Philadelphia University + Thomas Jefferson University

CEUS Projects

Pressure measurement is an effective, low-risk way of assessing the heath of an organ, and is especially useful in the heart and liver for assessing the risk of cardiac disease and portal hypertension, respectively. Typically, this is done by inserting a catheter into an incision in a patient’s thigh and then passing the catheter through an artery all the way to the heart or liver.

However, Jefferson researchers have devised a way to use CEUS to take measurements with nothing more invasive than the standard microbubble injection. After the bubbles have entered the bloodstream, physicians wait briefly to let the bubbles circulate, while an ultrasound beam is directed at either the heart or liver. As the bubbles pass through the beam, they expand and contract in a predictable way in response to the sonic field. These expansions and contractions are modulated by the pressure in the organ—greater expansion means less pressure, while less expansion often indicates greater organ pressure and an increased likelihood of disease.

Contact: Flemming Forsberg, PhD; Jaydev Dave, PhD

Many solid tumors are now being treated using minimally invasive techniques. Liver tumors can be treated via chemoembolization, the standard of care for patients with locally advanced hepatocellular carcinoma. This therapy involves depositing chemo-eluting beads into the blood vessels that feed the tumor or liver lesion in order to provide treatment as directly as possible. The impact is usually measured after 4-6 weeks using contrast-enhanced MRI. Similarly, renal cell cancers are now routinely treated by ablating the tumor using either heat or freezing techniques.

CEUS provides an easy and minimally invasive means of assessing the outcome of these procedures. The physical properties of the bubbles make them ideal for highlighting blood vessels and the structures they supply. Because it does not require any form of radioactivity, it is possible to provide imaging follow-up as frequently as every day should it ever be deemed clinically necessary. Additionally, the microbubbles are not hazardous to patients with decreased kidney function, making them a safer alternative to MRI or CT follow-up. More advanced work is also being done on the use of real time volumetric, or 4D, CEUS to better evaluate such patients.

Contact: John Eisenbrey, PhD; Collette Shaw, MD; Andrej Lyshchik, MD, PhD

When a cancer metastasizes, it can spread through the lymphatic system. A sentinel lymph node is the node whose proximity to a malignant area makes it most likely to first come into contact with potential cancer metastases. The ability to assess the state of sentinel lymph nodes gives physicians’ vital information about potentially spreading malignancies.

The standard diagnostic method involves using dye or radioisotopes to observe the flow of lymph channels away from an area of clinical concern. However, these approaches require hours of preparation before a biopsy is performed, while physicians have only a narrow window to observe the relevant structures before the dye or isotope has spread too far.

Our researchers have devised a novel technique enabling them to use microbubble contrast to survey the lymph nodes in animal models. CEUS allows for a greater window of observation without the wait time of other biopsy methods. It also allows physicians to obtain detailed anatomical information without the open surgery required by the dye method. Additionally, our investigators have found that contrast bubbles are more stable in the body, which extends the time a study can be carried out and ultimately allows physicians to obtain better results.

Contact: Flemming Forsberg, PhD; Ji-Bin Liu, MD

The appearance of prostate cancer on ultrasound imaging is similar to that of the normal tissue, potentially complicating the kind of precision-imaging that makes minimally invasive intervention possible. CEUS enables physicians to get a clear picture of the prostate, and to clearly distinguish malignancies from benign or “normal” structures.

Contact: Ethan Halpern, MD

Therapeutic Applications

In addition to enhancing the diagnostic capabilities of ultrasound, Jefferson researchers are pioneering new ways of using the microbubbles to treat cancer and infection. See below for studies that are currently underway.

Tumors are often highly resistant to the effects of radiation therapy due to the fact that the tumor microenvironment is low in oxygen (hypoxic). However, it has been shown that even slight increases in the presence of oxygen can go a long way to sensitizing tumors to the effects of radiation.

In light of this, our ultrasound researchers have devised a specially-designed microbubble that contains therapeutic amounts of oxygen. These can be injected and allowed to circulate in the microenvironment before being burst with a high-intensity ultrasound beam. This releases the oxygen contained in the bubbles, oxygenating the tumor to target levels and enabling radiation to be administered more effectively.

Contact: John Eisenbrey, PhD; Patrick O’Kane, MD

Pancreatic cancer is the third most common cancer diagnosed in the United States, with more than 53,000 new cases in 2016. It is the fourth leading cause of cancer-related death in both men and women. Despite its prevalence, there has been no significant improvement in survival for pancreatic ductal adenocarcinoma (PDAC) patients over the past 30+ years.

However, our researchers are now the first in North America to use microbubbles to enhance the delivery of chemotherapy. Similar to work done by Drs. Eisenbrey and O’Kane, this study investigates the effects of bursting microbubbles in the vasculature of the tumor microenvironment. The force from the destruction of the bubbles weakens the blood-vessels surrounding tumors and making them more permeable to therapeutics. The main focus of this work is a five year, NCI-funded, multi-center clinical trial conducted by TJU and our Norwegian partners enrolling 120 patients with metastatic or locally advanced and surgically unresectable PDAC.

Contact: Flemming Forsberg, PhD