Significance: Morphological changes in the epidermis layer are critical for the diagnosis and assessment of various skin diseases. Due to its noninvasiveness, optical coherence tomography (OCT) is a good candidate for observing microstructural changes in skin. Convolutional neural network (CNN) has been successfully used for automated segmentation of the skin layers of OCT images to provide an objective evaluation of skin disorders. Such method is reliable, provided that a large amount of labeled data is available, which is very time-consuming and tedious. The scarcity of patient data also puts another layer of difficulty to make the model more generalizable.Aim: We developed a semisupervised representation learning method to provide data augmentations.Approach: We used rodent models to train neural networks for accurate segmentation of clinical data.Result: The learning quality is maintained with only one OCT labeled image per volume that is acquired from patients. Data augmentation introduces a semantically meaningful variance, allowing for better generalization. Our experiments demonstrate the proposed method can achieve accurate segmentation and thickness measurement of the epidermis.Conclusion: This is the first report of semisupervised representative learning applied to OCT images from clinical data by making full use of the data acquired from rodent models. The proposed method promises to aid in the clinical assessment and treatment planning of skin diseases.
Significance: In order to elucidate therapeutic treatment to accelerate wound healing, it is crucial to understand the process underlying skin wound healing, especially re-epithelialization. Epidermis and scab detection is of importance in the wound healing process as their thickness is a vital indicator to judge whether the re-epithelialization process is normal or not. Since optical coherence tomography (OCT) is a real-time and non-invasive imaging technique that can perform a cross-sectional evaluation of tissue microstructure, it is an ideal imaging modality to monitor the thickness change of epidermal and scab tissues during wound healing processes in micron-level resolution. Traditional segmentation on epidermal and scab regions was performed manually, which is time-consuming and impractical in real time.
Aim: We aim to develop a deep-learning-based skin layer segmentation method for automated quantitative assessment of the thickness of in vivo epidermis and scab tissues during a time course of healing within a rodent model.
Approach: Five convolution neural networks were trained using manually labeled epidermis and scab regions segmentation from 1000 OCT B-scan images (assisted by its corresponding angiographic information). The segmentation performance of five segmentation architectures was compared qualitatively and quantitatively for validation set.
Results: Our results show higher accuracy and higher speed of the calculated thickness compared with human experts. The U-Net architecture represents a better performance than other deep neural network architectures with 0.894 at F1-score, 0.875 at mean intersection over union, 0.933 at Dice similarity coefficient, and 18.28 μm at an average symmetric surface distance. Furthermore, our algorithm is able to provide abundant quantitative parameters of the wound based on its corresponding thickness maps in different healing phases. Among them, normalized epidermal thickness is recommended as an essential hallmark to describe the re-epithelialization process of the rodent model.
Conclusions: The automatic segmentation and thickness measurements within different phases of wound healing data demonstrates that our pipeline provides a robust, quantitative, and accurate method for serving as a standard model for further research into effect of external pharmacological and physical factors.
Dynamic optical coherence elastography (OCE) tracks elastic wave propagation speed within tissue, enabling quantitative three-dimensional imaging of the elastic modulus. We show that propagating mechanical waves are mode converted at interfaces, creating a finite region on the order of an acoustic wavelength where there is not a simple one-to-one correspondence between wave speed and elastic modulus. Depending on the details of a boundary’s geometry and elasticity contrast, highly complex propagating fields produced near the boundary can substantially affect both the spatial resolution and contrast of the elasticity image. We demonstrate boundary effects on Rayleigh waves incident on a vertical boundary between media of different shear moduli. Lateral resolution is defined by the width of the transition zone between two media and is the limit at which a physical inclusion can be detected with full contrast. We experimentally demonstrate results using a spectral-domain OCT system on tissue-mimicking phantoms, which are replicated using numerical simulations. It is shown that the spatial resolution in dynamic OCE is determined by the temporal and spatial characteristics (i.e., bandwidth and spatial pulse width) of the propagating mechanical wave. Thus, mechanical resolution in dynamic OCE inherently differs from the optical resolution of the OCT imaging system.
Pathological change tends to alter tissue mechanical properties, e.g. tissue stiffness. Current elastography technology use tissue stiffness as a signature to diagnose and localize diseases. Our team focus on vibrational optical coherence elastography (OCE) for its capability to increase signal to noise ratio as well as its high resolution comparing other elastography modalities. The result highly relies on the stimulation frequency for vibrational mode might change as frequency varies. A proper frequency range is required however, there hasn’t been a consensus among the research groups. In order to find the proper frequencies, several parameters measured from real experiment are input in transient model of ANSYS to simulate vibrational pattern of the sample with driving frequencies vary from 100Hz to 1000Hz. An upper limit of frequency has been discovered finally.
Corneal injury is potentially leading to ulceration which remains a major health concern in ocular surface diseases. In vitro studies of new ophthalmic drugs selection are usually performed using excised cornea from slaughtered animals or laboratory animals. However, the outcomes from animal models do not completely reflect the human corneal repair and regeneration process. In vitro human corneal models suit better for the rapid testing of the drug uptake in response to drug’s administration and posology. Therefore, this study aims at establishing an in-vitro 3D corneal model to characterise the corneal wound healing process. Moreover, a functional assessment of corneal morphology and strength change during the healing process is of urgent need. A phase-sensitive optical coherence tomography (OCT) system with a spectral-domain configuration was utilised to probe the structure and mechanical strength of the wounded corneal tissues. In this preliminary study, a human corneal 3D model was successfully established using tissue-engineering techniques and corneal injuries were mimicked with adjustable lesion size and depth. During the healing process, OCT provided an accurate indication of the tissue repair and regeneration. These results will be of great clinical impact to understand the biomechanics of the cornea healing process and the therapeutic effectiveness of regenerative medicine.
HIFU is a truly noninvasive, acoustic therapeutic technique that utilizes high intensity acoustic field in the focus to kill the targeted tissue for disease treatment purpose. The mechanical properties of targeted tissue changes before and after treatment, and this change can be accurately detected by shear wave elastography. Hence, shear wave elastography is usually used for monitoring HIFU treatment asynchronously. To improve the low spatial resolution in ultrasound shear wave elastography, and to perform diseases diagnosis, treatment and monitoring in the same system, a new setup that combines HIFU and PhS-OCT system was proposed in this study. This proposed setup could do 1) HIFU treatment when the transducer works at high energy level, 2) ultrasound induced shear wave optical coherence elastography for HIFU treatment asynchronous monitoring when the transducer works at low energy level. Ex-vivo bovine liver tissue was treated at the same energy level for different time (0s, 1s, 5s, 9s) in this research. Elastography was performed on the lesion area of the sample after HIFU treatment, and the elastogram was reconstructed by the time of flight time method. The elastogram results clearly show the boundary of HIFU lesion area and surrounding normal tissue, even for 1s treatment time. And the average elasticity of the lesion grows linearly as the treatment time increases. Combined with OCT needle probe, the proposed method has a large potential not only to be used for superficial diseases treatment, but also to be used for high-precision-demanded diseases treatment, e.g. nervous disease treatment.
Surface acoustic wave (SAW) elastography has been proven to be a non-invasive, non-destructive method for accurately characterizing tissue elastic properties. Current SAW elastography technique tracks generated surface acoustic wave impulse point by point which are a few millimeters away. Thus, reconstructed elastography has low lateral resolution. To improve the lateral resolution of current SAW elastography, a new method was proposed in this research. A M-B scan mode, high spatial resolution phase sensitive optical coherence tomography (PhS-OCT) system was employed to track the ultrasonically induced SAW impulse. Ex-vivo porcine skin specimen was tested using this proposed method. A 2D fast Fourier transform based algorithm was applied to process the acquired data for estimating the surface acoustic wave dispersion curve and its corresponding penetration depth. Then, the ex-vivo porcine skin elastogram was established by relating the surface acoustic wave dispersion curve and its corresponding penetration depth. The result from the proposed method shows higher lateral resolution than that from current SAW elastography technique, and the approximated skin elastogram could also distinguish the different layers in the skin specimen, i.e. epidermis, dermis and fat layer. This proposed SAW elastography technique may have a large potential to be widely applied in clinical use for skin disease diagnosis and treatment monitoring.
Ablative fractional skin laser is widely applied for various skin conditions, especially for cosmetic repairing and promoting the located drug delivery. Although the influence of laser treatment over the skin has been explored before in means of excision and biopsy with microscopy, these approaches are invasive, only morphological and capable of distorting the skin. In this paper the authors use fresh porcine skin samples irradiated by the lasers, followed by detected by using Optical Coherence Tomography (OCT). This advanced optical technique has the ability to present the high resolution structure image of treated sample. The results shows that laser beams can produce holes left on the surface after the irradiation. The depth of holes can be affected by changes of laser energy while the diameter of holes have no corresponding relation. Plus, OCT, as a valuable imaging technology, is capable of monitoring the clinical therapy procedure and assisting the calibration.
Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.
By combining with the phase sensitive optical coherence tomography (PhS-OCT), vibration and surface acoustic wave (SAW) methods have been reported to provide elastography of skin tissue respectively. However, neither of these two methods can provide the elastography in full skin depth in current systems. This paper presents a feasibility study on an optical coherence elastography method which combines both vibration and SAW in order to give the quantitative mechanical properties of skin tissue with full depth range, including epidermis, dermis and subcutaneous fat. Experiments are carried out on layered tissue mimicking phantoms and invivo human forearm and palm skin. A ring actuator generates vibration while a line actuator were used to excited SAWs. A PhS-OCT system is employed to provide the ultrahigh sensitive measurement of the generated waves. The experimental results demonstrate that by the combination of vibration and SAW method the full skin bulk mechanical properties can be quantitatively measured and further the elastography can be obtained with a sensing depth from ~0mm to ~4mm. This method is promising to apply in clinics where the quantitative elasticity of localized skin diseases is needed to aid the diagnosis and treatment.
Objectives. Prostate cancer is the most frequently diagnosed malignancy in men. Digital rectal examination (DRE) - a known clinical tool based on alteration in the mechanical properties of tissues due to cancer has traditionally been used for screening prostate cancer. Essentially, DRE estimates relative stiffness of cancerous and normal prostate tissue. Optical coherence elastography (OCE) are new optical imaging techniques capable of providing cross-sectional imaging of tissue microstructure as well as elastogram in vivo and in real time. In this preliminary study, OCE was used in the setting of the human prostate biopsies ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. 120 prostate biopsies were obtained by TRUS guided needle biopsy procedures from 9 patients with clinically suspected cancer of the prostate. The biopsies were approximately 0.8mm in diameter and 12mm in length, and prepared in Formalin solution. Quantitative assessment of biopsy samples using OCE was obtained in kilopascals (kPa) before histopathologic evaluation. The results obtained from OCE and standard histopathologic evaluation were compared provided the cross-validation. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE (histopathology was a reference standard). Results. OCE could provide quantitative elasticity properties of prostate biopsies within benign prostate tissue, prostatic intraepithelial neoplasia, atypical hyperplasia and malignant prostate cancer. Data analysed showed that the sensitivity and specificity of OCE for PCa detection were 1 and 0.91, respectively. PCa had significantly higher stiffness values compared to benign tissues, with a trend of increasing in stiffness with increasing of malignancy. Conclusions. Using OCE, microscopic resolution elastogram is promising in diagnosis of human prostatic diseases. Further studies using this technique to improve the detection and staging of malignant cancer of the prostate are ongoing.
Damage of collagen fibers in tendons is often directly related to changes in a tendon’s mechanical properties. Direct quantitative elasticity measurement of tendons will provide important information in tendon dysfunction diagnosis and treatment assessment. A feasibility study of quantifying the mechanical properties of a degenerated tendon model by a nondestructive imaging modality, which combines optical coherence elastography and acoustic radiation force (ARF) method, is presented. The degenerated tendon model was produced by the partial degradation of chicken tendons through incubation with collagenase at different concentrations and incubation times. A 30-kHz longitudinal ultrasound transducer was used to provide an ARF signal, which was detected by an ultra-high sensitive phase sensitive optical coherence tomography (PhS-OCT) system. The experimental results demonstrate that the combination of ARF method and PhS-OCT can measure the elasticity of tendon quantitatively. The corresponding changes in tendon elasticity due to the application of collagenase have been revealed by this new imaging modality. This method can potentially be used in the assessment of tissue engineering products and in the diagnosis and treatment progression of tendon diseases.
The combined use of surface acoustic wave (SAW) and phase-sensitive optical coherence tomography (PhS-OCT) is useful to evaluate the elasticity of layered biological tissues, such as normal skin. However, the pathological tissue is often originated locally, leading to the alternation of mechanical properties along both axial and lateral directions. We present a feasibility study on whether the SAW technique is sensitive to detect the alternation of mechanical property along the lateral direction within tissue, which is important for clinical utility of this technique to localize diseased tissue. Experiments are carried out on purposely designed tissue phantoms and ex vivo chicken breast samples, simulating the localized change of elasticity. A PhS-OCT system is employed not only to provide the ultra-high sensitive measurement of the generated surface waves on the tissue surface, but also to provide the real time imaging of the tissue to assist the elasticity evaluation of the heterogeneous tissue. The experimental results demonstrate that with PhS-OCT used as a pressure sensor, the SAW is highly sensitive to the elasticity change of the specimen in both vertical and lateral directions with a sensing depth of ∼ 5 mm with our current system setup, thus promising its useful clinical applications where the quantitative elasticity of localized skin diseases is needed to aid in diagnosis and treatment.
This paper presents the combination of phase sensitive optical coherence tomography (PhS-OCT) imaging system and
surface wave method to achieve quantitative evaluation and elastography of the mechanical properties of in vivo human
skin. PhS-OCT measures the surface acoustic waves (SAWs) generated by impulse stimulation from a home-made
shaker, and provide the B-frame images for the sample. The surface wave phase velocity dispersion curves were
calculated, from which the elasticity of different skin layers were determined. The combination of phase velocities from
adjacent two locations generates a quantitative elastography of sample. The experimental results agree well with
theoretical expectations and may offer potential use in clinical situations.
Laser ultrasonic technique has the potential as an access for quantifying skin property for diagnosis and accurate
assessment for skin diseases. This paper presents a finite element (FE) modelling technique which studies the effect laser
wavelength has on the generated surface acoustic waveforms in a multilayered skin model. By comparison, this paper
discusses the suitability of using laser generated surface waveforms for the accurate non-destructive evaluation of skin
layer mechanical and geometrical properties using surface wave phase velocity analysis.
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