Repeatability and reproducibility of desorption electrospray ionization-mass spectrometry (DESI-MS) for the imaging analysis of human cancer tissue: a gateway for clinical applications

2015 ◽  
Vol 7 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Nima Abbassi-Ghadi ◽  
Emrys A. Jones ◽  
Kirill A. Veselkov ◽  
Juzheng Huang ◽  
Sacheen Kumar ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Cancer ◽  
Desorption Electrospray Ionization ◽  
Clinical Applications ◽  
Cancer Tissue ◽  
Ionization Mass ◽  
Imaging Analysis ◽  
Desi Ms ◽  
Repeatability And Reproducibility ◽  
Human Cancer Tissue

The repeatability and reproducibility of DESI-MS for the measurement of lipid ion intensities in human cancer tissue is 22 ± 7% and 18 ± 8%, respectively.

Distinctive lipid profiles of human breast cancer and adjacent normal tissues by desorption electrospray ionization mass spectrometry imaging.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1132-1132
Author(s):  
Diana L. Caragacianu ◽  
Xiaohui Liu ◽  
Isaiah Norton ◽  
Jennifer Ide ◽  
Andrea Richardson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Normal Tissue ◽  
Mass Spectrometry Imaging ◽  
Desorption Electrospray Ionization ◽  
Cancer Tissue ◽  
Ionization Mass ◽  
Proof Of Concept ◽  
Ms Imaging ◽  
Desi Ms

1132 Background: Routine intra-operative distinction between normal breast tissue and tumor is currently not possible in breast conserving surgery (BCS). This limitation affects the success of surgery, resulting in up to 40% requiring more than one operative procedure. Desorption electrospray ionization mass spectrometry (DESI MS) has been successfully used to discriminate between normal and cancerous human tissues from anatomical sites such as the liver and brain. The aim of this proof of concept study was to determine the feasibility of using DESI MS imaging for tissue identification and differentiation of breast cancer versus normal tissue. Methods: DESI MS imaging was carried out on 14 human invasive breast cancer samples. Breast cancer and adjacent normal paired human tissue sections (margin of tumor, 2cm and 5 cm from tumor) from 14 patients undergoing mastectomy were flash frozen in liquid nitrogen, sectioned, and thaw mounted to glass slides. All samples were imaged using DESI MS at 200 μm imaging resolution. DESI MS images were overlaid and compared with hematoxylin and eosin (H&E) images of the same sections. Results: Discrimination between cancer and adjacent normal tissue was achieved on the basis of the spatial distribution and varying intensities of particular fatty acids and lipid species. Several fatty acids such as oleic acid (m/z 281) and arachidonic acid (m/z 303) displayed much greater signal intensities in the cancer specimen compared to low or undetectable intensities in normal tissue. The cancer margins delineated by the DESI MS images of these molecules were consistent with H and E images of the tumor edge. Cancerous tissue was distinguished from normal tissue based on the qualitative assessment of molecular signatures and the distinction was in agreement with expert histopathology evaluation in 85% of samples. Conclusions: Our findings offer proof of concept that examination and classification of breast normal and cancer tissue by mass spectrometry imaging is highly accurate. The results are encouraging for development of a MS-based method that could be utilized intra-operatively for rapid detection of residual cancer tissue in the lumpectomy bed in BCS.

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

2020 ◽  
Vol 132 (1) ◽  
pp. 180-187 ◽  
Author(s):  
Clint M. Alfaro ◽  
Valentina Pirro ◽  
Michael F. Keating ◽  
Eyas M. Hattab ◽  
R. Graham Cooks ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Isocitrate Dehydrogenase ◽  
Tumor Resection ◽  
Desorption Electrospray Ionization ◽  
Extent Of Resection ◽  
Ionization Mass ◽  
Idh Mutation ◽  
Mutation Status ◽  
Desi Ms

OBJECTIVEThe 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.METHODSBanked glioma specimens (n = 37) were analyzed by desorption electrospray ionization–MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). The method was used intraoperatively to analyze tissue smears obtained from glioma patients undergoing resection and to rapidly diagnose IDH mutation status (< 5 minutes). Fifty-one tumor core biopsies from 25 patients (14 wild type [WT] and 11 mutant) were examined and data were analyzed using analysis of variance and receiver operating characteristic curve analysis.RESULTSThe optimized DESI-MS method discriminated between IDH-WT and IDH-mutant gliomas, with an average sensitivity and specificity of 100%. The average normalized DESI-MS 2HG signal was an order of magnitude higher in IDH-mutant glioma than in IDH-WT glioma. The DESI 2HG signal intensities correlated with independently measured 2HG concentrations (R2 = 0.98). In 1 case, an IDH1 R132H–mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report. A second craniotomy and tumor resection was performed after the final pathology provided a diagnosis most consistent with an IDH-mutant glioblastoma. During the second craniotomy, high levels of 2HG in the tumor core biopsies were detected.CONCLUSIONSThis study demonstrates the capability to differentiate rapidly between IDH-mutant gliomas and IDH-WT conditions by DESI-MS during tumor resection. DESI-MS analysis of tissue smears is simple and can be easily integrated into the standard intraoperative pathology consultation. This approach may aid in solving differential diagnosis problems associated with low-grade gliomas and could influence intraoperative decisions regarding extent of resection, ultimately improving patient outcome. Research is ongoing to expand the patient cohort, systematically validate the DESI-MS method, and investigate the relationships between 2HG and tumor heterogeneity.

61 UNVEILING THE ROLE OF LIPIDS IN ORGANOGESIS: MOLECULAR ANATOMY BY DESORPTION ELECTROSPRAY IONIZATION MASS SPECTROMETRY IMAGING MASS SPECTROMETRY

2016 ◽  
Vol 28 (2) ◽  
pp. 160
Author(s):  
V. Pirro ◽  
P. O. Favaron ◽  
C. R. Ferreira ◽  
L. S. Eberlin ◽  
R. S. Barreto ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spinal Cord ◽  
Desorption Electrospray Ionization ◽  
Ionization Mass ◽  
Differential Distribution ◽  
Desi Ms ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Digestive Glands

Even though the role of lipids in pandemic diseases such as obesity and diabetes is a focus of increasing research, the role of lipids during organogenesis, when diverse diseases may be triggered, is unexplored. Also, pig embryonic tissues represent an attractive option for organ transplantation. This study introduces a detailed morphological analysis of swine fetal tissues with matching location of lipids acquired by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for the study of differential distribution of free fatty acids (FFA) and phospholipids (PL) in specific organs during fetal development. Samples from a pig fetuses around Day 50 of pregnancy were sectioned at a cryotome and mounted onto glass slides. Fixative agents were not used. DESI-MS images were run with a step size of 300 µm using a morphologically friendly (non-destructive) solvent combination, namely dimethylformamide/acetonitrile 1 : 1 (v/v). Data were acquired in the negative ion mode in the m/z range of 150 to 1000 from different sections representing the whole swine fetus body. Ion images were constructed using BioMAP software. After imaging, the whole-body tissue samples were stained with hematoxylin and eosin (H&E) and were overlaid to the DESI-MS lipid images. Differential distribution of FFA, phosphatidylcholines (PC), phosphatidylserines (PS), sulphatides (ST), and phosphatidylinositols (PI) was observed among organs, especially on nervous and circulatory systems, and digestive glands. Most lipids concentrated in the brain, spinal cord, and digestive glands such as the liver. For example, arachidonic acid was most abundant in neuronal tissue, whereas docosahexaenoic acid predominated in the liver and digestive glands. Distribution of PS (36 : 1) of m/z 788 was observed in all tissues except for the digestive system, but PS (40 : 6) of m/z 834.7 was exclusive of brain and spinal cord. Lipids related to brain and spinal cord were mostly polyunsaturated fatty acids as well as specific PS lipids. Arachidonic and eicosatrienoic acids are more concentrated in hindbrain and spinal cord, whereas PS was more abundant in the brain than in the spinal cord. There is no information on PS chemical composition during brain and spinal cord development, but PS concentration in the nervous tissue membranes varies with age, brain areas, cell type, and subcellular components. Several reports indicate that alteration in PS synthesis might participate in the mechanism of brain damage. Also, PS has been found to be altered in brain tumours. Oleic acid, fatty acid dimers, and the signalling lipid PI (38 : 3) were most significant for the digestive system and liver. Liver is one of the main organs involved in fatty acid metabolism (besides adipose tissue and muscle). By overlying morphological and molecular information, lipids seem to be a major player in the organogenesis process.

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