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.

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.

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.

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.

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.

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.

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.

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.

Early detection of enamel demineralization by optical coherence tomography.

Enamel is the outermost layer of the tooth that protects it from invasion. In general, an acidic environment accelerates tooth demineralization, leading to the formation of cavities. Scanning electron microscopy (SEM) is conventionally used as an in vitro tool for the observation of tooth morphology changes with acid attacks. Yet, SEM has intrinsic limitations for the potential application of in vivo detection in the early demineralization process. In this study, a high-resolution optical coherence tomography (OCT) system with the axial and transverse resolutions of 2.0 and 2.7 µm in teeth has been utilized for characterizing the effect of the acidic environment (simulated by phosphoric acid) on the enamel topology. The scattering coefficient and the surface roughness of enamel can be directly derived from the OCT results, enabling a quantitative evaluation of the topology changes with demineralization. The dynamic process induced by the acid application is also recorded and analyzed with OCT, depicting the evolution of the demineralization process on enamel. Notably, the estimated enamel scattering coefficient and surface roughness significantly increase with the application time of acid and the results illustrate that the values of both parameters after demineralization are significantly larger than those obtained before the demineralization, illustrating both parameters could be effective to differentiate the healthy and demineralized teeth and determine the severity. The obtained results unambiguously illustrate that demineralization of the tooth surface can be successfully detected by OCT and further used as an indicator of early-stage cavity formation.

Non-Invasive Quantification of the Growth of Cancer Cell Colonies by a Portable Optical Coherence Tomography.

Investigation of tumor development is essential in cancer research. In the laboratory, living cell culture is a standard bio-technology for studying cellular response under tested conditions to predict in vivo cellular response. In particular, the colony formation assay has become a standard experiment for characterizing the tumor development in vitro. However, quantification of the growth of cell colonies under a microscope is difficult because they are suspended in a three-dimensional environment. Thus, optical coherence tomography (OCT) imaging was develop in this study to monitor the growth of cell colonies. Cancer cell line of Huh 7 was used and the cells were applied on a layer of agarose hydrogel, i.e., a non-adherent surface. Then, cell colonies were gradually formed on the surface. The OCT technique was used to scan the cell colonies every day to obtain quantitative data for describing their growth. The results revealed the average volume increased with time due to the formation of cell colonies day-by-day. Additionally, the distribution of cell colony volume was analyzed to show the detailed information of the growth of the cell colonies. In summary, the OCT provides a non-invasive quantification technique for monitoring the growth of the cell colonies. From the OCT images, objective and precise information is obtained for higher prediction of the in vivo tumor development.

A curvature-tunable random laser.

The application of random lasers has been restricted due to the absence of a well-defined resonant cavity, as the lasing action mainly depends on multiple light scattering induced by intrinsic disorders of the laser medium to establish the required optical feedback that hence increases the difficulty in efficiently tuning and modulating random lasing emissions. This study investigated whether the transport mean free path of emitted photons within disordered scatterers composed of ZnO nanowires is tunable by a curvature bending applied to the flexible polyethylene terephthalate (PET) substrate underneath, thereby creating a unique light source that can be operated above and below the lasing threshold for desirable spectral emissions. For the first time, the developed curvature-tunable random laser is implemented for in vivo biological imaging with much lower speckle noise compared to the non-lasing situation through simple mechanical bending, which is of great potential for studying the fast-moving physiological phenomenon such as blood flow patterns in mouse ear skin. It is expected that the experimental demonstration of the curvature-tunable random laser can provide a new route to develop disorder-based optoelectronic devices.

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.

Flexible random lasers with tunable lasing emissions.

In this study, we experimentally demonstrated a flexible random laser fabricated on a polyethylene terephthalate (PET) substrate with a high degree of tunability in lasing emissions. Random lasing oscillation arises mainly from the resonance coupling between the emitted photons of gain medium (Rhodamine 6G, R6G) and the localized surface plasmon (LSP) of silver nanoprisms (Ag NPRs), which increases the effective cross-section for multiple light scattering, thus stimulating the lasing emissions. More importantly, it was found that the random lasing wavelength is blue-shifted monolithically with the increase in bending strains exerted on the PET substrate, and a maximum shift of ∼15 nm was achieved in the lasing wavelength, when a 50% bending strain was exerted on the PET substrate. Such observation is highly repeatable and reversible, and this validates that we can control the lasing wavelength by simply bending the flexible substrate decorated with the Ag NPRs. The scattering spectrum of the Ag NPRs was obtained using a dark-field microscope to understand the mechanism for the dependence of the wavelength shift on the exerted bending strains. As a result, we believe that the experimental demonstration of tunable lasing emissions based on the revealed structure is expected to open up a new application field of random lasers.

Assessment of temporary cerebral effects induced by focused ultrasound with optical coherence tomography angiography.

Focused ultrasound (FUS) in combination with microbubbles temporally and locally increases the permeability of the blood-brain barrier (BBB) for facilitating drug delivery. However, the temporary effects of FUS on the brain microstructure and microcirculation need to be addressed. We used label-free optical coherence tomography (OCT) and OCT angiography (OCTA) to investigate the morphological and microcirculation changes in mouse brains due to FUS exposure at different power levels. Additionally, the recovery progress of the induced effects was studied. The results show that FUS exposure causes cerebral vessel dilation and can be identified and quantitatively analyzed via OCT/OCTA. Micro-hemorrhages can be detected when an excessive FUS exposure power is applied, causing the degradation of OCTA signal owing to strong scattering by leaked red blood cells (RBCs) and weaker backscattered intensity from RBCs in vessels. The vessel dilation effect due to FUS exposure was found to abate in several hours. This study demonstrates that the FUS-induced cerebral transiently dilated effects can be in-vivo differentiated and monitored with OCTA, and shows the feasibility of using OCT/OCTA as a novel tool for long-time monitoring of cerebral vascular dynamics during FUS-BBB opening process.

In vivo detection of UV-induced acute skin effects using optical coherence tomography.

Ultraviolet (UV) rays have been identified as a carcinogen with long-term irradiation and are an important risk factor for skin cancer. Here, we report the use of optical coherence tomography/optical coherence tomography angiography (OCT/OCTA) to study acute UV-induced effects on skin in vivo. To understand the relationship between the acute effects and irradiated UV power density, three groups were irradiated with different power densities in our experiments. Furthermore, the same skin area was repeatedly scanned with OCT during UV irradiation to investigate the progress of the induced acute effects and after irradiation for observation of skin recovery. Subsequently, the OCT/OCTA results were quantitatively analyzed to acquire skin thickness and blood-vessel density for comparison. UV-induced acute effects on morphology and microcirculation can be identified from OCT/OCTA results, which showed the increases in the skin thickness and blood-vessel density and even severe damage types such as blisters. The results of quantitative analyses also illustrated that the severity of damage induced by UV irradiation can be distinguished and the skin recovery can be monitored with OCT. Our results indicate that OCT can be a promising tool for early detection of UV-induced acute skin damage.

Noninvasive structural and microvascular anatomy of oral mucosae using handheld optical coherence tomography.

In this study, we demonstrated the feasibility of using a handheld optical coherence tomography (OCT) for in vivo visualizations of the microstructural and microvascular features of various oral mucosal types. To scan arbitrary locations of the oral mucosa, a scanning probe was developed, composed of a probe body fabricated by a 3D printer, miniaturized two-axis galvanometer, relay lenses, and reflective prism. With a 3D printing technique, the probe weight and the system volume were greatly reduced, enabling the effective improvement of imaging artifacts from unconscious motion and system complexity. Additionally, in our design, the distal end of the probe can be switched to fit various oral conditions, and the optical parameters of the probe, such as the transverse resolution, working distance, and probe length can be easily varied. The results showed that the epithelium and lamina propria layers, as well as the fungiform papilla and salivary gland, were differentiated. Moreover, various microcirculation features at different mucosal sites were identified that are potentially effective indicators for the diagnosis of premalignant lesions. The demonstrated results indicate that the developed OCT system is a promising tool for noninvasive imaging of oral mucosae.

Determination on the Coefficient of Thermal Expansion in High-Power InGaN-based Light-emitting Diodes by Optical Coherence Tomography.

The coefficient of thermal expansion (CTE) is a physical quantity that indicates the thermal expansion value of a material upon heating. For advanced thermal management, the accurate and immediate determination of the CTE of packaging materials is gaining importance because the demand for high-power lighting-emitting diodes (LEDs) is currently increasing. In this study, we used optical coherence tomography (OCT) to measure the CTE of an InGaN-based (λ = 450 nm) high-power LED encapsulated in polystyrene resin. The distances between individual interfaces of the OCT images were observed and recorded to derive the instantaneous CTE of the packaged LED under different injected currents. The LED junction temperature at different injected currents was established with the forward voltage method. Accordingly, the measured instantaneous CTE of polystyrene resin varied from 5.86 × 10-5 °C-1 to 14.10 × 10-5 °C-1 in the junction temperature range 25-225 °C and exhibited a uniform distribution in an OCT scanning area of 200 × 200 µm. Most importantly, this work validates the hypothesis that OCT can provide an alternative way to directly and nondestructively determine the spatially resolved CTE of the packaged LED device, which offers significant advantages over traditional CTE measurement techniques.

Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice.

Dissolving microneedles (MNs) display high efficiency in delivering poorly permeable drugs and vaccines. Here, two-layer dissolving polymeric MN patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were fabricated with a two-step casting and centrifuging process to localize the insulin in the needle and achieve efficient transdermal delivery of insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine 6G and fluorescein isothiocyanate-labeled insulin (insulin-FITC) can gradually diffuse from the puncture sites to deeper tissue. Ex vivo drug-release profiles showed that 50% of the insulin was released and penetrated across the skin after 1 h, and the cumulative permeation reached 80% after 5 h. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MN patches on diabetic mice for glucose regulation. The total area above the glucose level versus time curve as an index of hypoglycemic effect was 128.4 ± 28.3 (% h) at 0.25 IU/kg. The relative pharmacologic availability and relative bioavailability (RBA) of insulin from MN patches were 95.6 and 85.7%, respectively. This study verified that the use of gelatin/CMC MN patches for insulin delivery achieved a satisfactory RBA compared to traditional hypodermic injection and presented a promising device to deliver poorly permeable protein drugs for diabetic therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 84-93, 2017.

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.

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.