title: Non-rigid landmark-based large-scale image registration in 3-D reconstruction of mouse and rat kidney nephrons.
abstract: BACKGROUND
  Serial histological sections are suffering from mechanical distortions that disturb the reconstruction of 3-D objects. We have corrected such artifacts with a non-rigid landmark-based method that respects the original geometry in the tissue block. The method is exemplified on a large scale in the registration of semi-thin serial sections of the mouse and rat kidneys, and has been tested on FFPE-sections.
  
  
  OBJECTIVE
  In this study of mouse and rat kidneys, we have measured and characterized the deformations introduced in the preparation of 2.5-μm-thick Epon sections and then eliminated them by a landmark-based non-rigid transformation (NRT).
  
  
  METHODS
  We obtained 2.5-μm-thick serial Epon sections from three mouse kidneys and three rat kidneys for 3-D reconstruction of the nephron tubules. First, the images from 3000 serial mouse and 13,000 serial rat sections underwent a classic rigid registration (CRR), and the distortions were measured and indexed. The section images underwent a further NRT in order to compensate for the deformations. The NRT used is a classic interactive landmark-based approach. The quality of the NRT was verified by comparing the geometry of the transformed images with corresponding block images.
  
  
  RESULTS
  After CRR, the 2.5-μm-thick sections had a linear deformation of up to 2%, the tubular lengths were overestimated with up to 1.5×, and it was most difficult to trace the tubules from section to section. After the additional NRT, the geometry of the images reflected the original geometry in the block, the tubular lengths were no longer overestimated, and the NRT highly facilitated the tracing of the tubular system.
  
  
  CONCLUSIONS
  NRT has facilitated the tracing of the tubular system in kidneys, a tracing, which would otherwise have been most difficult to perform. NRT has yielded substantial new knowledge to segmental and spatial nephron organization in the mouse and rat kidneys.
authors.affiliation: Department of Rheumatology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China(1); Department of Biomedicine - Anatomy, Aarhus University, Aarhus, Denmark. Electronic address: yanling@ana.au.dk.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, China Medical University, Shenyang, China. Electronic address: shjchang@mail.cmu.edu.cn.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: China Medical University, Department of Histology and Embryology, China Medical University, Shenyang, China. Electronic address: zhaixy@mail.cmu.edu.cn.
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Zhai
authors.affiliation: Department of Biomedicine - Anatomy, Aarhus University, Aarhus, Denmark. Electronic address: jst@ana.au.dk.
authors.forename: Jesper Skovhus
authors.initials: JS
authors.lastname: Thomsen
authors.affiliation: Department of Biomedicine - Anatomy, Aarhus University, Aarhus, Denmark. Electronic address: eic@ana.au.dk.
authors.forename: Erik I
authors.initials: EI
authors.lastname: Christensen
authors.affiliation: Department of Biomedicine - Anatomy, Aarhus University, Aarhus, Denmark. Electronic address: aa@neuro.au.dk.
authors.forename: Arne
authors.initials: A
authors.lastname: Andreasen
mesh_terms: D000818:Animals; D006651:Histocytochemistry / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007668:Kidney / Q000033:anatomy & histology*; D051379:Mice; D008867:Microtomy; D009399:Nephrons / Q000033:anatomy & histology*; D051381:Rats
keywords: Alignment; Epon; Histological; Semi-thin; Serial sections