title: 3D volume reconstruction from serial breast specimen radiographs for mapping between histology and 3D whole specimen imaging.
abstract: OBJECTIVE
  In breast imaging, radiological in vivo images, such as x-ray mammography and magnetic resonance imaging (MRI), are used for tumor detection, diagnosis, and size determination. After excision, the specimen is typically sliced into slabs and a small subset is sampled. Histopathological imaging of the stained samples is used as the gold standard for characterization of the tumor microenvironment. A 3D volume reconstruction of the whole specimen from the 2D slabs could facilitate bridging the gap between histology and in vivo radiological imaging. This task is challenging, however, due to the large deformation that the breast tissue undergoes after surgery and the significant undersampling of the specimen obtained in histology. In this work, we present a method to reconstruct a coherent 3D volume from 2D digital radiographs of the specimen slabs.
  
  
  METHODS
  To reconstruct a 3D breast specimen volume, we propose the use of multiple target neighboring slices, when deforming each 2D slab radiograph in the volume, rather than performing pairwise registrations. The algorithm combines neighborhood slice information with free-form deformations, which enables a flexible, nonlinear deformation to be computed subject to the constraint that a coherent 3D volume is obtained. The neighborhood information provides adequate constraints, without the need for any additional regularization terms.
  
  
  RESULTS
  The volume reconstruction algorithm is validated on clinical mastectomy samples using a quantitative assessment of the volume reconstruction smoothness and a comparison with a whole specimen 3D image acquired for validation before slicing. Additionally, a target registration error of 5 mm (comparable to the specimen slab thickness of 4 mm) was obtained for five cases. The error was computed using manual annotations from four observers as gold standard, with interobserver variability of 3.4 mm. Finally, we illustrate how the reconstructed volumes can be used to map histology images to a 3D specimen image of the whole sample (either MRI or CT).
  
  
  CONCLUSIONS
  Qualitative and quantitative assessment has illustrated the benefit of using our proposed methodology to reconstruct a coherent specimen volume from serial slab radiographs. To our knowledge, this is the first method that has been applied to clinical breast cases, with the goal of reconstructing a whole specimen sample. The algorithm can be used as part of the pipeline of mapping histology images to ex vivo and ultimately in vivo radiological images of the breast.
authors.affiliation: Centre for Medical Image Computing, University College London, WC1E 6BT, London, UK.
authors.forename: Thomy
authors.initials: T
authors.lastname: Mertzanidou
authors.affiliation: Centre for Medical Image Computing, University College London, WC1E 6BT, London, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Hipwell
authors.affiliation: Centre for Medical Image Computing, University College London, WC1E 6BT, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Reis
authors.affiliation: Centre for Medical Image Computing, University College London, WC1E 6BT, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hawkes
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Babak
authors.initials: B
authors.lastname: Ehteshami Bejnordi
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Dalmis
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Vreemann
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Platel
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Laak
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Karssemeijer
authors.affiliation: Department of Pathology, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Meyke
authors.initials: M
authors.lastname: Hermsen
authors.affiliation: Department of Pathology, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Bult
authors.affiliation: Department of Radiology, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Ritse
authors.initials: R
authors.lastname: Mann
mesh_terms: D000465:Algorithms; D016477:Artifacts; D001940:Breast / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D006652:Histological Techniques / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008327:Mammography / Q000379:methods*; D017711:Nonlinear Dynamics; D015588:Observer Variation; D014057:Tomography, X-Ray Computed / Q000379:methods
keywords: 3D volume reconstruction; breast histology-radiology registration; serial breast specimen images