Diffusion maps of bone mets indicate therapy response

Diffusion-weighted MR of the bone may indicate within days whether and how well patients with metastatic cancer of the bone are responding to treatment. The software to support such conclusions is now being developed for commercial release later this year by Cedara Software.

"We believe it could be a breakthrough for the individualization of patient treatment response," said Brian D. Ross, Ph.D., codirector of the molecular imaging program at the University of Michigan Comprehensive Cancer Center and a professor of radiology and biological chemistry at UM.

Although the means for doing such analyses may soon be available, its practical application may still be a ways off. The software has been validated only in preclinical research. Until the value of this technique can be proven to the satisfaction of third-party payers, the MR scans needed for this software to indicate whether a patient is responding to treatment will not be reimbursed.

Toward this end, clinical studies are scheduled to begin at UM this spring. There is already good reason to believe, however, that this technique, called functional diffusion mapping, will spur the scans to be done in the future.

The UM researchers have shown that functional diffusion mapping can identify brain tumor patients who are responding to chemotherapy or radiation after only three weeks of treatment, more than two months earlier than traditional tests. The preclinical tests on mice show that diffusion mapping of bone may allow such an assessment to be made even sooner for patients with metastatic cancer of the bone. Such a test would fill an enormous gap in patient management.

"Currently, we have no way of detecting bone tumor response to therapy," Ross said. "The magnitude of this problem is huge; as many as 500,000 people in the U.S. have metastatic breast or prostate cancer to the bone."

Ross and Alnawaz Rehemtulla, Ph.D., a professor of radiation oncology and environmental health sciences at UM, have founded a company in Ann Arbor called ImBio, which has licensed the commercialization rights of the diffusion technique from the university. Their software, which tracks the movement of water in bone, runs on Cedara Software's I-Response workstation, which is being developed by the Merge Healthcare subsidiary specifically to foster collaboration between radiologists and radiation oncologists.

"For this to be readily translatable and easily usable within the medical community, there had to be a standardization of the software," Ross said. "So we partnered with Cedara Software to develop a turnkey package-a workstation solution-for functional diffusion mapping analysis of tumors."

The UM researchers used I-Response in their preclinical studies, which tracked bone water diffusion during the course of the animals' chemotherapy. Because living tumor cells slow the movement of water, the death of these cells is accompanied by an increase in water diffusion. An increase in diffusion indicates effectiveness of the treatment in this animal model of prostate cancer metastasis.

Using functional diffusion mapping, the researchers identified a statistically significant change in diffusion as early as seven days after the start of treatment. At the end of the study, they removed the tumors and found the functional diffusion map had predicted the tumors' response to treatment.

"Not only is the diffusion approach translatable from rodent to man because it is a similar MRI acquisition sequence, but the analysis of that data is also very translatable," Ross said.

These kinds of analyses need not focus only on the bone or even the brain, he said. Virtually any tumor in the body could be mapped with MR diffusion as an indicator of response to therapy. In upcoming clinical trials, Ross hopes to compare traditional outcome measurements with functional diffusion mapping analyses and actual patients' survival. If results are positive, functional diffusion mapping could have a major impact on the management of patients and healthcare costs.

"Patients wouldn't have to endure a month of ineffective and extensive treatments if they are found not to be responding early on," he said. "With treatments costing $500 to $1000 a day, this technique would pay for itself very quickly."