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.
Recently, mass-spectrometry methods show its utility in tumor boundary location.The effect of differences between research and clinical protocols such as low-and high-resolution measurements and sample storage have to be understood and taken into account to transfer methods from bench to bedside. In this study, we demonstrate a simple way to compare mass spectra obtained by different experimental protocols, assess its quality, and check for the presence of outliers and batch effect in the dataset. We compare the mass spectra of both fresh and frozen-thawed astrocytic brain tumor samples obtained with the inline cartridge extraction prior to electrospray ionization. Our results reveal the importance of both positive and negative ion mode mass spectrometry for getting reliable information about sample diversity. We show that positive mode highlights the difference between protocols of mass spectra measurement, such as fresh and frozen-thawed samples, whereas negative mode better characterizes the histological difference between samples. We also show how the use of similarity spectrum matrix helps to identify the proper choice of the measurement parameters, so data collection would be kept reliable, and analysis would be correct and meaningful.
K E Y W O R D Sbrain tumor, data conversion, inline cartridge extraction, low-and high-resolution comparison, spectra stability and reproducibility
| INTRODUCTIONFast tissue profiling methods for mass spectrometers allowed developing methods of rapid analysis of biological substances. [1][2][3][4][5][6][7] There are a lot of attempts to incorporate mass spectrometry into the clinical routine for surgery assistance purposes. [8][9][10][11][12] Mass spectra of complex mixtures of biological molecules, even those whose mass is up to 1000 Da, is still rather a difficult task, because of the enormous diversity of molecules contained in biological tissues. 13,14 Despite the common practice of LC-MS/MS to be used as an instrument for accurate identification of complex mixture components, it could not be used as a routine technique for rapid analyses. 15 Therefore, rapid analyses
Detection of the brain tumor margins is one of the most significant problems in neurosurgery. Several mass spectrometry-based approaches have been proposed recently for tumor boundary detection. One of them, spray from tissue does not require sample preparation but needs special algorithms for analysis of its spectra. Here we proposed the feature selection algorithm designed for analysis of spray-from-tissue data.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.