Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing

Author(s)Berke,Ian M.
Author(s)Miola,Joseph P.
Author(s)David,Michael A.
Author(s)Smith,Melanie K.
Author(s)Price,Christopher
Ordered AuthorIan M. Berke, Joseph P. Miola, Michael A. David, Melanie K. Smith, Christopher Price
UD AuthorDavidson, Michael J;Price, Christopher
Date Accessioned2017-07-25T19:33:18Z
Date Available2017-07-25T19:33:18Z
Copyright Date2016 Berke et al
Publication Date3/1/16
DescriptionPublisher's PDF
AbstractIn situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent Developmentelopments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro-and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues.
DepartmentUniversity of Delaware, Department of Biomedical Engineering
CitationBerke, I. M., Miola, J. P., David, M. A., Smith, M. K., & Price, C. (2016). Seeing through musculoskeletal tissues: Improving in situ imaging of bone and the lacunar canalicular system through optical clearing. Plos One, 11(3), e0150268. doi:10.1371/journal.pone.0150268
DOI10.1371/journal.pone.0150268
ISSN1932-6203
URLhttp://udspace.udel.edu/handle/19716/21601
LanguageEnglish
PublisherPublic Library Science
dc.rightsCC BY 4.0
dc.sourcePLoS One
dc.source.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150268
TitleSeeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing
TypeArticle
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