New Imaging System Seeks to Aid in Imaging Brain Gliomas

Researchers funded by the National Institute of Biomedical Imaging and Bioengineering have developed an imaging system that rapidly and accurately detects a molecular marker found in brain gliomas. The imaging system may improve the precision of difficult brain gliomas surgeries by enabling complete tumor removal, while reducing residual damage to brain tissue and neural function.

R. Graham Cooks, PhD, at Purdue University, developed the imaging system, known as desorption electrospray ionization mass spectrometry (DESI MS), and the brain study was done with collaborators at Harvard Medical School and Dana Farber Cancer Institute. The group described their work in the July 29 issue of the Proceedings of the National Academy of Science. Researchers hope that DESI MS will be a significant improvement over the current method of distinguishing brain tumor tissue from healthy tissue, which relies on a lengthy and difficult procedure for surgeons and patients.

Current protocol calls for the use of frozen section pathology, which involves removing suspected tumor tissue and having it analyzed by pathologists. The freezing and staining method, developed more than 150 years ago, takes about 20 minutes and is too slow to be repeated multiple times during surgery.

The new technique solves some of the current method’s problems. Researchers use mass spectrometry to identify metabolites that are present only in brain tumors. As surgery progresses, tissue samples are removed and sprayed with a charged liquid that splashes onto the surface of the tissue, lifting off droplets; the droplets are then sucked into a mass spectrometer, where the mass and charge of the metabolites are measured. Brain gliomas produce large amounts of a tumor metabolite, 2-hydroxyglutarate (2-HG), which is captured in the droplets. This very rapid, objective method allows for clear delineation of tumor vs nontumor tissue, so surgeons can remove all, and only, tumor tissue.

The DESI MS system was first tested on glioma specimens from 35 patients. Of the 35 samples, 21 contained high levels of 2-HG, a product of the mutant form of a gene known as IDH, which is associated with tumor formation. The results clearly demonstrated that DESI MS can detect 2-HG in tumor tissue with very high sensitivity and specificity.

The researchers tested the system in an operating room by installing a complete DESI MS system in the Advanced Multimodality Image Guided Operating suite at the National Center for Image-Guided Therapy at Brigham and Women’s Hospital. The surgical suite is an operating room with built-in imaging devices such as MRI, so the surgeon can use it to map the tumor preoperatively. Tissue sections from tumors from two patients were examined using DESI MS. In both cases, the postoperative analysis confirmed that intraoperative DESI MS had accurately detected the presence of 2-HG in each tumor.

The researchers chose detection of 2-HG to test the DESI MS system because about 80% of gliomas and glioblastomas are associated with mutations in the IDH gene, which results in high levels of 2-HG. The approach described here could be applicable to the resection of all 2-HG–producing tumors.
SOURCE: National Institute of Biomedical Imaging and Bioengineering