Shining a light on brain tumors
Llewellyn “Trey” Jalbert knows what cancer looks like up close. Before applying to be a Ph.D. candidate in the Joint UC Berkeley/UCSF Graduate Program in Bioengineering, he had spent two years as a research associate examining MRI images of patients with malignant brain tumors in the UCSF lab of Professor Sarah Nelson. Then, Jalbert himself was diagnosed with cancer—a malignant melanoma—and underwent surgery.
“It felt very surreal and scary, because when melanoma does metastasize, it often goes to the brain and the spinal cord—all the places that I had been imaging,” Jalbert says. “It connected things on a very intimate and personal level—all of a sudden, I was the one on the table getting the MRI.” After successful treatment, Jalbert is now engaged in a study funded by the National Institutes of Health to develop new imaging techniques for patients with highly aggressive cancer tumors in the brain, called gliomas.
Employing powerful electromagnets in a non-invasive technique called magnetic resonance spectroscopy (MRS), Jalbert maps the brains of patients with malignant brain tumors to detect chemical clues. “When you shine light in the brain, you get a diversity of signals back,” says Jalbert. “These spectral signals correspond with specific chemicals or metabolites that are present in cells. This information can be used by clinicians to diagnose and monitor patients.”
“We want to provide non-invasive biomarkers to aid oncologists in selecting the therapy that is personalized to the patient,” says Sarah Nelson, now Jalbert’s graduate advisor and a professor of bioengineering at UC Berkeley and UCSF. “We are trying to move into the future and use genomic methods in combination with cutting-edge imaging.”
For example, surgeons typically take biopsies of brain tissue to determine its genetic makeup and how far the tumor has advanced. But gliomas are an unruly mess of different types of cells, and if the wrong section is sampled, it may not show a true picture of the tumor.
“If we can provide a map to the surgeon,” says Nelson, “then they can take tissue from those areas where the tumor is most likely to be malignant.”
In a recent study published in Science Translational Medicine, Jalbert and his lab mates acquired spectra of 104 tissue samples from the brains of 52 patients, looking for a rare chemical: a metabolite called 2-hydroxyglutarate, or 2HG. Jalbert and his colleagues found a strong link between the detection of 2HG and the presence of the mutations associated with improved outcome. Patients who possess gliomas with this mutation respond better to certain chemotherapies and can live five to seven times longer than those without it.
Based on this relationship, 2HG could be used as a non-invasive biomarker for gliomas as well as for other cancers that share this mutation, including colorectal cancer, prostate cancer and acute myeloid leukemia. This potentially could save some patients the risk and pain of additional surgeries. Now Nelson’s lab is repeating similar experiments in tissue samples and in patients.
As an undergraduate at Berkeley, Jalbert studied astrophysics. “Coincidentally, I was using spectroscopy to look at the composition of stars and galaxies,” he says. “I never expected to be using those same techniques on actual human beings!” As he uses the spectroscopy and image analysis methods he learned in astrophysics to visualize cancer, Jalbert enjoys the multidisciplinary nature of bioengineering. “There is a lot of advanced physics involved in medical imaging,” Jalbert says. “Thankfully, galaxy clusters and neurons look a lot alike.”