The Department would like to recognize Associate Professor Dr. Lauren Burke for serving as Principal Co-Investigator of an industry-sponsored co-investigation ($73.8+K), entitled, “Contrast-Enhanced Ultrasound for Kidney Cancer Subtyping,” awarded in July 2019. Dr. Burke joins Principal Investigator and Assistant Professor of Medicine Dr. Emily Chang as co-investigators of a clinical trial sponsored by Lantheus Medical Imaging, Inc. Over 12 months, they will examine use of novel contrast-enhanced ultrasound (CEUS) methodology to predict kidney mass histologic subtype in kidney cancer diagnosis and staging.

This study expands upon Dr. Chang’s research focus at UNC Kidney Center in studying applications of novel radiologic techniques in imaging for patients with kidney disease. Dr. Burke’s established record in US clinical research reinforces Dr. Chang’s current work in developing novel ultrasound methodologies to more accurately diagnose a range of nephrologic conditions. Improved renal imaging has increased detection of small kidney masses, leading to a rise in kidney cancer incidence. Both investigators are responding to the need to expand beyond exclusive use of contrast-enhanced CT and MRI of kidney masses to diagnose and stage kidney malignancies.

In some cases, there are challenges to using CT/MRI technology for kidney mass imaging –time-elapsed images, decreased sensitivity due to contrast extravasation, and patient contraindications. These shortcomings have limited precise diagnosis and staging in certain patients, challenging management decisions.

By contrast, certain unique capabilities of CEUS – real-time images, dynamic contrast visualization, and purely intravascular contrast agent to detect lesion enhancement – position this methodology as a tool to supplement contrast CT/MRI in kidney mass imaging. Though characterized by poor sensitivity, to date, CEUS has shown excellent sensitivity and specificity in detecting renal malignancies in several small studies.  Significant, first-of-kind results would allow Drs. Burke and Chang to advance clinical trial renal research on novel methodology used in kidney cancer imaging beyond CT/MRI. Dr. Burke contributes the needed US expertise for the co-investigators to examine whether a novel CEUS technique can improve upon certain shortcomings of imaging with CT/MRI for suspected kidney cancer.

Key to this investigation is determining whether 3D CEUS improves upon 2D CEUS, the only approach used to date in CEUS clinical research. To develop the study tool, the co-investigators will adapt a routine 2D CEUS imaging technique to generate three-dimensional (3D) CEUS images of kidney masses.

Over 12 months, Drs. Burke and Chang will apply the novel 3D CEUS technique to produce kidney mass renderings of 40 UNC study subjects with suspected kidney cancer and planned surgical nephrectomy. The FDA-approved Lantheus product used in contrast echocardiography will be used: Definity®, an injectable US ventricular contrast agent that sharpens endocardial delineation in suboptimal echograms. Study subjects will be infused with varying doses of Definity® microbubbles to conduct: 1) low bolus MI imaging with sweeps (undiluted contrast agent); 2) followed by a Flash-Replenishment (F-R) infusion imaging (diluted contrast agent).

Using 3D CEUS-generated metrics from this study, the co-investigators will compare 12-month study subject data on low MI bolus imaging with Flash-Replenishment (F-R) infusion. Accompanied by a review of pathologic examination data, Drs. Burke and Chang aim to determine diagnostic accuracy and histologic subtype and stage predictive capabilities of the two novel CEUS imaging techniques.

Ultimately, the co-investigators seek to address critical gaps in kidney mass diagnosis and staging.

Asst. Professor Dr. Emily Chang – UNC Division of Nephrology & Hypertension

Asst. Professor Dr. Emily Chang – UNC Division of Nephrology & HypertensionChang stated: “It is our hope that advancing 2D to 3D CEUS-generated renderings of kidney mass vasculature will produce deeper pathologic data about mass enhancement that facilitate histologic subtype differentiation. Significant study results will provide new approaches to predicting kidney mass diagnosis and staging, aiding provider guidance in surgical planning and potentially avoiding costly, unnecessary procedures.”

Burke noted: “We are excited to explore new uses for contrast enhanced ultrasound.  We are hopeful that this project may help better delineate renal mass characteristics to have a big impact in the future for the care of these patients.”