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New brain probe traces tumors

By Alannah Phelan

Brain tissue during tumor surgery. The bright pink areas are cancerous tissue.

Performing surgery to remove a brain tumor requires surgeons to walk a very fine line. If they leave tumor tissue behind, the tumor is likely to regrow; if they cut out too much normal tissue, they could cause permanent brain damage.

To improve their ability to differentiate between tumor cells and healthy tissue, surgeons can have patients take an oral dose of the chemical 5-aminolevulinic acid (ALA). An enzyme metabolizes ALA, producing the fluorescent protein protoporphyrin IX (PpIX). Tumor cells have a higher metabolic rate than normal cells, so they accumulate more PpIX—and therefore glow when exposed to blue light.

But this method is often not sensitive enough to highlight brain tumors that are less metabolically active, like low-grade gliomas. To address this problem, M.D.-Ph.D. student Pablo Valdes, Ph.D., and his research mentors—David Roberts, M.D., the chief of neurosurgery at DHMC, and Keith Paulsen, Ph.D., a professor of biomedical engineering at Thayer—used a probe (which they helped develop) that combines violet-blue and white light to simultaneously analyze both the concentration of PpIX and four other tumor biomarkers: PpIX breakdown products, oxygen saturation, hemoglobin concentration, and irregularity of cell shape and size. The probe reads how light travels when it hits the tissue, sends this data to a computer, runs it through an algorithm, and produces a straightforward answer as to whether the tissue is cancerous.

In a pilot study, Roberts operated on 10 patients with gliomas. He used a microscope throughout the surgery to see the fluorescence and used the hand-held probe to evaluate sections of the tissue where the fluorescence was not definitive. After the surgeries were complete, a pathologist evaluated how accurately the probe had identified tumor tissue.

The results, published in the Journal of Biomedical Optics, are striking. Diagnoses based on only fluorescence had an accuracy of 64%. But when Roberts used the probe as well, the accuracy increased to 94%, meaning that Roberts was much more successful in differentiating between tumor tissue and normal tissue. Although the study was small, it introduces a promising method to help surgeons remove only what they want and nothing more.


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Geisel School of Medicine at DartmouthDartmouth-Hitchcock Medical CenterWhite River Junction VAMCNorris Cotton Cancer CenterDartmouth College