Coherent Raman Scattering Fiber Endoscopy

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Optics Letters (Impact Factor: 3.29). 07/2011; 36(13):2396-8. DOI: 10.1364/OL.36.002396
Source: PubMed


Coherent Raman scattering methods allow for label-free imaging of tissue with chemical contrast and high spatial and temporal resolution. However, their imaging depth in scattering tissue is limited to less than 1 mm, requiring the development of endoscopes to obtain images deep inside the body. Here, we describe a coherent Raman endoscope that provides stimulated Raman scattering images at seven frames per second using a miniaturized fiber scanner, a custom-designed objective lens, and an optimized scheme for collection of scattered light from the tissue. We characterize the system and demonstrate chemical selectivity in mouse tissue images.

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    • "It has already been shown that CARS technology can be implemented in miniaturized exoscopes [39] or an endoscopic setup [40], [41], which allows video-rate CARS imaging of nervous tissue in vivo [42]. Recent research demonstrated that a scan rate of seven frames per second can be achieved also with endoscopic systems [43]. This imaging speed is well compatible with an intraoperative visualization of brain tumor borders for the neurosurgeon during ongoing surgery. "
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    ABSTRACT: Background Coherent anti-Stokes Raman scattering (CARS) microscopy provides fine resolution imaging and displays morphochemical properties of unstained tissue. Here, we evaluated this technique to delineate and identify brain tumors. Methods Different human tumors (glioblastoma, brain metastases of melanoma and breast cancer) were induced in an orthotopic mouse model. Cryosections were investigated by CARS imaging tuned to probe C-H molecular vibrations, thereby addressing the lipid content of the sample. Raman microspectroscopy was used as reference. Histopathology provided information about the tumor's localization, cell proliferation and vascularization. Results The morphochemical contrast of CARS images enabled identifying brain tumors irrespective of the tumor type and properties: All tumors were characterized by a lower CARS signal intensity than the normal parenchyma. On this basis, tumor borders and infiltrations could be identified with cellular resolution. Quantitative analysis revealed that the tumor-related reduction of CARS signal intensity was more pronounced in glioblastoma than in metastases. Raman spectroscopy enabled relating the CARS intensity variation to the decline of total lipid content in the tumors. The analysis of the immunohistochemical stainings revealed no correlation between tumor-induced cytological changes and the extent of CARS signal intensity reductions. The results were confirmed on samples of human glioblastoma. Conclusions CARS imaging enables label-free, rapid and objective identification of primary and secondary brain tumors. Therefore, it is a potential tool for diagnostic neuropathology as well as for intraoperative tumor delineation.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "During the last few years, novel, all-fiber, multimodal (TPF + SHG + CARS) microscope systems have been presented [5]–[7] that can be combined with endoscopy [7], which would greatly increase the utility of nonlinear microscopy for pre-clinical applications and tissue imaging [8]. Application of DCF for pulse shortening, however, might be limited by splicing losses in all fiber laser systems, or by modefield distortions limiting the focusability of the laser beam exiting the optical fiber delivery and pulse compression system. "
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    ABSTRACT: The relationship between transmission group delay and stored energy in optical fibers is discussed. We show by numerical computations that the group delay of an optical pulse of finite bandwidth transmitted through a piece of a low loss optical fiber of unit length is proportional to the energy stored by the standing wave electromagnetic field. The stored energy-group delay ratio typically approaches unity as the confinement loss converges to zero. In case of a dispersion tailored Bragg fiber, we found that the stored energy-group delay ratio decreased while the confinement loss increased compared to those of the standard quarterwave Bragg fiber configuration. Furthermore, a rapid variation in the group delay versus wavelength function due to mode-crossing events (in hollow core photonic bandgap fibers for instance) or resonances originating from slightly coupled cavities, surface or leaking modes in index guiding, photonic bandgap, or photonic crystal fibers always results in a rapid change in the mode-field distribution, which seriously affects splicing losses and focusability of the transmitted laser beam. All of these factors must be taken into consideration during the design of dispersion tailored fibers for different applications.
    Full-text · Article · Sep 2014 · IEEE Journal of Selected Topics in Quantum Electronics
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    • "Real-time processing is also important because currently ICA takes 1.5-13 minutes (see supplementary Table S1). Furthermore, the implementation of the presented technique in SRS endoscopy [23] [24] would be advantageous for in vivo "
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    ABSTRACT: To date, medical imaging of tissues has largely relied on time-consuming staining processes, and there is a need for rapid, label-free imaging techniques. Stimulated Raman scattering microscopy offers a three-dimensional, real-time imaging capability with chemical specificity. However, it can be difficult to differentiate between several constituents in tissues because their spectral characteristics can overlap. Furthermore, imaging speeds in previous multispectral stimulated Raman scattering imaging techniques were limited. Here, we demonstrate label-free imaging of tissues by 30 frames/s stimulated Raman scattering microscopy with frame-by-frame wavelength tunability. To produce multicolour images showing different constituents, spectral images were processed by modified independent component analysis, which can extract small differences in spectral features. We present various imaging modalities such as two-dimensional spectral imaging of rat liver, two-colour three-dimensional imaging of a vessel in rat liver, spectral imaging of several sections of intestinal villi in mouse, and in vivo spectral imaging of mouse ear skin.
    Full-text · Article · Nov 2012 · Nature Photonics
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