The ability to measure the mechanical properties of tissue and materials in vivo with high spatial resolution would have a broad range of biomedical applications. Conventional mechanical testing has been widely used, but is invasive and difficult to apply to biological samples in vivo, whereas acoustic techniques such as ultrasound and elastography are not well suited for quantitative measurement requiring high sensitivity and accuracy. The objective of this program is to develop a new method based on Brillouin light scattering to probe the biomechanical properties, non-invasively and quantitatively with microscopic resolution. Brillouin scattering is an inelastic process mediated by acoustic phonons, similar to Raman scattering by vibrational phonons. The first specific aim of this proposed study is to develop a Brillouin microscope by combining a novel high-extinction fully-parallel spectrometer with high-resolution confocal imaging. The feasibility of this instrument in tissue engineering and ophthalmology will be tested. The second specific aim is to measure the viscoelastic moduli of cross-linked collagen scaffolds for cartilage repair. Biomechanical microenvironments within collagen-cell constructs will be imaged over time with cellular resolution. The third specific aim is to measure the viscoelastic properties of the crystalline lens, cornea, and vitreous in mice and monitor their age-dependent changes in vivo longitudinally. A successful demonstration may open up a new possibility for understanding and evaluating various age-related ocular problems in vivo. Measuring tissue mechanical properties in vivo and with high spatial resolution remains a significant challenge. The ability to measure and image the biomechanical properties of tissue and biomaterials in vivo by Brillouin microscopy would have broad applications in tissue engineering, cataract surgery, drug delivery, intraoperative tissue characterization, as well as basic investigations to understand the role of tissue biomechanics in various diseases and age-related problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB008472-02
Application #
7632189
Study Section
Microscopic Imaging Study Section (MI)
Program Officer
Zhang, Yantian
Project Start
2008-06-15
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2011-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$219,240
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Scarcelli, Giuliano; Yun, Seok Hyun (2012) In vivo Brillouin optical microscopy of the human eye. Opt Express 20:9197-202
Scarcelli, Giuliano; Pineda, Roberto; Yun, Seok Hyun (2012) Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci 53:185-90
Scarcelli, Giuliano; Kim, Pilhan; Yun, Seok Hyun (2011) In vivo measurement of age-related stiffening in the crystalline lens by Brillouin optical microscopy. Biophys J 101:1539-45
Scarcelli, Giuliano; Yun, Seok Hyun (2011) Multistage VIPA etalons for high-extinction parallel Brillouin spectroscopy. Opt Express 19:10913-22
Scarcelli, Giuliano; Yun, Seok Hyun (2007) Confocal Brillouin microscopy for three-dimensional mechanical imaging. Nat Photonics 2:39-43