Long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array modes.

We propose to realize a long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array (VIPA) modes. By filtering the continuous spectrum of a supercontinuum source through a side-entrance Fabry-Perot etalon configured at two input angles, two groups of VIPA modes are generated. A method based on unmatched dispersion is proposed for non-aliasing reconstruction of the true depth from the interference spectrum under-sampled at two groups of VIPA modes. With the high spectral resolution provided by the VIPA modes instead of the grating-based spectrometer, only a 10 dB falloff in sensitivity over a range of 10 mm was demonstrated. The feasibility of the proposed method was confirmed by topography of a sample of gauge blocks and a model of three-dimensional (3D) printed tooth. The occlusal surface of the tooth model was further quantitatively evaluated, demonstrating its potential application in long range 3D topography.

High-accuracy noninvasive continuous glucose monitoring using OCT angiography-purified blood scattering signals in human skin.

The accuracy of noninvasive continuous glucose monitoring (CGM) through near-infrared scattering is challenged by mixed scattering signals from different compartments, where glucose has a positive correlation with a blood scattering coefficient but a negative correlation with a tissue scattering coefficient. In this study, we developed a high-accuracy noninvasive CGM based on OCT angiography (OCTA)-purified blood scattering signals. The blood optical scattering coefficient (BOC) was initially extracted from the depth attenuation of backscattered light in OCT and then purified by eliminating the scattering signals from the surrounding tissues under the guidance of a 3D OCTA vascular map in human skin. The purified BOC was used to estimate the optical blood glucose concentration (BGC) through a linear calibration. The optical and reference BGC measurements were highly correlated (R = 0.94) without apparent time delay. The mean absolute relative difference was 6.09%. All optical BGC measurements were within the clinically acceptable Zones A + B, with 96.69% falling in Zone A on Parke's error grids. The blood glucose response during OGTT was mapped with a high spatiotemporal resolution of the single vessel and 5 seconds. This noninvasive OCTA-based CGM shows promising accuracy for clinical use. Future research will involve larger sample sizes and diabetic participants to confirm these preliminary findings.

Mapping port wine stain in vivo by optical coherence tomography angiography and multi-metric characterization.

Port wine stain (PWS) is a congenital cutaneous capillary malformation composed of ecstatic vessels, while the microstructure of these vessels remains largely unknown. Optical coherence tomography angiography (OCTA) serves as a non-invasive, label-free and high-resolution tool to visualize the 3D tissue microvasculature. However, even as the 3D vessel images of PWS become readily accessible, quantitative analysis algorithms for their organization have mainly remained limited to analysis of 2D images. Especially, 3D orientations of vasculature in PWS have not yet been resolved at a voxel-wise basis. In this study, we employed the inverse signal-to-noise ratio (iSNR)-decorrelation (D) OCTA (ID-OCTA) to acquire 3D blood vessel images in vivo from PWS patients, and used the mean-subtraction method for de-shadowing to correct the tail artifacts. We developed algorithms which mapped blood vessels in spatial-angular hyperspace in a 3D context, and obtained orientation-derived metrics including directional variance and waviness for the characterization of vessel alignment and crimping level, respectively. Combining with thickness and local density measures, our method served as a multi-parametric analysis platform which covered a variety of morphological and organizational characteristics at a voxel-wise basis. We found that blood vessels were thicker, denser and less aligned in lesion skin in contrast to normal skin (symmetrical parts of skin lesions on the cheek), and complementary insights from these metrics led to a classification accuracy of ∼90% in identifying PWS. An improvement in sensitivity of 3D analysis was validated over 2D analysis. Our imaging and analysis system provides a clear picture of the microstructure of blood vessels within PWS tissues, which leads to a better understanding of this capillary malformation disease and facilitates improvements in diagnosis and treatment of PWS.

Mapping variation of extracellular matrix in human keloid scar by label-free multiphoton imaging and machine learning.

Significance: Rapid diagnosis and analysis of human keloid scar tissues in an automated manner are essential for understanding pathogenesis and formulating treatment solutions. Aim: Our aim is to resolve the features of the extracellular matrix in human keloid scar tissues automatically for accurate diagnosis with the aid of machine learning. Approach: Multiphoton microscopy was utilized to acquire images of collagen and elastin fibers. Morphological features, histogram, and gray-level co-occurrence matrix-based texture features were obtained to produce a total of 28 features. The minimum redundancy maximum relevancy feature selection approach was implemented to rank these features and establish feature subsets, each of which was employed to build a machine learning model through the tree-based pipeline optimization tool (TPOT). Results: The feature importance ranking was obtained, and 28 feature subsets were acquired by incremental feature selection. The subset with the top 23 features was identified as the most accurate. Then stochastic gradient descent classifier optimized by the TPOT was generated with an accuracy of 96.15% in classifying normal, scar, and adjacent tissues. The area under curve of the classification results (scar versus normal and adjacent, normal versus scar and adjacent, and adjacent versus normal and scar) was 1.0, 1.0, and 0.99, respectively. Conclusions: The proposed approach has great potential for future dermatological clinical diagnosis and analysis and holds promise for the development of computer-aided systems to assist dermatologists in diagnosis and treatment.

Functional OCT angiography reveals early retinal neurovascular dysfunction in diabetes with capillary resolution.

Altered retinal neurovascular coupling may contribute to the development and progression of diabetic retinopathy (DR) but remains highly challenging to measure due to limited resolution and field of view of the existing functional hyperemia imaging. Here, we present a novel modality of functional OCT angiography (fOCTA) that allows a 3D imaging of retinal functional hyperemia across the entire vascular tree with single-capillary resolution. In fOCTA, functional hyperemia was evoked by a flicker light stimulation, recorded by a synchronized time-lapse OCTA (i.e., 4D), and extracted precisely from each capillary segment (space) and stimulation period (time) in the OCTA time series. The high-resolution fOCTA revealed that the retinal capillaries, particularly the intermediate capillary plexus, exhibited apparent hyperemic response in normal mice, and significant functional hyperemia loss (P < 0.001) at an early stage of DR with few overt signs of retinopathy and visible restoration after aminoguanidine treatment (P < 0.05). Retinal capillary functional hyperemia has strong potential to provide sensitive biomarkers of early DR, and retinal fOCTA would provide new insights into the pathophysiology, screening and treatment of early DR.

Mapping the 3D remodeling of the extracellular matrix in human hypertrophic scar by multi-parametric multiphoton imaging using endogenous contrast.

The hypertrophic scar is an aberrant form of wound healing process, whose clinical efficacy is limited by a lack of understanding of its pathophysiology. Remodeling of collagen and elastin fibers in the extracellular matrix (ECM) is closely associated with scar progression. Herein, we perform label-free multiphoton microscopy (MPM) of both fiber components from human skin specimens and propose a multi-fiber metrics (MFM) analysis model for mapping the structural remodeling of the ECM in hypertrophic scars in a highly-sensitive, three-dimensional (3D) manner. We find that both fiber components become wavier and more disorganized in scar tissues, while content accumulation is observed from elastin fibers only. The 3D MFM analysis can effectively distinguish normal and scar tissues with better than 95% in accuracy and 0.999 in the area under the curve value of the receiver operating characteristic curve. Further, unique organizational features with orderly alignment of both fibers are observed in scar-normal adjacent regions, and an optimized combination of features from 3D MFM analysis enables successful identification of all the boundaries. This imaging and analysis system uncovers the 3D architecture of the ECM in hypertrophic scars and exhibits great translational potential for evaluating scars in vivo and identifying individualized treatment targets.

A clean approach for detoxification of industrial chromium-bearing stainless steel slag: Selective crystallization control and binary basicity effect.

The complete detoxification and resource utilization of stainless steel slag are still facing challenges. In this paper, the harmless treatment of industrial stainless steel slag was realized by using a high temperature modification-crystallization control approach, and the influence of binary basicity (B) on selective enrichment of Cr-containing spinel in the slag and corresponding detoxification effect were systematically explored. Results demonstrated that the enrichment degree of Cr and the amount of Cr-bearing spinel separately reached 98.62 wt% and 13.32 wt% when B= 1.2. The reason was that low alkalinity promoted the reaction of Cr in slag to form Cr-containing spinel, thus improving the enrichment of Cr in the spinel and reducing the occurrence probability of Cr in the matrix phase. Furthermore, the toxicity test of modified slag powder was proceeded according to Chinese standard HJ/T 299-2007 and American standard EPA (Toxicity Characteristic Leaching Procedure, TCLP), and the feasibility of using modified slags as admixture for producing cement was discussed. Even if TCLP was adopted, the Cr leaching concentration in modified slag powder with B= 1.2 was only 1.59 mg/L, which was far lower than the national limit of heavy metal leaching concentration (15 mg/L) of solid waste. Remarkably, when the powder was formed as cement, the Cr leaching concentration was even lower than ICP-OES detection line. Meanwhile, its mechanical property was better than that of cement prepared without powder, indicating the detoxified slag powder met the requirements of concrete admixture. This paper provides a new way with certain economic value for detoxification and large-scale utilization of stainless steel slag.

Three-dimensional optical coherence digital-null deformography of multi-refractive-surface optics with nanometer sensitivity.

Knowledge of the lens deformation during the reliability test is critical for lens design and fabrication. Refractive surface distorts the optical path of probing light, and poses a great challenge to measuring the test-induced nanoscale changes of all refractive lens surfaces simultaneously. In this work, we present an optical coherence digital-null deformography (ODD). A digital null, i.e., the interference signals (including intensity and phase) of the backscattered probing light from each lens surface, was recorded prior to the test with a phase-sensitive optical coherence tomography (OCT). Then the post-test lens was physically aligned to the digital null by actuating a hexapod iteratively with a digital null alignment (DNA) method, so that the refractive distortion was matched. Finally, the changes between the aligned lens and its digital null were measured with an intensity centroid shift (ICS) at micron scale and a joint wavenumber (k)-depth (z) domain phase shift (kz-PhS) at nanoscale. We demonstrate that the proposed kz-PhS has a sensitivity of 4.15 nm and a range of 5 µm without phase wrapping; and the sensitivities of DNA are z translation 0.04 µm, x/y translation 0.24 µm, tilt 0.0003°, and rotation 0.03°. A lens drop test was performed with ODD. Circumventing refractive distortion by the null measurement, ODD can visualize the test-induced changes of all refractive surfaces non-destructively and simultaneously, and it will greatly facilitate lens design and fabrication.

Identification of human ovarian cancer relying on collagen fiber coverage features by quantitative second harmonic generation imaging.

Ovarian cancer has the highest mortality rate among all gynecological cancers, containing complicated heterogeneous histotypes, each with different treatment plans and prognoses. The lack of screening test makes new perspectives for the biomarker of ovarian cancer of great significance. As the main component of extracellular matrix, collagen fibers undergo dynamic remodeling caused by neoplastic activity. Second harmonic generation (SHG) enables label-free, non-destructive imaging of collagen fibers with submicron resolution and deep sectioning. In this study, we developed a new metric named local coverage to quantify morphologically localized distribution of collagen fibers and combined it with overall density to characterize 3D SHG images of collagen fibers from normal, benign and malignant human ovarian biopsies. An overall diagnosis accuracy of 96.3% in distinguishing these tissue types made local and overall density signatures a sensitive biomarker of tumor progression. Quantitative, multi-parametric SHG imaging might serve as a potential screening test tool for ovarian cancer.

Highly accurate, automated quantification of 2D/3D orientation for cerebrovasculature using window optimizing method.

Significance: Deep-imaging of cerebral vessels and accurate organizational characterization are vital to understanding the relationship between tissue structure and function. Aim: We aim at large-depth imaging of the mouse brain vessels based on aggregation-induced emission luminogens (AIEgens), and we create a new algorithm to characterize the spatial orientation adaptively with superior accuracy. Approach: Assisted by AIEgens with near-infrared-II excitation, three-photon fluorescence (3PF) images of large-depth cerebral blood vessels are captured. A window optimizing (WO) method is developed for highly accurate, automated 2D/3D orientation determination. The application of this system is demonstrated by establishing the orientational architecture of mouse cerebrovasculature down to the millimeter-level depth. Results: The WO method is proved to have significantly higher accuracy in both 2D and 3D cases than the method with a fixed window size. Depth- and diameter-dependent orientation information is acquired based on in vivo 3PF imaging and the WO analysis of cerebral vessel images with a penetration depth of 800 µm in mice. Conclusions: We built an imaging and analysis system for cerebrovasculature that is conducive to applications in neuroscience and clinical fields.

Mapping physiological and pathological functions of cortical vasculature through aggregation-induced emission nanoprobes assisted quantitative, in vivo NIR-II imaging.

Cerebrovascular disease includes all disorders that affect cerebrovascular and cerebral circulation. Unfortunately, there is currently a lack of a systematic method to image blood vessels directly and achieve accurate quantification. Herein, we build a non-invasive, quantitative imaging and characterization system applicable to mapping physiological and pathological functions of cortical vasculature. Assisted by aggregation-induced emission (AIE) luminogens with either excitation or emission at near-infrared-II (NIR-II) region, large-depth and/or high signal-to-background ratio images of cerebral blood vessels from mice and marmosets are captured, based on which we develop an optical metric of vessel thickness in an automated, pixel-wise manner and both two-dimensional (2D) and three-dimensional (3D) contexts. By monitoring time-dependent cerebrovascular images in marmosets, periodic changes in the diameter of vibrating cerebral blood vessels are found to be regulated mainly by heartbeat. In mice photothrombosis model, vessel alterations throughout the whole process of thrombotic stroke are found to be stage-dependent. From a large field of view, the distance-dependent vessel thickness variation before and right after stroke is obtained away from the thrombus site. Importantly, a buffer zone exists right surrounding the lesion, indicating the inhomogeneity of vascular morphological changes. Biologically excretable AIE nanoparticles are used for assessing physiological and pathological functions, offering great potential for clinical translation.

Dynamic inverse SNR-decorrelation OCT angiography with GPU acceleration.

Dynamic OCT angiography (OCTA) is an attractive approach for monitoring stimulus-evoked hemodynamics; however, a 4D (3D space and time) dataset requires a long acquisition time and has a large data size, thereby posing a great challenge to data processing. This study proposed a GPU-based real-time data processing pipeline for dynamic inverse SNR-decorrelation OCTA (ID-OCTA), offering a measured line-process rate of 133 kHz for displaying OCT and OCTA cross-sections in real time. Real-time processing enabled automatic optimization of angiogram quality, which improved the vessel SNR, contrast-to-noise ratio, and connectivity by 14.37, 14.08, and 9.76%, respectively. Furthermore, motion-contrast 4D angiographic imaging of stimulus-evoked hemodynamics was achieved within a single trail in the mouse retina. Consequently, a flicker light stimulus evoked an apparent dilation of the retinal arterioles and venules and an elevation of the decorrelation value in the retinal plexuses. Therefore, GPU ID-OCTA enables real-time and high-quality angiographic imaging and is particularly suitable for hemodynamic studies.

Optimized number of the primary singular values for image reconstruction in reflection matrix based optical coherence tomography.

A reflection matrix based optical coherence tomography (OCT) is recently proposed and expected to extend the imaging-depth limit twice. However, the imaging depth and hence the image quality heavily depend on the number of primary singular values considered for image reconstruction. To this regard, we propose a method based on correlation between image pairs reconstructed from different number of singular values and corresponding remainders. The obtained correlation curve and another feature curve fetched from the former are then fed to a long short-term memory (LSTM) network classifier to identify the optimized number of primary singular values for image reconstruction. Simulated targets with different combinations of filling fraction and signal-to-noise ratio (SNR) are reconstructed by the developed method as well as two current adopted methods for comparison. The results demonstrate that the proposed method is robust to recover the image with satisfactory similarity close to the reference one. To our knowledge, this is the first comprehensive study on the optimized number of the primary singular values considered for image reconstruction in reflection matrix based OCT.

Identification of endoplasmic reticulum formation mechanism by multi-parametric, quantitative super-resolution imaging.

The endoplasmic reticulum (ER) is a highly dynamic membrane-bound organelle in eukaryotic cells which spreads throughout the whole cell and contacts and interacts with almost all organelles, yet quantitative approaches to assess ER reorganization are lacking. Herein we propose a multi-parametric, quantitative method combining pixel-wise orientation and waviness features and apply it to the time-dependent images of co-labeled ER and microtubule (MT) from U2OS cells acquired from two-dimensional structured illumination microscopy (2D SIM). Analysis results demonstrate that these morphological features are sensitive to ER reshaping and a combined use of them is a potential biomarker for ER formation. A new, to the best of our knowledge, mechanism of MT-associated ER formation, termed hooking, is identified based on distinct organizational alterations caused by interaction between ER and MT which are different from those of the other three mechanisms already known, validated by 100% discrimination accuracy in classifying four MT-associated ER formation mechanisms.

Fast simulation and design of the fiber probe with a fiber-based pupil filter for optical coherence tomography using the eigenmode expansion approach.

Fiber probes for optical coherence tomography (OCT) recently employ a short section of step-index multimode fiber (SIMMF) to generate output beams with extended depth of focus (DOF). As the focusing region of the output beam is generally close to the probe end, it is not feasible to adopt the methods for bulk-optics with spatial pupil filters to the fiber probes with fiber-based filters. On the other hand, the applicable method of the beam propagation method (BPM) to the fiber probes is computationally inefficient to perform parameter scan and exhaustive search optimization. In this paper, we propose the method which analyzes the non-Gaussian beams from the fiber probes with fiber-based filters using the eigenmode expansion (EME) method. Furthermore, we confirm the power of this method in designing fiber-based filters with increased DOF gain and uniformly focusing by introducing more and higher-order fiber modes. These results using the EME method are in good agreement with that by the BPM, while the latter takes 1-2 orders more computation time. With higher-order fiber modes involved, a novel probe design with increased DOF gain and suppressed sidelobe is proposed. Our findings reveal that the fiber probes based on SIMMFs are able to achieve about four times DOF gain at maximum with uniformly focusing under acceptable modal dispersion. The EME method enables fast and accurate simulation of fiber probes based on SIMMFs, which is important in the design of high-performance fiber-based micro-imaging systems for biomedical applications.

How does experience impact the adoption willingness of battery electric vehicles? The role of psychological factors.

Battery electric vehicles (BEV) have become the most effective and environmentally friendly means to replace internal combustion vehicles. However, given the fact that BEV are a relatively new product category, and the majority of car users have little experience of using BEV, consumers often have a misconception about BEV, and thus tend to avoid purchasing an electric vehicle. This paper aims to explore the role of customer experience and demonstrate how this experience affects the adoption willingness of BEV. Based on driving experience and the theory of planned behavior, the authors constructed a framework of influencing factors for electric vehicle adoption willingness with the incorporation of consumer experience as the antecedents of adoption willingness. Using sample data from Jiangsu province, China, our empirical analysis shows that the mean values of the subjective norm, perceived behavioral control, attitudes, and adoption willingness of experienced consumers are significantly higher than those of inexperienced consumers. Further, the adoption willingness is positively influenced by experience through direct and indirect paths, which confirms the significant mediating effects of subjective norm, perceived behavioral control, and attitudes (battery life, cruising range, low noise, and low emission).

Uniform focusing with an extended depth range and increased working distance for optical coherence tomography by an ultrathin monolith fiber probe.

It is difficult to maintain high transverse resolution over an increased depth range using miniature probes for optical coherence tomography (OCT) due to the rapid divergence of light and the space limitation. To solve this problem, we introduce a fiber-based filter in the proposed probe to manipulate its output beam. Significant mode interference (MI) is exploited to enhance the depth of focus (DOF), and the mode phase difference is tuned to achieve a uniform axial intensity within the DOF. The magnified MI field instead of the diffracted one is adopted as the final pupil filter in the probe to increase its working distance (WD). The probe is fabricated with a diameter of 125 µm and a total length of 2.6 mm for its distal fiber optics. Compared to the conventional probe with similar minimal lateral resolution of better than 4.4 µm, the proposed probe achieves two times that of the DOF gain and 1.7 times that of the WD. Improvements in performance of the probe are demonstrated by OCT imaging using a fresh lemon and human skin. With merits of enhanced imaging quality and easy fabrication, the proposed probe poses great potential for important applications, especially for endoscopic imaging of human internal organs in vivo.

Longitudinal in vivo intrinsic optical imaging of cortical blood perfusion and tissue damage in focal photothrombosis stroke model.

A thorough understanding of the spatiotemporal dynamics of blood supply and tissue viability is of great importance in stroke researches. In the current study, vascular and cellular responses to focal ischemia were monitored with optical coherence tomography on chronic rat photothrombotic stroke model. The 3D mapping of blood perfusion and cellular scattering were achieved by analyzing the temporal dynamics and depth attenuation of intrinsic backscattered light respectively. Optical coherence tomography revealed that vessels of different types presented various spatial and temporal dynamics during the photothrombotic occlusion and the later recovery period. The large distal middle cerebral arteries presented a spontaneous recanalization and the small pial microvessels presented a reperfusion along with newly appeared vessels from the peripheral into the core area. The cortical capillary perfusion presented a weak recovery. Compared to the male group, the female rats showed a faster vascular recovery after photothrombotic. Moreover, the dynamic changes of the cellular scattering signal showed a high spatial and temporal correlation with the cortical capillary perfusion. Combined with well-designed photothrombotic stroke model and chronic optical window, optical coherence tomography imaging offers a unique approach to improve the understanding of stroke procedure and evaluate the treatment outcomes.

Photon ensemble correlation spectroscopy enables decorrelation-rate-limited ultrafast measurement of diffusive particle dynamics.

In contrast to conventional dynamic light scattering (DLS) measurement via a single sampling volume (SV) observation over a long time span, we propose a novel technique named "photon ensemble correlation spectroscopy" for ultrafast characterization of diffusive particle dynamics through decorrelation analysis of complex-valued DLS scattering signals from an ensemble of independent SVs. We confirm that the ensemble analysis provides a decorrelation-rate-limited ultrafast measurement and demonstrates the feasibility of imaging spatially resolved particle dynamics. Moreover, the use of complex-valued signals gives additional superiority in terms of reliability.

Lens-free all-fiber probe with an optimized output beam for optical coherence tomography.

A high-efficiency lensless all-fiber probe for optical coherence tomography (OCT) is presented. The probe is composed of a segment of large-core multimode fiber (MMF), a segment of tapered MMF, and a length of single-mode fiber (SMF). A controllable output beam can be designed by a simple adjustment of its probe structure parameters (PSPs), instead of the selection of fibers with different optical parameters. A side-view probe with a diameter of 340 µm and a rigid length of 6.37 mm was fabricated, which provides an effective imaging range of ∼0.6 mm with a full width at half-maximum beam diameter of less than 30 µm. The insertion loss of the probe was measured to be 0.81 dB, ensuring a high sensitivity of 102.25 dB. Satisfactory images were obtained by the probe-based OCT system, demonstrating the feasibility of the probe for endoscopic OCT applications.