Showing papers by "Xingde Li published in 2010"

Evaluation of Temperature-Sensitive, Indocyanine Green-Encapsulating Micelles for Noninvasive Near-Infrared Tumor Imaging

Abstract: Purpose Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To address these issues, ICG was encapsulated and stabilized within polymeric micelles formed from the thermo-sensitive block copolymer Pluronic F-127, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), to increase the stability and circulation time of ICG.

Forward-viewing resonant fiber-optic scanning endoscope of appropriate scanning speed for 3D OCT imaging.

Abstract: A forward-viewing resonant fiber-optic endoscope of a scanning speed appropriate for a high-speed Fourier-domain optical coherence tomography (FD-OCT) system was developed to enable real-time, three-dimensional endoscopic OCT imaging. A new method was explored to conveniently tune the scanning frequency of a resonant fiber-optic scanner, by properly selecting the fiber-optic cantilever length, partially changing the mechanical property of the cantilever, and adding a weight to the cantilever tip. Systematic analyses indicated the resonant scanning frequency can be tuned over two orders of magnitude spanning from ~10Hz to ~kHz. Such a flexible scanning frequency range makes it possible to set an appropriate scanning speed of the endoscope to match the different A-scan rates of a variety of FD-OCT systems. A 2.4-mm diameter, 62.5-Hz scanning endoscope appropriate to work with a 40-kHz swept-source OCT (SS-OCT) system was developed and demonstrated for 3D OCT imaging of biological tissues.

Generic real-time uniform K-space sampling method for high-speed swept-source optical coherence tomography.

Abstract: We developed a universal, real-time uniform K-space sampling (Rt-UKSS) method for high-speed swept-source optical coherence tomography (SS-OCT). An external clock uniform in K-space was generated. The clock was synchronized with the zero-crossing time of an interferometric calibration signal and used as triggers for a high-speed data acquisition system in a point-by-point fashion, hence enabling uniform data sampling in K-space. Different from the numerical calibration algorithm commonly used in an SS-OCT system, the method reported here does not require over-sampling, thus greatly reducing the demand for digitization, data processing and storage speed. The Rt-UKSS method is adaptive and applicable to a generic SS-OCT system of a wide range of A-scan rates without special adjustment. We successfully implemented the Rt-UKSS method in an SS-OCT system based on a Fourier-domain mode-locked laser (FDML) of a 40-kHz scanning rate. Real-time imaging of biological tissues using such a system was demonstrated with a measured axial resolution of 9.3 μm and detection sensitivity greater than 120dB.

Robust High-Resolution Fine OCT Needle for Side-Viewing Interstitial Tissue Imaging

Abstract: Fine optical coherence tomography (OCT) imaging needles that can be integrated with a standard biopsy needle have been developed with a new optics design to improve the optical quality and mechanical robustness, where a fiber-optic lens (that is spliced to a single-mode fiber) and a microreflector are encased within a microglass tube. The design also minimizes the cylindrical lens effect induced by the glass tube and eases the needle assembly process. Real-time cross-sectional OCT imaging of various tissue samples were performed ex vivo using the miniature-imaging needle along with a 1300-nm swept-source OCT system. The preliminary results demonstrate the improved mechanical and optical performance and suggest the potential of the fine OCT needle for minimally invasive interstitial imaging and image-guided biopsy.

Fiber-optic nonlinear endomicroscopy with focus scanning by using shape memory alloy actuation.

Abstract: A miniature fiber optic endomicroscope with built-in dynamic focus scanning capability is developed for the first time for 3-D two-photon fluorescence (TPF) imaging of biological samples. Fast 2-D lateral beam scan- ning is realized by resonantly vibrating a double-clad fiber cantilever with a tubular piezoactuator. Slow axial scan- ning is achieved by moving the distal end of the imaging probe with an extremely compact electrically driven shape memory alloy (SMA). The 10-mm-long SMA allows 150- μm contractions with a driving voltage varying only from 50 to 100 mV. The response of the SMA contraction with the applied voltage is nonlinear, but repeatable and can be ac- curately calibrated. Depth-resolved imaging of acriflavine- stained biological tissues and unstained white paper with the endomicroscope is performed, and the results demon- strate the feasibility of 3-D nonlinear optical imaging with the SMA-based scanning fiber-optic endomicroscope. C 2010

Combined influences of chromatic aberration and scattering in depth-resolved two-photon fluorescence endospectroscopy

Abstract: The influence of chromatic aberration of an objective lens in two-photon fluorescence (TPF) endospectroscopy of scattering media has been systematically investigated through both experiments and numerical simulations. Experiments were carried out on a uniform 3D scattering gelatin phantom embedded with TiO2 granules (to mimic tissue scattering) and fluorescein-tagged polystyrene beads. It was found that fluorescence spectral intensity and lineshape varied as a function of depth when measured with a gradient-index (GRIN) lens which has severe chromatic aberration. The spectral distortion caused by the chromatic aberration became diminishing as the imaging depth increased. Ray tracing analysis and Monte Carlo simulations were carried out to study the interplay of chromatic aberration and scattering in the depth-resolved TPF spectra. The simulation results suggest that the collected fluorescence signals from deeper layers included more out-of-focus photons that experienced a few or multiple scatterings, which diminish the influence of chromatic aberration on the measured TPF spectra. The simulated collection efficiencies of TPF at different wavelengths and depths can be used to properly recover the true depth-resolved TPF spectra of a relatively uniform scattering medium.

Two-photon Fluorescence Endomicroscopy

Abstract: Two-photon fluorescence (TPF) microscopy is a powerful technique for high-resolution imaging of biological tissues, enabling depth-resolved morphological and functional assessment of biological tissues via a non-invasive route (Denk et al., 1990; Helmchen & Denk, 2005; Konig, 2000; Zipfel et al., 2003). In TPF microscopy, a molecule (i.e., the fluorophore) can absorb two photons quasi-simultaneously (10-15 10-18 s) and emit a single photon during relaxation from the excited state to the ground state. The probability for the fluorescent emission is thus quadratically dependent on the excitation light intensity. With a focusing unit, much more two-photon fluorescence is generated from the focal spot than where the beam is diffused. Effectively, excitation is restricted to the very small focal volume (~1 femtoliter), resulting in the inherent optical sectioning ability without the need for a pinhole to reject out-of-focus photons. This optical sectioning capability permits wholefield fluorescence collection and thus enhances the collection efficiency in highly scattering tissues. In TPF microscopy, near-infrared (NIR) femtosecond laser is generally employed for effective excitation, which increases the penetration depth and reduces image deterioration due to the less scattering in turbid tissues. In addition, NIR excitation likely causes less photodamage outside the focal volume. With the advances in micro-optics and micro-mechanical components, a TPF endomicroscopy system is becoming attractive as a basic research tool with a much smaller form factor and lower cost compared to a conventional TPF microscope. Moreover, the TPF endomicroscopy system has a great potential to transform the powerful TPF technology for in vivo studies and clinical applications. Recently, increasing interests have been focusing on the development of TPF endomicroscope with a small size which can go through the accessory port of a standard endoscope for in vivo and clinical studies while maintaining the TPF imaging ability similar to a standard TPF microscope. Major challenges for TPF endomicroscopy devices are efficient delivery of single-mode ultrashort pulses, wide-field collection of the TPF signals, fast 2-D/3-D beam scanning with a miniature objective lens of good optical properties, and overall miniaturization of the probe assembly (Bao et al., 2008; Engelbrecht et al., 2008; Flusberg et al., 2005a; Flusberg et al., 2005b; Fu et al., 2006; Gobel et al., 2004a; Helmchen et al., 2001; Hoy et al., 2008; Jung & Schnitzer, 2003; Jung et al., 2008; Konig et al., 2007; Le Harzic et al., 2008; Levene et al., 2004; Myaing et al., 2006; Wu et al., 2009a; Wu et al., 2009b).

Thermo/pH-Responsive and Reversible NIR Fluorescent Probes for Optical Molecular Imaging

Abstract: We developed near-infrared fluorescent probes responsive to local temperature and pH change/modulation. The probes are based on cross-linked pluronic/PEI nanocapsules loaded with ICG which can be used for DNA or siRNA delivery and imaging.

Bioconjugated ICG/Dox-Micellar Nanocapsules for Optical Molecular Imaging and Targeted Therapy

Abstract: We reported on an approach to encapsulate indocyanine green and anticancer drug with polymeric micelles which can be bioconjugated for near-infrared molecular fluorescence imaging and potentially targeted therapy.

Interplay of Chromatic Aberration and Scattering in Depth-Resolved Two-Photon Fluorescence Endospectroscopy

Abstract: The influence of chromatic aberration of an objective lens and tissue scattering on depth-resolved two-photon fluorescence spectra measured by a fiber-optic endomicroscope is investigated. Proper calibration is proposed to restore the true depth-dependent fluorescence spectra.

Gold Nanocages for Spectroscopic OCT Imaging with A Swept Source at 1060 nm

Abstract: Gold nanocages were synthesized to shift the surface plasmon resonance peak to ~900 nm. We demonstrate these nanocages can be used as contrast agents for conventional and spectroscopic OCT at 1060 nm.

Forward-viewing Endoscope of Appropriate Scanning Speed for 3D OCT Imaging

Abstract: A forward-viewing fiber-optic endoscope was developed with the scanning speed appropriate for 3-D real-time OCT imaging when using a high-speed swept source. The scanning speed was systematically analyzed. In-vivo 3-D oral cavity imaging was performed.

Real-time Calibration for High-speed Swept-Source OCT

Abstract: We demonstrated a real-time calibration method for high-speed SS-OCT. An external clock was generated to trigger the high-speed data acquisition system point by point and enable uniform data sampling in frequency domain (K-space).

Fiber-optic Nonlinear Endomicrocopy for Intrinsic Imaging of Biological Tissues

Abstract: We report on a fiber-optic scanning endomicroscopy system based on a customized double-clad fiber (DCF) and a miniature compound lens that enables two-photon autofluorescence imaging of biological tissues for the first time.

Introduction: Advances in Optical Coherence Tomography, Photoacoustic Imaging, and Microscopy

Abstract: The editors introduce the Biomedical Optics Express feature issue, “Advances in Optical Coherence Tomography, Photoacoustic Imaging, and Microscopy,” which combines three technical areas from the 2010 Optical Society of America (OSA), Biomedical Optics (BIOMED) Topical Meeting held on 11–14 April in Miami, Florida, and includes contributions from conference attendees.