Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy

Timothy J. Muldoon, Mark C. Pierce, Dawn L. Nida, Michelle D. Williams, Ann Gillenwater, Rebecca Richards-Kortum

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

Conventional histopathology involves sampling, sectioning and staining of tissue specimens prior to microscopic evaluation, and provides diagnostic information at a single location and point in time. In vivo microscopy and molecular-targeted optical labeling are two rapidly developing fields, which together have the potential to provide anatomical and functional indications of disease by staining and imaging tissue in situ. To address the need for high-resolution imaging instrumentation, we have developed a compact, robust, and inexpensive fiber-optic microendoscopy system based around wide-field LED illumination, a flexible 1 mm diameter fiber-optic bundle, and a color CCD camera. We demonstrate the subcellular resolution imaging capabilities of the system through a series of experiments, beginning with simultaneous imaging of three different cancer cell lines in culture, each targeted with a distinct fluorescent label. We used the narrow diameter probe to access subcutaneous tumors in an in vivo murine model, allowing direct comparison of microendoscopy images with macroscopic images and histopathology. A surgically resected tissue specimen from the human oral cavity was imaged across the clinical margin, demonstrating qualitative and quantitative distinction between normal and cancerous tissue based on sub-cellular image features. Finally, the fiber-optic microendoscope was used on topically-stained normal human oral mucosa in vivo, resolving epithelial cell nuclei and membranes in real-time fluorescence images. Our results demonstrate that this imaging system can potentially complement conventional diagnostic techniques, and support efforts to translate emerging molecular-diagnostic and therapeutic agents into clinical use.

Original languageEnglish (US)
Pages (from-to)16413-16423
Number of pages11
JournalOptics Express
Volume15
Issue number25
DOIs
StatePublished - Dec 12 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Atomic and Molecular Physics, and Optics

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