Oncology poised to gain from perfusion studies

Stroke is typically the headline application in all discussions of perfusion CT. Now interest in this technique is growing from a very different direction: oncology imaging.

The development of anti-angiogenic cancer drugs has highlighted the importance of vascularity to cancer imaging specialists. While radiologists have traditionally used a lesion's size to monitor treatment, it can take several weeks for changes in size to indicate the effect of therapy. For patients receiving anti- angiogenic drugs, the health of a tumor's microvessel network may be a much better indicator of outcome. This same marker could also be used to evaluate the efficacy of new drugs during the development process.

"It has been shown that by measuring the perfusion of tissue, the effectiveness of an anti-angiogenic therapy can be determined in advance of ever seeing any change in tumor size," said Dr. Geoffrey Rubin, chief of cardiovascular imaging at Stanford University in Palo Alto, California.

Advances in CT technology are bringing this potential application closer to clinical practice. The rapid scan times and high resolution delivered by state-of-the-art CT systems are making it possible to quantify tumor perfusion, said Dr. Elliot Fishman, director of diagnostic imaging and body CT at Johns Hopkins University Hospital in Baltimore, Maryland.

"We have the ability to look at tumors in certain organs-for example, the liver or kidney-and determine the degree of angiogenesis based on the degree of vascularity," he said.

Radiologists at the University Medical Center Mannheim, part of the University of Heidelberg in Germany, are investigating a method of acquiring perfusion data based on dual-source energy-dependent imaging. In conventional perfusion CT studies, patients undergo dynamic contrast-enhanced CT. With this alternative technique, patients are scanned just once, as they would be for tumor staging, but with the two x-ray tubes operating at different energy levels. The data can then be reconstructed to selectively show the iodine content in the tissue and the tumor (Figure 1).

"Theoretically, conventional dynamic CT is more precise because it allows absolute quantification of perfusion. With dual energy, we are doing nondynamic or static imaging of the iodine content," said Dr. Christian Fink, head of CT. "The advantage of dual-energy CT is that the technique is less complicated and the radiation dose is much lower.

Based on our preliminary experience, we believe that iodine content is a good surrogate for tissue perfusion."

All postprocessing steps are handled by dedicated software on the dual-source scanner. The resulting images are color-coded to show the presence of iodine.

"With dynamic CT imaging, you usually have to define a region of interest in the arterial input; for example, in the blood supply vessel and the tumor. With dual-energy tumor perfusion imaging, you don't have to do this. There is no complicated analysis," Fink said.

The technique is being performed on all oncology patients who are undergoing anti-angiogenic drug treatment at the Mannheim center. Its use should be considered part of a scientific study at present, though it could become a "very interesting application" in the future, Fink said.

Radiologists at University Hospital Grosshadern in Munich are also examining the potential of energy-dependent imaging with dual-source CT for cancer therapy monitoring (Figure 2). Investigations are at an early stage, said Dr. Konstantin Nikolaou, associate chair of radiology and section chief of CT. The technique is undergoing trials in the first instance on patients with gastrointestinal stroma tumors. These tumors are typically hypervascularized and often associated with liver metastases.

The team has access to a work-in-progress 128-slice adaptive imaging CT system that has been designed specifically with perfusion studies in mind. This scanner could provide radiologists with truly time-resolved perfusion data, showing contrast flow in and out of the tumor, Nikolaou said.

He predicts that interest in functional imaging will continue to grow in oncology and regards perfusion CT as "perfect" for monitoring anti-angiogenic drugs. The speed with which response can be evaluated may allow patients to stop treatment at an earlier stage or switch sooner to a more appropriate or effective therapy regimen.

"With anti-angiogenic therapies, you don't want to wait eight weeks and measure the size of the tumor, which maybe won't even change," Nikolaou said. "If you look at perfusion or dual-energy imaging of the iodine content, you may look at treatment response within, say, 10 or 15 days. This saves money and time for the patient and the hospital."