Skip to main content Accessibility help
×
Home
Hostname: page-component-559fc8cf4f-8sgpw Total loading time: 0.345 Render date: 2021-03-02T06:04:13.620Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true }

High-Resolution Episcopic Microscopy (HREM): A Tool for Visualizing Skin Biopsies

Published online by Cambridge University Press:  08 September 2014

Stefan H. Geyer
Affiliation:
MRC National Institute for Medical Research, London, NW7 1AA, UK Centre for Anatomy and Cell Biology, Medical University of Vienna, Waehringer Street 13, A-1090 Vienna, Austria
Maria M. Nöhammer
Affiliation:
Centre for Anatomy and Cell Biology, Medical University of Vienna, Waehringer Street 13, A-1090 Vienna, Austria
Markus Mathä
Affiliation:
Centre for Anatomy and Cell Biology, Medical University of Vienna, Waehringer Street 13, A-1090 Vienna, Austria
Lukas Reissig
Affiliation:
Centre for Anatomy and Cell Biology, Medical University of Vienna, Waehringer Street 13, A-1090 Vienna, Austria
Ines E. Tinhofer
Affiliation:
Centre for Anatomy and Cell Biology, Medical University of Vienna, Waehringer Street 13, A-1090 Vienna, Austria Department of Plastic and Reconstructive Surgery, Medical University Vienna, Waehringer Street 13, A-1090 Vienna, Austria
Wolfgang J. Weninger
Affiliation:
Centre for Anatomy and Cell Biology, Medical University of Vienna, Waehringer Street 13, A-1090 Vienna, Austria
Corresponding

Abstract

We evaluate the usefulness of digital volume data produced with the high-resolution episcopic microscopy (HREM) method for visualizing the three-dimensional (3D) arrangement of components of human skin, and present protocols designed for processing skin biopsies for HREM data generation. A total of 328 biopsies collected from normally appearing skin and from a melanocytic nevus were processed. Cuboidal data volumes with side lengths of ~2×3×6 mm3 and voxel sizes of 1.07×1.07×1.5 µm3 were produced. HREM data fit ideally for visualizing the epidermis at large, and for producing highly detailed volume and surface-rendered 3D representations of the dermal and hypodermal components at a structural level. The architecture of the collagen fiber bundles and the spatial distribution of nevus cells can be easily visualized with volume-rendering algorithms. We conclude that HREM has great potential to serve as a routine tool for researching and diagnosing skin pathologies.

Type
Biological Applications
Copyright
© Microscopy Society of America 2014 

Access options

Get access to the full version of this content by using one of the access options below.

References

Alex, A., Weingast, J., Weinigel, M., Kellner-Hofer, M., Nemecek, R., Binder, M., Pehamberger, H., Konig, K. & Drexler, W. (2013). Three-dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology. J Biophotonics 6(4), 352362.CrossRefGoogle ScholarPubMed
Bamforth, S.D., Chaudhry, B., Bennett, M., Wilson, R., Mohun, T.J., Van Mierop, L.H., Henderson, D.J. & Anderson, R.H. (2013). Clarification of the identity of the mammalian fifth pharyngeal arch artery. Clin Anat 26(2), 173182.CrossRefGoogle ScholarPubMed
Boone, M.A., Norrenberg, S., Jemec, G.B. & Del Marmol, V. (2012). Imaging of basal cell carcinoma by high-definition optical coherence tomography: Histomorphological correlation. A pilot study. Br J Dermatol 167(4), 856864.CrossRefGoogle ScholarPubMed
Branzan, A.L., Landthaler, M. & Szeimies, R.M. (2007). In vivo confocal scanning laser microscopy in dermatology. Lasers Med Sci 22(2), 7382.CrossRefGoogle ScholarPubMed
Dalimier, E. & Salomon, D. (2012). Full-field optical coherence tomography: A new technology for 3D high-resolution skin imaging. Dermatology 224(1), 8492.CrossRefGoogle ScholarPubMed
Dunlevy, L., Bennett, M., Slender, A., Lana-Elola, E., Tybulewicz, V.L., Fisher, E.M. & Mohun, T. (2010). Down’s syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse. Cardiovasc Res 88(2), 287295.CrossRefGoogle ScholarPubMed
Egawa, G., Natsuaki, Y., Miyachi, Y. & Kabashima, K. (2013). Three-dimensional imaging of epidermal keratinocytes and dermal vasculatures using two-photon microscopy. J Dermatol Sci 70(2), 143145.CrossRefGoogle ScholarPubMed
Fagrell, B. (1995). Advances in microcirculation network evaluation: An update. Int J Microcirc Clin Exp 15(Suppl 1), 3440.CrossRefGoogle ScholarPubMed
Geyer, S.H., Maurer, B., Pötz, L., Singh, J. & Weninger, W.J. (2012). High-resolution episcopic microscopy data-based measurements of the arteries of mouse embryos: Evaluation of significance and reproducibility under routine conditions. Cells Tissues Organs 195(6), 524534.CrossRefGoogle ScholarPubMed
Geyer, S.H., Nöhammer, M.M., Tinhofer, I.E. & Weninger, W.J. (2013). The dermal arteries of the human thumb pad. J Anat 223(6), 603609.CrossRefGoogle ScholarPubMed
Geyer, S.H. & Weninger, W.J. (2012). Some mice feature 5th pharyngeal arch arteries and double-lumen aortic arch malformations. Cells Tissues Organs 196, 9098.CrossRefGoogle ScholarPubMed
Geyer, S.H. & Weninger, W.J. (2013). Metric characterization of the aortic arch of early mouse fetuses and of a fetus featuring a double lumen aortic arch malformation. Ann Anat 195(2), 175182.CrossRefGoogle ScholarPubMed
Grazziotin, T.C., Cota, C., Buffon, R.B., Araujo Pinto, L., Latini, A. & Ardigo, M. (2010). Preliminary evaluation of in vivo reflectance confocal microscopy features of Kaposi’s sarcoma. Dermatology 220(4), 346354.CrossRefGoogle ScholarPubMed
Hegyi, J., Hegyi, V., Messer, G., Arenberger, P., Ruzicka, T. & Berking, C. (2009). Confocal laser-scanning capillaroscopy: A novel approach to the analysis of skin capillaries in vivo. Skin Res Technol 15(4), 476481.CrossRefGoogle ScholarPubMed
Ikeda, A., Umeda, N., Tsuda, K. & Ohta, S. (1991). Scanning electron microscopy of the capillary loops in the dermal papillae of the hand in primates, including man. J Electron Microsc Tech 19(4), 419428.CrossRefGoogle ScholarPubMed
Inoue, H. (1978). Three-dimensional observations of microvasculature of human finger skin. Hand 10(2), 144149.CrossRefGoogle ScholarPubMed
Kawamata, S., Ozawa, J., Hashimoto, M., Kurose, T. & Shinohara, H. (2003). Structure of the rat subcutaneous connective tissue in relation to its sliding mechanism. Arch Histol Cytol 66(3), 273279.CrossRefGoogle ScholarPubMed
König, K. & Riemann, I. (2003). High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution. J Biomed Opt 8(3), 432439.CrossRefGoogle ScholarPubMed
Lee, H.W., Lee, D.K., Lee, M.W., Choi, J.H., Moon, K.C. & Koh, J.K. (2005). Two cases of angiomyxolipoma (vascular myxolipoma) of subcutaneous tissue. J Cutan Pathol 32(5), 379382.CrossRefGoogle ScholarPubMed
Liu, G., Jia, W., Sun, V., Choi, B. & Chen, Z. (2012). High-resolution imaging of microvasculature in human skin in-vivo with optical coherence tomography. Opt Express 20(7), 76947705.CrossRefGoogle ScholarPubMed
Manelli, A., Sangiorgi, S., Ronga, M., Reguzzoni, M., Bini, A. & Raspanti, M. (2005). Plexiform vascular structures in the human digital dermal layer: A SEM-corrosion casting morphological study. Eur J Morphol 42(4–5), 173177.CrossRefGoogle ScholarPubMed
Metscher, B. (2009). MicroCT for comparative morphology: Simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues. BMC Physiol 9(1), 11.CrossRefGoogle ScholarPubMed
Miyamoto, K. & Kudoh, H. (2013). Quantification and visualization of cellular NAD(P)H in young and aged female facial skin with in vivo two-photon tomography. Br J Dermatol 169(Suppl 2), 2531.CrossRefGoogle Scholar
Mohun, T., Adams, D.J., Baldock, R., Bhattacharya, S., Copp, A.J., Hemberger, M., Houart, C., Hurles, M.E., Robertson, E., Smith, J.C., Weaver, T. & Weninger, W. (2013). Deciphering the Mechanisms of Developmental Disorders (DMDD): A new programme for phenotyping embryonic lethal mice. Dis Model Mech 6(3), 562566.CrossRefGoogle ScholarPubMed
Mohun, T.J. & Weninger, W.J. (2011). Imaging heart development using high-resolution episcopic microscopy. Curr Opin Genet Dev 21(5), 573578.CrossRefGoogle ScholarPubMed
Mohun, T.J. & Weninger, W.J. (2012 a). Embedding embryos for high-resolution episcopic microscopy (HREM). Cold Spring Harb Protoc 2012(6), 678680.CrossRefGoogle Scholar
Mohun, T.J. & Weninger, W.J. (2012 b). Generation of volume data by episcopic three-dimensional imaging of embryos. Cold Spring Harb Protoc 2012(6), 681682.Google ScholarPubMed
Pieles, G., Geyer, S.H., Szumska, D., Schneider, J., Neubauer, S., Clarke, K., Dorfmeister, K., Franklyn, A., Brown, S.D., Bhattacharya, S. & Weninger, W.J. (2007). MicroMRI-HREM pipeline for high-throughput, high-resolution phenotyping of murine embryos. J Anat 211(1), 132137.CrossRefGoogle ScholarPubMed
Sangiorgi, S., Manelli, A., Congiu, T., Bini, A., Pilato, G., Reguzzoni, M. & Raspanti, M. (2004). Microvascularization of the human digit as studied by corrosion casting. J Anat 204(2), 123131.CrossRefGoogle ScholarPubMed
Schneider, J.E. & Bhattacharya, S. (2004). Making the mouse embryo transparent: Identifying developmental malformations using magnetic resonance imaging. Birth Defects Res C Embryo Today 72(3), 241249.CrossRefGoogle ScholarPubMed
Sharpe, J., Ahlgren, U., Perry, P., Hill, B., Ross, A., Hecksher-Sorensen, J., Baldock, R. & Davidson, D. (2002). Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science 296(5567), 541545.CrossRefGoogle ScholarPubMed
Stefanowska, J., Zakowiecki, D. & Cal, K. (2010). Magnetic resonance imaging of the skin. J Eur Acad Dermatol Venereol 24(8), 875880.CrossRefGoogle Scholar
Strauch, B. & de Moura, W. (1990). Arterial system of the fingers. J Hand Surg Am 15(1), 148154.CrossRefGoogle ScholarPubMed
Tremblay, P.L., Hudon, V., Berthod, F., Germain, L. & Auger, F.A. (2005). Inosculation of tissue-engineered capillaries with the host’s vasculature in a reconstructed skin transplanted on mice. Am J Transplant 5(5), 10021010.CrossRefGoogle Scholar
Veiro, J.A. & Cummins, P.G. (1994). Imaging of skin epidermis from various origins using confocal laser scanning microscopy. Dermatology 189(1), 1622.CrossRefGoogle ScholarPubMed
Weninger, W.J. & Geyer, S.H. (2008). Episcopic 3D imaging methods: Tools for researching gene function. Curr Genomics 9, 282289.CrossRefGoogle ScholarPubMed
Weninger, W.J. & Geyer, S.H. (2009). Three-dimensional (3D) visualisation of the cardiovascular system of mouse embryos and fetus. Open Cardiovasc Imag J 1, 112.CrossRefGoogle Scholar
Weninger, W.J., Geyer, S.H., Mohun, T.J., Rasskin-Gutman, D., Matsui, T., Ribeiro, I., Costa Lda, F., Izpisua-Belmonte, J.C. & Müller, G.B. (2006). High-resolution episcopic microscopy: A rapid technique for high detailed 3D analysis of gene activity in the context of tissue architecture and morphology. Anat Embryol 211(3), 213221.CrossRefGoogle ScholarPubMed
Weninger, W.J. & Mohun, T.J. (2007). Three-dimensional analysis of molecular signals with episcopic imaging techniques. Methods Mol Biol 411, 3546.CrossRefGoogle ScholarPubMed
Zalaudek, I., Argenziano, G., Di Stefani, A., Ferrara, G., Marghoob, A.A., Hofmann-Wellenhof, R., Soyer, H.P., Braun, R. & Kerl, H. (2006). Dermoscopy in general dermatology. Dermatology 212(1), 718.CrossRefGoogle ScholarPubMed
Zhang, E.Z., Povazay, B., Laufer, J., Alex, A., Hofer, B., Pedley, B., Glittenberg, C., Treeby, B., Cox, B., Beard, P. & Drexler, W. (2011). Multimodal photoacoustic and optical coherence tomography scanner using an all optical detection scheme for 3D morphological skin imaging. Biomed Opt Express 2(8), 22022215.CrossRefGoogle ScholarPubMed

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 38
Total number of PDF views: 96 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 2nd March 2021. This data will be updated every 24 hours.

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

High-Resolution Episcopic Microscopy (HREM): A Tool for Visualizing Skin Biopsies
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

High-Resolution Episcopic Microscopy (HREM): A Tool for Visualizing Skin Biopsies
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

High-Resolution Episcopic Microscopy (HREM): A Tool for Visualizing Skin Biopsies
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *