Noninvasive cross‐sectional imaging of proximal caries using swept‐source optical coherence tomography (SS‐OCT) in vivo

The aim of this study was to determine the diagnostic accuracy of swept‐source optical coherent tomography (SS‐OCT) in detecting and estimating the depth of proximal caries in posterior teeth in vivo. SS‐OCT images and bitewing radiographs were obtained from 86 proximal surfaces of 53 patients. Six examiners scored the locations according to a caries lesion depth scale (0–4) using SS‐OCT and the radiographs. The results were compared with clinical observations obtained after the treatment. SS‐OCT could detect the presence of proximal caries in tomograms that were synthesized based on the backscatter signal obtained from the proximal carious lesion through occlusal enamel. SS‐OCT showed significantly higher sensitivity and larger area under the receiver operating characteristic curve than radiographs for the detection of cavitated enamel lesions and dentin caries (Student's t ‐test, p < 0.05). SS‐OCT appears to be a more reliable and accurate method than bitewing radiographs for the detection and estimation of the depth of proximal lesions in the clinical environment. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Effect of hydration on assessment of early enamel lesion using swept‐source optical coherence tomography

Establishing reproducible methodologies for assessment of early enamel lesions using optical coherence tomography (OCT) appears to be challenging. This in vitro study longitudinally evaluated the subsurface enamel lesion progression after 3, 9 and 15 days by cross‐sectional scanning using 1310 nm centered swept‐source OCT (SS‐OCT) under hydrated and dry conditions. The positive difference between the depth‐integrated OCT signals at dry and hydrated conditions were calculated and adopted as dehydration parameter (DH). A linear regression was found between DH and the square root of demineralization time (R² = 0.99). Significant differences were found in DH between sound and demineralized enamel, and between different periods of demineralization (p < 0.001). Hydration state affects the reflectivity of demineralized porous enamel, and the effect can be potentially used for assessment of early enamel lesion using OCT. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Simultaneous detection of cerebral blood perfusion and cerebral edema using swept‐source optical coherence tomography

The progression of ischemic cerebral edema (CE) is closely related to the level of cerebral blood perfusion (CBP) and affects each other. Simultaneous detection of CBP and CE is helpful in understanding the mechanisms of ischemic CE development. In this article, a wide field of view swept‐source optical coherence tomography system was used to detect CE status and CBP levels simultaneously in middle cerebral artery occlusion rats. Images reflecting these two physiological states can be reconstructed with only one C‐scan. We quantify these two physiological states into four parameters, which contain two vascular parameters (vascular displacement distance and vascular perfusion density) and two edema parameters (optical attenuation coefficient and edema area). The association between the two vascular parameters and the two edema parameters was analyzed. The results show that there is a strong linear relationship between blood flow parameters and edema parameters. This work provides a new option for CE in vivo detection, and is very likely to play an important role in the development of relevant drugs or in selection of treatment options.      

Quantitative discrimination of NPC cell lines using optical coherence tomography

We tried to explore the intrinsic differences in the optical properties of the four representative NPC cell lines on the models of radiobiology and metastasis by OCT. The scattering coefficients and anisotropies were extracted by fitting the average a‐scan attenuation curves based on the multiple scatter effect. The values of scattering coefficients and anisotropy factors were 5.21 ± 0.11, 5.30 ± 0.09, 5.92 ± 0.21, 6.97 ± 0.22, and 0.892 ± 0.009, 0.886 ± 0.006, 0.884 ± 0.009, 0.86 ± 0.01 for CNE1, CNE2, 5‐8F and 6‐10B pellets (p < 0.05, P = 0.07 for CNE1 and CNE2), respectively. The results showed that the radiobiology and metastasis cell's model could be distinguished obviously; which implied that the corresponding types of NPC tissue might be potentially differentiated by OCT. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Whole‐brain microcirculation detection after ischemic stroke based on swept‐source optical coherence tomography

The occurrence and development of ischemic stroke are closely related to cerebral blood flow. Real‐time monitoring of cerebral perfusion level is very useful for understanding the mechanisms of the disease. A wide field of view (FOV) is conducive to capturing lesions and observing the progression of the disease. In this paper, we attempt to monitor the whole‐brain microcirculation in middle cerebral artery occlusion (MCAO) rats over time using a wide FOV swept‐source OCT (SS‐OCT) system. A constrained image registration algorithm is used to remove motion artifacts that are prone to occur in a wide FOV angiography. During ischemia, cerebral perfusion levels in the left and right hemispheres, as well as in the whole brain were quantified and compared. Changes in the shape and location of blood vessels were also recorded. The results showed that the trend in cerebral perfusion levels of both hemispheres was highly consistent during MCAO, and the position of the blood vessels varied over time. This work will provide new insights of ischemic stroke and is helpful to assess the effectiveness of potential treatment strategies.      

High‐definition optical coherence tomography of melanocytic skin lesions

High‐definition optical coherence tomography (HD‐OCT) scanners have recently been developed. We assessed micromorphological HD‐OCT correlates of benign naevi (BN) and malignant melanoma (MM). 28 BN and 20 MM were studied using HD‐OCT and histology. Epidermal honeycomb/cobblestone pattern, regular junctional cell nests, and edged papillae are more often observed in BN, whereas fusion of rete ridges, pagetoid cells and junctional and/or dermal nests with atypical cells are more frequently seen in MM. A high overlap of HD‐OCT features in BN and MM was observed and in 20% of MM we did not find evidence for malignancy in OCT images at all. Using HD‐OCT it is possible to visualize architectural and cellular alterations of melanocytic skin lesions. The overlap of HD‐OCT features seen in BN and MM and the absence of suspicious HD‐OCT features in some MM represents an important limitation of HD‐OCT affecting the sensitivity of HD‐OCT in diagnosing MM.

High‐definition optical coherence tomography and the corresponding vertically sectioned histology of a compound naevus.     

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

Corneal transplantation by full‐thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high‐quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three‐dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept‐source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude‐scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth‐intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery.      

Full‐field swept‐source optical coherence tomography and neural tissue classification for deep brain imaging

Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real‐time neurosurgical guidance tool. We present, to our knowledge, the first full‐field swept‐source optical coherence tomography system operating near a wavelength of 1310 nm. The proof‐of‐concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.     

In vivo detection of endotracheal tube biofilms in intubated critical care patients using catheter‐based optical coherence tomography

The formation of biofilms in the endotracheal tubes (ETTs) of intubated patients on mechanical ventilation is associated with a greater risk of ventilator‐associated pneumonia and death. New technologies are needed to detect and monitor ETTs in vivo for the presence of these biofilms. Longitudinal OCT imaging was performed in mechanically ventilated subjects at 24‐hour intervals until extubation to detect the formation and temporal changes of in vivo ETT biofilms. OCT‐derived attenuation coefficient images were used to differentiate between mucus and biofilm. Extubated ETTs were examined with optical and electron microscopy, and all imaging results were correlated with standard‐of‐care clinical test reports. OCT and attenuation coefficient images from four subjects were positive for ETT biofilms and were negative for two subjects. The processed and stained extubated ETTs and clinical reports confirmed the presence/absence of biofilms in all subjects. Our findings confirm that OCT can detect and differentiate between biofilm‐positive and biofilm‐negative groups (P < 10^?5). OCT image‐based features may serve as biomarkers for direct in vivo detection of ETT biofilms and help drive investigation of new management strategies to reduce the incidence of VAP.      

Pilot feasibility study of in vivo intraoperative quantitative optical coherence tomography of human brain tissue during glioma resection

This study investigates the feasibility of in vivo quantitative optical coherence tomography (OCT) of human brain tissue during glioma resection surgery in six patients. High‐resolution detection of glioma tissue may allow precise and thorough tumor resection while preserving functional brain areas, and improving overall survival. In this study, in vivo 3D OCT datasets were collected during standard surgical procedure, before and after partial resection of the tumor, both from glioma tissue and normal parenchyma. Subsequently, the attenuation coefficient was extracted from the OCT datasets using an automated and validated algorithm. The cortical measurements yield a mean attenuation coefficient of 3.8 ± 1.2 mm^?1 for normal brain tissue and 3.6 ± 1.1 mm^?1 for glioma tissue. The subcortical measurements yield a mean attenuation coefficient of 5.7 ± 2.1 and 4.5 ± 1.6 mm^?1 for, respectively, normal brain tissue and glioma. Although the results are inconclusive with respect to trends in attenuation coefficient between normal and glioma tissue due to the small sample size, the results are in the range of previously reported values. Therefore, we conclude that the proposed method for quantitative in vivo OCT of human brain tissue is feasible during glioma resection surgery.     

General model for depth‐resolved estimation of the optical attenuation coefficients in optical coherence tomography

We present the proof of concept of a general model that uses the tissue sample transmittance as input to estimate the depth‐resolved attenuation coefficient of tissue samples using optical coherence tomography (OCT). This method allows us to obtain an image of tissue optical properties instead of intensity contrast, guiding diagnosis and tissues differentiation, extending its application from thick to thin samples. The performance of our method was simulated and tested with the assistance of a home built single‐layered and multilayered phantoms (~100 μm each layer) with known attenuation coefficient on the range of 0.9 to 2.32 mm^?1. It is shown that the estimated depth‐resolved attenuation coefficient recovers the reference values, measured by using an integrating sphere followed by the inverse adding doubling processing technique. That was corroborated for all situations when the correct transmittance value is used with an average difference of 7%. Finally, we applied the proposed method to estimate the depth‐resolved attenuation coefficient for a thin biological sample, demonstrating the ability of our method on real OCT images.     

Three‐dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology

A preliminary clinical trial using state‐of‐the‐art multiphoton tomography (MPT) and optical coherence tomography (OCT) for three‐dimensional (3D) multimodal in vivo imaging of normal skin, nevi, scars and pathologic skin lesions has been conducted. MPT enabled visualization of sub‐cellular details with axial and transverse resolutions of <2 μm and <0.5 μm, respectively, from a volume of 0.35 × 0.35 × 0.2 mm³ at a frame rate of 0.14 Hz (512 × 512 pixels). State‐of‐the‐art OCT, operating at a center wavelength of 1300 nm, was capable of acquiring 3D images depicting the layered architecture of skin with axial and transverse resolutions ～8 μm and ～20 μm, respectively, from a volume of 7 × 3.5 × 1.5 mm³ at a frame rate of 46 Hz (1024 × 1024 pixels). This study demonstrates the clinical diagnostic potential of MPT/OCT for pre‐screening relatively large areas of skin using 3D OCT to identify suspicious regions at microscopic level and subsequently using high resolution MPT to obtain zoomed in, sub‐cellular level information of the respective regions (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Heart‐beat‐phase‐coherent Doppler optical coherence tomography for measuring pulsatile ocular blood flow

We introduce a Doppler OCT (DOCT) platform that is fully synchronized with the heart‐beat via a pulse oximeter. The system allows reconstructing heart‐beat‐phase‐coherent quantitative DOCT volumes. The method is to acquire a series of DOCT volumes and to record the pulse in parallel. The heartbeat data is used for triggering the start of each DOCT volume acquisition. The recorded volume series is registered to the level of capillaries using a cross‐volume registration. The information of the pulse phase is used to rearrange the tomograms in time, to obtain a series of phase coherent DOCT volumes over a pulse. We present Doppler angle independent quantitative evaluation of the absolute pulsatile blood flow within individual retinal vessels as well as of the total retinal blood flow over a full heartbeat cycle. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Investigation of optical attenuation imaging using optical coherence tomography for monitoring of scars undergoing fractional laser treatment

We demonstrate the use of the near‐infrared attenuation coefficient, measured using optical coherence tomography (OCT), in longitudinal assessment of hypertrophic burn scars undergoing fractional laser treatment. The measurement method incorporates blood vessel detection by speckle decorrelation and masking, and a robust regression estimator to produce 2D en face parametric images of the attenuation coefficient of the dermis. Through reliable co‐location of the field of view across pre‐ and post‐treatment imaging sessions, the study was able to quantify changes in the attenuation coefficient of the dermis over a period of ～20 weeks in seven patients. Minimal variation was observed in the mean attenuation coefficient of normal skin and control (untreated) mature scars, as expected. However, a significant decrease (13 ± 5%, mean ± standard deviation) was observed in the treated mature scars, resulting in a greater distinction from normal skin in response to localized damage from the laser treatment. By contrast, we observed an increase in the mean attenuation coefficient of treated (31 ± 27%) and control (27 ± 20%) immature scars, with numerical values incrementally approaching normal skin as the healing progressed. This pilot study supports conducting a more extensive investigation of OCT attenuation imaging for quantitative longitudinal monitoring of scars.

En face 2D OCT attenuation coefficient map of a treated immature scar derived from the pre‐treatment (top) and the post‐treatment (bottom) scans. (Vasculature (black) is masked out.) The scale bars are 0.5 mm.     

Prolonged in vivo functional assessment of the mouse oviduct using optical coherence tomography through a dorsal imaging window

The oviduct (or fallopian tube) serves as an environment for gamete transport, fertilization and preimplantation embryo development in mammals. Although there has been increasing evidence linking infertility with disrupted oviduct function, the specific roles that the oviduct plays in both normal and impaired reproductive processes remain unclear. The mouse is an important mammalian model to study human reproduction. However, most of the current analyses of the mouse oviduct rely on static histology or 2D visualization, and are unable to provide dynamic and volumetric characterization of this organ. The lack of imaging access prevents longitudinal live analysis of the oviduct and its associated reproductive events, limiting the understanding of mechanistic aspects of fertilization and preimplantation pregnancy. To address this limitation, we report a 3D imaging approach that enables prolonged functional assessment of the mouse oviduct in vivo. By combining optical coherence tomography with a dorsal imaging window, this method allows for extended volumetric visualization of the oviduct dynamics, which was previously not achievable. The approach is used for quantitative analysis of oviduct contraction, spatiotemporal characterization of cilia beat frequency and longitudinal imaging. This new approach is a useful in vivo imaging platform for a variety of live studies in mammalian reproduction.      

Evaluation of oral mucosa collagen condition with cross‐polarization optical coherence tomography

The goal of the research was analysis of the effect of collagen condition in formation of cross‐polarized CP OCT images. We used of the CP OCT technique for studying collagen condition on an example of oral mucosa. Special histologic picrosirius red (PSR) staining of cheek mucosa specimens was used with subsequent assessing of the result of collagen staining in polarized light. High correlation (r = 0.692, p = 0.0001) between OCT signal standard deviation (SD) in cross‐polarized images and brightness of PSR stained collagen fibers in cheek mucosa specimens was demonstrated in patients with inflammatory intestine and oral mucosa diseases. We have found that the OCT signal SD in cross‐polarized images reflects two boundary conditions of collagen disorganization, namely, loss of fiber properties at active inflammation which attenuates the signal and fibrosis that occurs due to synthesis of a new remodeled collagen which amplifies the OCT signal. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Contrast‐enhanced optical coherence tomography for melanoma detection: An in vitro study

Optical coherence tomography (OCT), with a high‐spatial resolution (<10 microns), intermediate penetration depth (~1.5 mm) and volumetric imaging capability is a great candidate to be used as a diagnostic‐assistant modality in dermatology. At this time, the accuracy of OCT for melanoma detection is lower than anticipated. In this letter, we studied for the first time, the use of a novel contrast agent consist of ultra‐small nanoparticles conjugated to a melanoma biomarker to improve the accuracy of OCT for differentiation of melanoma cells from nonmelanoma cells, in vitro. We call this approach SMall nanoparticle Aggregation‐enhanced Radiomics of Tumor (SMART)‐OCT imaging. This initial proof of concept study is the first step toward the broad utilization of this method for high accuracy all types of tumor detection applications.     

Jones matrix‐based speckle‐decorrelation angiography using polarization‐sensitive optical coherence tomography

We show that polarization‐sensitive optical coherence tomography angiography (PS‐OCTA) based on full Jones matrix assessment of speckle decorrelation offers improved contrast and depth of vessel imaging over conventional OCTA. We determine how best to combine the individual Jones matrix elements and compare the resulting image quality to that of a conventional OCT scanner by co‐locating and imaging the same skin locations with closely matched scanning setups. Vessel projection images from finger and forearm skin demonstrate the benefits of Jones matrix‐based PS‐OCTA. Our study provides a promising starting point and a useful reference for future pre‐clinical and clinical applications of Jones matrix‐based PS‐OCTA.     

Flexible wide‐field optical micro‐angiography based on Fourier‐domain multiplexed dual‐beam swept source optical coherence tomography

Wide‐field optical coherence tomography angiography (OCTA) is gaining interest in clinical imaging applications. In this pursuit, it is challenging to maintain the imaging resolution and sensitivity throughout the wide field of view (FoV). Here, we propose a novel method/system of dual‐beam arrangement and Fourier‐domain multiplexing to achieve wide‐field OCTA when imaging the uneven surface samples. The proposed system provides 2 separate FoVs, with flexibility that the imaging area, focus of the imaging beam and imaging depth range can be individually adjusted for each FoV, leading to either (1) increased system imaging FoV or (2) capability of targeting 2 regions of interests that locate at depths with large difference between each other. We demonstrate this novel method by employing 100 kHz laser source in a swept source OCTA to achieve an effective 200 kHz sweeping rate, covering a 22 × 22 mm FoV. The results are verified by a SS‐OCTA system employing a 200 kHz laser source, together with the experimental demonstrations when imaging whole brain vasculature in rodent models and skin blood perfusion in human fingers, show‐casing the capability of proposed system to image live large samples with complex surface topography.