated pressures across the portal venous system and early intervention is challenging as patients are typically asymptomatic until later stages of disease. Survival for patients depends on the timing of diagnosis and severity of the complications that arise from the elevated pressures. Further, poor correlation between hepatic histologic findings and a patient’s clinical presentation can lead to further delay in diagnosis. Complications that typically arise from portal hypertension are splenomegaly, esophageal varices, variceal hemorrhage, ascites, hepatic encephalopathy, hepatorenal syndrome and ultimately, death; the risk of hepatocellular carcinoma, which is common in cirrhosis, is also increased by the presence of portal hypertension. The clinical standard for estimating portal pressure is the hepatic venous pressure gradient (HVPG). The HVPG is obtained through a systemic venous access, usually the transjugular vein, utilizing a balloon-tip catheter to gather pressure measurements. An HVPG between 5 and 9 mmHg is considered subclinical portal hypertension, while an HVPG above or equal to 10 constitutes clinically significant portal hypertension (CSPH). The invasiveness of an HVPG measurement does not allow for frequent measurements, which is needed to manage CSPH in an ideal way, as even a small increase in HVPG (on the order of 1-2 mmHg) leads to large increases in the likelihood of complications. Thus, a noninvasive method for estimating this pressure that can be performed routinely is needed.
 
Our group has developed and validated an ultrasound-based method called subharmonic-aided pressure estimation (SHAPE), which relies on the use of ultrasound contrast agents (UCAs). UCAs act as non-linear oscillators that produce significant energy components ranging from subharmonics to ultraharmonics when exposed to high enough acoustic pressures (> 200 kPa). Tissues do not generate significant subharmonic components, making it the optimal component for SHAPE. SHAPE is performed using subharmonic imaging complimented by an acoustic pressure optimization algorithm, to make use of the highest sensitivity to hydrostatic pressure changes in the UCAs. In this project, we will perform SHAPE with two different UCAs, in the same patients, to explore whether any differences exist in their performances (Aim 1), we will also determine SHAPE’s ability to predict complications and evaluate response to treatment (Aims 2 and 3), and finally we will conduct an initial pilot study comparing SHAPE’s ability to screen patient’s for esophageal varices compared to the clinical standard of endoscopic screening (Aim 4). In summary, this work intends to further leverage SHAPE as an effective and ideal noninvasive alternative to invasive measures such as HVPG and endoscopic screening, in the setting of portal hypertension.

The School of Biomedical Engineering, Science and Health Systems is pleased to announce its 7th Annual Immune Modulation & Engineering Symposium (IMES).