Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in Beijing, China: analysis of results from China's top 3 hospital, 2009-2019.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China. METHODS: A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed. RESULTS: A total of 3134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17-79 years). The women aged 35-49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26 and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal. CONCLUSIONS: In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Evaluating changes of blood flow in retina, choroid, and outer choroid in rats in response to elevated intraocular pressure by 1300 nm swept-source OCT.

We report the development of a 1300 nm swept-source optical coherence tomography (SS-OCT) system specifically designed to perform OCT imaging and optical microangiography (OMAG) in rat eyes in vivo and its use in evaluating the effects of intraocular pressure (IOP) elevation on ocular circulation. The swept laser is operated in single longitude mode with a 90 nm bandwidth centered at 1300 nm and 200 kHz A-line rate, providing remarkable sensitivity fall-off performance along the imaging depth, a larger field of view of 2.5 × 2.5 mm2 (approximately 35°), and more time-efficient imaging acquisition. The advantage of the SS-OCT/OMAG is highlighted by an increased imaging depth of the entire posterior thickness of optic nerve head (ONH) and its surrounding vascular anatomy, to include, for the first time in vivo, the vasculature at the scleral opening, allowing visualization of the circle of Zinn-Haller and posterior ciliary arteries (PCAs). Furthermore, the capillary-level resolution angiograms achieved at the retinal and choroidal layers over a larger field of view enable a significantly improved quantification of the response of vascular area density (VAD) to elevated IOP. The results indicate that reduction in perfusion of the choroid in response to elevated IOP is delayed compared to that seen in the retina; while choroidal VAD doesn't reach 50% of baseline until ~70 mmHg, the same effect is seen for the retinal VAD at ~60 mmHg. The superior image quality offered by SS-OCT may allow more comprehensive investigation of IOP-related ocular perfusion changes and their pathological roles in glaucomatous optic nerve damage.

Multifunctional in vivo imaging for monitoring wound healing using swept-source polarization-sensitive optical coherence tomography.

BACKGROUND AND OBJECTIVE: Wound healing involves a complex and dynamic biological process in response to tissue injury. Monitoring of the cascade of cellular events is useful for wound management and treatment. The aim of this study is to demonstrate the potential of multifunctional polarization-sensitive optical coherence tomography (PS-OCT) to longitudinally monitor the self-healing process in a murine cutaneous wound model. MATERIALS AND METHODS: A multi-functional PS-OCT system based on swept source OCT configuration (1,310 nm central wavelength) was designed to obtain simultaneously microstructural, blood perfusion, and birefringent information of a biological tissue in vivo. A 1-mm-diameter wound was generated in a mouse pinna with a complete biopsy punch. Afterwards, the self-healing process of the injured tissue was observed every week over 6-week period using the multifunctional system to measure changes in the tissue birefringence. Further OCT angiography (OCTA) was used in post data processing to obtain blood perfusion information over the injured tissue. RESULTS: Three complementary images indicating the changes in anatomical, vascular, and birefringent information of tissue around wound were simultaneously provided from a 3-dimensional (3-D) PS-OCT data set during the wound repair over 1 month. Specifically, inflammatory and proliferative phases of wound healing were characterized by thickened epidermal tissue (from OCT images) and angiogenesis (from OCT angiography images) around wound. Also, it was observed that the regenerating tissues had highly realigned birefringent structures (from PS-OCT images). CONCLUSION: This preliminary study suggests that the proposed multi-functional imaging modality has a great potential to improve the understanding of wound healing through non-invasive, serial monitoring of vascular and tissue responses to injury. Lasers Surg. Med. 50:213-221, 2018. © 2017 Wiley Periodicals, Inc.

Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions.

BACKGROUND: In clinical dermatology, the identification of subsurface vascular and structural features known to be associated with numerous cutaneous pathologies remains challenging without the use of invasive diagnostic tools. OBJECTIVE: To present an advanced optical coherence tomography angiography (OCTA) method to directly visualize capillary-level vascular and structural features within skin in vivo. METHODS: An advanced OCTA system with a 1310 nm wavelength was used to image the microvascular and structural features of various skin conditions. Subjects were enrolled and OCTA imaging was performed with a field of view of approximately 10 × 10 mm. Skin blood flow was identified using an optical microangiography (OMAG) algorithm. Depth-resolved microvascular networks and structural features were derived from segmented volume scans, representing tissue slabs of 0-132, 132-330, and 330-924 µm, measured from the surface of the skin. RESULTS: Subjects with both healthy and pathological conditions, such as benign skin lesions, psoriasis, chronic graft-versus-host-disease (cGvHD), and scleroderma, were OCTA scanned. Our OCTA results detailed variations in vascularization and local anatomical characteristics, for example, depth-dependent vascular, and structural alterations in psoriatic skin, alongside their resolve over time; vascular density changes and distribution irregularities, together with corresponding structural depositions in the skin of cGvHD patients; and vascular abnormalities in the nail folds of a patient with scleroderma. CONCLUSION: OCTA can image capillary blood flow and structural features within skin in vivo, which has the potential to provide new insights into the pathophysiology, as well as dynamic changes of skin diseases, valuable for diagnoses, and non-invasive monitoring of disease progression and treatment. Lasers Surg. Med. 50:183-193, 2018. © 2018 Wiley Periodicals, Inc.

OCT-based angiography of human dermal microvascular reactions to local stimuli: Implications for increasing capillary blood collection volumes.

OBJECTIVES: To measure and compare microvascular responses within the skin of the upper arm to local stimuli, such as heating or rubbing, through the use of optical coherence tomography angiography (OCTA), and to investigate its impact on blood volume collection. MATERIALS AND METHODS: With the use of heat packs or rubbing, local stimulation was applied to the skin of either the left or right upper arm. Data from the stimulated sites were obtained using OCTA comparing pre- and post-stimulation microvascular parameters, such as vessel density, mean vessel diameter, and mean avascular pore size. Additionally, blood was collected using a newly designed collection device and volume was recorded to evaluate the effect of the skin stimulation. RESULTS: Nineteen subjects were recruited for local stimulation study (including rubbing and heating) and 21 subjects for blood drawn study. Of these subjects, 14 agreed to participate in both studies. OCTA was successful in monitoring and measuring minute changes in the microvasculature of the stimulated skin. Compared to baseline, significant changes after local heating and rubbing were respectively found in vessel density (16% [P = 0.0004] and 33% [P < 0.0001] increase), mean vessel diameter (14% and 11% increase) and mean avascular pore size (5% [P = 0.0068] and 8% [P = 0.0005] decrease) after stimulations. A gradual recovery was recorded for each parameter, with no difference being measured after 30 minutes. Blood collection volumes significantly increased after stimulations of heating (48% increase; P = 0.049) and rubbing (78% increase; P = 0.048). Significant correlations were found between blood volume and microvascular parameters except mean avascular pore size under the heating condition. CONCLUSIONS: OCTA can provide important information regarding microvascular adaptations to local stimuli. With that, both heating and rubbing of the skin have positive effects on blood collection capacity, with rubbing having the most significant effect. Lasers Surg. Med. 50:908-916, 2018. © 2018 Wiley Periodicals, Inc.

Performance of megahertz amplified optical time-stretch optical coherence tomography (AOT-OCT).

Enabled by the ultrahigh-speed all-optical wavelength-swept mechanism and broadband optical amplification, amplified optical time-stretch optical coherence tomography (AOT-OCT) has recently been demonstrated as a practical alternative to achieve ultrafast A-scan rate of multi-MHz in OCT. With the aim of identifying the optimal scenarios for MHz operation in AOT-OCT, we here present a theoretical framework to evaluate its performance metric. In particular, the analysis discusses the unique features of AOT-OCT, such as its superior coherence length, and the relationship between the optical gain and the A-scan rate. More importantly, we evaluate the sensitivity of AOT-OCT in the MHz regime under the influence of the amplifier noise. Notably, the model shows that AOT-OCT is particularly promising when operated at the A-scan rate well beyond multi-MHz--not trivially achievable by any existing swept-source OCT platform. A sensitivity beyond 90 dB, close to the shot-noise limit, can be maintained in the range of 2 - 10 MHz with an optical net gain of ~10 dB. Experimental measurement also shows excellent agreement with the theoretical prediction. While distributed fiber Raman amplification is mainly considered in this paper, the theoretical model is generally applicable to any type of amplification schemes. As a result, our analysis serves as a useful tool for further optimization of AOT-OCT system--as a practical alternative to enable MHz OCT operation.

Megahertz all-optical swept-source optical coherence tomography based on broadband amplified optical time-stretch.

We demonstrate all-optical ultrahigh-speed swept-source optical coherence tomography (OCT) based on amplified optical time-stretch (AOT). Such an inertia-free wavelength-swept mechanism, via group velocity dispersion, enables us to realize OCT with an A-scan rate well above MHz. More importantly, the key significance of AOT-OCT is its simultaneous broadband Raman amplification during the time-stretch process-greatly enhancing the detection sensitivity compared with prior attempts to apply optical time-stretch to OCT. Here, we report on an AOT-OCT system which is operated at an A-scan rate of 7.14 MHz, a superior roll-off performance (>2 mm/dB), a record-high sensitivity of time-stretch-based OCT (>80 dB) with a broadband gain bandwidth of 80 nm, which results in an axial resolution of ∼15 µm. Our AOT-OCT system is thus able to, for the first time to the best of our knowledge, perform time-stretch-based OCT of biological tissue in vivo. It represents a major step forward in utilizing AOT as an alternative for achieving practical MHz OCT, without any long-term mechanical stability concerns as in typical swept-source OCT or bypassing the speed limitation of the image sensor employed in spectral-domain OCT.

Breathing laser as an inertia-free swept source for high-quality ultrafast optical bioimaging.

We demonstrate an all-fiber breathing laser as inertia-free swept source (BLISS), with an ultra-compact design, for the emerging ultrafast bioimaging modalities. The unique feature of BLISS is its broadband wavelength-swept operation (∼60 nm) with superior temporal stability in terms of both long term (0.08 dB over 27 h) and shot-to-shot power variations (2.1%). More importantly, it enables a wavelength sweep rate of >10 MHz (∼7×108 nm/s)­orders-of-magnitude faster than the existing swept sources based on mechanical or electrical tuning techniques. BLISS thus represents a practical and new generation of swept source operating in the unmet megahertz swept-rate regime that aligns with the pressing need for scaling the optical bioimaging speed in ultrafast phenomena study or high-throughput screening applications. To showcase its utility in high-speed optical bioimaging, we here employ BLISS for ultrafast time-stretch microscopy and multi-MHz optical coherence tomography of the biological specimen at a single-shot line-scan rate or A-scan rate of 11.5 MHz.

Visualization enhancement by PCA-based image fusion for skin burns assessment in polarization-sensitive OCT.

Polarization-sensitive optical coherence tomography (PS-OCT) is a functional imaging tool for measuring tissue birefringence characteristics. It has been proposed as a potentially non-invasive technique for evaluating skin burns. However, the PS-OCT modality usually suffers from high system complexity and relatively low tissue-specific contrast, which makes assessing the extent of burns in skin tissue difficult. In this study, we employ an all-fiber-based PS-OCT system with single-state input, which is simple and efficient for skin burn assessment. Multiple parameters, such as phase retardation (PR), degree of polarization uniformity (DOPU), and optical axis orientation, are obtained to extract birefringent features, which are sensitive to subtle changes in structural arrangement and tissue composition. Experiments on ex vivo porcine skins burned at different temperatures were conducted for skin burn investigation. The burned depths estimated by PR and DOPU increase linearly with the burn temperature to a certain extent, which is helpful in classifying skin burn degrees. We also propose an algorithm of image fusion based on principal component analysis (PCA) to enhance tissue contrast for the multi-parameter data of PS-OCT imaging. The results show that the enhanced images generated by the PCA-based image fusion method have higher tissue contrast, compared to the en-face polarization images by traditional mean value projection. The proposed approaches in this study make it possible to assess skin burn severity and distinguish between burned and normal tissues.

Dual-channel air-pulse optical coherence elastography for frequency-response analysis.

Microliter air-pulse optical coherence elastography (OCE) has recently been proposed for the characterization of soft-tissue biomechanics using transient, sub-nanometer to micrometer-scale natural frequency oscillations. However, previous studies have not been able to provide real-time air-pulse monitoring during OCE natural frequency measurement, which could lead to inaccurate measurement results due to the unknown excitation spectrum. To address this issue, we introduce a dual-channel air-pulse OCE method, with one channel stimulating the sample and the other being simultaneously measured with a pressure sensor. This allows for more accurate natural frequency characterization using the frequency response function, as proven by a comprehensive comparison under different conditions with a diverse range of excitation spectra (from broad to narrow, clean to noisy) as well as a diverse set of sample response spectra. We also demonstrate the capability of the frequency-response analysis in distinguishing samples with different stiffness levels: the dominant natural frequencies increased with agar concentrations (181-359 Hz, concentrations: 1-2%, and maximum displacements: 0.12-0.47 µm) and intraocular pressures (IOPs) for the silicone cornea (333-412 Hz, IOP: 5-40 mmHg, and maximum displacements: 0.41-0.52 µm) under a 200 Pa stimulation pressure. These frequencies remained consistent across different air-pulse durations (3 ms to 35 ms). The dual-channel OCE approach that uses transient, low-pressure stimulation and high-resolution imaging holds the potential to advance our understanding of sample frequency responses, especially when investigating delicate tissues such as the human cornea in vivo.

In vivo corneal elastography: A topical review of challenges and opportunities.

Clinical measurement of corneal biomechanics can aid in the early diagnosis, progression tracking, and treatment evaluation of ocular diseases. Over the past two decades, interdisciplinary collaborations between investigators in optical engineering, analytical biomechanical modeling, and clinical research has expanded our knowledge of corneal biomechanics. These advances have led to innovations in testing methods (ex vivo, and recently, in vivo) across multiple spatial and strain scales. However, in vivo measurement of corneal biomechanics remains a long-standing challenge and is currently an active area of research. Here, we review the existing and emerging approaches for in vivo corneal biomechanics evaluation, which include corneal applanation methods, such as ocular response analyzer (ORA) and corneal visualization Scheimpflug technology (Corvis ST), Brillouin microscopy, and elastography methods, and the emerging field of optical coherence elastography (OCE). We describe the fundamental concepts, analytical methods, and current clinical status for each of these methods. Finally, we discuss open questions for the current state of in vivo biomechanics assessment techniques and requirements for wider use that will further broaden our understanding of corneal biomechanics for the detection and management of ocular diseases, and improve the safety and efficacy of future clinical practice.

Corneal Surface Wave Propagation Associated with Intraocular Pressures: OCT Elastography Assessment in a Simplified Eye Model.

Assessing corneal biomechanics in vivo has long been a challenge in the field of ophthalmology. Despite recent advances in optical coherence tomography (OCT)-based elastography (OCE) methods, controversy remains regarding the effect of intraocular pressure (IOP) on mechanical wave propagation speed in the cornea. This could be attributed to the complexity of corneal biomechanics and the difficulties associated with conducting in vivo corneal shear-wave OCE measurements. We constructed a simplified artificial eye model with a silicone cornea and controllable IOPs and performed surface wave OCE measurements in radial directions (54-324°) of the silicone cornea at different IOP levels (10-40 mmHg). The results demonstrated increases in wave propagation speeds (mean ± STD) from 6.55 ± 0.09 m/s (10 mmHg) to 9.82 ± 0.19 m/s (40 mmHg), leading to an estimate of Young's modulus, which increased from 145.23 ± 4.43 kPa to 326.44 ± 13.30 kPa. Our implementation of an artificial eye model highlighted that the impact of IOP on Young's modulus (ΔE = 165.59 kPa, IOP: 10-40 mmHg) was more significant than the effect of stretching of the silicone cornea (ΔE = 15.79 kPa, relative elongation: 0.98-6.49%). Our study sheds light on the potential advantages of using an artificial eye model to represent the response of the human cornea during OCE measurement and provides valuable insights into the impact of IOP on wave-based OCE measurement for future in vivo corneal biomechanics studies.

Deep-learning visualization enhancement method for optical coherence tomography angiography in dermatology.

Optical coherence tomography angiography (OCTA) in dermatology usually suffers from low image quality due to the highly scattering property of the skin, the complexity of cutaneous vasculature, and limited acquisition time. Deep-learning methods have achieved great success in many applications. However, the deep learning approach to improve dermatological OCTA images has not been investigated due to the requirement of high-performance OCTA systems and difficulty of obtaining high-quality images as ground truth. This study aims to generate proper datasets and develop a robust deep learning method to enhance the skin OCTA images. A swept-source skin OCTA system was employed to create low-quality and high-quality OCTA images with different scanning protocols. We propose a model named vascular visualization enhancement generative adversarial network and adopt an optimized data augmentation strategy and perceptual content loss function to achieve better image enhancement effect with small amount of training data. We demonstrate the superiority of the proposed method in skin OCTA image enhancement by quantitative and qualitative comparisons.

Exploiting few mode-fibers for optical time-stretch confocal microscopy in the short near-infrared window.

Dispersive fiber is well-regarded as the most viable candidate for realizing efficient optical time-stretch process--an ultrafast spectroscopic measurement technique based on the wavelength-to-time mapping via group velocity dispersion (GVD). Despite optical time-stretch has been anticipated to benefit a wide range of high-throughput biomedical diagnoses, the lack of commercially-available dispersive fibers which can operate in the "biomedically-favorable" short near-infrared (~800 nm - 1100 nm) range hinders practical time-stretch-based biomedical spectroscopy and microscopy. We here explore and demonstrate the feasibility of using the standard telecommunication single-mode fibers (e.g. SMF28 and dispersion compensation fiber (DCF)) as few-mode fibers (FMFs) for optical time-stretch confocal microscopy in the 1 µm range. By evaluating GVD of different FMF modes and thus the corresponding time-stretch performances, we show that the fundamental modes (LP(01)) of SMF28 and DCF, having sufficiently high dispersion-to-loss ratios, are particularly useful for practical time-stretch spectroscopy and microscopy at 1 µm, without the need for the specialty 1 µm SMF. More intriguingly, we also show that the higher-order FMF modes (e.g. LP(11)) could be excited and utilized for time-stretch imaging. Such additional degree of freedom creates a new avenue for optimizing and designing the time-stretch operations, such as by tailored engineering of the modal-dispersion as well as the GVD of the individual FMF modes.

Spatially adaptive blind deconvolution methods for optical coherence tomography.

Optical coherence tomography (OCT) is a powerful noninvasive imaging technique for detecting microvascular abnormalities. Following optical imaging principles, an OCT image will be blurred in the out-of-focus domain. Digital deconvolution is a commonly used method for image deblurring. However, the accuracy of traditional digital deconvolution methods, e.g., the Richardson-Lucy method, depends on the prior knowledge of the point spread function (PSF), which varies with the imaging depth and is difficult to determine. In this paper, a spatially adaptive blind deconvolution framework is proposed for recovering clear OCT images from blurred images without a known PSF. First, a depth-dependent PSF is derived from the Gaussian beam model. Second, the blind deconvolution problem is formalized as a regularized energy minimization problem using the least squares method. Third, the clear image and imaging depth are simultaneously recovered from blurry images using an alternating optimization method. To improve the computational efficiency of the proposed method, an accelerated alternating optimization method is proposed based on the convolution theorem and Fourier transform. The proposed method is numerically implemented with various regularization terms, including total variation, Tikhonov, and l1 norm terms. The proposed method is used to deblur synthetic and experimental OCT images. The influence of the regularization term on the deblurring performance is discussed. The results show that the proposed method can accurately deblur OCT images. The proposed acceleration method can significantly improve the computational efficiency of blind demodulation methods.

Pulsatile Trabecular Meshwork Motion: An Indicator of Intraocular Pressure Control in Primary Open-Angle Glaucoma.

(1) Background: To investigate the value of pulsatile trabecular meshwork (TM) motion in predicting the diurnal intraocular pressure (IOP) fluctuation of primary open-angle glaucoma (POAG). (2) Methods: This cross-sectional study recruited 20 normal patients and 30 patients with POAG. Of the POAG group, 20 had stable diurnal IOP and 10 had high IOP fluctuation. A clinical prototype phase-sensitive optical coherence tomography (PhS-OCT) model was used to measure TM pulsatile motion with maximum velocity (MV) and cumulative displacement (CDisp). (3) Results: MV and CDisp were higher in the external region in both normal and POAG patients. All MV and CDisp reduced significantly in the POAG group (p < 0.001). In the POAG group, except MV in the external region (p = 0.085), MV and CDisp in the nasal area were significantly higher than those in the temporal area (p < 0.05). The MV and CDisp in the external region in the nasal area of POAG patients with high IOP fluctuation were much lower than those with stable IOP (pEMV3 = 0.031, pECDisp3 < 0.001); (4) Conclusions: Pulsatile TM motion reduced in POAG patients relevant to the level of diurnal IOP fluctuation. This study presents the segmental variance of TM stiffness in human living eyes and suggests the clinical potential of the measurement of pulsatile TM motion with PhS-OCT for the evaluation of diurnal IOP fluctuation.

Self-attentional microvessel segmentation via squeeze-excitation transformer Unet.

Automatic vessel segmentation is a key step of clinical or pre-clinical vessel bio-markers for clinical diagnosis. In previous research, the segmentation architectures are mainly based on Convolutional Neural Networks (CNN). However, due to the limitation of the receipt of field (ROF) of convolution operation, it is difficult to further improve the accuracy of the CNN-based methods. To solve this problem, a Squeeze-Excitation Transformer U-net (SETUnet) is proposed to break the ROF limitation of CNN. The proposed squeeze-excitation Transformer can introduce the self attention mechanism into the vessel segmentation task by generating a global attention mapping according to the entire vessel image. To test the performance of the proposed SETUnet, the SETUnet is trained and tested on several public vessel data-sets. The results show that the SETUnet outperforms several state-of-the-art vessel segmentation neural networks, especially on the connectivity of the segmented vessels.

Spatial Assessment of Heterogeneous Tissue Natural Frequency Using Micro-Force Optical Coherence Elastography.

Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.

High resolution imaging and quantification of the nailfold microvasculature using optical coherence tomography angiography (OCTA) and capillaroscopy: a preliminary study in healthy subjects.

Background: A wide range of diseases, such as systemic sclerosis, can be diagnosed by imaging the nailfold microcirculation, which is conventionally performed using capillaroscopy. This study applied optical coherence tomography angiography (OCTA) as a novel high resolution imaging method for the qualitative and quantitative assessment of the nailfold microvasculature, and compared OCTA imaging with capillaroscopy. Methods: For qualitative assessment, high resolution OCTA imaging was used to achieve images that contained a wide field of view of the nailfold microvasculature through mosaic scanning. OCTA imaging was also used to observe the characteristic changes in the microvasculature under external compression of the upper arm. For quantitative evaluation, the capillary density and the capillary diameter of the nailfold microvasculature were assessed with both OCTA and capillaroscopy by repeated measurements over 2 days in 13 normal subjects. The results were analyzed using the intraclass correlation coefficient (ICC). Results: OCTA imaging showed the typical nailfold microvasculature pattern, part of which was not directly seen with the capillaroscopy. OCTA imaging revealed significant changes in the nailfold microvasculature when a large external pressure was applied via arm compression, but no significant changes were observed using capillaroscopy. The capillary density measured by OCTA and capillaroscopy was 6.8±1.5 and 7.0±1.2 loops/mm, respectively, which was not significantly different (P=0.51). However, the capillary diameter measured by OCTA was significantly larger than that measured using capillaroscopy (19.1±2.5 vs. 13.3±2.3 µm, P<0.001). The capillary diameter measurements using OCTA and capillaroscopy were highly reproducible (ICC =0.926 and 0.973, respectively). While the capillary diameter measured with OCTA was significantly larger, it was rather consistent with the diameter measured using capillaroscopy (ICC =0.705). Conclusions: This study demonstrated that OCTA is a potentially viable and reproducible tool for the imaging and quantification of the capillaries in the nailfold microvasculature. The results of this study provide a solid basis for future applications of OCTA in qualitative and quantitative assessment of nailfold microcirculation in vivo.

Quantitative assessment of vascular features in port wine stains through optical coherence tomography angiography.

BACKGROUND: Vascular lesions such as port wine stains (PWS) lead to facial and psychological problems, which require careful and precise treatments. The key point of treating PWS is to selectively destroy the abnormal blood vessels. Hence, the in vivo monitoring of targeted vessels is crucial. Optical coherence tomography angiography (OCTA), an emerging label-free imaging tool, facilitates the evaluation of skin structure and vasculature at a high resolution. In this study, we utilised OCTA to capture the structural and vascular morphology in patients with PWS. Moreover, we quantitatively characterised the morphological features of different types of PWS. METHODS: This observational clinical study was conducted on 3 patients with flat PWS and 3 patients with thickened PWS. The age range was 4-27 years, and all of them had not received any treatment before this study. The OCTA images of the PWS lesions and contralateral skin were compared. Vascular morphology was characterized, and ectatic vessel depth was quantified according to the OCTA images. RESULTS: The blood vessels of the PWS lesions tend to had larger diameters and higher densities than those in the contralateral normal skin. The vessel diameters of PWS lesions were 73 ± 14 µm, with high heterogeneity ranging from 10 to >150 µm, however, the vessel diameters of normal skin were 28 ± 2 µm, ranging from 10 µm to 60 µm. In terms of different PWS lesions, the thickened type showed a trend of larger vessel diameter and higher density than those of the purplish red type. The ectatic vessels were located at the depth of 216 ± 13 µm in the PWS skin. CONCLUSIONS: OCTA can facilitate the in vivo three-dimensional visualization of structure and vasculature for PWS lesions. Various quantitative analysis parameters, such as vessel diameter, density, and depth, are typically measured using OCTA. This fact demonstrates the superior capability of OCTA for the precise and comprehensive assessment of PWS lesions.