Virtual biopsy of rat tympanic membrane using higher harmonic generation microscopy

Wen Jeng Lee, Chia Fone Lee, Szu Yu Chen, Yuh Shyang Chen, Chi Kuang Sun

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Multiharmonic optical microscopy has been widely applied in biomedical research due to its unique capability to perform noninvasive studies of biomaterials. In this study, virtual biopsy based on back-propagating multiple optical harmonics, combining second and third harmonics, is applied in unfixed rat tympanic membrane. We show that third harmonic generation can provide morphologic information on the epithelial layers of rat tympanic membrane as well as radial collagen fibers in middle fibrous layers, and that second harmonic generation can provide information on both radial and circular collagen fibers in middle fibrous layers. Through third harmonic generation, the capillary and red blood cells in the middle fibrous layer are also noted. Additionally, the 3-D relationship to adjacent bony structures and spatial variations in thickness and curvature are obtained. Our study demonstrates the feasibility of using a noninvasive optical imaging system for comprehensive evaluation of the tympanic membrane.

Original languageEnglish
Article number046012
JournalJournal of Biomedical Optics
Issue number4
StatePublished - Jul 2010


  • Middle ear modeling
  • Multiharmonic generation microscopy
  • Tympanic membrane


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