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High-Definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-Resolution Optical Coherence Tomography

In this paper, five types of tissues, human enamel, human cortical bone, human trabecular bone, muscular tissue, and fatty tissue were imaged <i>ex vivo</i> using optical coherence tomography (OCT). The specimens were prepared in blocks of 5 x 5 x 3 mm (width x length x height). The OCT imaging system was a swept source OCT system operating at wavelengths ranging between 1250 nm and 1360 nm with an average power of 18 mW and a scan rate of 50 to 100 kHz. The imaging probe was placed on top of a 2 x 2 cm stabilizing device to maintain a standard distance from the samples. Ten image samples from each type of tissue were obtained. To acquire images with minimum inhomogeneity, imaging was performed multiple times at different points. Based on the observed texture differences between OCT images of soft and hard tissues, spatial and spectral features were quantitatively extracted from the OCT images. The Radon transform from angles of 0 deg to 90 deg was computed, averaged over all the angles, normalized to peak at unity, and then fitted with Gaussian function. The mean absolute values of the spatial frequency components of the OCT image were considered as a feature, where 2-D fast Fourier transform (FFT) was done to OCT images. These OCT features can reliably differentiate between a range of hard and soft tissues, and could be extremely valuable in assisting dentists for <i>in vivo</i> evaluation of oral tissues and early detection of pathologic changes in tissues.

This study aimed to evaluate a novel real-time rotational optical coherence tomography (OCT) imaging system (OCTIS) with a fiber-optic probe to look at endometrium and to correlate the OCTIS images with standard histology. OCT could obtain real-time images resembling histological examination. With recent development of customized probes, it allows OCT to be used in the field of gynecology.This is a pilot, prospective, ex-vivo and observational study. Women underwent hysterectomy for various gynecological conditions were recruited and OCTIS images were obtained from endometrium of 15 fresh uterus specimens immediately after hysterectomy. The excised uterus was cut open and OCTIS imaging was obtained. The scanned region of endometrium was excised for histological examination and OCTIS images were precisely compared to corresponding histological images and ultrasound images. Blinded qualitative analysis on OCTIS images was performed by 2 assessors to determine inter-rating reliability on the histopathological diagnosis.Epithelium, glands, cysts, and stroma of endometrium were clearly seen by the OCTIS. Different phases of menstrual cycle of normal endometrium could be differentiated and pathological condition such as hyperplastic and dysplasic endometrium, which corresponded well with histological findings, could be identified. The inter-rater reliability between assessors on overall OCTIS endometrium and neoplastic OCTIS endometrium was moderate (Kendall τb of 0.58) and substantial (Kendall τb of 0.76), respectively.OCTIS can provide real-time, high-resolution and rotational imaging modality to view endometrial structure with high consistency with histological examination and satisfactory agreement between observers. It has a great potential to be developed in the clinical use of endometrial assessment for gynecological applications.

We report studies of the analyses of and compensation for group dispersion to improve the axial resolution of high-speed optical coherence tomography (OCT) by acousto-optic modulation (AOM). Theoretical modeling and experiments reveal that the high-order group dispersion induced by acousto-optic crystals broadens the measured coherence length (Lc) and thus degrades the axial resolution of OCT imaging. Based on our experimental studies, we can compensate for the dispersion to less than 50% broadening of the source Lc by adjusting the grating-lens-based optical delay in the reference arm and can further eliminate it by inserting like acousto-optic crystals in the sample arm of the OCT system. The results demonstrate that this AOM-mediated OCT system permits high-performance OCT imaging at A-scan rates of as much as 4 kHz by use of a resonant scanner. Because of its ultrastable direct frequency modulation, this AOM-mediated OCT system can potentially improve the performance of high-speed Doppler OCT techniques.

Regenerative therapies such as stem cell therapies are an area of active investigation that will likely play an important role in the future to improve vision loss from retinal diseases including macular degeneration and retinitis pigmentosa. It is important to visualize these cells after administration to determine their fate and effect. In this study, an advanced non-invasive photoacoustic microscopy (PAM) and optical coherence tomography (OCT) imaging system was developed to monitor cells in vivo. To boost the sensitivity of PAM and OCT, novel ultrapure functionalized chain-like gold nanoparticle (CGNP) clusters were synthesized and cultured into a precursor human retinal pigment epithelial cell line with differentiated properties (ARPE-19) cells. The fabricated CGNP clusters have redshifted plasmonic peak absorption from 520nm to 650nm, resulting in reduced background signal from hemoglobin. The position of cells following subretinal injection into the rabbit retina having laser injury is selectively tracked longitudinally in vivo using integrated photoacoustic microscopy (PAM) and OCT over 3 months in 3 rabbits. PAM images obtained at two different optical wavelengths of 578 nm and 650 nm were overlaid on the same image plane and on the OCT image allowed to distinguish transplanted cells from the adjacent native choroidal vessels and track the migration of the cells over time. Quantification of PAM and OCT signals illustrated that the PAM signal increased by 30-fold, and OCT signal increased by 180 %. Histological analysis confirmed that ARPE-19 cells migrated to the injured sites and correlated with the location noted on the PAM/OCT imaging. This work provides a comprehensive imaging and nanoparticle system that could be used for labeling and tracking of cell-based regenerative therapies.

We have developed a custom analog CMOS circuit to perform the signal processing for an optical coherence tomography imaging system. The circuit is realized in a 1.5 microm low-noise analog CMOS technology. The circuitry extracts the Doppler frequency from the signal and electrically mixes this with the original signal to provide a filtered A-scan. The circuitry was used to produce a two-dimensional image of an onion.

Application of the nonlinear Kalman filtering method to logarithmically amplified low-coherence fringe signals measured from paper samples is considered. Experimental results of dynamic fringe envelope recovery in optical coherence tomography (OCT) systems are presented. The analog fringe envelope and digital dynamic fringe envelope recoveries from noisy signals are compared. The results show that the nonlinear discrete Kalman filtering method can be applied to estimate envelopes of logarithmically transformed low-coherence fringe signals with high noise immunity. Logarithmic amplification reduces quantization error in dealing with small signal values. The experimental results obtained demonstrate the possibility of purely digital signal processing in OCT.

Objective: Numerous ablation techniques have been developed to alleviate urethral obstruction and improve urodynamics in benign prostatic hyperplasia. Most techniques, however, rely on visual observation of surface changes for ablation end points. The feasibility of using real-time optical coherence tomography (OCT) for minimally invasive imaging to guide and monitor prostate resection is demonstrated with representative techniques of laser and radiofrequency ablation. Empiric comparisons of ablation dynamics are made, and the use of OCT as a high-resolution, subsurface modality for image guidance is evaluated.Materials and Methods: Optical coherence tomography is a high-resolution, high-speed near-infrared imaging technique analogous to ultrasound imaging, except that reflections of light are detected rather than sound. High-speed OCT is used to image the dynamic process of laser and radiofrequency ablation of in vitro human prostate tissue. OCT images of ablation sites are compared with corresponding histology.Results: Based on comparisons between OCT images and corresponding histology, OCT imaged transurethral prostate tissue morphology, including urethral sinuses and submucosal glands. Real-time OCT imaging provided rapid feedback and control of ablation dynamics. The compact and portable OCT technology is amenable to minimally invasive beam-delivery devices.Conclusions: Optical coherence tomography offers a minimally invasive means of assessing transurethral prostate morphology. Real-time OCT has the potential to provide image guidance of prostate resection for many of the existing surgical treatments directed at alleviating urethral obstruction associated with benign prostatic hyperplasia.

A frequency swept source optical coherence tomography (OCT) imaging system is proposed. The frequency swept source used in the system is a Fourier-domain mode-locked (FDML) laser which has a narrow instantaneous linewidth due to the nonlinear spectrum narrowing effect generated by the nonlinear semiconductor optical amplifier (SOA) used in the FDML laser ring cavity. Therefore, the OCT imaging system has the ability to achieve a large imaging depth. The concept is verified in the experiment, which demonstrates a clear two-dimensional target image and a large imaging depth up to 14 mm.

Although interest in optical coherence tomography (OCT) has increased markedly during the past decade in many fields of ophthalmology, there are only a few reports of the use of spectral domain (SD)-OCT in paediatric ophthalmology. In this article, the authors describe the use of SD-OCT in children as a new indication for OCT. Paediatric patients with aniridia were examined for the presence of keratopaty, cataract, glaucoma and foveal hypoplasia. Children with cataracts were followed for six months after surgery. The type of cataract, intraocular lens position, posterior capsule opacity and corneal incision healing were visualised by SD-OCT. In total, 24 eyes with aniridia and seven eyes with congenital cataract were enrolled. OCT was able successfully to detect ocular conditions associated with aniridia. After cataract extraction, OCT was also used to follow corneal incision healing and the development of posterior capsule opacity. In children with aniridia and congenital cataract, OCT can provide clinically relevant information. With the introduction of new generation, high-speed OCT, paediatric ophthalmology is likely to become a new and interesting target for OCT.

The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.

To measure total corneal power using optical coherence tomography (OCT). Refractive surgery practices at 2 academic eye centers in Cleveland, Ohio, and Los Angeles, California, USA. Thirty-two eyes of 17 patients having myopic laser in situ keratomileusis (LASIK) were enrolled in a prospective observational study. Manifest refraction, OCT, and Placido ring corneal topography with the Atlas 995 (Carl Zeiss Meditec, Inc.) were performed preoperatively and 3 months after laser in situ keratomileusis (LASIK). A high-speed (2000 axial scans/second) corneal and anterior segment OCT prototype was used. The total corneal power was calculated by summation of the anterior and posterior surface powers, and the value was compared with that determined by simulated keratometry. Two methods of measuring total corneal power were tested: the direct method, which used OCT to measure both corneal surfaces directly, and the hybrid method, which combined OCT with anterior corneal topography. The repeatability (pooled standard deviation) of measuring total corneal power using the hybrid method was 3 times better than that using the direct method. It was 0.23 diopter (D) before LASIK and 0.26 D after LASIK. Preoperative total power was 1.13 D (2.6%) lower than the simulated keratometry. Compared to the LASIK-induced change in spherical equivalent refraction, the change in total corneal power was equivalent, while the change in simulated keratometry power was significantly smaller (-18.8%) (P<.001). Keratometry using the traditional index of 1.3375 overestimated the total power in preoperative corneas and underestimated LASIK-induced refractive change. Measuring both corneal surfaces using a combination of OCT and Placido ring topography provided a better measure of total corneal power that closely tracked the refractive change in post-LASIK eyes.

Noninvasive and high-speed optical coherence tomography (OCT) systems have been widely deployed for daily clinical uses. High-resolution OCTs are advancing rapidly; however, grey-level OCT images are not easy to read for pathologists due to the lack of diagnosis specificity compared with hematoxylin and eosin (H&amp;E) stained images. This work presents an OCT to H&amp;E image translation model to convert the OCT images to H&amp;E-like stained images using unpaired OCT and H&amp;E datasets. “H&amp;E like” means the stratum corneum (SC) boundary and the dermal-epidermal junction (DEJ) of the OCT and the translated images are consistent. Pre-trained segmentation models for the DEJ and the SC are exploited to enhance the performance of anatomical image translation and reduce the DEJ and SC lower boundary errors to ±2.3 and ±1.7 μm, respectively. A pre-trained VGG16 network extracts the features of the nuclei. Pearson's correlation coefficient of the nuclei location and size consistency is 84% ± 1%. As a result, in vivo medical image translation accuracy with cellular resolution was achieved.

To image and measure iris tumors with optical coherence tomography (OCT). High-speed (2,000-4,000 axial-scan/sec and 4-16 frames/sec) 1.3-micron wavelength anterior segment OCT prototypes were used to image 6 eyes of 6 patients with a variety of iris lesions, including focal iris nevus, diffuse iris nevus, amelanotic iris nevus, iris melanocytosis, and iris melanoma. OCT images were compared with slit-lamp photography and ultrasound biomicroscopy. OCT at 1.3-micron wavelength could penetrate the full thickness of the iris lesions and allow three-dimensional measurement of lesion size. Internal reflectivity is correlated with pigmentation. OCT is a convenient non-contact method that provides imaging of the clinically important angle structures (scleral spur and angle recess). OCT is a new imaging modality that complements slit-lamp photography and ultrasound biomicroscopy for serial evaluation of iris

To quantify keratometry and wavefront aberration of the anterior corneal surface and epithelium-Bowman's layer interface using anterior segment optical coherence tomography (OCT). Twenty-five normal eyes and 25 eyes with keratoconus were retrospectively analyzed. The anterior corneal edge and epithelium-Bowman's layer interface were segmented from 12 distortion-corrected OCT B-scans. Axial tangential curvatures and wavefront aberration were calculated by ray tracing and 6th order Zernike analyses. All eyes underwent simultaneous imaging with Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany). The Pentacam elevation data were used for aberration analyses using the same ray-tracing method. The paired t test was used to compare the variables. In normal eyes, mean steep axis and maximum keratometry of OCT of the anterior corneal surface and epithelium-Bowman's layer interface were significantly greater than the same of the Pentacam anterior corneal surface (P < .05). Mean root mean square of higher order aberrations of the OCT surfaces was greater than the same of the Pentacam surface by a factor of 4. In eyes with keratoconus, mean steep axis and maximum keratometry of the OCT epithelium-Bowman's layer interface was the greatest (P < .05). Mean root mean square of the higher order aberrations and vertical coma of the OCT epithelium-Bowman's layer interface was the greatest (P < .05). In general, the aberrations of the OCT epithelium-Bowman's layer interface were significantly greater than those of the Pentacam anterior corneal surface. A noncontact method to quantify the topography and aberrations of corneal surfaces with OCT was presented. OCT measurements yielded greater curvature and aberrations than Pentacam in both normal and keratoconic eyes. [J Refract Surg. 2017;33(5):330-336.].