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Three-dimensional reconstruction of the distribution of elemental tags in single cells using laser ablation ICP-mass spectrometry via registration approaches

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A Correction to this article was published on 28 March 2019

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Abstract

This paper describes a workflow towards the reconstruction of the three-dimensional elemental distribution profile within human cervical carcinoma cells (HeLa), at a spatial resolution down to 1 μm, employing state-of-the-art laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) instrumentation. The suspended cells underwent a series of fixation/embedding protocols and were stained with uranyl acetate and an Ir-based DNA intercalator. A priori, laboratory-based absorption micro-computed tomography (μ-CT) was applied to acquire a reference frame of the morphology of the cells and their spatial distribution before sectioning. After CT analysis, a trimmed 300 × 300 × 300 μm3 block was sectioned into a sequential series of 132 sections with a thickness of 2 μm, which were subjected to LA-ICP-MS imaging. A pixel acquisition rate of 250 pixels s−1 was achieved, through a bidirectional scanning strategy. After acquisition, the two-dimensional elemental images were reconstructed using the timestamps in the laser log file. The synchronization of the data required an improved optimization algorithm, which forces the pixels of scans in different ablation directions to be spatially coherent in the direction orthogonal to the scan direction. The volume was reconstructed using multiple registration approaches. Registration using the section outline itself as a fiducial marker resulted into a volume which was in good agreement with the morphology visualized in the μ-CT volume. The 3D μ-CT volume could be registered to the LA-ICP-MS volume, consisting of 2.9 × 107 voxels, and the nucleus dimensions in 3D space could be derived.

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  • 28 March 2019

    The authors would like to call the reader’s attention to the fact that unfortunately the originally provided affiliation for Dr. Tomoko Asaoka was not correct.

References

  1. Hare DJ, Lee JK, Beavis AD, van Gramberg A, George J, Adlard PA, et al. Three-dimensional atlas of Iron, copper, and zinc in the mouse cerebrum and brainstem. Anal Chem. 2012;84(9):3990–7. https://doi.org/10.1021/ac300374x.

    Article  CAS  PubMed  Google Scholar 

  2. Paul B, Hare DJ, Bishop DP, Paton C, Nguyen VT, Cole N, et al. Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging. Chem Sci. 2015;6:5383–93. https://doi.org/10.1039/c5sc02231b

  3. Gundlach-Graham A, Gunther D. Toward faster and higher resolution LA-ICPMS imaging: on the co-evolution of LA cell design and ICPMS instrumentation. Anal Bioanal Chem. 2016;408(11):2687–95. https://doi.org/10.1007/s00216-015-9251-8.

    Article  CAS  PubMed  Google Scholar 

  4. Van Malderen SJM, Managh AJ, Sharp BL, Vanhaecke F. Recent developments in the design of rapid response cells for laser ablation-inductively coupled plasma-mass spectrometry and their impact on bioimaging applications. J Anal Atom Spectrom. 2016;31(2):423–39. https://doi.org/10.1039/c5ja00430f.

    Article  Google Scholar 

  5. Pisonero J, Bouzas-Ramos D, Traub H, Cappella B, Álvarez-Llamas C, Richter S, et al. Critical evaluation of fast and highly resolved elemental distribution in single cells using LA-ICP-SFMS. J Anal Atom Spectrom. 2018. https://doi.org/10.1039/c8ja00096d.

  6. Skraskova K, Khmelinskii A, Abdelmoula WM, De Munter S, Baes M, McDonnell L, et al. Precise anatomic localization of accumulated lipids in Mfp2 deficient murine brains through automated registration of SIMS images to the Allen brain atlas. J Am Soc Mass Spectrom. 2015;26(6):948–57. https://doi.org/10.1007/s13361-015-1146-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Verbeeck N, Yang J, De Moor B, Caprioli RM, Waelkens E, Van de Plas R. Automated anatomical interpretation of ion distributions in tissue: linking imaging mass spectrometry to curated atlases. Anal Chem. 2014;86(18):8974–82. https://doi.org/10.1021/ac502838t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Abdelmoula WM, Skraskova K, Balluff B, Carreira RJ, Tolner EA, Lelieveldt BP, et al. Automatic generic registration of mass spectrometry imaging data to histology using nonlinear stochastic embedding. Anal Chem. 2014;86(18):9204–11. https://doi.org/10.1021/ac502170f.

    Article  CAS  PubMed  Google Scholar 

  9. Seeley EH, Caprioli RM. Molecular imaging of proteins in tissues by mass spectrometry. Proc Natl Acad Sci U S A. 2008;105(47):18126–31. https://doi.org/10.1073/pnas.0801374105.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lanekoff I, Thomas M, Carson JP, Smith JN, Timchalk C, Laskin J. Imaging nicotine in rat brain tissue by use of nanospray desorption electrospray ionization mass spectrometry. Anal Chem. 2013;85(2):882–9. https://doi.org/10.1021/ac302308p.

    Article  CAS  PubMed  Google Scholar 

  11. Thiele H, Heldmann S, Trede D, Strehlow J, Wirtz S, Dreher W, et al. 2D and 3D MALDI-imaging: conceptual strategies for visualization and data mining. Biochim Biophys Acta. 2014;1844(1 Pt A):117–37. https://doi.org/10.1016/j.bbapap.2013.01.040.

    Article  CAS  PubMed  Google Scholar 

  12. Maes F, Collignon A, Vandermeulen D, Marchal G, Suetens P. Multi-modality image registration by maximization of mutual information. Proceedings of the Ieee Workshop on Mathematical Methods in Biomedical Image Analysis. 1996:14–22. https://doi.org/10.1109/Mmbia.1996.534053.

  13. Pluim JP, Maintz JB, Viergever MA. Mutual-information-based registration of medical images: a survey. IEEE Trans Med Imaging. 2003;22(8):986–1004. https://doi.org/10.1109/TMI.2003.815867.

    Article  PubMed  Google Scholar 

  14. Seeley EH, Wilson KJ, Yankeelov TE, Johnson RW, Gore JC, Caprioli RM, et al. Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease. Bone. 2014;61:208–16. https://doi.org/10.1016/j.bone.2014.01.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Neumann EK, Comi TJ, Spegazzini N, Mitchell JW, Rubakhin SS, Gillette MU, et al. Multimodal chemical analysis of the brain by high mass resolution mass spectrometry and infrared spectroscopic imaging. Anal Chem. 2018;90(19):11572–80. https://doi.org/10.1021/acs.analchem.8b02913.

    Article  CAS  PubMed  Google Scholar 

  16. Van Malderen SJ, Laforce B, Van Acker T, Nys C, De Rijcke M, de Rycke R, et al. Three-dimensional reconstruction of the tissue-specific multielemental distribution within Ceriodaphnia dubia via multimodal registration using laser ablation ICP-mass spectrometry and X-ray spectroscopic techniques. Anal Chem. 2017;89(7):4161–8. https://doi.org/10.1021/acs.analchem.7b00111.

    Article  CAS  PubMed  Google Scholar 

  17. Duenas ME, Essner JJ, Lee YJ. 3D MALDI mass spectrometry imaging of a single cell: spatial mapping of lipids in the embryonic development of zebrafish. Sci Rep. 2017;7(1):14946. https://doi.org/10.1038/s41598-017-14949-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Passarelli MK, Newman CF, Marshall PS, West A, Gilmore IS, Bunch J, et al. Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging. Anal Chem. 2015;87(13):6696–702. https://doi.org/10.1021/acs.analchem.5b00842.

    Article  CAS  PubMed  Google Scholar 

  19. Robinson MA, Graham DJ, Castner DG. ToF-SIMS depth profiling of cells: z-correction, 3D imaging, and sputter rate of individual NIH/3T3 fibroblasts. Anal Chem. 2012;84(11):4880–5. https://doi.org/10.1021/ac300480g.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fletcher JS, Rabbani S, Henderson A, Lockyer NP, Vickerman JC. Three-dimensional mass spectral imaging of HeLa-M cells--sample preparation, data interpretation and visualisation. Rapid Commun Mass Spectrom. 2011;25(7):925–32. https://doi.org/10.1002/rcm.4944.

    Article  CAS  PubMed  Google Scholar 

  21. Giesen C, Wang HA, Schapiro D, Zivanovic N, Jacobs A, Hattendorf B, et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat Methods. 2014;11(4):417–22. https://doi.org/10.1038/nmeth.2869.

    Article  CAS  PubMed  Google Scholar 

  22. Catena R, Montuenga LM, Bodenmiller B. Ruthenium counterstaining for imaging mass cytometry. J Pathol. 2018;244(4):479–84. https://doi.org/10.1002/path.5049.

    Article  CAS  PubMed  Google Scholar 

  23. Frick DA, Giesen C, Hemmerle T, Bodenmiller B, Günther D. An internal standardisation strategy for quantitative immunoassay tissue imaging using laser ablation inductively coupled plasma mass spectrometry. J Anal At Spectrom. 2015;30(1):254–9. https://doi.org/10.1039/c4ja00293h.

    Article  CAS  Google Scholar 

  24. Van Malderen SJM, van Elteren JT, Vanhaecke F. Development of a fast laser ablation-inductively coupled plasma-mass spectrometry cell for sub-μm scanning of layered materials. J Anal At Spectrom. 2014;30(1):119–25. https://doi.org/10.1039/c4ja00137k.

    Article  CAS  Google Scholar 

  25. Teledyne CETAC Technologies Inc. Aerosol Rapid Introduction System. http://www.teledynecetac.com/product/laser-ablation/aris. Accessed 15/07/2016.

  26. Laforce B, Masschaele B, Boone MN, Schaubroeck D, Dierick M, Vekemans B, et al. Integrated three-dimensional microanalysis combining X-ray microtomography and X-ray fluorescence methodologies. Anal Chem. 2017;89(19):10617–24. https://doi.org/10.1021/acs.analchem.7b03205.

    Article  CAS  PubMed  Google Scholar 

  27. Evans D, Müller W. Automated extraction of a five-year LA-ICP-MS trace element data set of ten common glass and carbonate reference materials: long-term data quality, optimisation and laser cell homogeneity. Geostand Geoanal Res. 2018;42(2):159–88. https://doi.org/10.1111/ggr.12204.

    Article  CAS  Google Scholar 

  28. Van Malderen SJM, van Elteren JT, Šelih VS, Vanhaecke F. Considerations on data acquisition in laser ablation-inductively coupled plasma-mass spectrometry with low-dispersion interfaces. Spectrochim Acta B At Spectrosc. 2018;140:29–34. https://doi.org/10.1016/j.sab.2017.11.007.

    Article  CAS  Google Scholar 

  29. Burger M, Schwarz G, Gundlach-Graham A, Käser D, Hattendorf B, Günther D. Capabilities of laser ablation inductively coupled plasma time-of-flight mass spectrometry. J Anal Atom Spectrom. 2017;32(10):1946–59. https://doi.org/10.1039/c7ja00236j.

    Article  CAS  Google Scholar 

  30. Harris C, Stephens M. A combined corner and edge detector. Paper presented at the Procedings of the Alvey Vision Conference 1988.

  31. Pulli K, Baksheev A, Kornyakov K, Eruhimov V. Real-time computer vision with OpenCV. Commun ACM. 2012;55(6). https://doi.org/10.1145/2184319.2184337.

  32. Lowe DG. Distinctive image features from scale-invariant keypoints. Int J Comput Vis. 2004;60(2):91–110. https://doi.org/10.1023/B:Visi.0000029664.99615.94.

    Article  Google Scholar 

  33. Herrmann AJ, Techritz S, Jakubowski N, Haase A, Luch A, Panne U, et al. A simple metal staining procedure for identification and visualization of single cells by LA-ICP-MS. Analyst. 2017;142(10):1703–10. https://doi.org/10.1039/c6an02638a.

    Article  CAS  PubMed  Google Scholar 

  34. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82. https://doi.org/10.1038/nmeth.2019.

    Article  CAS  Google Scholar 

  35. Bolte S, Cordelieres FP. A guided tour into subcellular colocalization analysis in light microscopy. J Microsc. 2006;224:213–32. https://doi.org/10.1111/j.1365-2818.2006.01706.x.

    Article  CAS  PubMed  Google Scholar 

  36. Walter J, Schermelleh L, Cremer M, Tashiro S, Cremer T. Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages. J Cell Biol. 2003;160(5):685–97. https://doi.org/10.1083/jcb.200211103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Monier K, Armas JC, Etteldorf S, Ghazal P, Sullivan KF. Annexation of the interchromosomal space during viral infection. Nat Cell Biol. 2000;2(9):661–5. https://doi.org/10.1038/35023615.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge financial and logistic support from the Flemish Research Foundation (FWO, research project 12S5718N) and Teledyne CETAC Technologies. All figures were generated using the Matplotlib 3.0.2 library.

Funding

This study was financially supported by the Flemish Research Foundation (FWO, research project 12S5718N) and Teledyne CETAC Technologies. SVM is a postdoctoral fellow of the FWO, BL acknowledges his Ph.D. grant from the government agency for Innovation by Science and Technology (IWT).

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Authors and Affiliations

  1. Atomic & Mass Spectrometry (A&MS) Research Unit, Department of Chemistry, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium

    Stijn J. M. Van Malderen, Thibaut Van Acker & Frank Vanhaecke

  2. X-ray Microspectroscopy and Imaging (XMI) Research Unit, Department of Chemistry, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium

    Brecht Laforce & Laszlo Vincze

  3. Department of Biomedical Molecular Biology and VIB Center for Inflammation Research, Ghent University, Technologiepark 71, 9052, Ghent, Belgium

    Michiel De Bruyne, Riet de Rycke & Tomoko Asaoka

  4. Ghent University Expertise Centre for Transmission Electron Microscopy and VIB BioImaging Core, Ghent University, Technologiepark 927, 9052, Ghent, Belgium

    Michiel De Bruyne & Riet de Rycke

Authors
  1. Stijn J. M. Van Malderen
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  2. Thibaut Van Acker
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Corresponding author

Correspondence to Frank Vanhaecke.

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Conflict of interest

Teledyne CETAC Technologies funds the PhD grant of author Thibaut Van Acker (promoter: Frank Vanhaecke) under contract A15-TT-0627. Stijn J. M. Van Malderen and Frank Vanhaecke are inventors of patent WO2016042165A1, on which part of the technology of the ablation cell used in this work is based. Stijn J. M. Van Malderen, Thibaut Van Acker, and Frank Vanhaecke conduct research at a research unit that has licensed intellectual property to Teledyne CETAC Technologies. The other authors have no conflict of interest.

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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry with guest editors Erin Baker, Kerstin Leopold, Francesco Ricci, and Wei Wang.

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Van Malderen, S.J.M., Van Acker, T., Laforce, B. et al. Three-dimensional reconstruction of the distribution of elemental tags in single cells using laser ablation ICP-mass spectrometry via registration approaches. Anal Bioanal Chem 411, 4849–4859 (2019). https://doi.org/10.1007/s00216-019-01677-6

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