A mass spectrometry method distinguished gliomas from nontumor brain tissue and classified tumors by molecular subtype and grade in approximately three minutes, according to a study published in Proceedings of the National Academy of Sciences.
The researchers developed the approach as a possible tool for assessing tissue during brain surgery. Gliomas can spread beyond the margins visible on imaging, making it difficult for surgeons to remove the tumor while preserving healthy brain tissue. Molecular tests used to classify gliomas are generally not available until after surgery.
“The information we are getting is currently not available under standard of care procedures,” said one of the lead researchers Mahdiyeh Shahi, a former Purdue University graduate student who is now a clinical chemistry postdoctoral fellow at the University of Minnesota Medical School, in the press release.
The study involved analyzing 86 human brain specimens, including 78 glioma and eight nontumor samples. A sterile syringe plunger was touched to the tissue to collect a small sample. The plunger was returned to the syringe, solvent was added, and the material was analyzed using syringe touch spray tandem mass spectrometry.
“The new method used in this study — syringe touch spray — uses an ordinary hypodermic to take a sample from the patient and perform mass spectrometry analysis,” said R. Graham Cooks, a professor of chemistry at Purdue and the second lead author.
Rather than assessing individual metabolites alone, the researchers compared the signal from one metabolite with another. These ratios were intended to reduce variation caused by sample collection and changing signal intensity without requiring an internal reference standard. In total, the team calculated 24,492 metabolite ratios.
Several ratios distinguished glioma from nontumor tissue. The ratio of N-acetylaspartate to carnitine produced 97 percent sensitivity, 100 percent specificity, and 98 percent accuracy when compared with the clinical diagnoses.
The method also classified gliomas by isocitrate dehydrogenase (IDH) mutation status, an important factor in diagnosis and prognosis. Mutant IDH causes tumor cells to accumulate 2-hydroxyglutarate. Ratios involving this metabolite completely separated 13 IDH-mutant samples from 24 IDH-wild-type samples within the study cohort.
Several ratios also completely separated eight grade 2 tumors from 20 grade 4 tumors and seven grade 3 tumors from 20 grade 4 tumors. Grade 4 gliomas had higher levels of alpha-aminoadipate, while grade 3 tumors contained more 2-hydroxyglutarate than grade 4 tumors.
To explore whether the method could identify cancer at surgical margins, the researchers mixed tumor and normal brain tissue in different proportions. Ratios involving 2-hydroxyglutarate, glutamate, and carnitine generally changed with the percentage of tumor cells.
However, some mixtures with substantial tumor content fell below the cutoff established using tumor-core tissue. This indicates that a threshold developed for the center of a tumor may miss cancer at the more heterogeneous margins.
“This technology would not replace the current standard of care during brain tumor surgery,” Cooks said. “Instead, it could provide surgeons with molecular information that is not currently available in the operating room, helping to guide surgical decisions during tumor removal, particularly at the tumor margins.”
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