Extending the depth of focus of fiber-optic optical coherence tomography using a chromatic dual-focus design.

We report a dual-focus fiber-optic probe designed to extend depth of focus (DOF) in high-resolution endoscopic optical coherence tomography. We exploited the broad spectral bandwidth of a supercontinuum source and, in the fiber probe, the foci of the 750-1000 nm and 1100-1450 nm inputs were axially chromatically shifted. The interference signals from the two spectral bands were measured with a Si camera-based spectrometer and an InGaAs camera-based spectrometer, respectively. We verified the feasibility of the design using a phantom composed of microparticles and swine small intestine tissue ex vivo. The results showed that a transverse resolution below 5 µm over 300 µm could be maintained, and that the extended DOF was 2 times larger than that of the single focus probe via the use of dual spectral band inputs and a chromatic focal shift.

Non-invasive image-guided laser microsurgery by a dual-wavelength fiber laser and an integrated fiber-optic multi-modal system.

A new approach to non-invasive image-guided laser micro-treatment is demonstrated by a dual-wavelength fiber laser source and an integrated fiber-based multi-modal system. The fiber-based source, operated in 1.55 and 1.2 µm simultaneously, was directly connected to an integrated fiber-based multi-modal system for imaging and laser micro-treatment at the same time. The 1.2 µm radiations, within the 1.2-1.35 µm bio-penetration window of skin, were utilized for spectral domain optical coherence tomography imaging. The 1.55 µm radiations, highly absorptive to waters, were utilized for laser microsurgery. The new approach, which is simple in configuration and accurately controls the positions and exposure time of the laser microsurgery, shows great promises for future clinical applications.

Acoustic-actuated optical coherence angiography.

Optical coherence tomography (OCT) angiography requires high sensitivity and image penetration for detailed microvascular monitoring. Unfortunately, no effective contrast-medium-enhanced scheme is currently available for imaging improvement. We here propose the simultaneous use of gas-filled microbubbles (MBs) and acoustic actuation to enhance the imaging contrast of OCT angiography. OCT-synchronized acoustic actuation was applied in the presence of MBs, and different moving object tracking angiographic algorithms were tested in in vitro tubing and in vivo mouse experiments. This scheme significantly enhanced the OCT angiography performance, including its sensitivity and penetration, and should advance the utilization of OCT as an effective microvascular diagnostic tool.

Evaluation of Laser-Assisted Trans-Nail Drug Delivery with Optical Coherence Tomography.

The nail provides a functional protection to the fingertips and surrounding tissue from external injuries. The nail plate consists of three layers including dorsal, intermediate, and ventral layers. The dorsal layer consists of compact, hard keratins, limiting topical drug delivery through the nail. In this study, we investigate the application of fractional CO2 laser that produces arrays of microthermal ablation zones (MAZs) to facilitate drug delivery in the nails. We utilized optical coherence tomography (OCT) for real-time monitoring of the laser-skin tissue interaction, sparing the patient from an invasive surgical sampling procedure. The time-dependent OCT intensity variance was used to observe drug diffusion through an induced MAZ array. Subsequently, nails were treated with cream and liquid topical drugs to investigate the feasibility and diffusion efficacy of laser-assisted drug delivery. Our results show that fractional CO2 laser improves the effectiveness of topical drug delivery in the nail plate and that OCT could potentially be used for in vivo monitoring of the depth of laser penetration as well as real-time observations of drug delivery.

Simultaneous 0.8, 1.0, and 1.3 µm multispectral and common-path broadband source for optical coherence tomography.

Simultaneous multispectral generation in 0.8, 1.0, and 1.3 µm wavelength ranges by efficient energy conversions of 1.0 µm wavelength femtosecond pulses through a nonlinear fiber was reported. The output spectral range of this multispectral light source was composed of 0.6-0.9 µm blue-shifted Cherenkov radiation (CR), 1.0 µm residual pump, and 1.1-1.7 µm red-shifted soliton self-frequency shift (SSFS) with more than 1 mW/nm power-spectral densities. Output characteristics of the multispectral light source were then quantitatively analyzed and the central wavelengths of CR and SSFS emissions can be further easily adjusted by changing the input power into wavelength conversion fiber. Example spectral-domain optical coherence tomography (OCT) images of an IR card and finger skin were also performed with the demonstrated source. Due to the advantages of its simplicity, easily operated, and wavelength tunability, the reported multispectral source could be widely applicable for various spectroscopic OCT applications.

Two-level optical coherence tomography scheme for suppressing spectral saturation artifacts.

We demonstrate a novel method for reducing saturation artifacts in spectral-domain optical coherence tomography (SD-OCT) systems. This method is based on a two-level SD-OCT system with a dual-line charge-coupled device (CCD) camera. We compensate the saturated signal detected by the first line using the unsaturated signal detected by the second line. The Fourier transform of the compensated spectrum shows effective suppression of saturation artifacts. This method was also successfully performed on phantom material and skin on a human finger. Our method causes neither back-scattering power loss nor signal-to-noise ratio (SNR) degradation. The only difference between the traditional system and our two-level system is our utilization of the dual-line CCD camera; no additional devices or complex designs are needed.

Current matching using CdSe quantum dots to enhance the power conversion efficiency of InGaP/GaAs/Ge tandem solar cells.

A III-V multi-junction tandem solar cell is the most efficient photovoltaic structure that offers an extremely high power conversion efficiency. Current mismatching between each subcell of the device, however, is a significant challenge that causes the experimental value of the power conversion efficiency to deviate from the theoretical value. In this work, we explore a promising strategy using CdSe quantum dots (QDs) to enhance the photocurrent of the limited subcell to match with those of the other subcells and to enhance the power conversion efficiency of InGaP/GaAs/Ge tandem solar cells. The underlying mechanism of the enhancement can be attributed to the QD's unique capacity for photon conversion that tailors the incident spectrum of solar light; the enhanced efficiency of the device is therefore strongly dependent on the QD's dimensions. As a result, by appropriately selecting and spreading 7 mg/mL of CdSe QDs with diameters of 4.2 nm upon the InGaP/GaAs/Ge solar cell, the power conversion efficiency shows an enhancement of 10.39% compared to the cell's counterpart without integrating CdSe QDs.

Evaluation of moisture-related attenuation coefficient and water diffusion velocity in human skin using optical coherence tomography.

In this study, time-resolved optical coherence tomography (OCT) scanning images of the process of water diffusion in the skin that illustrate the enhancement in the backscattered intensities due to the increased water concentration are presented. In our experiments, the water concentration in the skin was increased by soaking the hand in water, and the same region of the skin was scanned and measured with the OCT system and a commercial moisture monitor every three minutes. To quantitatively analyze the moisture-related optical properties and the velocity of water diffusion in human skin, the attenuation coefficients of the skin, including the epidermis and dermis layers, were evaluated. Furthermore, the evaluated attenuation coefficients were compared with the measurements made using the commercial moisture monitor. The results demonstrate that the attenuation coefficient increases as the water concentration increases. Furthermore, by evaluating the positions of center-of mass of the backscattered intensities from OCT images, the diffusion velocity can be estimated. In contrast to the commercial moisture monitor, OCT can provide three-dimensional structural images of the skin and characterize its optical property, which together can be used to observe morphological changes and quantitatively evaluate the moisture-related attenuation coefficients in different skin layers.

Quantitative Evaluation of Caries and Calculus with Ultrahigh-Resolution Optical Coherence Tomography.

Dental caries on the crown's surface is caused by the interaction of bacteria and carbohydrates, which then gradually alter the tooth's structure. In addition, calculus is the root of periodontal disease. Optical coherence tomography (OCT) has been considered to be a promising tool for identifying dental caries; however, diagnosing dental caries in the early stage still remains challenging. In this study, we proposed an ultrahigh-resolution OCT (UHR-OCT) system with axial and transverse resolutions of 2.6 and 1.8 µm for differentiating the early-stage dental caries and calculus. The same teeth were also scanned by a conventional spectral-domain OCT (SD-OCT) system with an axial resolution of 7 µm. The results indicated that early-stage carious structures such as small cavities can be observed using UHR-OCT; however, the SD-OCT system with a lower resolution had difficulty identifying it. Moreover, the estimated surface roughness and the scattering coefficient of enamel were proposed for quantitatively differentiating the different stages of caries. Furthermore, the thickness of the calculus can be estimated from the UHR-OCT results. The results have demonstrated that UHR-OCT can detect caries and calculus in their early stages, showing that the proposed method for the quantitative evaluation of caries and calculus is potentially promising.

Use of two-dimensional nanorod arrays with slanted ITO film to enhance optical absorption for photovoltaic applications.

Two-dimensional (2D) Si-nanorod arrays offer a promising architecture that has been widely recognized as attractive devices for photovoltaic applications. To further reduce the Fresnel reflection that occurs at the interface between the air and the 2D Si-nanorod array because of the large difference in their effective refractive indices, we propose and adopt a slanted ITO film as an intermediate layer by using oblique-angle sputtering deposition. The nearly continuous surface of the slanted ITO film is lossless and has high electrical conductivity; therefore, it could serve as an electrode layer for solar cells. As a result, the combination of the above-mentioned nanostructures exhibits high optical absorption over a broad range of wavelengths and incident angles, along with a calculated short-circuit current density of JSC = 32.81 mA/cm2 and a power generation efficiency of η = 22.70%, which corresponds to an improvement of approximately 42% over that of its bare single-crystalline Si counterpart.

In Vivo Identification of Skin Photodamage Induced by Fractional CO2 and Picosecond Nd:YAG Lasers with Optical Coherence Tomography.

Fractional laser treatment is commonly used for dermatological applications, enabling effective induction of collagen regeneration and significantly reducing recovery time. However, it is challenging to observe laser-induced photodamage beneath the tissue surface in vivo, making the non-invasive evaluation of treatment outcomes difficult. For in vivo real-time study of the photodamage induced by fractional pulsed CO2 and Nd:YAG lasers commonly utilized for clinical therapy, a portable spectral-domain optical coherence tomography (SD-OCT) system was implemented for clinical studies. The photodamage caused by two lasers, including photothermal and photoacoustic effects, was investigated using OCT, together with the correlation between photodamage and exposure energy. Additionally, to investigate the change in the optical properties of tissue due to photodamage, the attenuation coefficients and damaged areas of normal skin and laser-treated skin were estimated for comparison. Finally, the recovery of the exposed skin with both lasers was also compared using OCT. The results show that OCT can be a potential solution for in vivo investigation of laser-induced tissue damage and quantitative evaluation.

Motion-insensitive optical coherence tomography based micro-angiography.

An improved image processing procedure for suppressing the phase noise due to a motion artifact acquired during optical coherence tomography scanning and effectively illustrating the blood vessel distribution in a living tissue is demonstrated. This new processing procedure and the widely used procedure for micro-angiography application are based on the selection of high-frequency components in the spatial-frequency spectrum of B-mode scanning (x-space), which are contributed from the image portions of moving objects. However, by switching the processing order between the x-space and k-space, the new processing procedure shows the superior function of effectively suppressing the phase noise due to a motion artifact. After the blood vessel positions are precisely acquired based on the new processing procedure, the projected blood flow speed can be more accurately calibrated based on a previously reported method. The demonstrated new procedure is useful for clinical micro-angiography application, in which a stepping motor of generating motion artifacts is usually used in the scanning probe.

Defect detection and property evaluation of indium tin oxide conducting glass using optical coherence tomography.

This study demonstrates a new approach for evaluating the properties of indium tin oxide (ITO) conducting glass and identifying defects using optical coherence tomography (OCT). A swept-source OCT system was implemented to scan the ITO conducting glass to enable two-dimensional or three-dimensional imaging. With OCT scanning, the defects can be clearly identified at various depths. Several parameters in addition to morphological information can be estimated simultaneously, including the thickness of the glass substrate, the refractive index, reflection coefficient, and transmission coefficient, all of which can be used to evaluate the quality of ITO conducting glass. This study developed a modified method for evaluating the refractive index of glass substrates without having to perform multiple scans as well as a segmentation algorithm to separate the interfaces. The results show the potential of OCT as an imaging tool for the inspection of defects in ITO conducting glass.

Assessing Suitability of Co@Au Core/Shell Nanoparticle Geometry for Improved Theranostics in Colon Carcinoma.

The interactions between cells and nanomaterials at the nanoscale play a pivotal role in controlling cellular behavior and ample evidence links cell intercommunication to nanomaterial size. However, little is known about the effect of nanomaterial geometry on cell behavior. To elucidate this and to extend the application in cancer theranostics, we have engineered core-shell cobalt-gold nanoparticles with spherical (Co@Au NPs) and elliptical morphology (Co@Au NEs). Our results show that owing to superparamagnetism, Co@Au NPs can generate hyperthermia upon magnetic field stimulation. In contrast, due to the geometric difference, Co@Au NEs can be optically excited to generate hyperthermia upon photostimulation and elevate the medium temperature to 45 °C. Both nanomaterial geometries can be employed as prospective contrast agents; however, at identical concentration, Co@Au NPs exhibited 4-fold higher cytotoxicity to L929 fibroblasts as compared to Co@Au NEs, confirming the effect of nanomaterial geometry on cell fate. Furthermore, photostimulation-generated hyperthermia prompted detachment of anti-cancer drug, Methotrexate (MTX), from Co@Au NEs-MTX complex and which triggered 90% decrease in SW620 colon carcinoma cell viability, confirming their application in cancer theranostics. The geometry-based perturbation of cell fate can have a profound impact on our understanding of interactions at nano-bio interface which can be exploited for engineering materials with optimized geometries for superior theranostic applications.

Computational multi-directional optical coherence tomography for visualizing the microstructural directionality of the tissue.

We demonstrate computational multi-directional optical coherence tomography (OCT) to assess the directional property of tissue microstructure. This method is the combination of phase-sensitive volumetric OCT imaging and post-signal processing. The latter comprises of two steps. The first step is an intensity-directional analysis, which determines the dominant en face fiber orientations. The second step is the phase-directional imaging, which reveals the sub-resolution depth-orientation of the microstructure. The feasibility of the method was tested by assessing muscle and tendon samples. Stripe patterns with several sizes were visualized in the phase-directional images. In order to interpret these images, the muscle and tendon structures were numerically modeled, and the phase-directional images were generated from the numerical model. The similarity of the experimental and numerical results suggested that the stripe patterns correspond to the muscle fiber bundle and its crimping.

Effect of A-scan rate and interscan interval on optical coherence angiography.

Optical coherence tomography angiography (OCTA) can provide rapid, volumetric, and noninvasive imaging of tissue microvasculature without the requirement of exogenous contrast agents. To investigate how A-scan rate and interscan time affected the contrast and dynamic range of OCTA, we developed a 1.06-µm swept-source OCT system enabling 100-kHz or 200-kHz OCT using two light sources. After system settings were carefully adjusted, almost the same detection sensitivity was achieved between the 100-kHz and 200-kHz modalities. OCTA of ear skin was performed on five mice. We used the variable interscan time analysis algorithm (VISTA) and the designated scanning protocol with OCTA images reconstructed through the correlation mapping method. With a relatively long interscan time (e.g., 12.5 ms vs. 6.25 ms for 200-kHz OCT), OCTA can identify more intricate microvascular networks. OCTA image sets with the same interscan time (e.g., 12.5 ms) were compared. OCTA images acquired with a 100-kHz A-scan rate showed finer microvasculature than did other imaging modalities. We performed quantitative analysis on the contrast from OCTA images reconstructed with different A-scan rates and interscan time intervals in terms of vessel area, total vessel length, and junction density.

Quantitative spectroscopic comparison of the optical properties of mouse cochlea microstructures using optical coherence tomography at 1.06†µm and 1.3†µm wavelengths.

Currently, the cochlear implantation procedure mainly relies on using a hand lens or surgical microscope, where the success rate and surgery time strongly depend on the surgeon's experience. Therefore, a real-time image guidance tool may facilitate the implantation procedure. In this study, we performed a systematic and quantitative analysis on the optical characterization of ex vivo mouse cochlear samples using two swept-source optical coherence tomography (OCT) systems operating at the 1.06-µm and 1.3-µm wavelengths. The analysis results demonstrated that the 1.06-µm OCT imaging system performed better than the 1.3-µm OCT imaging system in terms of the image contrast between the cochlear conduits and the neighboring cochlear bony wall structure. However, the 1.3-µm OCT imaging system allowed for greater imaging depth of the cochlear samples because of decreased tissue scattering. In addition, we have investigated the feasibility of identifying the electrode of the cochlear implant within the ex vivo cochlear sample with the 1.06-µm OCT imaging. The study results demonstrated the potential of developing an image guidance tool for the cochlea implantation procedure as well as other otorhinolaryngology applications.

Oral Cancer Theranostic Application of FeAu Bimetallic Nanoparticles Conjugated with MMP-1 Antibody.

Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron-gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.

Au nanorings for enhancing absorption and backscattering monitored with optical coherence tomography.

Preparation of a high-concentration Au nanoring (NR) water solution and its applications to the enhancement of image contrast in optical coherence tomography (OCT) and the generation of the photothermal effect in a bio-sample through localized surface plasmon (LSP) resonance are demonstrated. Au NRs are first fabricated on a sapphire substrate with colloidal lithography and secondary sputtering of Au, and then transferred into a water solution through a liftoff process. By controlling the NR geometry, the LSP dipole resonance wavelength in tissue can cover a spectral range of 1300 nm for OCT scanning of deep tissue penetration. The extinction cross sections of the fabricated Au NRs in water are estimated to give levels of 10(-10)-10(-9) cm(2) near their LSP resonance wavelengths. The fabricated Au NRs are then delivered into pig adipose samples for OCT scanning. It is observed that, when resonant Au NRs are delivered into such a sample, LSP resonance-induced Au NR absorption results in a photothermal effect, making the opaque pig adipose cells transparent. Also, the delivered Au NRs in the intercellular substance enhance the image contrast of OCT scanning through LSP resonance-enhanced scattering. By continuously OCT scanning a sample, both photothermal and image contrast enhancement effects are observed. However, by continually scanning a sample with a low scan frequency, only the image contrast enhancement effect is observed.

Ultrahigh-resolution optical coherence tomography/angiography with an economic and compact supercontinuum laser.

In this study, a Q-switch pumped supercontinuum laser (QS-SCL) is used as a light source for in vivo imaging via ultrahigh-resolution optical coherence tomography and angiography (UHR-OCT/OCTA). For this purpose, an OCT system based on a spectral-domain detection scheme is constructed, and a spectrometer with a spectral range of 635 - 875 nm is designed. The effective full-width at half maximum of spectrum covers 150 nm, and the corresponding axial and transverse resolutions are 2 and 10 µm in air, respectively. The relative intensity noise of the QS-SCL and mode-locked SCL is quantitatively compared. Furthermore, a special processing algorithm is developed to eliminate the intrinsic noise of QS-SCL. This work demonstrates that QS-SCLs can effectively reduce the cost and size of UHR-OCT/OCTA instruments, making clinical applications feasible.