47 results found
Wu V, Tillner J, Jones E, et al., 2022, High resolution ambient MS imaging of biological samples by desorption electro-flow focussing ionization, Analytical Chemistry, Vol: 94, Pages: 10035-10044, ISSN: 0003-2700
In this study, we examine the suitability of desorption electro-flow focusing ionization (DEFFI) for mass spectrometry imaging (MSI) of biological tissue. We also compare the performance of desorption electrospray ionization (DESI) with and without the flow focusing setup. The main potential advantages of applying the flow focusing mechanism in DESI is its rotationally symmetric electrospray jet, higher intensity, more controllable parameters, and better portability due to the robustness of the sprayer. The parameters for DEFFI have therefore been thoroughly optimized, primarily for spatial resolution but also for intensity. Once the parameters have been optimized, DEFFI produces similar images to the existing DESI. MS images for mouse brain samples, acquired at a nominal pixel size of 50 μm, are comparable for both DESI setups, albeit the new sprayer design yields better sensitivity. Furthermore, the two methods are compared with regard to spectral intensity as well as the area of the desorbed crater on rhodamine-coated slides. Overall, the implementation of a flow focusing mechanism in DESI is shown to be highly suitable for imaging biological tissue and has potential to overcome some of the shortcomings experienced with the current geometrical design of DESI.
Henderson F, Jones E, Denbigh J, et al., 2020, 3D DESI-MS lipid imaging in a xenograft model of glioblastoma: a proof of principle., Sci Rep, Vol: 10
Desorption electrospray ionisation mass spectrometry (DESI-MS) can image hundreds of molecules in a 2D tissue section, making it an ideal tool for mapping tumour heterogeneity. Tumour lipid metabolism has gained increasing attention over the past decade; and here, lipid heterogeneity has been visualised in a glioblastoma xenograft tumour using 3D DESI-MS imaging. The use of an automatic slide loader automates 3D imaging for high sample-throughput. Glioblastomas are highly aggressive primary brain tumours, which display heterogeneous characteristics and are resistant to chemotherapy and radiotherapy. It is therefore important to understand biochemical contributions to their heterogeneity, which may be contributing to treatment resistance. Adjacent sections to those used for DESI-MS imaging were used for H&E staining and immunofluorescence to identify different histological regions, and areas of hypoxia. Comparing DESI-MS imaging with biological staining allowed association of different lipid species with hypoxic and viable tissue within the tumour, and hence mapping of molecularly different tumour regions in 3D space. This work highlights that lipids are playing an important role in the heterogeneity of this xenograft tumour model, and DESI-MS imaging can be used for lipid 3D imaging in an automated fashion to reveal heterogeneity, which is not apparent in H&E stains alone.
Shrestha B, Roman G, Hattan S, et al., 2020, High Spatial Resolution Molecular Tissue Imaging by Desorption Electrospray Ionization using Novel Sprayer Assembly., J Biomol Tech, Vol: 31, Pages: S17-S18
Desorption electrospray ionization (DESI) mass spectrometry (MS) is an ambient ionization source with a wide array of applications from high-throughput screening to molecular imaging. In this study, our objective was to design a novel sprayer using electro-flow focusing and examine if tighter focused beam can perform a higher spatial resolution DESI imaging. DESI imaging mass spectrometry (MS) is performed by obtaining a pixel-by-pixel mass spectrum of a sample by impinging focused electrospray droplets on a confined point, such as pixel. Thus, the spatial resolution or pixel size of DESI imaging is primarily defined by the area of the electrospray impact on the surface. A stable and highly focused electrospray is a prerequisite for a high spatial resolution DESI imaging experiment. An imaging sprayer should be capable of generating a robust MS signal from a few dozen microns sample area - from the first pixel to the last millionth pixel. To briefly summarize our results, a novel DESI sprayer was designed based on precision machined ion-key emitters (Waters Corporation). Under the optimal conditions, DESI solvent guided through the orifice by a sheathing nebulization gas was capable of creating a highly concentric and stable flow stream of < 20 µm in diameter. The stability, as well as, the size of the DESI spray was related to solvent flow, high voltage, and nebulization gas flow. DESI imaging beam was optimized by using shadowgraph imaging of electrospray plume. DESI ion source was interfaced with a quadrupole time-of-flight mass spectrometer (SYNAPT G2-XS, Waters Corporation). DESI solvent (95-98% methanol) was regulated using a binary LC pump (ACQUITY UPLC M-Class, Waters Corporation). In conclusion, the novel sprayer with electro-flow focusing technique that combined electrospray and flow focusing, was capable of high-resolution DESI imaging of metabolites and lipids in rat brain and chicken liver sections below 50 microns.
Abbassi-Ghadi N, Antonowicz S, McKenzie J, et al., 2020, De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma, Cancer Research, Vol: 80, Pages: 2764-2774, ISSN: 0008-5472
The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.
Davidson NB, Koch NI, Sarsby J, et al., 2019, Rapid identification of species, sex and maturity by mass spectrometric analysis of animal faeces., BMC Biol, Vol: 17
BACKGROUND: We describe a new approach to the recovery of information from faecal samples, based on the analysis of the molecular signature generated by rapid evaporative ionisation mass spectrometry (REIMS). RESULTS: Faecal pellets from five different rodent species were analysed by REIMS, and complex mass spectra were acquired rapidly (typically a few seconds per sample). The uninterpreted mass spectra (signatures) were then used to seed linear discriminant analysis and classification models based on random forests. It was possible to classify each species of origin with a high rate of accuracy, whether faeces were from animals maintained under standard laboratory conditions or wild-caught. REIMS signatures were stable to prior storage of the faecal material under a range of different conditions and were not altered rapidly or radically by changes in diet. Further, within species, REIMS signatures could be used to discriminate faeces from adult versus juvenile mice, male versus female mice and those from three different laboratory strains. CONCLUSIONS: REIMS offers a completely novel method for the rapid analysis of faecal samples, extending faecal analysis (previously focused on DNA) to an assessment of phenotype, and has considerable potential as a new tool in the armamentarium of the field biologist.
Jones EA, Simon D, Karancsi T, et al., 2019, Matrix Assisted Rapid Evaporative Ionization Mass Spectrometry., Anal Chem, Vol: 91, Pages: 9784-9791
Rapid evaporative ionization mass spectrometry (REIMS) is a highly versatile technique allowing the sampling of a range of biological solid or liquid samples with no sample preparation. The cost of such a direct approach is that certain sample types provide only moderate amounts of chemical information. Here, we introduce a matrix assisted version of the technique (MA-REIMS), where an aerosol of a pure solvent, such as isopropanol, is mixed with the sample aerosol generated by rapid evaporation of the sample, and it is shown to enhance the signal intensity obtained from a REIMS sampling event by over 2 orders of magnitude. Such an increase greatly expands the scope of the technique, while providing additional benefits such as reducing the fouling of the REIMS source and allowing for a simple method of constant introduction of a calibration correction compound for accurate mass measurements. A range of experiments are presented in order to investigate the processes that occur within this modified approach, and applications where such enhancements are critical, such as intrasurgical tissue identification, are discussed.
Henderson F, Johnston HR, Badrock AP, et al., 2019, Enhanced Fatty Acid Scavenging and Glycerophospholipid Metabolism Accompany Melanocyte Neoplasia Progression in Zebrafish, CANCER RESEARCH, Vol: 79, Pages: 2136-2151, ISSN: 0008-5472
Towers MW, Karancsi T, Jones EA, et al., 2018, Optimised Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI-MSI) for the Analysis of Proteins/Peptides Directly from Tissue Sections on a Travelling Wave Ion Mobility Q-ToF., J Am Soc Mass Spectrom, Vol: 29, Pages: 2456-2466
Desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) is typically known for the ionisation of small molecules such as lipids and metabolites, in singly charged form. Here we present a method that allows the direct detection of proteins and peptides in multiply charged forms directly from tissue sections by DESI. Utilising a heated mass spectrometer inlet capillary, combined with ion mobility separation (IMS), the conditions with regard to solvent composition, nebulising gas flow, and solvent flow rate have been explored and optimised. Without the use of ion mobility separation prior to mass spectrometry analysis, only the most abundant charge series were observed. In addition to the dominant haemoglobin subunit(s) related trend line in the m/z vs drift time (DT) 2D plot, trend lines were found relating to background solvent peaks, residual lipids and, more importantly, small proteins/large peptides of lower abundance. These small proteins/peptides were observed with charge states from 1+ to 12+, the majority of which could only be resolved from the background when using IMS. By extracting charge series from the 2D m/z vs DT plot, a number of proteins could be tentatively assigned by accurate mass. Tissue images were acquired with a pixel size of 150 μm showing a marked improvement in protein image resolution compared to other liquid-based ambient imaging techniques such as liquid extraction surface analysis (LESA) and continuous-flow liquid microjunction surface sampling probe (LMJ-SSP) imaging. Graphical Abstract ᅟ.
Lamont L, Eijkel GB, Jones EA, et al., 2018, Targeted Drug and Metabolite Imaging: Desorption Electrospray Ionization Combined with Triple Quadrupole Mass Spectrometry., Anal Chem, Vol: 90, Pages: 13229-13235
Mass spectrometry imaging (MSI) has proven to be a valuable tool for drug and metabolite imaging in pharmaceutical toxicology studies and can reveal, for example, accumulation of drug candidates in early drug development. However, the lack of sample cleanup and chromatographic separation can hamper the analysis due to isobaric interferences. Multiple reaction monitoring (MRM) uses unique precursor ion-product ion transitions to add specificity which leads to higher selectivity. Here, we present a targeted imaging platform where desorption electrospray ionization is combined with a triple quadrupole (QqQ) system to perform MRM imaging. The platform was applied to visualize (i) lipids in mouse brain tissue sections and (ii) a drug candidate and metabolite in canine liver tissue. All QqQ modes were investigated to show the increased detection time provided by MRM as well as the possibility to perform dual polarity imaging. This is very beneficial for lipid imaging because some phospholipid classes ionize in opposite polarity (e.g., phosphatidylcholine/sphingomyelin in positive ion mode and phosphatidylserine/phosphatidylethanolamine in negative ion mode). Drug and metabolite images were obtained to show its strength in drug distribution studies. Multiple MRM transitions were used to confirm the local presence and selective detection of pharmaceutical compounds.
Kendall AC, Koszyczarek MM, Jones EA, et al., 2018, Lipidomics for translational skin research: A primer for the uninitiated., Exp Dermatol, Vol: 27, Pages: 721-728
Healthy skin depends on a unique lipid profile to form a barrier that confers protection and prevents excessive water loss, aids cell-cell communication and regulates cutaneous homoeostasis and inflammation. Alterations in the cutaneous lipid profile can have severe consequences for skin health and have been implicated in numerous inflammatory skin conditions. Thus, skin lipidomics is increasingly of interest, and recent developments in mass spectrometry-based analytical technologies can deliver in-depth investigation of cutaneous lipids, providing insight into their role and mechanism of action. The choice of tissue sampling technique and analytical approach depends on the location and chemistry of the lipid of interest. Lipidomics can be conducted by various mass spectrometry approaches, including different chromatography and ionisation techniques. Targeted mass spectrometry is a sensitive approach for measuring low-abundance signalling lipids, such as eicosanoids, endocannabinoids and ceramides. This approach requires specific extraction, chromatography and mass spectrometry protocols to quantitate the lipid targets. Untargeted mass spectrometry reveals global changes and allows analysis of hundreds of complex lipids across a range of lipid classes, including phospholipids, glycerophospholipids, cholesteryl esters and sphingolipids. Mass spectrometry lipid imaging, including matrix-assisted laser desorption ionisation mass spectrometry and desorption electrospray ionisation mass spectrometry, can reveal information about abundance and anatomical distribution of lipids within a single skin sample. Skin lipidomics can provide qualitative and quantitative data on hundreds of biologically relevant lipid species with different properties and activities, all found within a single skin sample, and support translational studies exploring the involvement of lipids in skin health and disease.
Esteve C, Jones EA, Kell DB, et al., 2017, Mass spectrometry imaging shows major derangements in neurogranin and in purine metabolism in the triple-knockout 3 x Tg Alzheimer mouse model, BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, Vol: 1865, Pages: 747-754, ISSN: 1570-9639
Tillner J, Wu V, Jones EA, et al., 2017, Faster, more reproducible DESI-MS for biological tissue imaging, Journal of The American Society for Mass Spectrometry, Vol: 28, Pages: 2090-2098, ISSN: 1044-0305
A new, more robust sprayer for desorption electrospray ionization (DESI) mass spectrometry imaging is presented. The main source of variability in DESI is thought to be the uncontrolled variability of various geometric parameters of the sprayer, primarily the position of the solvent capillary, or more specifically, its positioning within the gas capillary or nozzle. If the solvent capillary is off-center, the sprayer becomes asymmetrical, making the geometry difficult to control and compromising reproducibility. If the stiffness, tip quality, and positioning of the capillary are improved, sprayer reproducibility can be improved by an order of magnitude. The quality of the improved sprayer and its potential for high spatial resolution imaging are demonstrated on human colorectal tissue samples by acquisition of images at pixel sizes of 100, 50, and 20 μm, which corresponds to a lateral resolution of 40-60 μm, similar to the best values published in the literature. The high sensitivity of the sprayer also allows combination with a fast scanning quadrupole time-of-flight mass spectrometer. This provides up to 30 times faster DESI acquisition, reducing the overall acquisition time for a 10 mm × 10 mm rat brain sample to approximately 1 h. Although some spectral information is lost with increasing analysis speed, the resulting data can still be used to classify tissue types on the basis of a previously constructed model. This is particularly interesting for clinical applications, where fast, reliable diagnosis is required. Graphical Abstract ᅟ.
Yan C, Parmeggiani F, Jones EA, et al., 2017, Real-Time Screening of Biocatalysts in Live Bacterial Colonies., J Am Chem Soc, Vol: 139, Pages: 1408-1411
Screening of bacterial colonies to identify new biocatalytic activities is a widely adopted tool in biotechnology, but is constrained by the requirements for colorimetric or tag-based detection methods. Herein we report a label-free screening platform for biotransformations in live colonies using desorption electrospray ionization coupled with ion mobility mass spectrometry imaging (DiBT-IMMS). The screening method is demonstrated for both ammonia lyases and P450 monooxygenases expressed within live bacterial colonies and is shown to enable multiplexing of enzyme variants and substrate libraries simultaneously.
Claude E, Jones EA, Pringle SD, 2017, DESI Mass Spectrometry Imaging (MSI)., Pages: 65-75
Desorption Electrospray Ionization (DESI) mass spectrometry is a technique that allows chemical information to be obtained directly from a wide range of surfaces. Using a 2D stage, DESI can be implemented in an imaging mode whereby MS spectra are collected by rastering the spray across the whole surface. Here, we describe the implementation and optimization of DESI imaging for metabolites and lipids from tissue sections using oa-TOF mass spectrometers.
Skraskova K, Claude E, Jones EA, et al., 2016, Enhanced capabilities for imaging gangliosides in murine brain with matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry coupled to ion mobility separation, METHODS, Vol: 104, Pages: 69-78, ISSN: 1046-2023
Aznar M, Alfaro P, Nerín C, et al., 2016, Progress in mass spectrometry for the analysis of set-off phenomena in plastic food packaging materials., J Chromatogr A, Vol: 1453, Pages: 124-133
In most cases, food packaging materials contain inks whose components can migrate to food by diffusion through the material as well as by set-off phenomena. In this work, different mass spectrometry approaches had been used in order to identify and confirm the presence of ink components in ethanol (95%) and Tenax(®) as food simulants. Three different sets of materials, manufactured with different printing technologies and with different structures, were analyzed. Sample analysis by ultra performance liquid chromatography mass spectrometry (UPLC-MS), using a quadrupole-time of flight (Q-TOF) as a mass analyser proved to be an excellent tool for identification purposes while ion mobility mass spectrometry (IM-MS) shown to be very useful for the confirmation of the candidates proposed. The results showed the presence of different non-volatile ink components in migration such as colorants (Solvent Red 49), plasticizers (dimethyl sebacate, tributyl o-acetyl citrate) or surfactants (SchercodineM, triethylene glycol caprilate). An oxidation product of an ink additive (triphenyl phosphine oxide) was also detected. In addition, a surface analysis technique, desorption electrospray mass spectrometry (DESI-MS), was used for analyzing the distribution of some ink components (tributyl o-acetyl citrate Schercodine L, phthalates) in the material. The detection of some of these compounds in the back-printed side confirmed the transference of this compound from the non-food to the food contact side. The results also showed that concentration of ink migrants decreased when an aluminum or polypropylene layer covered the ink. When aluminum was used, concentration of most of ink migrants decreased, and for 5 out of the 9 even disappeared.
Abbassi-Ghadi N, Golf O, Kumar S, et al., 2016, Imaging of esophageal lymph node metastases by desorption electrospray ionization mass spectrometry, Cancer Research, Vol: 76, Pages: 5647-5656, ISSN: 1538-7445
Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intra-observer variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were co-registered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within lymph nodes. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched immunohistochemistry images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign lymph node tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value and negative predictive value of 89.5, 100, 100 and 97.2 per-cent, respectively, when compared to gold-standard immunohistochemistry. DESI-MSI has the potential to be a diagnostic tool for peri-operative identification of LNM and compares favorably with techniques currently used by histopathology experts.
Tillner J, McKenzie JS, Jones EA, et al., 2016, Investigation of the Impact of Desorption Electrospray Ionization Sprayer Geometry on Its Performance in Imaging of Biological Tissue., Analytical Chemistry, Vol: 88, Pages: 4808-4816, ISSN: 0003-2700
In this study, the impact of sprayer design and geometry on performance in desorption electrospray ionization mass spectrometry (DESI-MS) is assessed, as the sprayer is thought to be a major source of variability. Absolute intensity repeatability, spectral composition, and classification accuracy for biological tissues are considered. Marked differences in tissue analysis performance are seen between the commercially available and a lab-built sprayer. These are thought to be associated with the geometry of the solvent capillary and the resulting shape of the primary electrospray. Experiments with a sprayer with a fixed solvent capillary position show that capillary orientation has a crucial impact on tissue complex lipid signal and can lead to an almost complete loss of signal. Absolute intensity repeatability is compared for five lab-built sprayers using pork liver sections. Repeatability ranges from 1 to 224% for individual sprayers and peaks of different spectral abundance. Between sprayers, repeatability is 16%, 9%, 23%, and 34% for high, medium, low, and very low abundance peaks, respectively. To assess the impact of sprayer variability on tissue classification using multivariate statistical tools, nine human colorectal adenocarcinoma sections are analyzed with three lab-built sprayers, and classification accuracy for adenocarcinoma versus the surrounding stroma is assessed. It ranges from 80.7 to 94.5% between the three sprayers and is 86.5% overall. The presented results confirm that the sprayer setup needs to be closely controlled to obtain reliable data, and a new sprayer setup with a fixed solvent capillary geometry should be developed.
Abbassi-Ghadi N, Jones EA, Gomez-Romero M, et al., 2015, A Comparison of DESI-MS and LC-MS for the Lipidomic Profiling of Human Cancer Tissue, Journal of the American Society for Mass Spectrometry, Vol: 27, Pages: 255-264, ISSN: 1044-0305
In this study, we make a direct comparison between desorptionelectrospray ionization-mass spectrometry (DESI-MS) and ultraperformance liquidchromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) platformsfor the profiling of glycerophospholipid (GPL) species in esophageal cancertissue. In particular, we studied the similarities and differences in the range of GPLsdetected and the congruency of their relative abundances as detected by eachanalytical platform. The main differences between mass spectra of the two modalitieswere found to be associated with the variance in adduct formation of common GPLs,rather than the presence of different GPL species. Phosphatidylcholines as formateadducts in UPLC-ESI-MS accounted for the majority of differences in negative ionmode and alkali metal adducts of phosphatidylcholines in DESI-MS for positive ion mode. Comparison of therelative abundance of GPLs, normalized to a common peak, revealed a correlation coefficient of 0.70 (P < 0.001).The GPL profile detected by DESI-MS is congruent to UPLC-ESI-MS, which reaffirms the role of DESI-MS forlipidomic profiling and a potential premise for quantification.
Thompson RB, Reffatto V, Bundy JG, et al., 2015, Correction: Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye (Proceedings of the National Academy of Sciences of the United States of America (2015) 112, 5, (1565-1570) DOI: 10.1073/pnas.1413347112), Proceedings of the National Academy of Sciences, Vol: 112, Pages: E3971-E3971, ISSN: 0027-8424
Guenther S, Muirhead LJ, Speller AVM, et al., 2015, Spatially resolved metabolic phenotyping of breast cancer by desorption electrospray ionization mass spectrometry, Cancer Research, Vol: 75, Pages: 1828-1837, ISSN: 0008-5472
Breast cancer is a heterogeneous disease characterized by varying responses to therapeutic agents and significant differences in long-term survival. Thus, there remains an unmet need for early diagnostic and prognostic tools and improved histologic characterization for more accurate disease stratification and personalized therapeutic intervention. This study evaluated a comprehensive metabolic phenotyping method in breast cancer tissue that uses desorption electrospray ionization mass spectrometry imaging (DESI MSI), both as a novel diagnostic tool and as a method to further characterize metabolic changes in breast cancer tissue and the tumor microenvironment. In this prospective single-center study, 126 intraoperative tissue biopsies from tumor and tumor bed from 50 patients undergoing surgical resections were subject to DESI MSI. Global DESI MSI models were able to distinguish adipose, stromal, and glandular tissue based on their metabolomic fingerprint. Tumor tissue and tumor-associated stroma showed evident changes in their fatty acid and phospholipid composition compared with normal glandular and stromal tissue. Diagnosis of breast cancer was achieved with an accuracy of 98.2% based on DESI MSI data (PPV 0.96, NVP 1, specificity 0.96, sensitivity 1). In the tumor group, correlation between metabolomic profile and tumor grade/hormone receptor status was found. Overall classification accuracy was 87.7% (PPV 0.92, NPV 0.9, specificity 0.9, sensitivity 0.92). These results demonstrate that DESI MSI may be a valuable tool in the improved diagnosis of breast cancer in the future. The identified tumor-associated metabolic changes support theories of de novo lipogenesis in tumor tissue and the role of stroma tissue in tumor growth and development and overall disease prognosis. Cancer Res; 75(9); 1828–37. ©2015 AACR.
Golf O, Strittmatter N, Karancsi T, et al., 2015, Rapid evaporative ionization mass spectrometry imaging platform for direct mapping from bulk tissue and bacterial growth media, Analytical Chemistry, Vol: 87, Pages: 2527-2534, ISSN: 0003-2700
Rapid evaporative ionization mass spectrometry (REIMS) technology allows real time intraoperative tissue classification and the characterization and identification of microorganisms. In order to create spectral libraries for training the classification models, reference data need to be acquired in large quantities as classification accuracy generally improves as a function of number of training samples. In this study, we present an automated high-throughput method for collecting REIMS data from heterogeneous organic tissue. The underlying instrumentation consists of a 2D stage with an additional high-precision z-axis actuator that is equipped with an electrosurgical diathermy-based sampling probe. The approach was validated using samples of human liver with metastases and bacterial strains, cultured on solid medium, belonging to the species P. aeruginosa, B. subtilis, and S. aureus. For both sample types, spatially resolved spectral information was obtained that resulted in clearly distinguishable multivariate clustering between the healthy/cancerous liver tissues and between the bacterial species.
Thompson RB, Reffatto V, Bundy JG, et al., 2015, Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye, Proceedings of the National Academy of Sciences of the United States of America, Vol: 112, Pages: 1565-1570, ISSN: 1091-6490
Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5–20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch’s membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch’s membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.
Abbassi-Ghadi N, Jones EA, Veselkov KA, et al., 2015, Repeatability and reproducibility of desorption electrospray ionization-mass spectrometry (DESI-MS) for the imaging analysis of human cancer tissue: a gateway for clinical applications, Analytical Methods: advancing methods and applications, Vol: 7, Pages: 71-80, ISSN: 1759-9660
In this study, we aim to demonstrate the repeatability and reproducibility of DESI-MS for the imaging analysis of human cancer tissue using a set of optimal geometric and electrospray solvent parameters. Oesophageal cancer tissue was retrieved from four quadrants of a freshly removed tumor specimen, snap frozen, cryo-sectioned and mounted on glass slides for DESI-MS image acquisition. Prior to assessing precision, optimal geometric and electrospray solvent parameters were determined to maximize the number of detected lipid species and associated Total Ion Count (TIC). The same settings were utilized for all subsequent experiments. Repeatability measurements were performed using the same instrument, by the same operator on a total of 16 tissue sections (four from each quadrant of the tumor). Reproducibility measurements were determined in a different laboratory, on a separate DESI-MS platform and by an independent operator on 4 sections of one quadrant and compared to the corresponding measurements made for the repeatability experiments. The mean ± SD CV of lipid ion intensities was found to be 22 ± 7% and 18 ± 8% as measures of repeatability and reproducibility, respectively. In conclusion, DESI-MS has acceptable levels of reproducibility for the analysis of lipids in human cancer tissue and is suitable for the purposes of clinical research and diagnostics.
Dekker TJA, Balluff BD, Jones EA, et al., 2014, Multicenter Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) Identifies Proteomic Differences in Breast-Cancer-Associated Stroma, JOURNAL OF PROTEOME RESEARCH, Vol: 13, Pages: 4730-4738, ISSN: 1535-3893
Strittmatter N, Rebec M, Jones EA, et al., 2014, Characterization and identification of clinically relevant microorganisms using rapid evaporative ionization mass spectrometry, Analytical Chemistry, Vol: 86, Pages: 6555-6562, ISSN: 0003-2700
Rapid evaporative ionization mass spectrometry (REIMS) was investigated for its suitability as a general identification system for bacteria and fungi. Strains of 28 clinically relevant bacterial species were analyzed in negative ion mode, and corresponding data was subjected to unsupervised and supervised multivariate statistical analyses. The created supervised model yielded correct cross-validation results of 95.9%, 97.8%, and 100% on species, genus, and Gram-stain level, respectively. These results were not affected by the resolution of the mass spectral data. Blind identification tests were performed for strains cultured on different culture media and analyzed using different instrumental platforms which led to 97.8–100% correct identification. Seven different Escherichia coli strains were subjected to different culture conditions and were distinguishable with 88% accuracy. In addition, the technique proved suitable to distinguish five pathogenic Candida species with 98.8% accuracy without any further modification to the experimental workflow. These results prove that REIMS is sufficiently specific to serve as a culture condition-independent tool for the identification and characterization of microorganisms.
Abbassi-Ghadi N, Veselkov K, Kumar S, et al., 2014, Discrimination of lymph node metastases using desorption electrospray ionisation-mass spectrometry imaging, Chemical Communications, Vol: 50, Pages: 3661-3664, ISSN: 1359-7345
Desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) has been used for the identification of cancer within lymph nodes with accurate spatial distribution in comparison to gold standard matched immuno-histopathological images. The metabolic profile of the cancerous lymph nodes was similar to that of the primary tumour site.
Veselkov KA, Mirnezami R, Strittmatter N, et al., 2014, Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 1216-1221, ISSN: 0027-8424
Mass spectrometry imaging (MSI) provides the opportunity toinvestigate tumor biology from an entirely novel biochemicalperspective and could lead to the identification of a new pool ofcancer biomarkers. Effective clinical translation of histology-drivenMSI in systems oncology requires precise colocalization of morphologicaland biochemical features as well as advanced methodsfor data treatment and interrogation. Currently proposed MSIworkflows are subject to several limitations, including nonoptimizedraw data preprocessing, imprecise image coregistration,and limited pattern recognition capabilities. Here we outline acomprehensive strategy for histology-driven MSI, using desorptionelectrospray ionization that covers (i) optimized data preprocessingfor improved information recovery; (ii) precise imagecoregistration; and (iii) efficient extraction of tissue-specific molecularion signatures for enhanced biochemical distinction of differenttissue types. The proposed workflow has been used to investigateregion-specific lipid signatures in colorectal cancer tissue. Uniquelipid patterns were observed using this approach according totissue type, and a tissue recognition system using multivariatemolecular ion patterns allowed highly accurate (>98%) identificationof pixels according to morphology (cancer, healthy mucosa,smooth muscle, and microvasculature). This strategy offers uniqueinsights into tumor microenvironmental biochemistry and shouldfacilitate compilation of a large-scale tissue morphology-specificMSI spectral database with which to pursue next-generation, fullyautomated histological approaches.
Mirnezami R, Veselkov K, Strittmatter N, et al., 2013, Novel data processing and image co-registration algorithm for region-specific lipid profiling in colorectal cancer tissue using DESI imaging mass spectrometry, 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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