Conventional mass spectrometry requires chemical separations, manipulations of samples and containment in a vacuum chamber for ionization and analysis. The DESI technique eliminates these requirements by performing the ionization step directly on surfaces outside of the mass spectrometers, making the process much simpler, faster and more applicable to surgical settings.
The researchers used DESI to evaluate the distribution and amounts of fatty substances called lipids within the brain tissue. A software program the team developed then used the results to characterize the brain tumors and detect boundaries between healthy and cancerous tissue. The researchers identified lipid patterns that corresponded to the different types and grades of cancer and concentrations of tumor cells through earlier studies of banked brain tumor tissue.
Livia Eberlin, who was a graduate student at Purdue at the time of the study and participated in the research, said the team expanded and improved the classification system for brain cancers by adding the meningioma tumor type, prior to the study.
“The classifier includes the two most common types of brain tumors, gliomas and meningiomas, which combined account for about 65 percent of all brain tumors,” said Eberlin, who is now a postdoctoral researcher at Stanford University. “The molecular information that is obtained from this kind of imaging technology allows for an analysis that is much more detailed than what other techniques can offer. We hope that it can one day help the thousands of people affected by brain cancer every year.”
The classification results for brain tumor type in the validation studies of banked tissue agreed with standard pathology methods 100 percent of the time. The researchers found that the results of the mass spectrometry analysis of samples taken from the patients during surgery agreed with pathology with very few exceptions, despite the complexity and heterogeneity of the surgical samples. The composition of samples taken from different regions of an individual tumor can differ and tumor cell concentrations are especially variable, Eberlin said.
The team plans to continue to add to and improve the classification software and to develop a miniature mass spectrometer that could be used during surgery, Cooks said. The team also will continue to examine the molecular patterns of cancerous tissue.
“Ambient ionization mass spectrometry allows us to look directly at unmanipulated tissue, just as a surgeon does, and get simple but extremely valuable molecular information,” Cooks said. “These molecules have a story to tell not just in terms of aiding diagnosis, but also perhaps in terms of prognosis and our understanding of this devastating disease.”
Brigham and Women’s Hospital has set up a mass spectrometer in the AMIGO suite and plans to begin testing the methodology for the detection of brain and breast cancer margins during surgery, Agar said.
In addition to Cooks and Eberlin, co-authors of the paper from Purdue include graduate student Alan Jarmusch. In addition to Agar and Golby, co-authors from Brigham and Women’s Hospital include Isaiah Norton, Daniel Orringer, Ian Dunn, Xiaohui Liu and Jennifer Ide of the Department of Neurosurgery; Keith Ligon and Sandro Santagata of the Department of Pathology; and Ferenc Jolesz of the Department of Radiology.
The National Institutes of Health, James S. McDonnell Foundation, Brain Science Foundation and the Daniel E. Ponton Fund for the Neurosciences, and the Klarman Family Foundation funded this research.
Brigham and Women’s Hospital is a nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. Through investigation and discovery conducted at its Biomedical Research Institute, the hospital is an international leader in basic, clinical and translational research on human diseases.