X-ray free-electron laser induced acoustic microscopy (XFELAM).

The X-ray free-electron laser (XFEL) has remarkably advanced X-ray imaging technology and enabled important scientific achievements. The XFEL's extremely high power, short pulse width, low emittance, and high coherence make possible such diverse imaging techniques as absorption/emission spectroscopy, diffraction imaging, and scattering imaging. Here, we demonstrate a novel XFEL-based imaging modality that uses the X-ray induced acoustic (XA) effect, which we call X-ray free-electron laser induced acoustic microscopy (XFELAM). Initially, we verified the XA effect by detecting XA signals from various materials, then we validated the experimental results with simulation outcomes. Next, in resolution experiments, we successfully imaged a patterned tungsten target with drilled various-sized circles at a spatial resolution of 7.8 ± 5.1 µm, which is the first micron-scale resolution achieved by XA imaging. Our results suggest that the novel XFELAM can expand the usability of XFEL in various areas of fundamental scientific research.

Pneumatic driven pulsatile ECMO in vitro evaluation with oxygen tanks.

Extracorporeal membrane oxygenation device is a procedure in which mechanical systems circulate blood and supply oxygen to patients with impaired cardiopulmonary function. Current venoarterial systems are associated with low patient survival rates and new treatments are needed to avoid left ventricular dilation, which is a major cause of death. In this study, a new mobile pulsatile ECMO with a pump structure that supplies pulsatile flow by using an oxygen tank as a power source is proposed. In vitro experiments conducted under mock circulation system as like patient conditions demonstrated that 2.8 L oxygen can sustain the outflow of 1 L/min of pulsatile blood flow for 53 min, while a 4.6 L tank was able to sustain the same flow for 85 min. The energy equivalent pressure evaluation index of the pulsatile blood pump shows that the mobile pulsatile ECMO could supply sufficient pulsatile blood flow compared to the existing pulsatile ECMO. Through in vitro experiments performed under mock circulation conditions, this new system was proven to supply sufficient oxygen and pulsatile blood flow using the pressure of an oxygen tank even while transporting a patient.

Theoretical and experimental comparison of the performance of gold, titanium, and platinum nanodiscs as contrast agents for photoacoustic imaging.

Exogenous contrast agents in photoacoustic imaging help improve spatial resolution and penetration depth and enable targeted molecular imaging. To screen efficient photoacoustic signaling materials as contrast agents, we propose a light absorption-weighted figure of merit (FOM) that can be calculated using material data from the literature and numerically simulated light absorption cross-sections. The calculated light absorption-weighted FOM shows that a Ti nanodisc has a photoacoustic conversion performance similar to that of an Au nanodisc and better than that of a Pt nanodisc. The photoacoustic imaging results of Ti, Au, and Pt nanodiscs, which are physically synthesized with identical shapes and dimensions, experimentally demonstrated that the Ti nanodisc could be a highly efficient contrast agent.

Hybrid-Type Transparent Organic Light Emitting Diode with High Contrast Using Switchable Windows.

Transparent organic light emitting diode (OLED) display is one of the most promising devices among next-generation information displays because of beneficial characteristics, such as self-emissive and optically clear properties. Nevertheless, in conventional transparent OLED display devices, there are serious intrinsic problems in terms of the transmittance in the dark state because of empty windows in the cell, so the contrast ratio of the transparent OLED display would be deteriorated even though it can exhibit excellent bright state. In general, the transparent mode using the OLED device applies an empty area in each pixel because an emitting device could never reveal the background image, so the transparent OLED should contain the empty area in the pixel for transparent images. This may cause the optical degradation in the dark state. To solve this problem, we propose hybrid-type transparent OLED display modes that apply a liquid crystal (LC) to the transparent window part of the empty space. In this paper, we applied two dichroic LC modes- which use an electrically controlled birefringence (ECB) mode (Heilmeier type) for the polarized mode and a cholesteric LC mode (Guest-Host mode) for the non-polarized mode-to the empty area. In each hybrid mode, we have observed optical performance, including the transmittance in the dark/bright state, contrast ratio and response time as a function of cell parameters. As a result, we confirmed that the dark state and the contrast ratio could be improved by applying the proposed modes without serious decay of the transmittance in the bright state.

Recent Advances in Contrast-Enhanced Photoacoustic Imaging: Overcoming the Physical and Practical Challenges.

For decades now, photoacoustic imaging (PAI) has been investigated to realize its potential as a niche biomedical imaging modality. Despite its highly desirable optical contrast and ultrasonic spatiotemporal resolution, PAI is challenged by such physical limitations as a low signal-to-noise ratio (SNR), diminished image contrast due to strong optical attenuation, and a lower-bound on spatial resolution in deep tissue. In addition, contrast-enhanced PAI has faced practical limitations such as insufficient cell-specific targeting due to low delivery efficiency and difficulties in developing clinically translatable agents. Identifying these limitations is essential to the continuing expansion of the field, and substantial advances in developing contrast-enhancing agents, complemented by high-performance image acquisition systems, have synergistically dealt with the challenges of conventional PAI. This review covers the past four years of research on pushing the physical and practical challenges of PAI in terms of SNR/contrast, spatial resolution, targeted delivery, and clinical application. Promising strategies for dealing with each challenge are reviewed in detail, and future research directions for next generation contrast-enhanced PAI are discussed.

DNN based reliability evaluation for telemedicine data.

Telemedicine data are measured directly by untrained patients, which may cause problems in data reliability. Many deep learning-based studies have been conducted to improve the quality of measurement data. However, they could not provide an accurate basis for judgment. Therefore, this study proposed a deep neural network filter-based reliability evaluation system that could present an accurate basis for judgment and verified its reliability by evaluating photoplethysmography signal and change in data quality according to judgment criteria through clinical trials. In the results, the deviation of 3% or more when the oxygen saturation was judged as normal according to each criterion was 0.3% and 0.82% for criteria 1 and 2, respectively, which was very low compared to the abnormal judgment (3.86%). The deviation of diastolic blood pressure (≥ 10 mmHg) according to criterion 3 was reduced by about 4% in the normal judgment compared to the abnormal. In addition, when multiple judgment conditions were satisfied, abnormal data were better discriminated than when only one criterion was satisfied. Therefore, the basis for judging abnormal data can be presented with the system proposed in this study, and the quality of telemedicine data can be improved according to the judgment result.

Deep Learning Enhances Multiparametric Dynamic Volumetric Photoacoustic Computed Tomography In Vivo (DL-PACT).

Photoacoustic computed tomography (PACT) has become a premier preclinical and clinical imaging modality. Although PACT's image quality can be dramatically improved with a large number of ultrasound (US) transducer elements and associated multiplexed data acquisition systems, the associated high system cost and/or slow temporal resolution are significant problems. Here, a deep learning-based approach is demonstrated that qualitatively and quantitively diminishes the limited-view artifacts that reduce image quality and improves the slow temporal resolution. This deep learning-enhanced multiparametric dynamic volumetric PACT approach, called DL-PACT, requires only a clustered subset of many US transducer elements on the conventional multiparametric PACT. Using DL-PACT, high-quality static structural and dynamic contrast-enhanced whole-body images as well as dynamic functional brain images of live animals and humans are successfully acquired, all in a relatively fast and cost-effective manner. It is believed that the strategy can significantly advance the use of PACT technology for preclinical and clinical applications such as neurology, cardiology, pharmacology, endocrinology, and oncology.

Normalization of photoplethysmography using deep neural networks for individual and group comparison.

Photoplethysmography (PPG) is easy to measure and provides important parameters related to heart rate and arrhythmia. However, automated PPG methods have not been developed because of their susceptibility to motion artifacts and differences in waveform characteristics among individuals. With increasing use of telemedicine, there is growing interest in application of deep neural network (DNN) technology for efficient analysis of vast amounts of PPG data. This study is about an algorithm for measuring a patient's PPG and comparing it with their own data stored previously and with the average data of several groups. Six deep neural networks were used to normalize the PPG waveform according to the heart rate by removing uninformative regions from the PPG, distinguishing between heartbeat and reflection pulses, dividing the heartbeat waveform into 10 segments and averaging the values according to each segments. PPG data were measured using telemedicine in both groups. Group 1 consisted of healthy people aged 25 to 35 years, and Group 2 consisted of patients between 60 and 75 years of age taking antihypertensive medications. The proposed algorithm could accurately determine which group the subject belonged with the newly measured PPG data (AUC = 0.998). On the other hand, errors were frequently observed in identification of individuals (AUC = 0.819).

Practical review on photoacoustic computed tomography using curved ultrasound array transducer.

Photoacoustic computed tomography (PACT) has become a promising imaging modality from laboratory to clinical research. Of many components of PACT system, the ultrasound (US) array transducer is an essential device to simultaneously receive photoacoustic (PA) signals from several directions in a parallel manner. Many research groups and companies have developed various types of US array transducers while accounting the properties of the PA waves to achieve better image quality, deeper imaging depth, faster imaging speed, and a wider field of view. In this review, we present the implementation and application of the state-of-the-art PACT systems using several types of curved US arrays: arc-shaped, ring-shaped, and hemispherical array transducers. Furthermore, we discuss the current limitations of PACT and also potential future directions for enhancing them.

In situ x-ray-induced acoustic computed tomography with a contrast agent: a proof of concept.

X-ray-induced acoustic computed tomography (XACT) has shown great potential as a hybrid imaging modality for real-time non-invasive x-ray dosimetry and low-dose three-dimensional (3D) imaging. While promising, one drawback of the XACT system is the underlying low signal-to-noise ratio (SNR), limiting its in vivo clinical use. In this Letter, we propose the first use of a conventional x-ray computed tomography contrast agent, Gastrografin, for improving the SNR of in situ XACT imaging. We obtained 3D volumetric XACT images of a mouse's stomach with orally injected Gastrografin establishing the proposal's feasibility. Thus, we believe, in the future, our proposed technique will allow in vivo imaging and expand or complement conventional x-ray modalities, such as radiotherapy and accelerators.

A Reference-Sampling Based Calibration-Free Fractional-N PLL with a PI-Linked Sampling Clock Generator.

Sampling-based PLLs have become a new research trend due to the possibility of removing the frequency divider (FDIV) from the feedback path, where the FDIV increases the contribution of in-band noise by the factor of dividing ratio square (N2). Between two possible sampling methods, sub-sampling and reference-sampling, the latter provides a relatively wide locking range, as the slower input reference signal is sampled with the faster VCO output signal. However, removal of FDIV makes the PLL not feasible to implement fractional-N operation based on varying divider ratios through random sequence generators, such as a Delta-Sigma-Modulator (DSM). To address the above design challenges, we propose a reference-sampling-based calibration-free fractional-N PLL (RSFPLL) with a phase-interpolator-linked sampling clock generator (PSCG). The proposed RSFPLL achieves fractional-N operations through phase-interpolator (PI)-based multi-phase generation instead of a typical frequency divider or digital-to-time converter (DTC). In addition, to alleviate the power burden arising from VCO-rated sampling, a flexible mask window generation method has been used that only passes a few sampling clocks near the point of interest. The prototype PLL system is designed with a 65 nm CMOS process with a chip size of 0.42 mm2. It achieves 322 fs rms jitter, -240.7 dB figure-of-merit (FoM), and -44.06 dBc fractional spurs with 8.17 mW power consumption.

Synchrotron X-ray induced acoustic imaging.

X-ray induced acoustic imaging (XAI) is an emerging biomedical imaging technique that can visualize X-ray absorption contrast at ultrasound resolution with less ionizing radiation exposure than conventional X-ray computed tomography. So far, medical linear accelerators or industrial portable X-ray tubes have been explored as X-ray excitation sources for XAI. Here, we demonstrate the first feasible synchrotron XAI (sXAI). The synchrotron generates X-rays, with a dominant energy of 4 to 30 keV, a pulse-width of 30 ps, a pulse-repetition period of 2 ns, and a bunch-repetition period of 940 ns. The X-ray induced acoustic (XA) signals are processed in the Fourier domain by matching the signal frequency with the bunch-repetition frequency. We successfully obtained two-dimensional XA images of various lead targets. This novel sXAI tool could complement conventional synchrotron applications.

Application of an Intraoperative Neuromonitoring System Using a Surface Pressure Sensor in Parotid Surgery: A Rabbit Model Study.

OBJECTIVES: Facial nerve monitoring (FNM) can be used to identify the facial nerve, to obtain information regarding its course, and to evaluate its status during parotidectomy. However, there has been disagreement regarding the efficacy of FNM in reducing the incidence of facial nerve palsy during parotid surgery. Therefore, instead of using electromyography (EMG) to identify the location and state of the facial nerve, we applied an intraoperative neuromonitoring (IONM) system using a surface pressure sensor to detect facial muscle twitching. The objective of this study was to investigate the feasibility of using the IONM system with a surface pressure sensor to detect facial muscle twitching during parotidectomy. METHODS: We evaluated the stimulus thresholds for the detection of muscle twitching in the orbicularis oris and orbicularis oculi, as well as the amplitude and latency of EMG and the surface pressure sensor in 13 facial nerves of seven rabbits, using the same stimulus intensity. RESULTS: The surface pressure sensor detected muscle twitching in the orbicularis oris and orbicularis oculi in response to a stimulation of 0.1 mA in all 13 facial nerves. The stimulus threshold did not differ between the surface pressure sensor and EMG. CONCLUSION: The application of IONM using a surface pressure sensor during parotidectomy is noninvasive, reliable, and feasible. Therefore, the IONM system with a surface pressure sensor to measure facial muscle twitching may be an alternative to EMG for verifying the status of the facial nerve.

Melatonin Exerts Anticancer Effects in Human Tongue Squamous Cell Carcinoma Cells by Promoting Autophagy.

BACKGROUND/AIM: The global prevalence of head and neck squamous cell carcinoma (HNSCC) remains high, and its prognosis poor. We investigated the anticancer effects of melatonin in human tongue squamous cell carcinoma cells (SCC-25) and its mechanisms of action. MATERIALS AND METHODS: MTT assay was used to determine cell viability. To assess the effects of melatonin on SCC-25 cell metastasis, we conducted cell formation, wound healing, transwell migration and invasion assay. Western blot analysis was performed to measure the levels of autophage marker proteins. RESULTS: We found that melatonin treatment significantly reduced the viability and colony formation ability of SCC-25 cells, impairing cell migration and invasion. Western blotting assay revealed that melatonin increased the levels of autophagy markers, such as LC-3B and Beclin-1. Consequently, melatonin induces autophage in SCC-25 cells. CONCLUSION: Melatonin may be a promising anticancer agent for the treatment of human tongue squamous cell carcinoma.

Application of Novel Intraoperative Neuromonitoring System Using an Endotracheal Tube With Pressure Sensor During Thyroid Surgery: A Porcine Model Study.

OBJECTIVES: The loss of signal during intraoperative neuromonitoring (IONM) using electromyography (EMG) in thyroidectomy is one of the biggest problems. We have developed a novel IONM system with an endotracheal tube (ETT) with an attached pressure sensor instead of EMG to detect laryngeal twitching. The aim of the present study was to investigate the feasibility and reliability of this novel IONM system using an ETT with pressure sensor during thyroidectomy in a porcine model. METHODS: We developed an ETT-attached pressure sensor that uses the piezoelectric effect to measure laryngeal muscle twitching. Stimulus thresholds, amplitude, and latency of laryngeal twitching evaluated using the pressure sensor were compared to those measured using transcartilage needle EMG. The measured amplitude changes by EMG and the pressure sensor during recurrent laryngeal nerve (RLN) traction injury were compared. RESULTS: No significant differences in stimulus threshold intensity between EMG and the pressure sensor were observed. The EMG amplitude detected at 0.3 mA, increased with increasing stimulus intensity. When the stimulus was more than 1.0 mA, the amplitude showed a plateau. In a RLN traction injury experiment, the EMG amplitude did not recover even 20 minutes after stopping RLN traction. However, the pressure sensor showed a mostly recovery. CONCLUSION: The change in amplitude due to stimulation of the pressure sensor showed a pattern similar to EMG. Pressure sensors can be feasibly and reliably used for RLN traction injury prediction, RLN identification, and preservation through the detection of laryngeal muscle twitching. Our novel IONM system that uses an ETT with an attached pressure sensor to measure the change of surface pressure can be an alternative to EMG in the future.

Versatile Single-Element Ultrasound Imaging Platform using a Water-Proofed MEMS Scanner for Animals and Humans.

Single-element transducer based ultrasound (US) imaging offers a compact and affordable solution for high-frequency preclinical and clinical imaging because of its low cost, low complexity, and high spatial resolution compared to array-based US imaging. To achieve B-mode imaging, conventional approaches adapt mechanical linear or sector scanning methods. However, due to its low scanning speed, mechanical linear scanning cannot achieve acceptable temporal resolution for real-time imaging, and the sector scanning method requires specialized low-load transducers that are small and lightweight. Here, we present a novel single-element US imaging system based on an acoustic mirror scanning method. Instead of physically moving the US transducer, the acoustic path is quickly steered by a water-proofed microelectromechanical (MEMS) scanner, achieving real-time imaging. Taking advantage of the low-cost and compact MEMS scanner, we implemented both a tabletop system for in vivo small animal imaging and a handheld system for in vivo human imaging. Notably, in combination with mechanical raster scanning, we could acquire the volumetric US images in live animals. This versatile US imaging system can be potentially used for various preclinical and clinical applications, including echocardiography, ophthalmic imaging, and ultrasound-guided catheterization.

GPU-accelerated 3D volumetric X-ray-induced acoustic computed tomography.

X-ray acoustic imaging is a hybrid biomedical imaging technique that can acoustically monitor X-ray absorption distribution in biological tissues through the X-ray induced acoustic effect. In this study, we developed a 3D volumetric X-ray-induced acoustic computed tomography (XACT) system with a portable pulsed X-ray source and an arc-shaped ultrasound array transducer. 3D volumetric XACT images are reconstructed via the back-projection algorithm, accelerated by a custom-developed graphics processing unit (GPU) software. Compared with a CPU-based software, the GPU software reconstructs an image over 40 times faster. We have successfully acquired 3D volumetric XACT images of various lead targets, and this work shows that the 3D volumetric XACT system can monitor a high-resolution X-ray dose distribution and image X-ray absorbing structures inside biological tissues.

Pulsatile flow pump based on an iterative controlled piston pump actuator as an in-vitro cardiovascular flow model.

In-vitro cardiovascular experiments provide an effective means for characterizing structural or hemodynamic features of medical devices before they are tested on animals or used in clinical practice. In-vitro experiments simulate complicated cardiovascular systems with blood pumps, vessels and valves, but without human or animal subjects. Therefore, such experiments are free from ethical issues and present large cost savings in comparison to in-vivo experiments. In this study, we aimed to design a fully programmable pulsatile flow pump that can consistently and accurately reproduce a wide range of physiological flow waveforms without costly transient flowmeter in the system. An iterative control algorithm (ICA) was used to minimize the differences between the desired and produced flow waveforms. Our results confirm that the developed pulsatile pump can replicate flow waveforms accurately, with root mean square errors (RMSEs) of 0.64 L/min and 0.52 mL for the flow rate and stroke volume, respectively.

Super Wide-Field Photoacoustic Microscopy of Animals and Humans In Vivo.

Acoustic-resolution photoacoustic micro-scopy (AR-PAM) is an emerging biomedical imaging modality that combines superior optical sensitivity and fine ultrasonic resolution in an optical quasi-diffusive regime (~1-3 mm in tissues). AR-PAM has been explored for anatomical, functional, and molecular information in biological tissues. Heretofore, AR-PAM systems have suffered from a limited field-of-view (FOV) and/or slow imaging speed, which have precluded them from routine preclinical and clinical applications. Here, we demonstrate an advanced AR-PAM system that overcomes both limitations of previous AR-PAM systems. The new AR-PAM system demonstrates a super wide-field scanning that utilized a 1-axis water-proofing microelectromechanical systems (MEMS) scanner integrated with two linear stepper motor stages. We achieved an extended FOV of 36 ×80 mm2 by mosaicking multiple volumetric images of 36 ×2.5 mm2 with a total acquisition time of 224 seconds. For one volumetric data (i.e., 36 ×2.5 mm2), the B-scan imaging speed over the short axis (i.e., 2.5 mm) was 83 Hz in humans. The 3D volumetric image was also provided by using MEMS mirror scanning along the X-axis and stepper-motor scanning along the Y-axis. The super-wide FOV mosaic image was realized by registering and merging all individual volumetric images. Finally, we obtained multi-plane whole-body in-vivo PA images of small animals, illustrating distinct multi-layered structures including microvascular networks and internal organs. Importantly, we also visualized microvascular networks in human fingers, palm, and forearm successfully. This advanced MEMS-AR-PAM system could potentially enable hitherto not possible wide preclinical and clinical applications.

Utility of CPR Machine Power and Change in Right Atrial Pressure for Estimating CPR Quality.

When a cardiac arrest occurs, it is necessary to perform cardiopulmonary resuscitation (CPR) as soon as possible. This requires maintaining the pressure depth at 5 cm at a rate of 100 cpm. For CPR machines, which are frequently used in ambulances, the return of spontaneous circulation (ROSC) is not superior to that of manual CPR, although CPR machines can maintain the compression rate and reciprocal distance of the compression plate more accurately. When the thoracic cavity is deformed due to repeated chest compressions, CPR machines must be adjusted. It is necessary to develop a method for measuring whether adequate CPR is achieved using CPR machines. CPR was performed on two pigs with a CPR machine, commencing 1 minute after the heart was stopped. Four CPR modes were used, with compression rates of 60 or 100 cpm and compression depths of 3 or 5 cm. The CPR machine was equipped with a load cell for measuring compression force, and a potentiometer for measuring compression depth. The measurement results obtained from the sensor were used to calculate the frequency components. The compression force and depth data were used to calculate the mechanical power of the CPR machine and mechanical impedance of the thoracic cavity. Changes in end-tidal carbon dioxide (ETCO2), coronary perfusion pressure (CPP), carotid blood flow (CBF), and right atrial pressure (RAP) were measured during performance of CPR; change in RAP refers to variation therein with chest compressions. Continuous CPR in both animals resulted in deformation of the chest cavity and a steady decline in impedance. The correlation between CPR power and change in RAP was 0.78, and that between compression force and CBF was 0.64. Impedance was not correlated with blood pressure or CBF. When the condition of the animal deteriorated due to cardiac arrest, the CPP decreased and ETCO2 increased. The CPR power and RAP varied according to the CPR mode rather than the condition of the animal. Measuring the CPR machine power does not require a separate procedure, such as catheter intubation, so should be suitable as an index of the quality of CPR in emergency situations.