February/March 2017

Kassa Darge, MD, PhD, Expands What Ultrasound Contrast Agents Can Do

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The Food and Drug Administration’s latest approval of a contrast agent for use in ultrasonography of the urinary tract in pediatric patients marks the end of an important chapter in the career of Kassa Darge, MD, PhD. A new one, though, has just begun. In December, Dr. Darge was named chair of the Department of Radiology and Radiologist-in-Chief at Children’s Hospital of Philadelphia, following an extensive national search.

For years, Dr. Darge has strived to obtain FDA clearance for new and expanded indications of Lumason (known globally as SonoVue® and manufactured by Bracco Diagnostics), by presenting his research to the agency and increasing awareness among his peers. Even his PhD work focused on contrast agents for intravesical application.

“It’s just amazing,” said a proud Dr. Darge of the FDA’s decision announced in January.

The agent now can be used to evaluate suspected or known vesicoureteral reflux (VUR) in children. VUR is a condition when urine flows up the ureters back toward the kidneys where the urine came from. VUR allows bacteria that may be in the bladder to travel with the refluxing urine to the kidney, which can cause recurrent urinary tract infections and renal damage.

Conventional methods to detect kidney reflux include fluoroscopy and scintigraphy. This FDA approval now gives physicians greater access to a modality that eliminates radiation. In addition, a contrast agent, basically microbubbles significantly smaller than red blood cells (1 mL of suspension of Lumason contains roughly 600 to 800 million microbubbles), improves the echogenicity of a patient’s blood or urine and results in better visualization and assessment.

This particular approval of Lumason “opens the floodgates” for research in other related areas, said Dr. Darge, who served as the pediatric radiology department chair at the University of Wuerzburg in Germany before coming to CHOP in 2007. “More indications need to be studied — each and every one.”

Fortunately, he hasn’t encountered any lack of excitement from fellow researchers looking to collaborate. “I get so many emails now,” he said with a laugh. “It’s so overwhelming.”

To further spread the word of the potential, he will be presenting on ultrasound contrast this year at the meetings of the Society of Pediatric Radiology, American Institute of Ultrasound in Medicine, and the International Contrast Ultrasound Society.

One area of interest for him zeros in on ultrasound contrast and focal lesions of the liver, which signal a possible mass. When conventional ultrasound is performed, physicians see these either as focal “discoloration” of the liver and/or distinct mass.

“Many times, just from the grayscale and Doppler ultrasound images, we cannot tell what these lesions are,” Dr. Darge explained. “When we inject ultrasound contrast agent, we have the opportunity to witness how blood flows in and out of the lesion, if at all. From the pattern of enhancement or no enhancement and washout, we have more information to classify the focal lesion in the liver.”

Similarly, future research will investigate focal lesions in the kidneys, as well as evaluation of the bowel in patients with inflammatory bowel disease, such as Crohn’s disease. Ultrasound contrast will allow for a better depiction of the inflamed bowel to gauge the severity.

“We will be able to decide if it’s fibrotic or just inflamed,” Dr. Darge said.

Another practical application will examine the benefits of ultrasound contrast during hip dislocation surgery, he said. The standard (and lengthy) procedure brings the patient out of the operating room to the magnetic resonance imaging machine (MRI) to check for proper alignment and to confirm blood flow isn’t compromised. Using ultrasound contrast in the operating room streamlines the process for everyone.

“If there is any problem, you can correct it then and there,” Dr. Darge said.

While CHOP leads the charge with ultrasound contrast research, Dr. Darge also heads investigation efforts in several other areas, including ultrasound elastography for evaluation of the liver and spleen. Elastography is a method to assess the mechanical properties of tissue. The spleen’s stiffness has been shown to correlate with the presence and degree of portal hypertension, he said. Further avenues of ultrasound elastography research involve the evaluation of the bladder to see if patients with neurogenic or abnormal bladder function have possible fibrotic change in the bladder wall.

“We also have started to look at the utility of elastography in boys with varicocele with the aim of possibly finding a parameter to help with the decision for surgery and its timing,” Dr. Darge noted.

And with magnetic resonance elastography, he’s systematically evaluating patients born with autosomal recessive polycystic kidney who develop liver fibrosis. Unlike ultrasound, magnetic resonance elastography allows for the evaluation of the whole liver, said Dr. Darge, adding he’s mentoring other research projects that compare the utility of positron emission tomography-MRI to the more established method of positron emission tomography-computed tomography in children.

All this work will continue to add to Dr. Darge’s impressive research portfolio, which encompasses nearly three decades with more than 200 publications and numerous grants. He first gained an interest in radiology while practicing tropical medicine in West Africa. Dr. Darge spent several months collaborating with the University of Heidelberg pediatric radiology department on the utilization of ultrasound to monitor drug effects on filarial worms, a creature that causes onchocerciasis (river blindness). Dr. Darge’s work on the project impressed the chief of radiology, and he offered him a radiology residency soon after.

Now, years later, Dr. Darge still has the same excitement and passion about improving patient outcomes with his research. Dr. Darge is also a professor of Pediatrics and professor of Radiology in Surgery at the Perelman School of Medicine at the University of Pennsylvania.

“I enjoy seeing how such advances facilitate and make easier diagnostic imaging in children,” he said.

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