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MRI Gives Early Lead On Tumor Response To Treatment

Cancer patients who now endure months of treatment -- and then weeks of anxious waiting to see if it worked -- may soon get word of their tumors' response within days of starting therapy, thanks to a new use for a widely available MRI technique.

In the first study of its kind, researchers from the University of Michigan Comprehensive Cancer Center are reporting success in analyzing diffusion MRI images to distinguish between dead and living brain tumor cells in both animals and humans.

They report that the imaging technique, which tracks the movement of water through and between cells, allowed them to assess the effect of therapy on the cancer without relying on measurable changes in tumor size.

Published in the Dec. 20 issue of the Journal of the National Cancer Institute, the early finding has the potential to dramatically change the way physicians plan and track the effectiveness of the cancer therapies they prescribe. It could spare patients the physical side effects of weeks of unsuccessful treatment, and the psychological effects of then waiting a month or more for an MRI scan to show if they're responding. And, it could aid in testing new anti-cancer agents.

"One of the biggest problems in dealing with many solid cancers is measuring their response to treatment in a timely way," says corresponding author Brian Ross, Ph.D. "Diffusion MRI seems to provide a way to gauge that response faster, and could individualize the clinical management of each patient."

Ross is an associate professor of radiology and biological chemistry and co-director -- with associate professor of radiation oncology and co-author Alnawaz Rehemtullah, Ph.D. -- of the U-M Health System's Center for Molecular Imaging.

Already widely in use to diagnose strokes, diffusion MRI can be done using nearly any closed MRI scanner and adds just a few minutes to a regular scan, says lead author and UMHS physicist Thomas Chenevert, Ph.D. The new study looks at brain tumors, but the U-M team has already shown the technique is useful in other solid cancers in animals and humans.

The researchers stress that the technique has not been, and is not yet ready to be, used in any cancer patient's actual treatment planning. To learn more about its worth, they're working with colleagues elsewhere on further studies of the approach. They're also continuing to test it at the U-M, and are planning a multi-center clinical trial for late 2001.

MRI, which stands for magnetic resonance imaging, makes images of the body's inner structure using a strong magnetic field that aligns the body's water molecules. Since water makes up the bulk of every kind of tissue, the images reflect the differences among various tissues' water content and density. So, for example, bone and muscle show up in different shades of gray.

MRI is now one of the most common forms of medical imaging technology, used to help study patients' anatomy and diagnose disease. It's also routinely used before and after cancer treatment, to aid physicians in measuring the size of tumors and assessing a patient's progress.

But even though cancer treatments such as chemotherapy or radiation kill tumor cells immediately, it can often be weeks before the body absorbs enough of the dead cells to produce a change in tumor size that's visible on an MRI scan. Meanwhile, the rest of the tumor may keep growing. If the tumor isn't responding at all, the delay wastes time that could be spent on other treatment.

The U-M team's approach seeks a more rapid answer using the extra information provided by diffusion MRI, which takes the concept of tracking water molecules a step further. Diffusion MRI can assess how easily water is moving across microscopic distances -- a continuous process called diffusion. Healthy cells have unbroken outer membranes that slow water's movement, but the membranes around dying or dead cells break down, allowing water to diffuse freely.

MRI machines can be programmed to be sensitive to the ease of this water movement in different areas of tissue. The use of diffusion MRI in stroke, for example, gives doctors a rapid view of brain regions where blood flow is cut off by a blood hemorrhage or clot.

The U-M post-scan processing technique takes the information from a diffusion MRI scan and analyzes it to give a measure of cells' membrane integrity throughout and near a tumor. It uses a measurement called the apparent diffusion coefficient, or ADC.

The new study compared scans taken before and after the animals and humans were treated for their brain tumors. Brain tumors, some of the hardest cancers to treat, cause 26 percent of childhood cancer deaths and 2 percent of adult cancer deaths.

The animal study looked at 16 rats with induced tumors treated with a range of doses of the chemotherapy drug BCNU. They had MRIs before treatment and every other day following treatment. Diffusion increased in the first week, even as tumor size actually grew. On the eighth day, ADC peaked. Soon after, the tumors began to regress, though they later grew back from surviving cells. The magnitude and length of the diffusion response increased with dose.

The two early human patients -- a 13-year-old girl and a 37-year-old man -- agreed to let the researchers analyze the conventional and diffusion MRI scans they received before, during and after treatment. Both had surgery and chemotherapy preceded or followed by radiation therapy.

The girl's tumor stopped growing but did not shrink appreciably following initial radiation treatment. It began growing again almost a year later. Early on in treatment, diffusion increased slightly during several months of therapy. Around the time when the tumor began growing again, the ADC went down dramatically, corresponding to an increase in the number of intact cell membranes.

The man's tumor responded better, and at six weeks after treatment began, the ADC peaked, going up by 86 percent. Over time, his tumor shrank to about half its original size.

The research was sponsored in part by the Charles A. Dana Foundation, the National Cancer Institute and the U-M Clinical Research Partnership Fund. - By Kara Gavin

[Contact: Kara Gavin, Valerie Gliem ]


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