Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging

Our plain-English summary of Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging, by O.M. Voloaca, M.R. Clench, G. Koellensperger, et al (Analytical Chemistry, 2022).

The study

• Authors: O.M. Voloaca, M.R. Clench, G. Koellensperger, L.M. Cole, S.L. Haywood-Small, S. Theiner
• Journal: Analytical Chemistry
• Published: 2022;94(5):2597-2606
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This is the first report of the use of laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA-ICP-TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA-ICP-TOFMS results correlated to Perls' Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA-ICP-TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification.

In plain English

This laboratory study tested a technique that maps chemical elements in thin tissue slices (LA-ICP-TOFMS) on malignant pleural mesothelioma samples. The authors first tuned the method on lab-grown mesothelioma cells mixed with amosite, crocidolite or chrysotile. Crocidolite showed high sodium, magnesium, silicon and iron, while amosite and chrysotile showed raised magnesium, silicon and iron. They then analyzed commercially obtained tissue from four mesothelioma patients: lung tissue from two, pleura from one and chest wall from one. In the two lung samples they found asbestos fibers, which they said were most likely forming ferruginous bodies, along with high strontium. In patient 1's lung tissue, the iron signal from the fibers or particles was around 20 times the signal from the surrounding tissue. The pleura sample contained deposits the authors attributed to talc pleurodesis, a medical treatment, with raised iron signals around them. No asbestos fibers were found in the chest wall sample. The authors said further quantitative analysis is needed to classify the particles as crocidolite. They concluded the work is a step toward using the method as a clinical tool.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory analytical-method study: the method was first optimized on cell models spiked with asbestos, then applied to human mesothelioma tissue sections (essentially a small case series of tissue samples)
• Who was studied: Tissue samples from 4 malignant pleural mesothelioma patients, commercially obtained (AMSBIO, UK) and selected to be diverse: lung (patients 1 and 2), pleura (patient 3) and chest wall (patient 4). Patient details are in a supplementary table not included in the text. The study also used a human mesothelioma cell line (MSTO-211H).
• Exposure: Cell models were spiked with reference amosite, crocidolite and chrysotile asbestos. For the patient tissue, the study looked at fibers and particles found in the samples; no patient exposure histories are given in the main text.
• Main results:
  • In the cell models, crocidolite showed high sodium, magnesium, silicon and iron; amosite and chrysotile showed raised magnesium, silicon and iron.
  • Asbestos fibers, which the authors said were most likely forming ferruginous bodies, were detected in 2 of the 4 patients, both lung tissue samples.
  • In patient 1's lung tissue, one feature resembled a long fiber about 200 micrometers long.
  • In patient 1's lung tissue, the measured iron signal from the fibers or particles was around 20 times the surrounding-tissue signal. This is a signal comparison, not a measured iron concentration.
  • In patient 1's lung tissue, one long particle seen under the microscope gave no significant metal signal. The authors read this as a non-asbestos foreign body.
  • In patient 2's lung tissue, the fibers stained blue with Perls' Prussian blue stain. The authors read this as ferric iron coating the asbestos bodies.
  • High levels of strontium were found in the particles in the two lung samples.
  • In patient 3's pleura sample, deposits the authors attributed to talc pleurodesis had raised magnesium and silicon and slightly raised aluminum and phosphorus. No distinct strontium signal was detected.
  • Around the talc deposits in the pleura sample, iron signals were up to 10 times higher than in the other patients' samples.
  • No asbestos fibers were detected in patient 4's chest wall sample.
  • In patient 4's chest wall sample, magnesium, iron and zinc signals were raised around a tissue scar.
• The authors' conclusion: The authors concluded that analyzing human mesothelioma tissue this way is a step toward using the technique as a clinical tool. They also wrote that the strontium findings strongly suggest a key role for strontium in mesothelioma development, and that talc particles led to tissue damage and inflammation.
• Limitations the authors state:
  • Quantitative analysis is still needed before the particles in the samples can be correctly classified as crocidolite.
  • It was difficult to resolve hard mineral fibers within soft tissue: some element signals changed or disappeared at higher laser energy.
  • Fibers may have moved during sample preparation, so their position in the tissue must be interpreted with care.
  • Only mesothelioma tissue was studied; the authors plan to add benign and healthy tissue samples in future work.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleural Mesothelioma, Asbestos Exposure, Latency, Overall Survival, Mineral Fiber, Pleura, Talc.

Related studies

• Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma — O.M. Voloaca, C.J. Greenhalgh, et al. (2020)
• Sample preparation method for visualization of nanoparticulate captured on mixed cellulose ester filter media by enhanced darkfield microscopy and hyperspectral imaging — N.M. Neu-Baker, A.C. Eastlake, et al. (2019)
• Synchrotron soft X-ray imaging and fluorescence microscopy reveal novel features of asbestos body morphology and composition in human lung tissues — L. Pascolo, A. Gianoncelli, et al. (2011)
• Chemo-physical properties of asbestos bodies in human lung tissues studied at the nano-scale by non-invasive, label free x-ray imaging and spectroscopic techniques — F. Bardelli, F. Brun, et al. (2021)
• Diode-Pumped Laser for Lung-Sparing Surgical Treatment of Malignant Pleural Mesothelioma — S. Bölükbas, C. Biancosino, et al. (2017)
• Elemental analysis of asbestos fibers by means of electron probe techniques — I.A. Rubin, C.J. Maggiore (1974)

Browse return to medical research.