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Correlating 3D morphology with molecular pathology: fibrotic remodelling in human lung biopsies
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  1. Manuela Kellner1,2,
  2. Judith Wehling2,3,
  3. Gregor Warnecke2,4,
  4. Marko Heidrich5,
  5. Nicole Izykowski2,3,
  6. Jens Vogel-Claussen2,6,
  7. Raoul-Amadeus Lorbeer5,
  8. Georgios Antonopoulos5,
  9. Sabina Janciauskiene2,7,8,
  10. Roman Grothausmann1,8,
  11. Lars Knudsen1,2,
  12. Tammo Ripken5,
  13. Heiko Meyer4,5,
  14. Hans Kreipe2,3,
  15. Matthias Ochs1,2,8,
  16. Danny Jonigk2,3,
  17. Mark Philipp Kühnel1,2,8
  1. 1Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany
  2. 2Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
  3. 3Institute for Pathology, Hannover Medical School, Hannover, Germany
  4. 4Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, Hannover, Germany
  5. 5Biomedical Optics Department, Laser Zentrum Hannover e.V., Hannover, Germany
  6. 6Department of Radiology, Hannover Medical School, Hannover, Germany
  7. 7Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany
  8. 8REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany
  1. Correspondence to Dr Mark Philipp Kühnel, Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover 30625, Germany; kuehnel.mark{at}mh-hannover.de

Abstract

Assessing alterations of the parenchymal architecture is essential in understanding fibrosing interstitial lung diseases. Here, we present a novel method to visualise fibrotic remodelling in human lungs and correlate morphological three-dimensional (3D) data with gene and protein expression in the very same sample. The key to our approach is a novel embedding resin that clears samples to full optical transparency and simultaneously allows 3D laser tomography and preparation of sections for histology, immunohistochemistry and RNA isolation. Correlating 3D laser tomography with molecular diagnostic techniques enables new insights into lung diseases. This approach has great potential to become an essential tool in pulmonary research.

  • Interstitial Fibrosis
  • Imaging/CT MRI etc
  • Allergic Alveolitis

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