title: Characterization of Heterotopic Ossification Using Radiographic Imaging: Evidence for a Paradigm Shift.
abstract: Heterotopic ossification (HO) is the growth of extra-skeletal bone which occurs following trauma, burns, and in patients with genetic bone morphogenetic protein (BMP) receptor mutations. The clinical and laboratory evaluation of HO is dependent on radiographic imaging to identify and characterize these lesions. Here we show that despite its inadequacies, plain film radiography and single modality microCT continue to serve as a primary method of HO imaging in nearly 30% of published in vivo literature. Furthermore, we demonstrate that detailed microCT analysis is superior to plain film and single modality microCT radiography specifically in the evaluation of HO formed through three representative models due to its ability to 1) define structural relationships between growing extra-skeletal bone and normal, anatomic bone, 2) provide accurate quantification and growth rate based on volume of the space-occupying lesion, thereby facilitating assessments of therapeutic intervention, 3) identify HO at earlier times allowing for evaluation of early intervention, and 4) characterization of metrics of bone physiology including porosity, tissue mineral density, and cortical and trabecular volume. Examination of our trauma model using microCT demonstrated two separate areas of HO based on anatomic location and relationship with surrounding, normal bone structures. Additionally, microCT allows HO growth rate to be evaluated to characterize HO progression. Taken together, these data demonstrate the need for a paradigm shift in the evaluation of HO towards microCT as a standard tool for imaging.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: R Cameron
authors.initials: RC
authors.lastname: Brownley
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Shawn
authors.initials: S
authors.lastname: Loder
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Oluwatobi
authors.initials: O
authors.lastname: Eboda
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Peterson
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Hwang
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Breuler
authors.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kaartinen
authors.affiliation: Albert Einstein School of Medicine, New York, NY, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: School of Dentistry, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
mesh_terms: D000818:Animals; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D009999:Ossification, Heterotopic / Q000000981:diagnostic imaging*; D055114:X-Ray Microtomography