René Hägerling1, Dominik Drees2, Aaron Scherzinger2,3, Cathrin Dierkes1, Silvia Martin-Almedina4, Stefan Butz5, Kristiana Gordon4, Michael Schäfers6,7, Klaus Hinrichs3,7, Pia Ostergaard4, Dietmar Vestweber5, Tobias Goerge8, Sahar Mansour4, Xiaoyi Jiang2,7, Peter S Mortimer4, Friedemann Kiefer1,6,7. 1. Mammalian Cell Signaling Laboratory, Max Planck Institute for Molecular Biomedicine, Münster, Germany. 2. Pattern Recognition and Image Analysis Group, Department of Computer Science, and. 3. Visualization and Computer Graphics Group, Department of Computer Science, University of Münster, Münster, Germany. 4. Molecular and Clinical Sciences Institute, St. George's University of London, London, United Kingdom. 5. Department Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany. 6. European Institute for Molecular Imaging, University of Münster, Münster, Germany. 7. DFG Cells-in-Motion Cluster of Excellence 1003, Münster, Germany. 8. Department of Dermatology, University Hospital of Münster, Münster, Germany.
Abstract
BACKGROUND: Lack of investigatory and diagnostic tools has been a major contributing factor to the failure to mechanistically understand lymphedema and other lymphatic disorders in order to develop effective drug and surgical therapies. One difficulty has been understanding the true changes in lymph vessel pathology from standard 2D tissue sections. METHODS: VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction), a light-sheet microscopy-based approach for the analysis of tissue biopsies, is based on digital reconstruction and visualization of microscopic image stacks. VIPAR allows semiautomated segmentation of the vasculature and subsequent nonbiased extraction of characteristic vessel shape and connectivity parameters. We applied VIPAR to analyze biopsies from healthy lymphedematous and lymphangiomatous skin. RESULTS: Digital 3D reconstruction provided a directly visually interpretable, comprehensive representation of the lymphatic and blood vessels in the analyzed tissue volumes. The most conspicuous features were disrupted lymphatic vessels in lymphedematous skin and a hyperplasia (4.36-fold lymphatic vessel volume increase) in the lymphangiomatous skin. Both abnormalities were detected by the connectivity analysis based on extracted vessel shape and structure data. The quantitative evaluation of extracted data revealed a significant reduction of lymphatic segment length (51.3% and 54.2%) and straightness (89.2% and 83.7%) for lymphedematous and lymphangiomatous skin, respectively. Blood vessel length was significantly increased in the lymphangiomatous sample (239.3%). CONCLUSION: VIPAR is a volume-based tissue reconstruction data extraction and analysis approach that successfully distinguished healthy from lymphedematous and lymphangiomatous skin. Its application is not limited to the vascular systems or skin. FUNDING: Max Planck Society, DFG (SFB 656), and Cells-in-Motion Cluster of Excellence EXC 1003.
BACKGROUND: Lack of investigatory and diagnostic tools has been a major contributing factor to the failure to mechanistically understand lymphedema and other lymphatic disorders in order to develop effective drug and surgical therapies. One difficulty has been understanding the true changes in lymph vessel pathology from standard 2D tissue sections. METHODS:VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction), a light-sheet microscopy-based approach for the analysis of tissue biopsies, is based on digital reconstruction and visualization of microscopic image stacks. VIPAR allows semiautomated segmentation of the vasculature and subsequent nonbiased extraction of characteristic vessel shape and connectivity parameters. We applied VIPAR to analyze biopsies from healthy lymphedematous and lymphangiomatous skin. RESULTS: Digital 3D reconstruction provided a directly visually interpretable, comprehensive representation of the lymphatic and blood vessels in the analyzed tissue volumes. The most conspicuous features were disrupted lymphatic vessels in lymphedematous skin and a hyperplasia (4.36-fold lymphatic vessel volume increase) in the lymphangiomatous skin. Both abnormalities were detected by the connectivity analysis based on extracted vessel shape and structure data. The quantitative evaluation of extracted data revealed a significant reduction of lymphatic segment length (51.3% and 54.2%) and straightness (89.2% and 83.7%) for lymphedematous and lymphangiomatous skin, respectively. Blood vessel length was significantly increased in the lymphangiomatous sample (239.3%). CONCLUSION:VIPAR is a volume-based tissue reconstruction data extraction and analysis approach that successfully distinguished healthy from lymphedematous and lymphangiomatous skin. Its application is not limited to the vascular systems or skin. FUNDING: Max Planck Society, DFG (SFB 656), and Cells-in-Motion Cluster of Excellence EXC 1003.
Authors: René Hägerling; Cathrin Pollmann; Martin Andreas; Christian Schmidt; Harri Nurmi; Ralf H Adams; Kari Alitalo; Volker Andresen; Stefan Schulte-Merker; Friedemann Kiefer Journal: EMBO J Date: 2013-01-08 Impact factor: 11.598
Authors: Nils Rouven Hansmeier; Ina Sophie Büschlen; Rose Yinghan Behncke; Sascha Ulferts; Radjesh Bisoendial; René Hägerling Journal: Int J Mol Sci Date: 2022-04-15 Impact factor: 6.208
Authors: Farsam Eliat; Rebecca Sohn; Henrik Renner; Theresa Kagermeier; Stefan Volkery; Heike Brinkmann; Nils Kirschnick; Friedemann Kiefer; Martha Grabos; Katharina Becker; Ivan Bedzhov; Hans R Schöler; Jan M Bruder Journal: Sci Rep Date: 2022-04-01 Impact factor: 4.996
Authors: Stefanie Bobe; Daniel Beckmann; Dorothee Maria Klump; Cathrin Dierkes; Nils Kirschnick; Esther Redder; Nadine Bauer; Michael Schäfers; Raghu Erapaneedi; Benjamin Risse; Serge A van de Pavert; Friedemann Kiefer Journal: Front Cell Dev Biol Date: 2022-08-16