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

Background: 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.

Ambient Lipidomic Analysis of Single Mammalian Oocytes and Preimplantation Embryos Using Desorption Electrospray Ionization (DESI) Mass Spectrometry.

Desorption electrospray ionization (DESI) is a spray-based ambient ionization method for mass spectrometry (MS) that generates ions in native atmospheric conditions (e.g., pressure and temperature).

Rapid determination of isocitrate dehydrogenase mutation status of human gliomas by extraction nanoelectrospray using a miniature mass spectrometer.

Isocitrate dehydrogenase (IDH) I and II mutations in gliomas cause an abnormal accumulation of 2-hydroxyglutarate (2-HG) in these tumor cells. These mutations have potential prognostic value in that knowledge of the mutation status can lead to improved surgical resection. Information on mutation status obtained by immunohistochemistry or genomic analysis is not available during surgery.

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

Objective: The authors describe a rapid intraoperative ambient ionization mass spectrometry (MS) method for determining isocitrate dehydrogenase (IDH) mutation status from glioma tissue biopsies. This method offers new glioma management options and may impact extent of resection goals. Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology.

Feasibility of desorption electrospray ionization mass spectrometry for diagnosis of oral tongue squamous cell carcinoma.

Rationale: Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated utility in differentiating tumor from adjacent normal tissue in both urologic and neurosurgical specimens. We sought to evaluate if this technique had similar accuracy in differentiating oral tongue squamous cell carcinoma (SCC) from adjacent normal epithelium due to current issues with late diagnosis of SCC in advanced stages.

Methods: Fresh frozen samples of SCC and adjacent normal tissue were obtained by surgical resection.

Analysis of human gliomas by swab touch spray-mass spectrometry: applications to intraoperative assessment of surgical margins and presence of oncometabolites.

Touch spray mass spectrometry using medical swabs is an ambient ionization technique (ionization of unprocessed sample in the open air) that has potential intraoperative application in quickly identifying the disease state of tissue and in better characterizing the resection margin. To explore this potential, we studied 29 human brain tumor specimens and obtained evidence that this technique can provide diagnostic molecular information that is relevant to brain cancer. Touch spray using medical swabs involves the physical sampling of tissue using a medical swab on a spatial scale of a few mm with subsequent ionization occurring directly from the swab tip upon addition of solvent and application of a high voltage.

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

Intraoperative desorption electrospray ionization-mass spectrometry (DESI-MS) is used to characterize tissue smears by comparison with a library of DESI mass spectra of pathologically determined tissue types. Measurements are performed in the operating room within 3 min. These mass spectra provide direct information on tumor infiltration into white or gray brain matter based on -acetylaspartate (NAA) and on membrane-derived complex lipids.

Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization - Mass Spectrometry Imaging.

Desorption electrospray ionization-mass spectrometry (DESI-MS) imaging was used to analyze unmodified human brain tissue sections from 39 subjects sequentially in the positive and negative ionization modes. Acquisition of both MS polarities allowed more complete analysis of the human brain tumor lipidome as some phospholipids ionize preferentially in the positive and others in the negative ion mode. Normal brain parenchyma, comprised of grey matter and white matter, was differentiated from glioma using positive and negative ion mode DESI-MS lipid profiles with the aid of principal component analysis along with linear discriminant analysis.

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated.

Ambient ionisation mass spectrometry for lipid profiling and structural analysis of mammalian oocytes, preimplantation embryos and stem cells.

Lipids play fundamental roles in mammalian embryo preimplantation development and cell fate. Triacylglycerol accumulates in oocytes and blastomeres as lipid droplets, phospholipids influence membrane functional properties, and essential fatty acid metabolism is important for maintaining the stemness of cells cultured in vitro. The growing impact that lipids have in the field of developmental biology makes analytical approaches to analyse structural information of great interest.

Investigations of analyte-specific response saturation and dynamic range limitations in atmospheric pressure ionization mass spectrometry.

With this study, we investigated why some small molecules demonstrate narrow dynamic ranges in electrospray ionization-mass spectrometry (ESI-MS) and sought to establish conditions under which the dynamic range could be extended. Working curves were compared for eight flavonoids and two alkaloids using ESI, atmospheric pressure chemical ionization (APCI), and heated electrospray ionization (HESI) sources. Relative to reserpine, the flavonoids exhibited narrower linear dynamic ranges with ESI-MS, primarily due to saturation in response at relatively low concentrations.