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.     

Automatic segmentation of the choroid in enhanced depth imaging optical coherence tomography images

Enhanced Depth Imaging (EDI) optical coherence tomography (OCT) provides high-definition cross-sectional images of the choroid in vivo, and hence is used in many clinical studies. However, the quantification of the choroid depends on the manual labelings of two boundaries, Bruch’s membrane and the choroidal-scleral interface. This labeling process is tedious and subjective of inter-observer differences, hence, automatic segmentation of the choroid layer is highly desirable. In this paper, we present a fast and accurate algorithm that could segment the choroid automatically. Bruch’s membrane is detected by searching the pixel with the biggest gradient value above the retinal pigment epithelium (RPE) and the choroidal-scleral interface is delineated by finding the shortest path of the graph formed by valley pixels using Dijkstra’s algorithm. The experiments comparing automatic segmentation results with the manual labelings are conducted on 45 EDI-OCT images and the average of Dice’s Coefficient is 90.5%, which shows good consistency of the algorithm with the manual labelings. The processing time for each image is about 1.25 seconds.OCIS codes: (100.0100) Image processing, (110.4500) Optical coherence tomography, (100.2960) Image analysis, (170.4470) Ophthalmology     

Comparison of peripapillary choroidal thickness measurements via spectral domain optical coherence tomography with and without enhanced depth imaging

Objectives: To compare peripapillary choroidal thickness (PP-CT) measurements using a spectral domain optical coherence tomography (SD-OCT) device with and without enhanced depth imaging (EDI).

Methods: Sixty healthy subjects aged from 18 to 40 years were included in this study. PP-CTs were measured in the right eyes by manual segmentation via SD-OCT both with and without EDI. The intraclass correlation coefficient (ICC) for each technique and comparison of PP-CT measurements between two techniques were evaluated. The correlation between retinal nerve fiber layer (RNFL) thickness and PP-CT was also explored on images of SD-OCT without EDI.

Results: The PP-CT measurements of 55 subjects were evaluated. The ICC was 0.999 (95% CI: 0.998–1.0, p < 0.001) for SD-OCT with EDI and 0.996 (95% CI: 0.995–0.997, p < 0.001) for SD-OCT without EDI. The mean PP-CT measurements in all regions and the overall mean PP-CT measurements between the two techniques were not different (p > 0.05). Additionally, there was no correlation between RNFL thickness and PP-CT (r = ?0.109; p = 0.335).

Conclusions: The PP-CT measurements via SD-OCT without EDI were consistent with the measurements via SD-OCT with EDI. Ophthalmologists who do not have access to EDI technology can use images of SD-OCT without EDI to measure the peripapillary choroid for research purposes. However, thicker peripapillary choroids cannot be measured using this technique and require further modifications or newer technologies, such as SD-OCT with EDI     

Porcine skin damage threshold from mid-infrared optical parametric oscillator radiation at 3.743 µm

There is increasing use of mid-infrared optical parametric oscillator radiation operating in the wavelength range of 3–5 µm. To expand existing damage data for skin exposure to lasers in this wavelength region, the in-vivo damage threshold at the wavelength of 3.743 µm was determined in a Guizhou miniature pig model for an exposure duration of 1.0 s. The irradiance of the laser spot was nearly Gaussian-distributed and the 1/e² beam diameter on the animal skin surface was fixed at 0.94 and 0.88 cm along horizontal and vertical directions. Damage lesion determinations were performed at 1- and 24-hour post-exposure. The probit analysis was employed to establish the ED₅₀ values. The ED₅₀ expressed in peak radiant exposure for the Gaussian spot was 4.04 J/cm² at the 24-hour post-exposure. Sufficient margin existed between the damage threshold and MPE from the current laser safety standard. The obtained data may contribute to the knowledge base for refinement of laser safety standard in the wavelength range of 2.6–1000 µm.     

Extended depth of focus adaptive optics spectral domain optical coherence tomography

We present an adaptive optics spectral domain optical coherence tomography (AO-SDOCT) with a long focal range by active phase modulation of the pupil. A long focal range is achieved by introducing AO-controlled third-order spherical aberration (SA). The property of SA and its effects on focal range are investigated in detail using the Huygens-Fresnel principle, beam profile measurement and OCT imaging of a phantom. The results indicate that the focal range is extended by applying SA, and the direction of extension can be controlled by the sign of applied SA. Finally, we demonstrated in vivo human retinal imaging by altering the applied SA.OCIS codes: (170.4500) Optical coherence tomography, (110.1080) Active or adaptive optics, (170.4470) Ophthalmology     

Optical detection of formaldehyde in air in the 3.6 µm range

The optical detector of formaldehyde designed for sensing cancer biomarkers in air exhaled from human lungs with possible application in free atmosphere is described. The measurements were performed at wavelengths ranging from 3595.77–3596.20 nm. It was stated that at the pressure of 0.01 atm this absorption band exhibits the best immunity to typical interferents that might occur at high concentration in human breath. Multipass absorption spectroscopy was also applied. The method of optical fringes quenching by wavelength modulation and signal averaging over the interferences period was presented. The application of such approaches enabled the detection limit of about single ppb to be achieved.     

High-resolution 1050 nm spectral domain retinal optical coherence tomography at 120 kHz A-scan rate with 6.1 mm imaging depth

We report a newly developed high speed 1050nm spectral domain optical coherence tomography (SD-OCT) system for imaging posterior segment of human eye. The system is capable of an axial resolution at ~10 µm in air, an imaging depth of 6.1 mm in air, a system sensitivity fall-off at ~6 dB/3mm and an imaging speed of 120,000 A-scans per second. We experimentally demonstrate the system’s capability to perform phase-resolved imaging of dynamic blood flow within retina, indicating high phase stability of the SDOCT system. Finally, we show an example that uses this newly developed system to image posterior segment of human eye with a large view of view (10 × 9 mm²), providing detailed visualization of microstructural features from anterior retina to posterior choroid. The demonstrated system parameters and imaging performances are comparable to those that a typical 1 µm swept source OCT would deliver for retinal imaging.OCIS codes: (170.4460) Ophthalmic optics and devices, (170.3880) Medical and biological imaging, (170.4500) Optical coherence tomography     

Impact of motion-associated noise on intrinsic optical signal imaging in humans with optical coherence tomography

A growing body of evidence suggests that phototransduction can be studied in the human eye in vivo by imaging of fast intrinsic optical signals (IOS). There is consensus concerning the limiting influence of motion-associated imaging noise on the reproducibility of IOS-measurements, especially in those employing spectral-domain optical coherence tomography (SD-OCT). However, no study to date has conducted a comprehensive analysis of this noise in the context of IOS-imaging. In this study, we discuss biophysical correlates of IOS, and we address motion-associated imaging noise by providing correctional post-processing methods. In order to avoid cross-talk of adjacent IOS of opposite signal polarity, cellular resolution and stability of imaging to the level of individual cones is likely needed. The optical Stiles-Crawford effect can be a source of significant IOS-imaging noise if alignment with the peak of the Stiles-Crawford function cannot be maintained. Therefore, complete head stabilization by implementation of a bite-bar may be critical to maintain a constant pupil entry position of the OCT beam. Due to depth-dependent sensitivity fall-off, heartbeat and breathing associated axial movements can cause tissue reflectivity to vary by 29% over time, although known methods can be implemented to null these effects. Substantial variations in reflectivity can be caused by variable illumination due to changes in the beam pupil entry position and angle, which can be reduced by an adaptive algorithm based on slope-fitting of optical attenuation in the choriocapillary lamina.OCIS codes: (170.2655) Functional monitoring and imaging, (110.4500) Optical coherence tomography, (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (330.7331) Visual optics, receptor optics, (330.5310) Vision - photoreceptors     

Cavity length control for Fourier domain mode locked (FDML) lasers with µm precision

In highly dispersion compensated Fourier domain mode locked (FDML) lasers, an ultra-low noise operation can only be achieved by extremely precise and stable matching of the filter tuning period and light circulation time in the cavity. We present a robust and high precision closed-loop control algorithm and an actively cavity length controlled FDML laser. The cavity length control achieves a stability of ∼0.18 mHz at a sweep repetition rate of ∼418 kHz which corresponds to a ratio of 4×10⁻¹⁰. Furthermore, we prove that the rapid change of the cavity length has no negative impact on the quality of optical coherence tomography using the FDML laser as light source.     

In vivo imaging of nanoparticle delivery and tumor microvasculature with multimodal optical coherence tomography

Current imaging techniques capable of tracking nanoparticles in vivo supply either a large field of view or cellular resolution, but not both. Here, we demonstrate a multimodality imaging platform of optical coherence tomography (OCT) techniques for high resolution, wide field of view in vivo imaging of nanoparticles. This platform includes the first in vivo images of nanoparticle pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying images of microvascular and tissue morphology. Gold nanorods (51.8 ± 8.1 nm by 15.2 ± 3.3 nm) were intravenously injected into mice, and their accumulation into mammary tumors was non-invasively imaged in vivo in three dimensions over 24 hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold nanorods reached peak distribution throughout the tumors by 16 hours, and remained well-dispersed up to 24 hours post-injection. In contrast, the overall accumulation of gold nanorods within the tumors peaked around 16 hours post-injection. The accumulation of gold nanorods within the tumors was validated post-mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies.OCIS codes: (110.4500) Optical coherence tomography, (160.4236) Nanomaterials, (350.5340) Photothermal effects     

Compensation of motion artifacts in intracoronary optical frequency domain imaging and optical coherence tomography

Intracoronary optical coherence tomography and optical frequency domain imaging (OFDI) have been utilized for two-dimensional and three-dimensional imaging of vascular microanatomy. Image quality and the spatial accuracy of multidimensional reconstructions, however, can be degraded due to artifacts resulting from relative motion between the intracoronary catheter and the vessel wall. To track the relative motion of a catheter with regard to the vessel, a motion tracking system was incorporated with a standard OFDI system by using wavelength division multiplexing techniques. Motion of the vessel was acquired by a frequency shift of the backscattered light caused by the Doppler effect. A single monochromatic beam was utilized for tracking the relative longitudinal displacements of a catheter-based fiber probe with regard to the vessel. Although two tracking beams are, in general, required to correct for longitudinal motion artifacts, the accurate reconstruction in a longitudinal view was achieved by the Doppler frequency information of a single beam. Our results demonstrate that the single beam based motion tracking scheme is a cost-effective, practical approach to compensating for longitudinal distortions due to cardiac dynamics, thus leading to accurate quantitative analysis of 3D intracoronary OFDI.     

In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography

We present in vivo volumetric images of human retinal micro-circulation using Fourier-domain optical coherence tomography (Fd-OCT) with the phase-variance based motion contrast method. Currently fundus fluorescein angiography (FA) is the standard technique in clinical settings for visualizing blood circulation of the retina. High contrast imaging of retinal vasculature is achieved by injection of a fluorescein dye into the systemic circulation. We previously reported phase-variance optical coherence tomography (pvOCT) as an alternative and non-invasive technique to image human retinal capillaries. In contrast to FA, pvOCT allows not only noninvasive visualization of a two-dimensional retinal perfusion map but also volumetric morphology of retinal microvasculature with high sensitivity. In this paper we report high-speed acquisition at 125 kHz A-scans with pvOCT to reduce motion artifacts and increase the scanning area when compared with previous reports. Two scanning schemes with different sampling densities and scanning areas are evaluated to find optimal parameters for high acquisition speed in vivo imaging. In order to evaluate this technique, we compare pvOCT capillary imaging at 3x3 mm(2) and 1.5x1.5 mm(2) with fundus FA for a normal human subject. Additionally, a volumetric view of retinal capillaries and a stitched image acquired with ten 3x3 mm(2) pvOCT sub-volumes are presented. Visualization of retinal vasculature with pvOCT has potential for diagnosis of retinal vascular diseases.     

Fingerprint imaging from the inside of a finger with full-field optical coherence tomography

Imaging below fingertip surface might be a useful alternative to the traditional fingerprint sensing since the internal finger features are more reliable than the external ones. One of the most promising subsurface imaging technique is optical coherence tomography (OCT), which, however, has to acquire 3-D data even when a single en face image is required. This makes OCT inherently slow for en face imaging and produce unnecessary large data sets. Here we demonstrate that full-field optical coherence tomography (FF-OCT) can be used to produce en face images of sweat pores and internal fingerprints, which can be used for the identification purposes.OCIS codes: (110.4500) Optical coherence tomography, (110.3080) Infrared imaging, (170.3880) Medical and biological imaging     

Quantitative comparison of contrast and imaging depth of ultrahigh-resolution optical coherence tomography images in 800-1700 nm wavelength region

We investigated the wavelength dependence of imaging depth and clearness of structure in ultrahigh-resolution optical coherence tomography over a wide wavelength range. We quantitatively compared the optical properties of samples using supercontinuum sources at five wavelengths, 800 nm, 1060 nm, 1300 nm, 1550 nm, and 1700 nm, with the same system architecture. For samples of industrially used homogeneous materials with low water absorption, the attenuation coefficients of the samples were fitted using Rayleigh scattering theory. We confirmed that the systems with the longer-wavelength sources had lower scattering coefficients and less dependence on the sample materials. For a biomedical sample, we observed wavelength dependence of the attenuation coefficient, which can be explained by absorption by water and hemoglobin.     

Quantitative multi-contrast in vivo mouse imaging with polarization diversity optical coherence tomography and angiography

Retinal microvasculature and the retinal pigment epithelium (RPE) play vital roles in maintaining the health and metabolic activity of the eye. Visualization of these retina structures is essential for pre-clinical studies of vision-robbing diseases, such as age-related macular degeneration (AMD). We have developed a quantitative multi-contrast polarization diversity OCT and angiography (QMC-PD-OCTA) system for imaging and visualizing pigment in the RPE using degree of polarization uniformity (DOPU), along with flow in the retinal capillaries using OCT angiography (OCTA). An adaptive DOPU averaging kernel was developed to increase quantifiable values from visual data, and QMC en face images permit simultaneous visualization of vessel location, depth, melanin region thickness, and mean DOPU values, allowing rapid identification and differentiation of disease symptoms. The retina of five different mice strains were measured in vivo, with results demonstrating potential for pre-clinical studies of retinal disorders.     

Multimodal photoacoustic and optical coherence tomography scanner using an all optical detection scheme for 3D morphological skin imaging

A noninvasive, multimodal photoacoustic and optical coherence tomography (PAT/OCT) scanner for three-dimensional in vivo (3D) skin imaging is described. The system employs an integrated, all optical detection scheme for both modalities in backward mode utilizing a shared 2D optical scanner with a field-of-view of ~13 × 13 mm(2). The photoacoustic waves were detected using a Fabry Perot polymer film ultrasound sensor placed on the surface of the skin. The sensor is transparent in the spectral range 590-1200 nm. This permits the photoacoustic excitation beam (670-680 nm) and the OCT probe beam (1050 nm) to be transmitted through the sensor head and into the underlying tissue thus providing a backward mode imaging configuration. The respective OCT and PAT axial resolutions were 8 and 20 μm and the lateral resolutions were 18 and 50-100 μm. The system provides greater penetration depth than previous combined PA/OCT devices due to the longer wavelength of the OCT beam (1050 nm rather than 829-870 nm) and by operating in the tomographic rather than the optical resolution mode of photoacoustic imaging. Three-dimensional in vivo images of the vasculature and the surrounding tissue micro-morphology in murine and human skin were acquired. These studies demonstrated the complementary contrast and tissue information provided by each modality for high-resolution 3D imaging of vascular structures to depths of up to 5 mm. Potential applications include characterizing skin conditions such as tumors, vascular lesions, soft tissue damage such as burns and wounds, inflammatory conditions such as dermatitis and other superficial tissue abnormalities.     

Expanding pentafluorouranates: hydrothermal synthesis and characterization of β-NaUF5 and β-NaUF5·H2O

Two new sodium uranium(iv) pentafluorides were synthesized from uranium dioxide, HF, and NaF using mild hydrothermal conditions. β-NaUF₅·H₂O has greater lattice energy than previously-known α-NaUF₅·H₂O and possesses lower symmetry with the latter compound being orthorhombic, whereas β-NaUF₅·H₂O is monoclinic. Trigonal β-NaUF₅ also possesses different connectivity between the [UF_n] building units than the α-phase, with higher symmetry and greater lattice energy than orthorhombic α-NaUF₅. The single crystal absorption spectra of these compounds are also reported and compared.

Two new sodium uranium(iv) pentafluorides eliminate the necessity of a copper catalyst in the synthesis of alkali metal uranium fluorides.     

Differentiation of pancreatic cysts with optical coherence tomography (OCT) imaging: an ex vivo pilot study

We demonstrate for the first time that optical coherence tomography (OCT) imaging can reliably distinguish between morphologic features of low risk pancreatic cysts (i.e., pseudocysts and serous cystadenomas) and high risk pancreatic cysts (i.e., mucinous cystic neoplasms and intraductal papillary mucinous neoplasms). In our study fresh pancreatectomy specimens (66) from patients with cystic lesions undergoing surgery were acquired and examined with OCT. A training set of 20 pathology-OCT correlated tissue specimens were used to develop criteria for differentiating between low and high risk cystic lesions. A separate (validation) set of 46 specimens were used to test the OCT criteria by three clinicians, blinded to histopathology findings. Histology was finally used as a 'gold' standard for testing OCT findings. OCT was able to reveal specific morphologic features of pancreatic cysts and thus to differentiate between low-risk and high-risk cysts with over 95% sensitivity and specificity. This pilot study suggests that OCT could be used by clinicians in the future to more reliably differentiate between benign and potentially malignant pancreatic cysts. However, in vivo use of OCT requires a probe that has to fit the bore of the pancreas biopsy needle. Therefore, we have developed such probes and planned to start an in vivo pilot study within the very near future.     

In vivo volumetric imaging of chicken retina with ultrahigh-resolution spectral domain optical coherence tomography

The chicken retina is an established animal model for myopia and light-associated growth studies. It has a unique morphology: it is afoveate and avascular; oxygen and nutrition to the inner retina is delivered by a vascular tissue (pecten) that protrudes into the vitreous. Here we present, to the best of our knowledge, the first in vivo, volumetric high-resolution images of the chicken retina. Images were acquired with an ultrahigh-resolution optical coherence tomography (UHROCT) system with 3.5 μm axial resolution in the retina, at the rate of 47,000 A-scans/s. Spatial variations in the thickness of the nerve fiber and ganglion cell layers were mapped by segmenting and measuring the layer thickness with a semi-automatic segmentation algorithm. Volumetric visualization of the morphology and morphometric analysis of the chicken retina could aid significantly studies with chicken retinal models of ophthalmic diseases.