Zenghai Lu

Polypyrrole Nanoparticles: A Potential Optical Coherence Tomography Contrast Agent for Cancer Imaging

A near-infrared (NIR) absorbing contrast agent based on polypyrrole nanoparticles is described. Quantitative optical coherence tomography studies on tissue phantoms and Mie scattering calculations indicate their potential application for early-stage cancer diagnosis.

Quantum dot selective area intermixing for broadband light sources

We report a comparison of different capping materials on the intermixing of modulation p-doped InAs/In(Ga)As quantum dots (QD). QD materials with different caps are shown to exhibit significant difference in their optical properties during the annealing process. The selective area intermixing technique is demonstrated to laterally integrate two and three different QD light emitting devices with a single electrical contact. A spectral bandwidth of 240nm centered at 1188nm is achieved in a device with two sections. By calculating the point spread function for the obtained emission spectra, and applying the Rayleigh criteria for resolution, an axial resolution of 3.5μm is deduced. A three section device realizes a spectral bandwidth of 310nm centered at 1145nm. This corresponds to an axial resolution of 2.4μm. Such a small predicted axial resolution is highly desirable in optical coherence tomography system and other coherence-based systems applications.

Optic axis determination by fibre-based polarization-sensitive swept-source optical coherence tomography

We describe a fibre-based variable-incidence angle (VIA) polarization-sensitive swept-source optical coherence tomography (PS-SS-OCT) system to determine the 3D optical axis of birefringent biological tissues. Single-plane VIA-PS-OCT is also explored which requires measurement of the absolute fast-axis orientation. A state-of-the-art PS-SS-OCT system with some improvements both in hardware and software was used to determine the apparent optical birefringence of equine tendon for a number of different illumination directions. Polar and azimuthal angles of cut equine tendon were produced by the VIA method and compared with the nominal values. A quarter waveplate (QWP) and equine tendon were used as test targets to validate the fast-axis measurements using the system. Polar and azimuthal angles of cut equine tendon broadly agreed with the expected values within about 8% of the nominal values. A theoretical and experimental analysis of the effect of the sample arm fibre on determination of optical axis orientation using a proposed definition based on the orientation of the eigenpolarization ellipse experimentally confirms that this algorithm only works correctly for special settings of the sample arm fibre. A proposed algorithm based on the angle between Stokes vectors on the Poincaré sphere is confirmed to work for all settings of the sample arm fibre. A calibration procedure is proposed to remove the sign ambiguity of the measured orientation and was confirmed experimentally by using the QWP.

Experimental validation of an extended Jones matrix calculus model to study the 3D structural orientation of the collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography

We report results to verify a theoretical framework to analyze the 3D depth-wise structural organization of collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography. Apparent birefringence data obtained from multi-angle measurements using a time domain polarization-sensitive optical coherence tomography system has been compared with simulated data based on the extended Jones matrix calculus. Experimental data has been shown to agree with the lamellar model previously proposed for the cartilage microstructure based on scanning electron microscopy data. This tool could have potential application in mapping the collagen structural orientation information of cartilage non-invasively during arthroscopy.

Evaluating the use of optical coherence tomography for the detection of epithelial cancers in vitro

Optical coherence tomography (OCT) is a noninvasive imaging methodology that is able to image tissue to depths of over 1 mm. Many epithelial conditions, such as melanoma and oral cancers, require an invasive biopsy for diagnosis. A noninvasive, real-time, point of care method of imaging depth-resolved epithelial structure could greatly improve early diagnosis and long-term monitoring in patients. Here, we have used tissue-engineered (TE) models of normal skin and oral mucosa to generate models of melanoma and oral cancer. We have used these to determine the ability of OCT to image epithelial differences in vitro. We report that while in vivo OCT gives reasonable depth information for both skin and oral mucosa, in vitro the information provided is less detailed but still useful. OCT can provide reassurance on the development of TE models of skin and oral mucosa as they develop in vitro. OCT was able to detect the gross alteration in the epithelium of skin and mucosal models generated with malignant cell lines but was less able to detect alteration in the epithelium of TE models that mimicked oral dysplasia or, in models where tumor cells had penetrated into the dermis.

Method to calibrate phase fluctuation in polarization-sensitive swept-source optical coherence tomography

We present a phase fluctuation calibration method for polarization-sensitive swept-source optical coherence tomography (PS-SS-OCT) using continuous polarization modulation. The method uses a low-voltage broadband polarization modulator driven by a synchronized sinusoidal burst waveform rather than an asynchronous waveform, together with the removal of the global phases of the measured Jones matrices by the use of matrix normalization. This makes it possible to average the measured Jones matrices to remove the artifact due to the speckle noise of the signal in the sample without introducing auxiliary optical components into the sample arm. This method was validated on measurements of an equine tendon sample by the PS-SS-OCT system.

Comparative study of the angle-resolved backscattering properties of collagen fibers in bovine tendon and cartilage

In a biological tissue, light scattering is based on the size and type of scatterers seen as refractive index variations that describe the optical properties shown. In this paper, we have implemented the variable incidence angle technique of multiple angle of illumination experiment on tendon and cartilage samples whose dominant constituents are genetically different types of collagen fibers, type I and type II, respectively. It is found that tendon displays a much greater angular anisotropy in its optical backscattering coefficient than the healthy cartilage. We propose that this is due to a more uniform distribution of fine fibrils than is found in tendon. Rayleigh-Gans approximation is used to give qualitative support to this idea.

Absolute fast axis determination using non-polarization-maintaining fiber-based polarization-sensitive optical coherence tomography

We report on a new calibration technique that permits the accurate extraction of sample Jones matrix and hence fast-axis orientation by using fiber-based polarization-sensitive optical coherence tomography (PS-OCT) that is completely based on non-polarization-maintaining fiber such as SMF-28. In this technique, two quarter-wave plates (QWPs) are used to completely specify the parameters of the system fibers in the sample arm so that the Jones matrix of the sample can be determined directly. The device was validated on measurements of a QWP and an equine tendon sample by a single-mode fiber-based swept-source PS-OCT system.

Performance comparison between 8- and 14-bit-depth imaging in polarization-sensitive swept-source optical coherence tomography.

Recently the effects of reduced bit-depth acquisition on swept-source optical coherence tomography (SS-OCT) image quality have been evaluated by using simulations and empirical studies, showing that image acquisition at 8-bit depth allows high system sensitivity with only a minimal drop in the signal-to-noise ratio compared to higher bit-depth systems. However, in these studies the 8-bit data is actually 12- or 14-bit ADC data numerically truncated to 8 bits. In practice, a native 8-bit ADC could actually possess a true bit resolution lower than this due to the electronic jitter in the converter etc. We compare true 8- and 14-bit-depth imaging of SS-OCT and polarization-sensitive SS-OCT (PS-SS-OCT) by using two hardware-synchronized high-speed data acquisition (DAQ) boards. The two DAQ boards read exactly the same imaging data for comparison. The measured system sensitivity at 8-bit depth is comparable to that for 14-bit acquisition when using the more sensitive of the available full analog input voltage ranges of the ADC. Ex-vivo structural and birefringence images of equine tendon indicate no significant differences between images acquired by the two DAQ boards suggesting that 8-bit DAQ boards can be employed to increase imaging speeds and reduce storage in clinical SS-OCT/PS-SS-OCT systems. One possible disadvantage is a reduced imaging dynamic range which can manifest itself as an increase in image artifacts due to strong Fresnel reflection.

Using swept source optical coherence tomography to monitor wound healing in tissue engineered skin

There is an increasing need for a robust simple to use non-invasive imaging technology for monitoring tissue engineered constructs as they develop. We have applied optical coherence tomography (OCT), a relatively new optical technique, to image tissue engineered constructs. Our aim was to evaluate the use of swept-source optical coherence tomography (SSOCT) to non-invasively image reconstructed skin as it developed over several weeks. The epidermis of the reconstructed skin was readily distinguished from the neodermis when examined with standard histology - a destructive imaging technique - of samples. The development of reconstructed skin based on deepithelialised acellular dermis (DED) was accurately monitored with SS-OCT over three weeks and confirmed with conventional histology. It was also possible to image changes in the epidermis due to the presence of melanoma and the healing of these 3D models after wounding with a scalpel, with or without the addition of a fibrin clot. SS-OCT is proving to be a valuable tool in tissue engineering, showing great promise for the non-invasive imaging of optically turbid tissue engineered constructs, including tissue engineered skin.