Laser induced fluorescence as a diagnostic tool integrated into a scanning fiber endoscope for mouse imaging

Scanning fiber endoscope (SFE) technology has shown promise as a minimally invasive optical imaging tool. To date, it is capable of capturing full-color 500-line images, at 15 Hz frame rate in vivo, as a 1.6 mm diameter endoscope. The SFE uses a singlemode optical fiber actuated at mechanical resonance to scan a light spot over tissue while backscattered or fluorescent light at each pixel is detected in time series using several multimode optical fibers. We are extending the capability of the SFE from a RGB reflectance imaging device to a diagnostic tool by imaging laser induced fluorescence (LIF) in tissue, allowing for correlation of endogenous fluorescence to tissue state. Design of the SFE for diagnostic imaging is guided by a comparison of single point spectra acquired from an inflammatory bowel disease (IBD) model to tissue histology evaluated by a pathologist. LIF spectra were acquired by illuminating tissue with a 405 nm light source and detecting intrinsic fluorescence with a multimode optical fiber. The IBD model used in this study was mdr1a-/- mice, where IBD was modulated by infection with Helicobacter bilis. IBD lesions in the mouse model ranged from mild to marked hyperplasia and dysplasia, from the distal colon to the cecum. A principle components analysis (PCA) was conducted on single point spectra of control and IBD tissue. PCA allowed for differentiation between healthy and dysplastic tissue, indicating that emission wavelengths from 620 - 650 nm were best able to differentiate diseased tissue and inflammation from normal healthy tissue.

[1]  Richard S. Johnston,et al.  A full-color scanning fiber endoscope , 2006, SPIE BiOS.

[2]  Lillian Maggio-Price,et al.  Helicobacter bilis infection accelerates and H. hepaticus infection delays the development of colitis in multiple drug resistance-deficient (mdr1a-/-) mice. , 2002, The American journal of pathology.

[3]  Takehiko Fujisawa,et al.  Effective detection of bronchial preinvasive lesions by a new autofluorescence imaging bronchovideoscope system. , 2005, Lung cancer.

[4]  Brian C Wilson,et al.  Molecular Fluorescence Excitation–Emission Matrices Relevant to Tissue Spectroscopy¶ , 2003, Photochemistry and photobiology.

[5]  J. C. Jones,et al.  A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. , 1998, Journal of immunology.

[6]  Eric J Seibel,et al.  Unique features of optical scanning, single fiber endoscopy * ** , 2002, Lasers in surgery and medicine.

[7]  Yoshimitsu Aoki,et al.  Early detection of bronchial lesions using newly developed videoendoscopy-based autofluorescence bronchoscopy. , 2006, Lung cancer.

[8]  Gregg Staerkel,et al.  Cervical Precancer Detection Using a Multivariate Statistical Algorithm Based on Laser‐Induced Fluorescence Spectra at Multiple Excitation Wavelengths , 1996, Photochemistry and photobiology.

[9]  Per G. Reinhall,et al.  Single-fiber flexible endoscope: general design for small size, high resolution, and wide field of view , 2001, European Conference on Biomedical Optics.

[10]  K. Forde,et al.  Colonoscopy in Mice , 2001, Surgical Endoscopy And Other Interventional Techniques.

[11]  I Itzkan,et al.  In vivo identification of colonic dysplasia using fluorescence endoscopic imaging. , 1999, Gastrointestinal endoscopy.

[12]  Georges Wagnières,et al.  In vivo autofluorescence imaging of early cancers in the human tracheobronchial tree with a spectrally optimized system. , 2003, Journal of biomedical optics.

[13]  Haishan Zeng,et al.  Real‐time endoscopic fluorescence imaging for early cancer detection in the gastrointestinal tract , 1998 .

[14]  H. Bergh,et al.  In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers. , 2001, Journal of biomedical optics.

[15]  Mark Tsang,et al.  Dual infection with Helicobacter bilis and Helicobacter hepaticus in p-glycoprotein-deficient mdr1a-/- mice results in colitis that progresses to dysplasia. , 2005, The American journal of pathology.