title: Framework for 3D histologic reconstruction and fusion with in vivo MRI: Preliminary results of characterizing pulmonary inflammation in a mouse model.
abstract: OBJECTIVE
  Pulmonary inflammation is associated with a variety of diseases. Assessing pulmonary inflammation on in vivo imaging may facilitate the early detection and treatment of lung diseases. Although routinely used in thoracic imaging, computed tomography has thus far not been compellingly shown to characterize inflammation in vivo. Alternatively, magnetic resonance imaging (MRI) is a nonionizing radiation technique to better visualize and characterize pulmonary tissue. Prior to routine adoption of MRI for early characterization of inflammation in humans, a rigorous and quantitative characterization of the utility of MRI to identify inflammation is required. Such characterization may be achieved by considering ex vivo histology as the ground truth, since it enables the definitive spatial assessment of inflammation. In this study, the authors introduce a novel framework to integrate 2D histology, ex vivo and in vivo imaging to enable the mapping of the extent of disease from ex vivo histology onto in vivo imaging, with the goal of facilitating computerized feature analysis and interrogation of disease appearance on in vivo imaging. The authors' framework was evaluated in a preclinical preliminary study aimed to identify computer extracted features on in vivo MRI associated with chronic pulmonary inflammation.
  
  
  METHODS
  The authors' image analytics framework first involves reconstructing the histologic volume in 3D from individual histology slices. Second, the authors map the disease ground truth onto in vivo MRI via coregistration with 3D histology using the ex vivo lung MRI as a conduit. Finally, computerized feature analysis of the disease extent is performed to identify candidate in vivo imaging signatures of disease presence and extent.
  
  
  RESULTS
  The authors evaluated the framework by assessing the quality of the 3D histology reconstruction and the histology-MRI fusion, in the context of an initial use case involving characterization of chronic inflammation in a mouse model. The authors' evaluation considered three mice, two with an inflammation phenotype and one control. The authors' iterative 3D histology reconstruction yielded a 70.1% ± 2.7% overlap with the ex vivo MRI volume. Across a total of 17 anatomic landmarks manually delineated at the division of airways, the target registration error between the ex vivo MRI and 3D histology reconstruction was 0.85 ± 0.44 mm, suggesting that a good alignment of the ex vivo 3D histology and ex vivo MRI had been achieved. The 3D histology-in vivo MRI coregistered volumes resulted in an overlap of 73.7% ± 0.9%. Preliminary computerized feature analysis was performed on an additional four control mice, for a total of seven mice considered in this study. Gabor texture filters appeared to best capture differences between the inflamed and noninflamed regions on MRI.
  
  
  CONCLUSIONS
  The authors' 3D histology reconstruction and multimodal registration framework were successfully employed to reconstruct the histology volume of the lung and fuse it with in vivo MRI to create a ground truth map for inflammation on in vivo MRI. The analytic platform presented here lays the framework for a rigorous validation of the identified imaging features for chronic lung inflammation on MRI in a large prospective cohort.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Mirabela
authors.initials: M
authors.lastname: Rusu
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08854.
authors.forename: Thea
authors.initials: T
authors.lastname: Golden
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08854.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gow
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Anant
authors.initials: A
authors.lastname: Madabhushi
mesh_terms: D000465:Algorithms; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006652:Histological Techniques / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008168:Lung / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000473:pathology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D