A novel direct spray-from-tissue ionization method for mass spectrometric analysis of human brain tumors

Abstract

Real-time feedback about dissected tissue during the neurosurgical procedure is strongly requested. A novel direct ionization mass spectrometric method for identifying pathological differences in tissues is proposed. The method is based on simultaneous extraction of tissue lipids and electrospray ionization which allows mass spectrometric data to be obtained directly from soft tissues. The advantage of this method is the stable flow of solvent, which leads to stable time-dependent spectra. The tissues included necrotized tissues and tumor tissues in different combinations. Capability for direct analysis of samples of dissected tissues during the neurosurgical procedure is demonstrated. Data validation is conducted by compound identification using precise masses from the MS profile, MS/MS, and isotopic distribution structure analysis. The method can be upgraded and applied for real-time identification of tissues during surgery. This paper describes the technique and its application perspective. For these purposes, other methods were compared with the investigated one and the results were shown to be reproducible. Differences in lipid profiles were observed even in tissues from one patient where distinctions between different samples could be poor. The paper presents a proof of concept for the method to be applied in neurosurgery particularly and in tissue analysis generically. The paper also contains preliminary results proving the possibility of observing differences in mass spectra of different tumors.

Endometriosis foci differentiation by rapid lipid profiling using tissue spray ionization and high resolution mass spectrometry

“…1) similar to that described earlier 10 but with minor modifications. Constant stream of H 2 O/methanol 1/9 is supplied to the tissue with flow rate of 1 mL/min by Dionex binary pump.…”

“…One of the ambient methods for a sample analysis with minimal pretreatment is suggested by Cooks’ group and named “leaf-spray” 9 . This method was further extrapolated for fast tissue analysis and turned into different variations of tissue spray 10–15 . The method has been applied to the analysis of brain tissues and various cancer tumors 10, 13 .…”

Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS

“…Differences in the lipid composition of renal cell carcinoma (19) and colon cancer (20) from their respective normal parenchyma were detected by positive ion probe electrospray ionization-MS. Touch spray, a probe method allowing user-guided sampling, serves to differentiate prostate cancer from normal tissue based on glycerophospholipid distributions (3). Similar methods of ionization have been used for the detection of lipids from lung (21) and brain cancer (22). DESI-MS imaging of stereotactically registered brain tumor samples (23) gave results that correlated with histopathology and illustrated the potential for determining tumor cell concentration near the resection margins (10).…”

The role of lipid metabolism disorders, atypical isoforms of protein kinase C, and mutational status of cytosolic and mitochondrial forms of isocitrate dehydrogenase in carcinogenesis of glial tumors

“…Первые работы, в которых описаны исследования тканей методами прямой масс-спектрометрии, были выполнены с использованием метода десорбционно-электроспрейной ионизации (DESI), в котором микроэкстракция исследуемых молекул из образца с их последующей ионизацией осуществляется при взаимодействии заряженных капель водно-метанольной смеси с исследуемым образцом. Это позволяет получить данные о липидном профиле опухолевой ткани, а также распределении в ткани различных характерных водорастворимых онкометаболитов [15][16][17]. Основными молекулярными маркерами липидной природы, на основе которых проводится идентификация тканей при помощи описанных выше методов, являются насыщенные и ненасыщенные жирные кислоты (ЖК), глицерофосфоинозитолы, глицерофосфосерины, плазминил-глицерофосфоэтаноламины и сульфатиды.…”