Piercing the body with precision  pg. 2

“That is why imaging is so powerful,” Yankeelov says. “You can get a more complete description of the tumor status, and you can do it non-invasively.”

That’s the aim of DCE-MRI, a modified MRI technique in which a contrast agent is injected into the patient to outline the profusion of fragile, leaky blood vessels that spring up to feed growing tumors.

Nearly 40 anti-angiogenic drugs, which inhibit the growth of these vessels, are now in clinical trials. Advanced imaging technologies like DCE-MRI, by detecting changes in blood flow and vessel permeability or “leakiness,” for example, may help doctors determine whether the tumor is responding—even after the first course of chemotherapy.

More work needs to be done, however, before DCE-MRI will be ready for the clinic. “I personally think (it) is really just another tool in the toolbox,” Yankeelov adds.

Newer imaging techniques can measure glucose metabolism, hypoxia (lack of oxygen) and the diffusion of water molecules in and out of cells—indicators of how big the tumor is, how “healthy” it is, and whether it is surviving attempts to kill it.

By tracking various markers that have been tagged with a radioisotope, PET also can tell whether a tumor is dying—or proliferating. Similarly, mass spectrometry techniques can detect changes in the expression of various proteins by tumors in response to treatment. Whether these techniques can predict the outcome of therapy and its impact on patient survival remains to be proven clinically.

Another technical challenge: “registering” the different images—mapping coordinates representing the same anatomical point so that the same “voxel,” or three-dimensional piece of data, lines up in each of them.

Fragile, leaky blood vessels nourishing a breast tumor re revealed with the help of dynamic contrast-enhanced MRI.  The red voxels (three-dimensional data points) produce a 3-D volume rendering of blood flow (perfusion) and leakiness (permeability) before treatment (A).
In the same patient after chemotherapy (B), a drastic reduction in perfusion/permeability indicates treatment is successfully "starving" the tumor by disrupting its blood supply.
(C) and (D) are single-slice images taken from the center of the 3-D volume renderings before and after treatment.  The hope is that this kind of analysis will enable doctors to determine early on whether the tumor is responding to therapy.
Courtesy of Tom Yankeelov, Ph.D.

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