title: Quantifying massive allograft healing of the canine femur in vivo and ex vivo: a pilot study.
abstract: BACKGROUND
  Allograft integration in segmental osseous defects is unpredictable. Imaging techniques have not been applied to investigate angiogenesis and bone formation during allograft healing in a large-animal model.
  
  
  OBJECTIVE
  We used dynamic contrast-enhanced (DCE)-MRI and cone beam (CB)-CT to quantify vascularity and bone volume in a canine femoral allograft model and determined their relationship with biomechanical testing and histomorphometry.
  
  
  METHODS
  Femoral ostectomy was performed in three dogs and reconstructed with a 5-cm allograft and compression plate. At 0.5, 3, and 6 months, we performed DCE-MRI to quantify vascular permeability (Ktrans) and perfused fraction and CB-CT to quantify bone volume. We also performed posteuthanasia torsional testing and dynamic histomorphometry of the grafted and nonoperated femurs.
  
  
  RESULTS
  DCE-MRI confirmed the avascular nature of allograft healing (perfused fraction, 2.08%-3.25%). CB-CT demonstrated new bone formation at 3 months (26.2, 3.7, and 2.2 cm(3)) at the graft-host junctions, which remodeled down at 6 months (14.0, 2.2, and 2.0 cm(3)). The increased bone volume in one subject was confirmed with elevated Ktrans (0.22) at 3 months. CB-CT-identified remodeled bone at 6 months was corroborated by histomorphometry. Allografted femurs recovered only 40% of their strength at 6 months.
  
  
  CONCLUSIONS
  CB-CT and DCE-MRI can discriminate differences in angiogenesis and bone formation in the canine allograft model, which has potential to detect a small (32%) drug or device effect on biomechanical healing with only five animals per group.
authors.affiliation: Phillip Spiegel Orthopaedic Research Laboratory, Foundation for Orthopaedic Research and Education, Tampa, FL, USA.
authors.forename: Brandon G
authors.initials: BG
authors.lastname: Santoni
authors.forename: Nicole
authors.initials: N
authors.lastname: Ehrhart
authors.forename: Ricardo
authors.initials: R
authors.lastname: Betancourt-Benitez
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Beck
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001860:Bone Plates; D001863:Bone Screws; D054893:Cone-Beam Computed Tomography; D004285:Dogs; D005269:Femur / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology / Q000637:transplantation*; D008279:Magnetic Resonance Imaging; D018919:Neovascularization, Physiologic; D019637:Orthopedic Procedures / Q000295:instrumentation; D016348:Osseointegration; D010012:Osteogenesis; D010027:Osteotomy; D010865:Pilot Projects; D020127:Recovery of Function; D013997:Time Factors; D054159:Torsion, Mechanical; D014184:Transplantation, Homologous; D014945:Wound Healing