Showing papers by "Xingde Li published in 2012"
TL;DR: The development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues is reported and its utility for monitoring the remodeling of cervical collagen during gestation in mice is demonstrated.
Abstract: We report the development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues and demonstrate its utility for monitoring the remodeling of cervical collagen during gestation in mice. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. SHG endomicroscopic imaging of ex vivo murine and human cervical tissues through intact epithelium has also been performed. Our findings demonstrate the feasibility of SHG endomicroscopy technology for staging normal pregnancy, and suggest its potential application as a minimally invasive tool for clinical assessment of abnormal cervical remodeling associated with preterm birth.
153 citations
TL;DR: An all-fiber-optic scanning, multimodal endomicroscope capable of simultaneous optical coherence tomography (OCT) and two-photon fluorescence (TPF) imaging and preliminary imaging results of cell cultures and mouse tissue ex vivo demonstrate the feasibility of simultaneous real-time OCT and TPF imaging in a scanningendomicroscopy setting for the first time.
Abstract: We report an all-fiber-optic scanning, multimodal endomicroscope capable of simultaneous optical coherence tomography (OCT) and two-photon fluorescence (TPF) imaging. Both imaging modalities share the same miniature fiber-optic scanning endomicroscope, which consists of a double-clad fiber with a core operating in single mode at both the OCT (1310 nm) and two-photon excitation (1550 nm) wavelengths, a piezoelectric two-dimensional fiber-optic beam scanner, and a miniature aspherical compound lens suitable for simultaneous acquisition of en face OCT and TPF images. A fiber-optic wavelength division multiplexer was employed in the integrated platform to combine the low coherence OCT light source and the femtosecond two-photon excitation laser into the same optical path. Preliminary imaging results of cell cultures and mouse tissue ex vivo demonstrate the feasibility of simultaneous real-time OCT and TPF imaging in a scanning endomicroscopy setting for the first time.
68 citations
TL;DR: Structural morphologies and fluorophore distribution could be clearly visualized, suggesting the potential of the dual-modality system for future in vivo and clinical applications.
Abstract: We present an all-fiber-optically based endoscope platform for simultaneous optical coherence tomography (OCT) and fluorescence imaging. This design entails the use of double-clad fiber (DCF) in the endoscope for delivery of OCT source and fluorescence excitation light while collecting the backscattered OCT signal through the single-mode core and fluorescence emission through the large inner cladding of the DCF. Circumferential beam scanning was performed by rotating a 45° reflector using a miniature DC motor at the distal end of the endoscope. Additionally, a custom DCF coupler and a wavelength division multiplexer (WDM) were utilized to seamlessly integrate both imaging modalities to achieve an entirely fiber-optically based dual-modality imaging system. We demonstrated simultaneous intraluminal 3D OCT and 2D (surface) fluorescence imaging in ex vivo rabbit esophagus using the dual-modal endomicroscopy system. Structural morphologies (provided by OCT) and fluorophore distribution (provided by the fluorescence module) could be clearly visualized, suggesting the potential of the dual-modality system for future in vivo and clinical applications.
67 citations
TL;DR: In vitro two-photon fluorescence imaging of cultured cells stained with a LIVE/DEAD viability assay showed that cells near the spiral scan center experienced obvious photodamage, whereas cells remained alive over the entire region under the LISSajous beam scanning, confirming the predicted advantage offered by the Lissajous scan over this spiral scan in an endomicroscopy setting.
Abstract: We compare the illumination uniformity and the associated effects of the spiral and Lissajous scanning patterns that are commonly used in an endomicroscope. Theoretical analyses and numerical simulations were first performed to quantitatively investigate the area illumination density in the spiral scanning pattern. The results revealed the potential problem of manifest photodamage due to the very high illumination density in the center of the spiral scan. Similar analyses of the Lissajous scanning pattern, which can be conveniently implemented on the same endomicroscope with no hardware modifications, showed a more uniform illumination density with about an 80-fold reduction in the peak illumination density. To underscore the benefit offered by the improved illumination uniformity, we conducted in vitro two-photon fluorescence imaging of cultured cells stained with a LIVE/DEAD viability assay using our home-built, fiber-optic, two-channel endomicroscopy system. Both the spiral and the Lissajous scans were implemented. Our experimental results showed that cells near the spiral scan center experienced obvious photodamage, whereas cells remained alive over the entire region under the Lissajous beam scanning, confirming the predicted advantage offered by the Lissajous scan over this spiral scan in an endomicroscopy setting.
40 citations
TL;DR: In this article, the authors explored the possibility of using gold (Au) nanocages as a new class of exogenous contrast agents for endomicroscopic nonlinear imaging.
18 citations
TL;DR: The findings indicate that a tiny lesion less than 3 mm in diameter can be localized with a position bias no more than 1 mm, and suggests the PIS method holds the promise for practical applications of whole-body cancer detection.
Abstract: Liver cancer is one of the most common malignant tumors worldwide. In order to enable the noninvasive detection of small liver tumors in mice, we present a parallel iterative shrinkage (PIS) algorithm for dual-modality tomography. It takes advantage of microcomputed tomography and multiview bioluminescence imaging, providing anatomical structure and bioluminescence intensity information to reconstruct the size and location of tumors. By incorporating prior knowledge of signal sparsity, we associate some mathematical strategies including specific smooth convex approximation, an iterative shrinkage operator, and affine subspace with the PIS method, which guarantees the accuracy, efficiency, and reliability for three-dimensional reconstruction. Then an in vivo experiment on the bead-implanted mouse has been performed to validate the feasibility of this method. The findings indicate that a tiny lesion less than 3 mm in diameter can be localized with a position bias no more than 1 mm; the computational efficiency is one to three orders of magnitude faster than the existing algorithms; this approach is robust to the different regularization parameters and the lp norms. Finally, we have applied this algorithm to another in vivo experiment on an HCCLM3 orthotopic xenograft mouse model, which suggests the PIS method holds the promise for practical applications of whole-body cancer detection.
14 citations
TL;DR: TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration, and showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2- fold in a complex sample.
Abstract: Matrix-assisted laser desorption/ionization (MALDI) has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentrat...
11 citations
TL;DR: The imaging capability of the probe is demonstrated by obtaining B-scan images of diseased larynx tissue and compare them with those obtained in a 1310 nm SS-OCT classical non-endoscopic system.
Abstract: A miniature endoscope probe for forward viewing in a 50 kHz swept source optical coherence tomography (SS-OCT)
configuration was developed. The work presented here is an intermediate step in our research towards in vivo
endoscopic laryngeal cancer screening. The endoscope probe consists of a miniature tubular lead zirconate titanate
(PZT) actuator, a single mode fiber (SMF) cantilever and a GRIN lens, with a diameter of 2.4 mm. The outer surface
of the PZT actuator is divided into four quadrants that form two pairs of orthogonal electrodes (X and Y). When
sinusoidal waves of opposite polarities are applied to one electrode pair, the PZT tube bends transversally with
respect to the two corresponding quadrants, and the fiber optic cantilever is displaced perpendicular to the PZT tube.
The cantilever's resonant frequency was found experimentally as 47.03 Hz. With the GRIN lens used, a lateral
resolution of ~ 13 μm is expected. 2D en face spiral scanning pattern is achieved by adjusting the phase between the
pairs of X and Y electrodes drive close to 90 degrees. Furthermore, we demonstrate the imaging capability of the
probe by obtaining B-scan images of diseased larynx tissue and compare them with those obtained in a 1310 nm SS-OCT
classical non-endoscopic system.
4 citations
3 citations
TL;DR: In this article, the authors reported the first scattering-dominant agent based on structured Au nanocages for enhancing OCT imaging contrast, which demonstrated significant in vivo contrast enhancement for the first time.
Abstract: We reported the first scattering-dominant agent based on structured Au nanocages for enhancing OCT imaging contrast. Animal tumor imaging with the Au nanocages was performed, demonstrating significant in vivo contrast enhancement for the first time
2 citations
06 May 2012
TL;DR: In this article, the authors report recent advances in ultrathin fiber-optic endomicroscopy technology with significant improvements on resolution and signal collection, and present in vivo and in vivo two-photon imaging of unstained biological tissues and potential clinical applications.
Abstract: We report recent advances in ultrathin fiber-optic endomicroscopy technology with significant improvements on resolution and signal collection. Ex vivo and in vivo two-photon imaging of unstained biological tissues and potential clinical applications will be presented.
TL;DR: Using an acousto-optic modulator that froze beam positions on frames captured by an ordinary CCD camera, this paper was able to calibrate the Lissajous scanning pattern on a fiberoptic nonlinear endomicroscope quickly and precisely.
Abstract: Using an acousto-optic modulator that froze beam positions on frames captured by an ordinary CCD camera, we were able to calibrate the Lissajous scanning pattern on a fiber-optic nonlinear endomicroscope quickly and precisely.
TL;DR: An all-fiber-optically based balloon catheter for simultaneous fluorescence imaging and OCT has been implemented and the performance is demonstrated on tissue phantom, ex vivo pig esophagus and mouse tumor imaging.
Abstract: An all-fiber-optically based balloon catheter for simultaneous fluorescence imaging and OCT has been implemented. The performance of this multimodal catheter is demonstrated on tissue phantom, ex vivo pig esophagus and mouse tumor imaging.
11 Dec 2012
TL;DR: Two forward-looking endoscope OCT probes of different sizes in a sweeping frequency OCT (SS-OCT) configuration were compared in terms of their performances for ex-vivo laryngeal cancer imaging.
Abstract: Larynx cancer is one of the most common primary head and neck cancers. For early-stage laryngeal cancer, both
surgery and radiotherapy are effective treatment modalities, offering a high rate of local control and cure. Optical
coherence tomography (OCT) is an established non-invasive optical biopsy method, capable of imaging ranges of 2-
3 mm into tissue. By using the principles of low coherence light interferometry, OCT can be used to distinguish
normal from unhealthy laryngeal mucosa in patients. Two forward-looking endoscope OCT probes of different sizes
in a sweeping frequency OCT (SS-OCT) configuration were compared in terms of their performances for ex-vivo
laryngeal cancer imaging.
The setup configuration of the first OCT probe unit was designed and constructed at the Institute of Applied Physics
RAS, Russia (diameter of 1.9 mm and the rigid part at the distal end is 13 mm long). The second OCT endoscope
probe was constructed at the Department of Biomedical Engineering at Johns Hopkins University, USA, using a
tubular piezoelectric actuator with quartered electrodes in combination with a resonant fiber cantilever (diameter of
2.4 mm, and rigid part of 45 mm).
Cross-sectional images of laryngeal lesions using the two OCT configurations were aquired and compared with
OCT images obtained in a 1310 nm SS-OCT classical non-endoscopic system. The work presented here is an
intermediate step in our research towards in-vivo endoscopic laryngeal cancer imaging.
TL;DR: The contrast agents based on structured Au nanocages for enhancing TPL endomicroscopic imaging showed significant contrast enhancement, and were reported to be the first of its kind.
Abstract: We reported the contrast agents based on structured Au nanocages for enhancing TPL endomicroscopic imaging. Cancer cells and tissues TPL endomicroscopy imaging with the Au nanocages were performed, demonstrating significant contrast enhancement.
TL;DR: In this article, a fiber-optic scanning second harmonic generation (SHG) endomicroscopy system was used to detect the morphological changes in cervical collagen fiber during gestation with sub-micrometer resolution.
Abstract: We present a fiber-optic scanning second harmonic generation (SHG) endomicroscopy system that can detect the morphological changes in cervical collagen fiber during gestation with sub-micrometer resolution.
TL;DR: In this paper, a flexible fiberoptic scanning endomicroscope with a 2mm diameter and a 32mm rigid length capable of imaging two-photon excitation fluorescence from intrinsic fluorophors and second harmonic generation from non-centerosymmetric molecules was presented.
Abstract: We present a flexible fiberoptic scanning endomicroscope with a 2-mm diameter and a 32-mm rigid length capable of imaging two-photon excitation fluorescence from intrinsic fluorophors and second harmonic generation from non-centerosymmetric molecules.
26 Nov 2012
TL;DR: In this article, the authors presented a two-photon fluorescence and SHG imaging of unstained biological tissues using an ultracompact fiber-optic platform of a 2mm diameter.
Abstract: We present recent advances on scanning endomicroscopy technologies which can perform nonlinear optical imaging with an ultracompact fiber-optic platform of a 2mm diameter. Two-photon fluorescence and SHG imaging of unstained biological tissues will be reported.
TL;DR: In this paper, a high-speed SS-OCT system along with a miniature side-viewing catheter was used to dynamically assess structures of the bronchus in vivo.
Abstract: We investigated the feasibility of a high-speed SS-OCT system along with a miniature side-viewing catheter to dynamically assess structures of the bronchus in vivo. Excellent correlations were achieved between OCT images and the corresponding histology.
TL;DR: Ex vivo human brain tissues from 8 glioma patients and 5 controls are imaged using SS-OCT, with higherglioma attenuation values and easily detectable and specific tumor features (microcyst, necrosis and pallisading) for intraoperative resections.
Abstract: Ex vivo human brain tissues from 8 glioma patients and 5 controls are imaged using SS-OCT, with higher glioma attenuation values and easily detectable and specific tumor features (microcyst, necrosis and pallisading) for intraoperative resections.