MAS-Net OCT: a deep-learning-based speckle-free multiple aperture synthetic optical coherence tomography.

High-resolution spectral domain optical coherence tomography (SD-OCT) is a vital clinical technique that suffers from the inherent compromise between transverse resolution and depth of focus (DOF). Meanwhile, speckle noise worsens OCT imaging resolving power and restricts potential resolution-enhancement techniques. Multiple aperture synthetic (MAS) OCT transmits light signals and records sample echoes along a synthetic aperture to extend DOF, acquired by time-encoding or optical path length encoding. In this work, a deep-learning-based multiple aperture synthetic OCT termed MAS-Net OCT, which integrated a speckle-free model based on self-supervised learning, was proposed. MAS-Net was trained on datasets generated by the MAS OCT system. Here we performed experiments on homemade microparticle samples and various biological tissues. Results demonstrated that the proposed MAS-Net OCT could effectively improve the transverse resolution in a large imaging depth as well as reduced most speckle noise.

Zr-MOF-Induced Smart Accumulation Enables Surface-Enhanced Raman Spectroscopic Detection of Dioxin at ppt Level in Food Samples.

The fast and economical detection of trace polychlorinated dibenzo-p-dioxins (PCDDs) in food samples by current mass spectrum-based methods is hindered by tedious sample preparation and bulky & expensive analytical instruments. Surface-enhanced Raman spectroscopy (SERS) successfully detects many organic pollutants in foods but not dioxins because the employed metal nanoparticles weakly adsorb hydrophobic PCDDs. Herein, we report the detection of PCDDs in milk with SERS for the first time using a bifunctional substrate consisting of Au nanoparticles embedded in a zirconium-based metal-organic framework shell (AuNP/Zr-MOF). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), as the most toxic PCDD, is detected as low as 1.2 parts per trillion (ppt) in real milk samples with massive interfering substances in 30 min, which is the lowest among all reported methods. The aromatic rings of Zr-MOF promote the smart accumulation of TCDD through π-π interactions, and Au-Cl interactions drive TCDD onto Au surfaces. Zr-MOF shells with pore sizes of 12.7 and 20 Å block the accessibility of larger interfering molecules. A one-step apparatus and protocol are established to be superior to traditional methods in terms of time and cost. This work provides new insight into a rational screening method for the detection of persistent organic pollutants in a real sample matrix.

Nitric oxide detection using principal component analysis spectral structure matching to the UV derivative spectrum.

Ultraviolet (UV) spectroscopy is widely applied in real-time environmental monitoring, especially in diesel vehicle nitrogen monoxide (NO) emissions. However, in field experiments, UV absorption spectrum may exist for different degrees of drifts. Spectral jitters may exist for various reasons such as optical power variation, electrical signal drift, and the refractive index jitters of the optical path for an extended period of time, which causes the detection system to be calibrated. And the pulse xenon lamps as the UV source are characterized by specific emission lines that interfere in spectral analysis directly. For these problems, we proposed the spectral structure matching method based on principal component analysis (PCA), which was compared with the conventional polynomial fitting method to observe feasibility and variability. Further, the UV derivative spectrum was applied to the system appropriately, due to the variation of the absorption peak, and was only related to the target gas by using the above method. We validated our method experimentally by performing the NO UV detection system with the calibration and the comparison test. The results suggested that the calibration relative error was less than 9% and the measurement relative error was less than 6% for this wide range by the proposed processes, which optimized the interference of spectral structures and fluctuation to the system and therefore provided better monitoring. This study may provide an alternative spectral analysis method that is unaffected on the specific emission lines of lamps and is not limited to the spectral region and the target gas.

Adaptive monostable stochastic resonance for processing UV absorption spectrum of nitric oxide.

When ultraviolet (UV) absorption spectroscopy technology is used for nitric oxide (NO) detection, the background noise will directly affect the accuracy of concentration inversion, especially in low concentrations. Traditional processing methods attempt to eliminate background noise, which damages the absorption spectrum characteristics. However, stochastic resonance (SR) can utilize the noise to extract a weak characteristic signal. This paper reports a monostable stochastic resonance (MSR) model for processing an UV NO absorption spectrum. By analyzing the characteristics of UV absorption spectrum of NO, the evaluation indexes were constructed, thereby an adaptive MSR method was designed for parameter optimization. The numerical simulation confirmed the absorbance peak can be amplified and spectral signal-to-noise ratio (SNR) can be in the stable range of the proposed method, when noise intensity increased. Finally, this experiment obtained a NO detection limit (3σ) of 1.456 ppm and the maximum relative deviation of concentration is 6.32% by this proposed method, which is satisfactory for processing of the UV NO absorption spectrum.

Snapshot Photoacoustic Topography Through an Ergodic Relay for High-throughput Imaging of Optical Absorption.

Current embodiments of photoacoustic imaging require either serial detection with a single-element ultrasonic transducer or parallel detection with an ultrasonic array, necessitating a trade-off between cost and throughput. Here, we present photoacoustic topography through an ergodic relay (PATER) for low-cost high-throughput snapshot widefield imaging. Encoding spatial information with randomized temporal signatures through ergodicity, PATER requires only a single-element ultrasonic transducer to capture a widefield image with a single laser shot. We applied PATER to demonstrate both functional imaging of hemodynamic responses and high-speed imaging of blood pulse wave propagation in mice in vivo. Leveraging the high frame rate of 2 kHz, PATER tracked and localized moving melanoma tumor cells in the mouse brain in vivo, which enabled flow velocity quantification and super-resolution imaging. Among the potential biomedical applications of PATER, wearable monitoring of human vital signs in particular is envisaged.

Understanding optical reflectance contrast for real-time characterization of epithelial precursor lesions.

Detecting early-stage epithelial cancers and their precursor lesions are challenging as lesions could be subtle and focally or heterogeneously distributed over large mucosal areas. Optical coherence tomography (OCT) that enables wide-field imaging of subsurface microstructures in vivo is a promising screening tool for epithelial diseases. However, its diagnostic capability has not been fully appreciated since the optical reflectance contrast is poorly understood. We investigated the back-scattered intensities from clustered or packed nanometer scale intracellular scatterers using finite-difference time-domain method and 1-µm resolution form of OCT, and uncovered that there existed correlations between the reflectance contrasts and the ultrastructural clustering or packing states of these scatterers, which allows us to interpret the physiological state of the cells. Specifically, both polarized goblet cells and foveolar cells exhibited asymmetric reflectance contrast, but they could be differentiated by the optical intensity of the mucin cup due to the different ultrastructural make-ups of the mucin granules; keratinocytes could demonstrate varied cytoplasmic intensity and their cytoplasmic contrast was closely correlated with the packing state of keratin filaments. Further preliminary study demonstrated that these new understandings of OCT image contrast enables the characterization of precancerous lesions, which could complement the current morphology-based criteria in realizing "virtual histology" and would have a profound impact for the screening and surveillance of epithelial cancers.

Geometry-Dependent Spectroscopic Contrast in Deep Tissues.

Nano-structures of biological systems can produce diverse spectroscopic effects through interactions with broadband light. Although structured coloration at the surface has been extensively studied, natural spectroscopic contrasts in deep tissues are poorly understood, which may carry valuable information for evaluating the anatomy and function of biological systems. Here we investigated the spectroscopic characteristics of an important geometry in deep tissues at the nanometer scale: packed nano-cylinders, in the near-infrared window, numerically predicted and experimentally proved that transversely oriented and regularly arranged nano-cylinders could selectively backscatter light of the long wavelengths. Notably, we found that the spectroscopic contrast of nanoscale fibrous structures was sensitive to the pressure load, possibly owing to the changes in the orientation, the degree of alignment, and the spacing. To explore the underlying physical basis, we further developed an analytical model based on the radial distribution function in terms of their radius, refractive index, and spatial distribution.

Contrast of nuclei in stratified squamous epithelium in optical coherence tomography images at 800 nm.

Imaging nuclei of keratinocytes in the stratified squamous epithelium has been a subject of intense research since nucleus associated cellular atypia is the key criteria for the screening and diagnosis of epithelial cancers and their precursors. However, keratinocyte nuclei have been reported to be either low scattering or high scattering, so that these inconsistent reports might have led to misinterpretations of optical images, and more importantly, hindered the establishment of optical diagnostic criteria. We disclose that they are generally low scattering in the core using Micro-optical coherence tomography (µOCT) of 1.28-µm axial resolution in vivo; those previously reported "high scattering" or "bright" signals from nuclei are likely from the nucleocytoplasmic boundary, and the low-scattering nuclear cores were missed possibly due to insufficient axial resolutions (~4µm). It is further demonstrated that the high scattering signals may be associated with flattening of nuclei and cytoplasmic glycogen accumulation, which are valuable cytologic hallmarks of cell maturation.

Cellular resolution corneal imaging with extended imaging range.

Current optical coherence tomography (OCT) technology, which is used for imaging the eye's anterior segment, has been established as a clinical gold standard for the diagnosis of corneal diseases. However, the cellular resolution level information that is critical for many clinical applications is still not available. The major technical challenges toward cellular resolution OCT imaging are the limited ranging depth and depth of focus (DOF). In this work, we present a novel ultrahigh resolution OCT system that achieves an isotropic spatial resolution of <2 µm in tissue. The proposed system could approximately double the ranging depth and extend the DOF using the dual-spectrometer design and the forward-model based digital refocusing method, respectively. We demonstrate that the novel system is capable of visualizing the full thickness of the pig cornea over the ranging depth of 3.5 mm and the border of the corneal endothelial cells 8 times Rayleigh range away from the focal plane. This technology has the potential to realize cellular resolution corneal imaging in vivo.

Clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning.

OBJECTIVE: To observe the clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning patients, and investigate the potential mechanism. METHODS: In this study, we enrolled 136 organophosphorus poisoning patients who received treatment in this hospital between January 2009 and December 2017, and they were divided into three groups according to the clinical treatment methods, i.e. Group A (comprehensive treatment with HP, n = 47), Group B (continuous intravenous infusion of atropine with micropump, n = 43) and Group C (regular intravenous infusion of atropine, n = 46). In addition to the close monitoring of vital signs, we recorded the atropinization time (min), cholinesterase reactivation time (h), total dose of atropine, recurrence, incidence rate of atropine poisoning (%), hospitalization time (d) and cure rate (%). RESULTS: In comparison with Group C, patients in Group A and B manifested more stable vital signs with lower total dose of atropine and incidence rate of atropine poisoning and shorter cholinesterase reactivation time, while the cure rate was remarkably increased (p < 0.05), and no significant differences were observed in atropinization time among three groups (p > 0.05). Compared to Group B and C, total dose of atropine in Group A was significantly decreased with obvious excellence in hospitalization time, reduction of complications and increases in cure rates (p < 0.05). Moreover, patients in Group A had the lowest mortality rate among three groups. CONCLUSION: In treatment of organophosphorus poisoning patients, HP and continuous intravenous infusion of atropine using micropump can elevate the survival rate, reduce the incidence of adverse reaction, shorten the reactivation time of cholinesterase and decrease the incidence rate of complications, which are superior to the traditional treatment method.

Extending the depth of focus of fiber-optic optical coherence tomography using a chromatic dual-focus design.

We report a dual-focus fiber-optic probe designed to extend depth of focus (DOF) in high-resolution endoscopic optical coherence tomography. We exploited the broad spectral bandwidth of a supercontinuum source and, in the fiber probe, the foci of the 750-1000 nm and 1100-1450 nm inputs were axially chromatically shifted. The interference signals from the two spectral bands were measured with a Si camera-based spectrometer and an InGaAs camera-based spectrometer, respectively. We verified the feasibility of the design using a phantom composed of microparticles and swine small intestine tissue ex vivo. The results showed that a transverse resolution below 5 µm over 300 µm could be maintained, and that the extended DOF was 2 times larger than that of the single focus probe via the use of dual spectral band inputs and a chromatic focal shift.

Extending axial focus of optical coherence tomography using parallel multiple aperture synthesis.

Compromising the inherent trade-off between transverse resolution and depth of focus (DOF) remains a long-standing issue in optical coherence tomography (OCT). In this work, we report a novel technique-parallel multiple aperture synthesis (pMAS) to simultaneously generate multiple optical apertures in an OCT sample arm by employing a two-surface coated mirror. In the proposed pMAS, the DOF is extended by a factor of 16.49 without sacrificing the transverse resolution for proof-of-concept experiments when multiple distinctive apertures are digitally synthesized. The microparticles and tissue experiments demonstrate the feasibility of pMAS to address the fundamental problem of limited DOF in high-resolution OCT.

Multiple aperture synthetic optical coherence tomography for biological tissue imaging.

An inherent compromise must be made between transverse resolution and depth of focus (DOF) in spectral domain optical coherence tomography (SD-OCT). Thus far, OCT has not been capable of providing a sufficient DOF to stably acquire cellular-resolution images. We previously reported a novel technique named multiple aperture synthesis (MAS) to extend the DOF in high-resolution OCT [Optica4, 701 (2017)]. In this technique, the illumination beam is scanned across the objective lens pupil plane by being steered at the pinhole using a custom-made microcylindrical lens. Images captured via multiple distinctive apertures were digitally refocused, which is similar to synthetic aperture radar. In this study, we applied this technique for the first time to image both a homemade microparticle sample and biological tissue. The results demonstrated the feasibility and efficacy of high-resolution biological tissue imaging with a dramatic DOF extension.

Endomicroscopic optical coherence tomography for cellular resolution imaging of gastrointestinal tracts.

Our ability to detect neoplastic changes in gastrointestinal (GI) tracts is limited by the lack of an endomicroscopic imaging tool that provides cellular-level structural details of GI mucosa over a large tissue area. In this article, we report a fiber-optic-based micro-optical coherence tomography (µOCT) system and demonstrate its capability to acquire cellular-level details of GI tissue through circumferential scanning. The system achieves an axial resolution of 2.48 µm in air and a transverse resolution of 4.8 µm with a depth-of-focus (DOF) of ~150 µm. To mitigate the issue of limited DOF, we used a rigid sheath to maintain a circular lumen and center the distal-end optics. The sensitivity is tested to be 98.8 dB with an illumination power of 15.6 mW on the sample. With fresh swine colon tissues imaged ex vivo, detailed structures such as crypt lumens and goblet cells can be clearly resolved, demonstrating that this fiber-optic µOCT system is capable of visualizing cellular-level morphological features. We also demonstrate that time-lapsed frame averaging and imaging speckle reduction are essential for clearly visualizing cellular-level details. Further development of a clinically viable µOCT endomicroscope is likely to improve the diagnostic outcome of GI cancers.

Visualizing Micro-anatomical Structures of the Posterior Cornea with Micro-optical Coherence Tomography.

Diagnosis of corneal disease and challenges in corneal transplantation require comprehensive understanding of corneal anatomy, particularly that of the posterior cornea. Micro-optical coherence tomography (µOCT) is a potentially suitable tool to meet this need, owing to its ultrahigh isotropic spatial resolution, high image acquisition rate and depth priority scanning mode. In this study, we explored the ability of µOCT to visualize micro-anatomical structures of the posterior cornea ex vivo and in vivo using small and large animals. µOCT clearly delineated cornea layers and revealed micro-anatomical structures, including not only polygonal endothelial cells, stellate keratocytes, collagen fibres and corneal nerve fibres but also new structures such as the dome-shaped basolateral side of endothelial cells and lattice structures at the interface between endothelium and Descemet's membrane. Based on these observations, a short post-harvest longitudinal study was conducted on rat cornea to test the feasibility of using µOCT to monitor the quality of endothelial cells. This study successfully reveals a series of morphological features and pathological changes in the posterior cornea at the cellular level in situ and in real time with µOCT. These findings enrich knowledge of corneal anatomy and suggest that µOCT may be a promising imaging tool in corneal transplantation.

Single-camera full-range high-resolution spectral domain optical coherence tomography.

We developed spectral domain optical coherence tomography using a dual-channel spectrometer for complex conjugate artifacts (CCA) suppression. We used a three-line charge coupled device to simultaneously detect two interferometric spectra with 2π/3 phase difference. The complex interferometric signal was reconstructed by trigonometric manipulation of two real interferometric spectra, and then full-range images were obtained by use of inverse Fourier transform. Artifacts at direct current (DC) and the ghost remnant of the CCA are common issues with the previously reported two-spectrometer method because the slight mismatching between two spectral detection channels had strong negative effects on CCA suppression and appeared to be the limiting factor on system performance. This novel dual-channel spectrometer uses the same spectrometer optics for the two spectral detection channels and, therefore, achieves better matching between two spectral detection channels and consequently better performance in CCA suppression as compared with the dual spectrometer solution. Full-range imaging with CCA suppression up to ∼25 dB was demonstrated when imaging an attenuated reflector. The efficacy of both CCA and DC suppressions also was validated by imaging the anterior segment of a rat eye ex vivo. The quality of CCA-suppressed images was significantly improved with regard to those obtained with the dual-spectrometer design.

Multifiber angular compounding optical coherence tomography for speckle reduction.

We report on an integrated fiber optic design to implement multifiber angular compounding optical coherence tomography, which enables angular compounding for speckle reduction. A multi-facet fiber array delivers three light beams to the sample with different incident angles. Back-reflective/back-scattered signals from these channels were simultaneously detected by a three-channel spectrometer. The axial and lateral resolution was measured to be ∼3 and ∼3.5 µm, respectively, in air with ∼100 dB sensitivity. We conducted ex vivo experiments on a rat esophagus to demonstrate a contrast to noise improvement of 1.58.

Correlation of the pathologic morphology on MRI with International Hip Dysplasia Institute classification in developmental dysplasia of the hip / 中国组织工程研究

BACKGROUND: T?nnis classification is commonly used to quantify the severity of developmental dysplasia of the hip (DDH), which relies on the presence of the epiphyseal ossification centre. Thereafter, a new classification system (IHDI method) has been developed by the International Hip Dysplasia Institute (IHDI). However, the pathologic morphology has not been defined based on the IHDI grade.OBJECTIVE: To analyze the correlation of the pathologic changes of the hip on MRI with IHDI classification.METHODS: Image data of 65 infants (89 hips) with DDH were analyzed retrospectively, with an average age of 20.4 months. The radiographic severity was graded by IHDI system, and the correlation between IHDI classification and pathological changes of the hip was analyzed, by observing the morphology and position of the limbus, and the cartilaginous acetabular index.RESULTS AND CONCLUSION: (1) A positive correlation was detected between severity of the IHDI grades and age at reduction (r=0.456, P < 0.001). (2) Unexpectedly, the cartilaginous femoral epiphysis still remained contacting with the acetabulum in a part of type III DDH. The cartilaginous acetabular index was significantly increased with IHDI grade increasing (P=0.028). (3) The limbus was everted in all of the type I hips; however, inverted or mixed shape accounted about 60% in the type II hips, 86% in the type III, and 97% in the type IV, respectively. (4) These results manifest that the DDH was severer, and the limbus trended to be more inverted with the increasing in IHDI grade. Moreover,understanding the correlation of the pathologic morphology with the IHDI classification is of great significance for planning an appropriate treatment scheme for DDH.

Gene expression and molecular characterization of a chaperone protein HtpG from Bacillus licheniformis.

Heat shock protein 90 (Hsp90/HtpG) is a highly abundant and ubiquitous ATP-dependent molecular chaperone consisting of three flexibly linked regions, an N-terminal nucleotide-binding domain, middle domain, and a C-terminal domain. Here the putative htpG gene of Bacillus licheniformis was cloned and heterologously expressed in Escherichia coli M15 cells. Native-gel electrophoresis, size exclusion chromatography, and cross-linking analysis revealed that the recombinant protein probably exists as a mixture of monomer, dimer and other oligomers in solution. The optimal conditions for the ATPase activity of B. licheniformis HtpG (BlHtpG) were 45°C and pH 7.0 in the presence of 0.5mM Mg(2+) ions. The molecular architecture of this protein was stable at higher temperatures with a transition point (Tm) of 45°C at neutral pH, whereas the Tm value was reduced to 40.8°C at pH 10.5. Acrylamide quenching experiment further indicated that the dynamic quenching constant (Ksv) of BlHtpG became larger at higher pH values. BlHtpG also experienced a significant change in the protein conformation upon the addition of ATP and organic solvents. Collectively, our experiment data may provide insights into the molecular properties of BlHtpG and identify the alteration of protein structure to forfeit the ATPase activity at alkaline conditions.

Spectral-domain optical coherence tomography with dual-balanced detection for auto-correlation artifacts reduction.

We developed a spectral domain optical coherence tomography (SD-OCT) to reduce auto-correlation artifacts (AC) using dual-balanced detection (DBD). AC were composed of the interference signals between different sample tissue depths, and shown up as artifacts in OCT images. This system employed a free-space Michelson interferometer, at the refraction plane of whose beam splitter, the light reflected experienced a π/2 phase shift with respect to the light transmitted. Then two phase-opposed interferometric spectra sharing the same spectrometer optics were obtained simultaneously using two lines of a three-line CCD. This new design was of lower cost compared to the dual spectrometer design reported previously. DBD enabled this SD-OCT to achieve two-fold increase in the interested signal amplitude inherently, and obtain a SNR increase of ~2.9 dB experimentally. To demonstrate the feasibility and performance of this SD-OCT system with DBD, we conducted an imaging experiment using a glass plate to obtain the optimal spectral matching between dual-balanced spectrometer channels. As a result, this SD-OCT achieved AC reduction up to about 9 dB and direct current (DC) term suppression up to about 30 dB by cancelling the identical components between dual-balanced spectrometer channels. The efficacy of AC reduction and DC suppression was validated by imaging the polymer coating of a drug-eluting stent and fresh swine corneal tissue ex vivo. The quality of DBD optimized images was significantly improved with regard to the single-channel images.