Thin flexible photoacoustic endoscopic probe with a distal-driven micro-step motor for pump-probe-based high-specific molecular imaging.

Conventional photoacoustic endoscopy (PAE) is mostly for structural imaging, and its molecular imaging ability is quite limited. In this work, we address this issue and present the development of a flexible acoustic-resolution-based photoacoustic endoscopic (AR-PAE) probe with an outer diameter of 8 mm. This probe is driven by a micro-step motor at the distal end, enabling flexible and precise angular step control to synchronize with the optical parametric oscillator (OPO) lasers. This probe retains the high spatial resolution, high penetration depth, and spectroscopic imaging ability of conventional AR-PAE. Moreover, it is capable for background-free high-specific photoacoustic molecular imaging with a novel pump-probe detection technique, as demonstrated by the distribution visualizing of the FDA approved contrast agent methylene blue (MB) in an ex-vivo pig ileum. This proposed method represents an important technical advancement in multimodal PAE, and can potentially make considerable contributions across various biomedical fields.

Dynamic monitoring of oxygen partial pressure in photodynamic therapy using pump-probe-based photoacoustic tomography.

Pump-probe-based photoacoustic tomography (PP-PAT) is an innovative and promising molecular imaging technique. In this study, we utilized PP-PAT for the first time, to the best of our knowledge, to monitor the dynamics of oxygen partial pressure (pO2) within murine tumors during photodynamic therapy (PDT) with methylene blue (MB). We developed, to our knowledge, a novel two-step fitting method to simultaneously map both the pO2 and the MB concentrations and implemented it with mexCuda to accelerate the pixel-wise-based calculation. The results demonstrated a penetration depth of up to 5 mm and revealed a significant decrease in pO2 during the PDT process, consistent with existing research findings. This study suggests that PP-PAT has the potential to become a valuable tool for intraoperative monitoring of PDT, thereby enhancing therapeutic efficacy.

Fenton-Like Reaction: Recent Advances and New Trends.

The Fenton reaction refers to the reaction in which ferrous ions (Fe2+) produce hydroxyl radicals and other reactive oxidizing substances by decomposing hydrogen peroxide (H2O2). This paper reviews the mechanism, application system, and materials employed in the Fenton reaction including conventional homogeneous and non-homogeneous Fenton reactions as well as photo-, electrically-, ultrasonically-, and piezoelectrically-triggered Fenton reactions, and summarizes the applications in the degradation of soil oil pollutions, landfill leachate, textile wastewater, and antibiotics from a practical point of view. The mineralization paths of typical pollutant are elucidated with relevant case studies. The paper concludes with a summary and outlook of the further development of Fenton-like reactions.

In vitro transdifferentiated signatures of goat preadipocytes into mammary epithelial cells revealed by DNA methylation and transcriptome profiling.

During mammary development, the transdifferentiation of mammary preadipocytes is one of the important sources for lactating mammary epithelial cells (MECs). However, there is limited knowledge about the mechanisms of dynamic regulation of transcriptome and genome-wide DNA methylation in the preadipocyte transdifferentiation process. Here, to gain more insight into these mechanisms, preadipocytes were isolated from adipose tissues from around the goat mammary gland (GM-preadipocytes). The GM-preadipocytes were cultured on Matrigel in conditioned media made from goat MECs to induce GM-preadipocyte-to-MEC transdifferentiation. The transdifferentiated GM-preadipocytes showed high abundance of keratin 18, which is a marker protein of MECs, and formed mammary acinar-like structures after 8 days of induction. Then, we performed transcriptome and DNA methylome profiling of the GM-preadipocytes and transdifferentiated GM-preadipocytes, respectively, and the differentially expressed genes and differentially methylated genes that play underlying roles in the process of transdifferentiation were obtained. Subsequently, we identified the candidate transcription factors in regulating the GM-preadipocyte-to-MEC transdifferentiation by transcription factor-binding motif enrichment analysis of differentially expressed genes and differentially methylated genes. Meanwhile, the secretory proteome of GM-preadipocytes cultured in conditioned media was also detected. By integrating the transcriptome, DNA methylome, and proteome, three candidate genes, four proteins, and several epigenetic regulatory axes were further identified, which are involved in regulation of the cell cycle, cell polarity establishment, cell adhesion, cell reprogramming, and adipocyte plasticity. These findings provide novel insights into the molecular mechanism of preadipocyte transdifferentiation and mammary development.

On-the-fly parameter estimation based on item response theory in item-based adaptive learning systems.

Online learning systems are able to offer customized content catered to individual learner's needs, and have seen growing interest from industry and academia alike in recent years. In contrast to the traditional computerized adaptive testing setting, which has a well-calibrated item bank with new items added periodically, the online learning system has two unique features: (1) the number of items is large, and they have likely not gone through costly field testing for item calibration; and (2) the individual's ability may change as a result of learning. The Elo rating system has been recognized as an effective method for fast updating of item and person parameters in online learning systems to enable personalized learning. However, the updating parameter in Elo has to be tuned post hoc, and Elo is only suitable for the Rasch model. In this paper, we propose the use of a moment-matching Bayesian update algorithm to estimate item and person parameters on the fly. With sequentially updated item and person parameters, a modified maximum posterior weighted information criterion (MPWI) is proposed to adaptively assign items to individuals. The Bayesian updated algorithm along with MPWI is validated in a simulated multiple-session online learning setting, and the results show that the new combo can achieve fast and reasonably accurate parameter estimations that are comparable to random selection, match-difficulty selection, and traditional online calibration. Moreover, the combo can still function reasonably well with as low as 20% of items being pre-calibrated in the item bank.

Acoustic-resolution-based spectroscopic photoacoustic endoscopy towards molecular imaging in deep tissues.

Due to many technical difficulties, the study of molecular photoacoustic endoscopic (PAE) imaging in deep tissues is limited. In this work, we have set up a multimodal acoustic-resolution-based PAE (AR-PAE) system to image the rabbit rectum and preliminarily explored the potential of molecular PAE for deep-seated targets in proof-of-concept. We developed an improved back-projection (IBP) algorithm for focused detection over the centimeter-scale imaging depth. We also developed a deep-learning-based algorithm to remove the electrical noise from the step motor to prevent data averaging for reduced scanning time. We injected a dose of indocyanine green (ICG) near the rabbit rectum and compared 2D and 3D photoacoustic/ultrasound (PA/US) images at different wavelengths. We proposed incorporating a small camera to guide the slow PA/US endoscopic scan. Results show that this system has achieved a lateral resolution of about 0.77/0.65 mm for PA/US images with a signal-to-noise ratio (SNR) of 25/38 dB at an imaging depth of 1.4 cm. We found that the rectum wall and the ICG can be well distinguished spectroscopically. Results also show that the PA images at 532 nm have higher signal intensity and reflection artifacts from pelvic tendons and bones than those at longer wavelengths such as 800 nm. The proposed methods and the intuitive findings in this work may guide and promote the development of high-penetration molecular PAE.

Transient triplet differential-based photoacoustic lifetime imaging with an automatic interleaved data acquisition method for improved scanning speed and stability.

Transient triplet differential (TTD) based photoacoustic lifetime (PALT) imaging provides valuable means for background-free molecular imaging and mapping of the oxygen partial pressure (pO2) in deep tissues. However, the broad application of this method is hindered by its long scanning time, poor accuracy, and low stability. This is mainly because most PALT systems execute the three data acquisition sequences separately without automatic control and neglect the long-time fluctuation of the laser output. In this work, we have proposed a novel automatic interleaved data acquisition method for PALT. This new method not only improved the scanning efficiency but also eliminated the long-time fluctuations of laser pulse energy. Results show that this new method can significantly improve the system's stability and help reduce the scanning time. With this new method, we obtained the 3D background-free TTD images for the first time. We also observed distinct hypoxia inside the tumor due to the high metabolic rate of cancer cells, demonstrating the high reliability of our proposed method. The proposed method in this work can significantly promote the application of PALT imaging in biomedical studies.

In-vivo imaging of melanoma with simultaneous dual-wavelength acoustic-resolution-based photoacoustic/ultrasound microscopy.

Melanoma is a common, highly fatal skin cancer. Photoacoustic imaging can achieve highly sensitive and high-contrast detection of melanin molecules in tissues, also inheriting the high penetration depth and high spatial resolution characteristics of ultrasound imaging, thus it is a very promising non-invasive diagnostic tool for early melanoma. In this work, we built an acoustic-resolution-based photoacoustic microscopy system, using 1064 nm/532 nm pulsed light to observe melanoma in the back of a mouse with simultaneous photoacoustic/ultrasound imaging. Through the fusion of multi-modal images, accurate positioning of melanoma and its surrounding normal tissues were realized. This work will further promote the application of photoacoustic imaging in the clinical diagnosis of early melanoma.

Three-dimensional synthetic aperture focusing photoacoustic microscopy based on the acoustic simulation generated delay time and weighted factor.

Acoustic resolution photoacoustic microscopy (ARPAM) is a promising imaging tool in biomedical applications for its advantage of penetration over other optical imaging techniques. However, the lateral resolution of ARPAM deteriorates significantly in the out-of-focus region. The synthetic aperture focusing technique (SAFT) is required to restore this kind of focus-related imaging distortion. The conventional SAFT method is based on the virtual detector (VD) conception, in which the phase of the received photoacoustic (PA) signal is calculated by assuming the focus of the transducer as a VD. Nevertheless, the phase of the received PA signal is not only determined by the geometrical parameters of the transducer, but also by the transducer's electromechanic response and the original PA signal. Ignoring these two factors will reduce the quality of the imaging results. In this work, a new SAFT method, which is based on acoustic simulation, is proposed for ARPAM. The measured PA signal from a point target at the focus is employed to evaluate the convolution of the transducer's electromechanic response and the original PA signal. This measured signal is used as the excitation in an acoustic simulation. The simulation, which is based on the geometrical and acoustic parameters of the transducer, is employed to calculate the delay time and weighted coefficient for the SAFT calculation. The phantom experiments with point and line targets indicate that the proposed method obtains imaging results with better lateral resolution and improved signal-noise ratio compared with the widely used VD-based SAFT method.

Finite-element reconstruction of 2D circular scanning photoacoustic tomography with detectors in far-field condition.

The finite-element method (FEM) has been a powerful numerical tool for the reconstruction of 2D circular scanning-based photoacoustic tomography (PAT) for its unrivaled ability to accommodate complex boundary conditions, quantitatively reconstruct different physical parameters, and enable low sampling frequency and fewer detector numbers. To reduce the computation cost, a smaller image domain is commonly used instead of the region surrounded by the transducer scanning trace. Then, the pressure data used for the reconstruction that is defined on the boundary of the image domain is usually obtained by directly time delaying the actual measured data. In this case, distortions will be aroused for targets that are away from the rotation center. In this work, we put forward a new data preprocessing method to overcome this problem with a virtual detector concept, in which the measured data for the virtual point detectors on the boundary of the reconstruction domain are generated by a summation of the signals from nearby true detectors. The complete removal of the distortions using our proposed algorithm was proven with experimental reconstruction results.

[Focal zone integral and multiple axial scanning based acoustic resolution photoacoustic microscopy with high lateral resolution in-depth].

Acoustic resolution photoacoustic microscopy (ARPAM) combines the advantages of high optical contrast, and high ultrasonic spatial resolution and penetration. However, in photoacoustic microscopy (PAM), the information from deep regions can be greatly affected by the shallow targets, and most importantly, the irreconcilable conflict between the lateral resolution and depth of fields has always be a major factor that limits the imaging quality. In this work, an ARPAM system was developed, in which a non-coaxial arrangement of light illumination and acoustic detection was adopted to alleviate the influence of the tissue surface on the deep targets, and a novel focal zone integral algorithm was applied with multiple axial scanning to improve the lateral resolution. Phantom experiment results show that, the build system can maintain a consistent high lateral resolution of 0.6 mm over a large range in axial direction, which is close to the theoretical calculations. The following tumor imaging results on nude mice indicate that, the proposed method can provide more in-depth information compared with the conventional back detection ARPAM method. With the development of fast repetition lasers and image scanning technologies, the proposed method may play an important role in cerebral vascular imaging, cervical cancer photoacoustic endoscopic detection, and superficial tumor imaging.

Improved back-projection method for circular-scanning-based photoacoustic tomography with improved tangential resolution.

While photoacoustic computed tomography (PACT) is generally built with planar transducers of finite size, most current reconstruction algorithms assume the transducer to be an ideal point, which leads to a spinning blur in the consequently obtained PACT images due to the model mismatch. In this work, we put forward an improved back-projection method that factors in the geometry of the transducers to improve the tangential resolution for the reconstruction of 2D circular-scanning-based photoacoustic tomography. Extensive simulations and experiments were carried out to study the adaptability and stability of the proposed method. Results show that this method can effectively restore the tangential distortion of the PACT image for both simulated and experimental data. Results indicated that the improvement of the tangential resolution is more obvious for transducers with larger size. We also demonstrated the application of this method to transducers other than planar, and results show that the reconstructed image quality can be significantly affected by the shape and position of the transducers used. This study may help to guide the selection of transducer and design of scanning strategy in PACT.

Implementation of the Tobacco-Free Campus Policy on College Campuses: Evidence From a Survey of College Students in Beijing.

OBJECTIVE: China issued a nationwide "Tobacco-Free Campus" Policy (TFCP) in January 2014, but it is unclear how well it was implemented across China's 2138 college campuses. We conducted an Internet survey of Beijing college students to evaluate the implementation of the TFCP in Beijing. METHODS: An Internet survey of 711 students from 37 colleges in Beijing was conducted in May 2015. Respondents reported on secondhand smoking (SHS) exposure on campus, knowledge on and actions taken against SHS, and tobacco marketing exposure on campus. RESULTS: Almost 90% of respondents were exposed to SHS on campus at least once in the past month. Approximately 37% of nonsmokers and 61% of smokers reported seeing a teacher smoking, and the majority of both smokers and nonsmokers reported seeing a classmate smoking in campus buildings. The likelihood and location of SHS exposure depend on the participant's demographics and own smoking behavior. Nonsmokers were more likely to be aware of the health risk of SHS than smokers. Although most participants were aware of the harms, only 13% and 9% tried to stop their last SHS exposure indoors and outdoors, respectively. Forty-seven students from 14 colleges noticed tobacco marketing activities on campus. CONCLUSIONS: The TFCP on Chinese college campuses was only partially enforced, particularly with regard to SHS. IMPLICATIONS: On January 29, 2014, the Chinese Ministry of Education issued the TFCP. A major barrier to effective tobacco control in China is the difficulty in implementing policies issued by the central government. At this point, it is unclear whether the TFCP was successfully implemented on China's college campuses. Major tobacco use monitoring efforts do not include college students. The present research describes the current tobacco control environment on Beijing's college campuses 15 months after the TFCP took effect. To our knowledge, this is the first paper in the English literature on tobacco environment and exposure (rather than a prevalence survey) of college students in China.

Photoacoustic endoscopy with hollow structured lens-focused polyvinylidine fluoride transducer.

Currently, most transducers in photoacoustic endoscopy (PAE) are ceramic based, which are complicated to fabricate and are expensive. In this work, we have for the first time presented a hollow structured epoxy lens-focused transducer that was based on a 52 µm thick polyvinylidine fluoride (PVDF) film for the purpose of PAE imaging. Intensive field characteristic tests were performed on transducers with different lens curvatures, and results show that with the 6 mm fixed aperture, a lateral resolution less than 0.5 mm can be obtained with a focal length around 19 mm, which is close to the theoretical calculations. The PAE application of the built transducer was also demonstrated with phantom experiments. Compared with the commonly used ceramic-based transducers, the proposed method has greatly reduced the design and fabrication cost of the hollow structured focused transducer as required in PAE, and facilitated the development of the PAE system in lab conditions. The built transducer may play an important role in the PAE imaging of some relatively large human structures and organs, such as the gastrointestinal tract and the cervical canal.

[Particle swarm optimization fuzzy modeling and closed-loop anaesthesia control based on cerebral state index].

Due to individual differences of the depth of anaesthesia (DOA) controlled objects, the drawbacks of monitoring index, the traditional PID controller of anesthesia depth could not meet the demands of nonlinear control. However, the adjustments of the rules of DOA fuzzy control often rely on personal experience and, therefore, it could not achieve the satisfactory control effects. The present research established a fuzzy closed-loop control system which takes the cerebral state index (CSI) value as a feedback controlled variable, and it also adopts the particle swarm optimization (PSO) to optimize the fuzzy control rule and membership functions between the change of CSI and propofol infusion rate. The system sets the CSI targets at 40 and 30 through the system simulation, and it also adds some Gaussian noise to imitate clinical disturbance. Experimental results indicated that this system could reach the set CSI point accurately, rapidly and stably, with no obvious perturbation in the presence of noise. The fuzzy controller based on CSI which has been optimized by PSO has better stability and robustness in the DOA closed loop control system.

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC.

BACKGROUND: Long noncoding RNAs (lncRNAs) are implicated in the tumor immunology of hepatocellular carcinoma (HCC). METHODS: HCC mRNA and lncRNA expression profiles were used to extract immune-related genes with the ImmPort database, and immune-related lncRNAs with the ImmLnc algorithm. The MOVICS package was used to cluster immune-related mRNA, immune-related lncRNA, gene mutation and methylation data on HCC from the TCGA. GEO and ICGC datasets were used to validate the model. Data from single-cell sequencing was used to determine the expression of genes from the model in various immune cell types. RESULTS: With this model, the area under the curve (AUC) for 1-, 3- and 5-year survival of HCC patients was 0.862, 0.869 and 0.912, respectively. Single-cell sequencing showed EREG was significantly expressed in a variety of immune cell types. Knockdown of the EREG target gene resulted in significant anti-apoptosis, pro-proliferation and pro-migration effects in HepG2 and HUH7 cells. Moreover, serum and liver tissue EREG levels in HCC patients were significantly higher than those of healthy control patients. CONCLUSION: We built a prognostic model with good accuracy for predicting HCC patient survival. EREG is a potential immunotherapeutic target and a promising prognostic biomarker.

Semiconducting Polymer Dots for Dual-Wavelength Differential Background-Suppressed Photoacoustic Imaging.

Photoacoustic imaging (PAI) can sensitively detect regions and substances with strong optical absorption, which means that diseased tissue can be imaged with high contrast in the presence of surrounding healthy tissue through the photoacoustic effect. However, its signal intensity and resolution may be limited by background signals generated by endogenous chromophores such as melanin and hemoglobin. A feasible method for practical application of this so-called background-suppressed PAI is still lacking. In this work, a dual-wavelength differential background noise-suppressed photoacoustic tomography is developed based on organic semiconducting polymer dots (Pdots). The Pdots have a strong absorption peak at 945 nm, and then the absorption decreases sharply with the increase of wavelength, and the absorption intensity drops to only about a quarter of the original value at 1050 nm. The present system significantly suppresses the strong background noise of blood through dual-wavelength differential PAI, enabling precise monitoring of the distribution information of theranostic agents in diseased tissues. The signal-to-noise ratio of the theranostic agent distribution map is increased by about 20 dB. This work provides a platform for real-time and accurate monitoring of tumors and drugs, which helps avoid damage to healthy tissue during treatment and has clinical significance in cancer treatment.

Three-dimensional photoacoustic tomography based on graphics-processing-unit-accelerated finite element method.

Compared with commonly used analytical reconstruction methods, the frequency-domain finite element method (FEM) based approach has proven to be an accurate and flexible algorithm for photoacoustic tomography. However, the FEM-based algorithm is computationally demanding, especially for three-dimensional cases. To enhance the algorithm's efficiency, in this work a parallel computational strategy is implemented in the framework of the FEM-based reconstruction algorithm using a graphic-processing-unit parallel frame named the "compute unified device architecture." A series of simulation experiments is carried out to test the accuracy and accelerating effect of the improved method. The results obtained indicate that the parallel calculation does not change the accuracy of the reconstruction algorithm, while its computational cost is significantly reduced by a factor of 38.9 with a GTX 580 graphics card using the improved method.

A Testlet Diagnostic Classification Model with Attribute Hierarchies.

In this article, a testlet hierarchical diagnostic classification model (TH-DCM) was introduced to take both attribute hierarchies and item bundles into account. The expectation-maximization algorithm with an analytic dimension reduction technique was used for parameter estimation. A simulation study was conducted to assess the parameter recovery of the proposed model under varied conditions, and to compare TH-DCM with testlet higher-order CDM (THO-DCM; Hansen, M. (2013). Hierarchical item response models for cognitive diagnosis (Unpublished doctoral dissertation). UCLA; Zhan, P., Li, X., Wang, W.-C., Bian, Y., & Wang, L. (2015). The multidimensional testlet-effect cognitive diagnostic models. Acta Psychologica Sinica, 47(5), 689. https://doi.org/10.3724/SP.J.1041.2015.00689). Results showed that (1) ignoring large testlet effects worsened parameter recovery, (2) DCMs assuming equal testlet effects within each testlet performed as well as the testlet model assuming unequal testlet effects under most conditions, (3) misspecifications in joint attribute distribution had an differential impact on parameter recovery, and (4) THO-DCM seems to be a robust alternative to TH-DCM under some hierarchical structures. A set of real data was also analyzed for illustration.

Spectroscopic photoacoustic/ultrasound/optical-microscopic multimodal intrarectal endoscopy for detection of centimeter-scale deep lesions.

The inadequacy of existing colorectal imaging tools has significantly obstructed the efficient detection of colorectal cancer. To address this issue, this work presents the cross-scale endoscopic imaging of rectal tumors with a combined photoacoustic/ultrasound tomography system and wide-field optical microscopy. This multimodal system combines the merits of centimeter-scale deep penetration, multi-spectral imaging, cross-scale imaging ability, low system cost, and 360° view in a single modality. Results indicated that the proposed system could reliably depict the location of the cancer invasion depth spectroscopically with indocyanine green The tumor angiogenesis can be well identified in the wide-field optical imaging mode, which helps to localize the tumors and guide the following photoacoustic/ultrasound scan. This work may facilitate the accurate characterization of colorectal cancer and promote the clinical translation of photoacoustic-based colorectal endoscopy.