Intraoperative Mass Spectrometry Platform for IDH Mutation Status Prediction, Glioma Diagnosis, and Estimation of Tumor Cell Infiltration.

Surgical tumor resection is the primary treatment option for diffuse glioma, the most common malignant brain cancer. The intraoperative diagnosis of gliomas from tumor core samples can be improved by use of molecular diagnostics. Further, residual tumor at surgical margins is a primary cause of tumor recurrence and malignant progression. This study evaluates a desorption electrospray ionization mass spectrometry (DESI-MS) system for intraoperative isocitrate dehydrogenase (IDH) mutation assessment, estimation of tumor cell infiltration as tumor cell percentage (TCP), and disease status. This information could be used to enhance the extent of safe resection and so potentially improve patient outcomes. A mobile DESI-MS instrument was modified and used in neurosurgical operating rooms (ORs) on a cohort of 49 human subjects undergoing craniotomy with tumor resection for suspected diffuse glioma. Small tissue biopsies (ntotal = 203) from the tumor core and surgical margins were analyzed by DESI-MS in the OR and classified using univariate and multivariate statistical methods. Assessment of IDH mutation status using DESI-MS/MS to measure 2-hydroxyglutarate (2-HG) ion intensities from tumor cores yielded a sensitivity, specificity, and overall diagnostic accuracy of 89, 100, and 94%, respectively (ncore = 71). Assessment of TCP (categorized as low or high) in tumor margin and core biopsies using N-acetyl-aspartic acid (NAA) intensity provided a sensitivity, specificity, and accuracy of 91, 76, and 83%, respectively (ntotal = 203). TCP assessment using lipid profile deconvolution provided sensitivity, specificity, and accuracy of 76, 85, and 81%, respectively (ntotal = 203). Combining the experimental data and using PCA-LDA predictions of disease status, the sensitivity, specificity, and accuracy in predicting disease status are 63%, 83%, and 74%, respectively (ntotal = 203). The DESI-MS system allowed for identification of IDH mutation status, glioma diagnosis, and estimation of tumor cell infiltration intraoperatively in a large human glioma cohort. This methodology should be further refined for clinical diagnostic applications.

Brown HM ，Alfaro CM ，Pirro V ，Dey M ，Hattab EM ，Cohen-Gadol AA ，Cooks RG ... -  《-》

Intraoperative assessment of isocitrate dehydrogenase mutation status in human gliomas using desorption electrospray ionization-mass spectrometry.

Alfaro CM ，Pirro V ，Keating MF ，Hattab EM ，Cooks RG ，Cohen-Gadol AA ... -  《-》

Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry.

Pirro V ，Alfaro CM ，Jarmusch AK ，Hattab EM ，Cohen-Gadol AA ，Cooks RG ... -  《-》

Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

Hua W ，Zhang W ，Brown H ，Wu J ，Fang X ，Shahi M ，Chen R ，Zhang H ，Jiao B ，Wang N ，Xu H ，Fu M ，Wang X ，Zhang J ，Zhang X ，Wang Q ，Zhu W ，Ye D ，Garcia DM ，Chaichana K ，Cooks RG ，Ouyang Z ，Mao Y ，Quinones-Hinojosa A ... -  《-》

Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer.

Brown HM ，Pu F ，Dey M ，Miller J ，Shah MV ，Shapiro SA ，Ouyang Z ，Cohen-Gadol AA ，Cooks RG ... -  《-》