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Photoacoustic (PA) imaging has become one of the major imaging methods because of its ability to record structural information and its high spatial resolution in biological tissues. Current commercialized PA imaging instruments are limited to varying degrees by their bulky size (i.e., the laser or scanning stage) or their use of complex optical components for light delivery. Here, we present a robust acoustic-resolution PA imaging system that consists of four adjustable optical fibers placed 90° apart around a 50 MHz high-frequency ultrasound (US) transducer. In the compact design concept of the PA probe, the relative illumination parameters (i.e., angles and fiber size) can be adjusted to fit different imaging applications in a single setting. Moreover, this design concept involves a user interface built in MATLAB. We first assessed the performance of our imaging system using in vitro phantom experiments. We further demonstrated the in vivo performance of the developed system in imaging (1) rat ear vasculature, (2) real-time cortical hemodynamic changes in the superior sagittal sinus (SSS) during left-forepaw electrical stimulation, and (3) real-time cerebral indocyanine green (ICG) dynamics in rats. Collectively, this alignment-free design concept of a compact PA probe without bulky optical lens systems is intended to satisfy the diverse needs in preclinical PA imaging studies.

Noninvasive anatomical and functional imaging has become an essential tool to evaluate tissue oxygen saturation dynamics in preclinical or clinical studies of hypoxia. Our dual-wavelength technique for photoacoustic (PA) imaging based on the differential absorbance spectrum of oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) can quantify tissue oxygen saturation using the intrinsic contrast property. PA imaging of tissue oxygen saturation can be used to monitor tumor-related hypoxia, which is a particularly relevant functional parameter of the tumor microenvironment that has a strong influence on tumor aggressiveness. The simultaneous acquisition of anatomical and functional information using dual-modality ultrasound (US) and PA imaging technology enhances the preclinical applicability of the method. Here, the developed dual-modality US/PA system was used to measure relative tissue oxygenation using the dual-wavelength technique. Tissue oxygen saturation was quantified in a pancreatic tumor mouse model. The differences in tissue oxygenation were detected by comparing pancreatic samples from normal and tumor-bearing mice at various time points after implantation. The use of an in vivo pancreatic tumor model revealed changes in hypoxia at various stages of tumor growth. The US/PA imaging data positively correlated with the results of immunohistochemical staining for hypoxia. Thus, our dual-modality US/PA imaging system can be used to reliably assess and monitor hypoxia in pancreatic tumor mouse models. These findings enable the use of a combination of US and PA imaging to acquire anatomical and functional information on tumor growth and to evaluate treatment responses in longitudinal preclinical studies.

Optical measurement is conducted by employing components such as a spectrometer or photodiode (PD) to detect light intensity. However, the size of spectrometer is large because of its complex optical path and component. Moreover, a PD usually detects the total light intensity instead of the intensity of light at a specific wavelength. Therefore, a novel inverse light-emitting diode (LED) sensor was developed to measure light intensity at specific wavelengths because of the reverse effect of LEDs. In the experiments conducted in this paper, red, green, and blue LEDs were used in combination as the inverse LED sensor and light source. Moreover, commercial equipment such as a PD, an illuminometer, a power meter, and Actiwatch 2 were simultaneously employed to detect the light intensities. The results revealed that the intensity ratio evaluated using the inverse LED sensor was proportional to that of the light source. This implies that the correlation between the incident light and measured intensities from the proposed inverse LED sensor was stronger than commercial equipment. The relationship between intensity ratio, irradiance distance, and illumination angle was also determined. The least difference between the measured and ideal evaluated intensity ratio was 2.4%. The proposed inverse LED sensor has following advantages: low cost, small size, high-wavelength selectivity, and high-intensity correlation. In a future study, light intensity can be measured using wearable devices comprising the proposed inverse LED sensor, and the presented relationship can be evaluated to investigate the effect between the light intensity and physiological mechanisms or diseases.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect that occurs secondary to anticancer treatments and has no known preventive or therapeutic strategy. Therapeutic hypothermia has been shown to be effective in protecting against central and peripheral nervous system injuries. However, the effects of therapeutic hypothermia on CIPN have rarely been explored. We induced lower back hypothermia (LBH) in an established paclitaxel-induced CIPN rat model and found that the paclitaxel-induced impairments observed in behavioral, electrophysiological, and histological impairments were inhibited by LBH when applied at an optimal setting of 24°C to the sciatic nerve and initiated 90 minutes before paclitaxel infusion. Lower back hypothermia also inhibited the paclitaxel-induced activation of astroglia and microglia in the spinal cord and macrophage infiltration into and neuronal injury in the dorsal root ganglia and sciatic nerves. Furthermore, LBH decreased the local blood flow and local tissue concentrations of paclitaxel. Finally, in NOD/SCID mice inoculated with cancer cells, the antiproliferative effect of paclitaxel was not affected by the distal application of LBH. In conclusion, our findings indicate that early exposure to regional hypothermia alleviates paclitaxel-induced peripheral neuropathy. Therapeutic hypothermia may therefore represent an economical and nonpharmaceutical preventive strategy for CIPN in patients with localized solid tumors.

Users often need to control and monitor the environmental variables of their homes, even when they are not at home. In this paper, we present a multifunctional, low-cost, and flexible system for smart home control and environmental monitoring. This system employs an embedded micro web server based on an Arduino Yún microcontroller with Internet connectivity that allows remote device control. The proposed system can be controlled via the Internet through an Android-based mobile app. To guarantee access regardless of Internet availability, the proposed system can also be controlled via standalone manual operation using a touch display. The proposed system transmits sensor data to a cloud platform and can receive commands from the server, allowing many devices to be automatically controlled. To demonstrate the feasibility and effectiveness of this system, devices such as light switches, power plugs, and various sensors, including temperature, gas, 2.5-μm particulate matter (PM2.5) and motion sensors, were integrated into a prototype of the proposed home control system. Finally, we implemented the prototype in a model home to validate the flexibility, scalability, usability and reliability of the system.

For emergency or intensive-care units (ICUs), patients with unclear consciousness or unstable hemodynamics often require aggressive monitoring by multiple monitors. Complicated pipelines or lines increase the burden on patients and inconvenience for medical personnel. Currently, many commercial devices provide related functionalities. However, most devices measure only one biological signal, which can increase the budget for users and cause difficulty in remote integration. In this study, we develop a wearable device that integrates electrocardiography (ECG), electroencephalography (EEG), and blood oxygen machines for medical applications with the hope that it can be applied in the future. We develop an integrated multiple-biosignal recording system based on a modular design. The developed system monitors and records EEG, ECG, and peripheral oxygen saturation (SpO2) signals for health purposes simultaneously in a single setting. We use a logic level converter to connect the developed EEG module (BR8), ECG module, and SpO2 module to a microcontroller (Arduino). The modular data are then smoothly encoded and decoded through consistent overhead byte stuffing (COBS). This developed system has passed simulation tests and exhibited proper functioning of all modules and subsystems. In the future, the functionalities of the proposed system can be expanded with additional modules to support various emergency or ICU applications.

We present a wearable device built on an Adafruit Circuit Playground Express (CPE) board and integrated with a photoplethysmographic (PPG) optical sensor for heart rate monitoring and multiple embedded sensors for medical applications&mdash, in particular, sleep physiological signal monitoring. Our device is portable and lightweight. Due to the microcontroller unit (MCU)-based architecture of the proposed device, it is scalable and flexible. Thus, with the addition of different plug-and-play sensors, it can be used in many applications in different fields. The innovation introduced in this study is that with additional sensors, we can determine whether there are intermediary variables that can be modified to improve our sleep monitoring algorithm. Additionally, although the proposed device has a relatively low cost, it achieves substantially improved performance compared to the commercially available Philips ActiWatch2 wearable device, which has been approved by the Food and Drug Administration (FDA). To assess the reliability of our device, we compared physiological sleep signals recorded simultaneously from volunteers using both our device and ActiWatch2. Motion and light detection data from our device were shown to be correlated to data simultaneously collected using the ActiWatch2, with correlation coefficients of 0.78 and 0.89, respectively. For 7 days of continuous data collection, there was only one instance of a false positive, in which our device detected a sleep interval, while the ActiWatch2 did not. The most important aspect of our research is the use of an open architecture. At the hardware level, general purpose input/output (GPIO), serial peripheral interface (SPI), integrated circuit (I2C), and universal asynchronous receiver-transmitter (UART) standards were used. At the software level, an object-oriented programming methodology was used to develop the system. Because the use of plug-and-play sensors is associated with the risk of adverse outcomes, such as system instability, this study heavily relied on object-oriented programming. Object-oriented programming improves system stability when hardware components are replaced or upgraded, allowing us to change the original system components at a low cost. Therefore, our device is easily scalable and has low commercialization costs. The proposed wearable device can facilitate the long-term tracking of physiological signals in sleep monitoring and related research. The open architecture of our device facilitates collaboration and allows other researchers to adapt our device for use in their own research, which is the main characteristic and contribution of this study.

This article provides a guide to design and build a handheld, real-time photoacoustic (PA) imaging system from simulation to realization for animal neurological disease models. A pulsed laser and array-based ultrasound (US) platform were utilized to develop the system for evaluating vascular functions in rats with focal ischemia or subcutaneous tumors. To optimize the laser light delivery, finite element (FE)-based simulation models were developed to provide information regarding light propagation and PA wave generation in soft tissues. Besides, simulations were also conducted to evaluate the ideal imaging resolution of the US system. As a result, a PA C-scan image of a designed phantom in 1% Lipofundin was reconstructed with depth information. Performance of the handheld PA system was tested in an animal ischemia model, which revealed that cerebral blood volume (CBV) changes at the cortical surface could be monitored immediately after ischemia induction. Another experiment on subcutaneous tumors showed the anomalous distribution of the total hemoglobin concentration (HbT) and oxygen saturation (SO2), while 3D and maximum intensity projection (MIP) PA images of the subcutaneous tumors are also presented in this article. Overall, this system shows promise for monitoring disease progression in vascular functional impairments.

Photoacoustic (PA) imaging is an attractive technology for imaging biological tissues because it can capture both functional and structural information with satisfactory spatial resolution. Current commercially available PA imaging systems are limited by their bulky size or inflexible user interface. We present a new handheld real-time ultrasound/photoacoustic imaging system (HARP) consisting of a detachable, high-numerical-aperture (NA) fiber bundle-based illumination system integrated with an array-based ultrasound (US) transducer and a data acquisition platform. In this system, different PA probes can be used for different imaging applications by switching the transducers and the corresponding jackets to combine the fiber pads and transducer into a single probe. The intuitive user interface is a completely programmable MATLAB-based platform. In vitro phantom experiments were conducted to test the imaging performance of the developed PA system. Furthermore, we demonstrated (1) in vivo brain vasculature imaging, (2) in vivo imaging of real-time stimulus-evoked cortical hemodynamic changes during forepaw electrical stimulation, and (3) in vivo imaging of real-time cerebral pharmacokinetics in rats using the developed PA system. The overall purpose of this design concept for a customizable US/PA imaging system is to help overcome the diverse challenges faced by medical researchers performing both preclinical and clinical PA studies.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of several chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and no effective treatment has been established so far. The mechanisms of CIPN damage are unclear, but are directly dose-related. We had earlier demonstrated, in rats, the influence of hypothermia in reducing nerve blood flow. Here, we hypothesize that continuous flow limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves. In this study, prior to assessing the effect of hypothermia in preventing CIPN in cancer subjects undergoing paclitaxel chemotherapy, we assess the safety and tolerable temperatures for limb hypothermia in healthy human subjects.In 15 healthy human subjects, hypothermia was administered as continuous flow cooling, unilaterally, via a thermoregulator setup covering the digits up to the elbow/knee, along with continuous skin temperature monitoring. Thermoregulator coolant temperatures between 25 °C and 20 °C were tested for tolerability, based on a carefully designed temperature regulation protocol, and maintained for three hours mimicking the duration of chemotherapy. Tolerability was evaluated using various safety and tolerability scores to monitor the subjects.At the end of the cooling session the healthy subjects presented without significant adverse effects, the main being brief mild skin erythema and transient numbness. Coolant temperatures as low as 22 °C were well tolerated continuously over three hours.Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use 22 °C thermoregulator temperature to investigate hypothermia in preventing CIPN in breast cancer patients receiving adjuvant weekly paclitaxel. This pilot study may contribute to alleviating chemotherapy dose limitation due to CIPN and increase the likelihood of success of chemotherapy.

To investigate the potential therapeutic effects of peripheral sensory stimulation during the hyperacute phase of stroke, the present study utilized electrophysiology and photoacoustic imaging techniques to evaluate neural and vascular responses of the rat cortex following ischemic insult. We employed a rat model of photothrombotic ischemia (PTI), which targeted the forelimb region of the primary somatosensory cortex (S1FL), due to its high reproducibility in creating localized ischemic injury. We also established a hybrid, dual-modality system, including six-channel electrocorticography (ECoG) and functional photoacoustic microscopy (fPAM), termed ECoG–fPAM, to image brain functional responses to peripheral sensory stimulation during the hyperacute phase of PTI. Our results showed that the evoked cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) recovered to 84 ± 7.4% and 79 ± 6.2% of the baseline, respectively, when stimulation was delivered within 2.5 h following PTI induction. Moreover, neural activity significantly recovered, with 77 ± 8.6%, 76 ± 5.3% and 89 ± 8.2% recovery for the resting-state inter-hemispheric coherence, alpha-to-delta ratio (ADR) and somatosensory evoked potential (SSEP), respectively. Additionally, we integrated the CBV or SO2 with ADR values as a recovery indicator (RI) to assess functional recovery after PTI. The RI indicated that 80 ± 4.2% of neurovascular function was preserved when stimulation was delivered within 2.5 h. Additionally, stimulation treatment within this optimal time window resulted in a minimal infarct volume in the ischemic hemisphere (4.6 ± 2.1%). In contrast, the infarct volume comprised 13.7 ± 1.7% of the ischemic hemisphere when no stimulation treatment was applied.

The advance of thrombolytic therapy has been hampered by the lack of optimization of the therapy during the hyperacute phase of focal ischemia. Here, we investigate neurovascular dynamics using a custom-designed hybrid electrocorticography (ECoG)-functional photoacoustic microscopy (fPAM) imaging system during the hyperacute phase (first 6 h) of photothrombotic ischemia (PTI) in male Wistar rats following recombinant tissue plasminogen activator (rtPA)-mediated thrombolysis. We reported, for the first time, the changes in neural activity and cerebral hemodynamic responses following rtPA infusion at different time points post PTI. Interestingly, very early administration of rtPA (< 1 h post PTI) resulted in only partial recovery of neurovascular dynamics (specifically , neural activity recovered to 71 ± 3.5% of baseline and hemodynamics to only 52 ± 2.6% of baseline) and late administration of rtPA (> 4 h post PTI) resulted in the deterioration of neurovascular function. A therapeutic window between 1 and 3 h post PTI was found to improve recovery of neurovascular function (i.e. significant restoration of neural activity to 93 ± 4.2% of baseline and hemodynamics to 81 ± 2.1% of baseline, respectively). The novel combination of fPAM and ECoG enables direct mapping of neurovascular dynamics and serves as a platform to evaluate potential interventions for stroke.

Current treatments for ischemic stroke have focused on the administration of a tissue plasminogen activator, although the associated side effects and subsequent reperfusion injury remain challenging. Peripheral electrical stimulation has shed light on therapeutic interventions for ischemia by increasing cerebral blood flow (CBF) to the target region through collateral circulation, although the mechanism remains elusive. Here, a focal photothrombotic ischemic (PTI) stroke was induced in the right hemispheric primary somatosensory forelimb cortex (S1FL) of rat brains, and the therapeutic effects of forelimb and hindlimb stimulation were characterized at the contralesional S1FL. We observed that PTI stroke rats that received forelimb stimulation exhibited significantly restored CBF of the ischemic penumbra ([Formula: see text] for the S1FL and [Formula: see text] for the primary somatosensory hindlimb cortex, respectively), electrocorticography (ECoG) delta band coherence of the intercortical S1FL ([Formula: see text]) at the 75th min poststroke and an ischemic infarct ([Formula: see text]) via collateral circulation recruitment. Importantly, anterior cerebral artery/middle cerebral artery (ACA-MCA) interarterial anastomotic regulation occurred upon forelimb stimulation and played roles in the recovery of neurovascular functions. These results indicated that receptive field-specific stimulation further restores CBF, neuronal activities, and tissue viability through the enhancement of ACA-MCA interarterial anastomosis-mediated collateral circulation and provides a feasible therapeutic intervention for stroke recovery.

Stroke is the second leading cause of death worldwide. Rapid and precise diagnosis is essential to expedite clinical decision and improve functional outcomes in stroke patients; therefore, real-time imaging plays an important role to provide crucial information for post-stroke recovery analysis. In this study, based on the multi-wavelength laser and 18.5 MHz array-based ultrasound platform, a real-time handheld photoacoustic (PA) system was developed to evaluate cerebrovascular functions pre- and post-stroke in rats. Using this system, hemodynamic information such as cerebral blood volume (CBV) can be acquired for assessment. One rat stroke model (i.e., photothrombotic ischemia (PTI)) was employed for evaluating the effect of local ischemia. For achieving better intrinsic PA contrast, Vantage and COMSOL simulations were applied to optimize the light delivery (e.g., interval between two arms) from customized fiber bundle, while phantom experiment was conducted to evaluate the imaging performance of this system. Results of phantom experiment showed that hairs (~150 μm diameter) and pencil lead (500 μm diameter) can be imaged clearly. On the other hand, results of in vivo experiments also demonstrated that stroke symptoms can be observed in PTI model poststroke. In the near future, with the help of PA specific contrast agent, the system would be able to achieve blood-brain barrier leakage imaging post-stroke. Overall, the real-time handheld PA system holds great potential in disease models involving impairments in cerebrovascular functions.

The development of many telemedicine systems focus on the utility of communication techniques. However, the comfort of long-term Electrocardiogram (ECG) monitoring in daily life is necessary and is also an important unresolved issue. A wearable mobile electrocardiogram monitoring system (WMEMS) is proposed to monitor ECG in this study. It mainly consists of a wearable ECG acquisition device, a mobile phone platform, and a healthcare server. A novel dry foam electrode is also designed and embedded in the wearable ECG acquisition device. The novel dry foam electrode can provide good conductivity to acquire ECG effectively without conduction gels. By using the adapting property of the dry foam electrode, the skin-electrode impedance and the motion artifacts under movement can also be reduced by adapting to irregular skin surface. Moreover, by using the mobile phone as the system platform, the proposed WMEMS can monitor the user's ECG state continuously and anywhere in the globe if they are under the coverage of Global System for Mobile communications (GSM) cellular network. Finally, WMEMS is tested for detecting atrial fibrillation in the hospital. It really provides a good performance and is a good prototype for ECG telemedicine applications.

Understanding brain function using electroencephalography (EEG) is an important issue for cerebral nervous system diseases, especially for epilepsy and Alzheimer's disease. Many EEG measurement systems are used reliably to study these diseases, but their bulky size and the use of wet sensors make them uncomfortable and inconvenient for users. To overcome the limitations of conventional EEG measurement systems, a wireless and wearable multichannel EEG measurement system is proposed in this paper. This system includes a wireless data acquisition device, dry spring-loaded sensors, and a size-adjustable soft cap. We compared the performance of the proposed system using dry versus conventional wet sensors. A significant positive correlation between readings from wet and dry sensors was achieved, thus demonstrating the performance of the system. Moreover, four different features of EEG signals (i.e., normal, eye-blinking, closed-eyes, and teeth-clenching signals) were measured by 16 dry sensors to ensure that they could be detected in real-life cognitive neuroscience applications. Thus, we have shown that it is possible to reliably measure EEG signals using the proposed system. This paper presents novel insights into the field of cognitive neuroscience, showing the possibility of studying brain function under real-life conditions.

Several neural decoding algorithms have successfully converted brain signals into commands to control a computer cursor and prosthetic devices. A majority of decoding methods, such as population vector algorithms (PVA), optimal linear estimators (OLE), and neural networks (NN), are effective in predicting movement kinematics, including movement direction, speed and trajectory but usually require a large number of neurons to achieve desirable performance. This study proposed a novel decoding algorithm even with signals obtained from a smaller numbers of neurons. We adopted sliced inverse regression (SIR) to predict forelimb movement from single-unit activities recorded in the rat primary motor (M1) cortex in a water-reward lever-pressing task. SIR performed weighted principal component analysis (PCA) to achieve effective dimension reduction for nonlinear regression. To demonstrate the decoding performance, SIR was compared to PVA, OLE, and NN. Furthermore, PCA and sequential feature selection (SFS) which are popular feature selection techniques were implemented for comparison of feature selection effectiveness. Among SIR, PVA, OLE, PCA, SFS, and NN decoding methods, the trajectories predicted by SIR (with a root mean square error, RMSE, of 8.47 ± 1.32 mm) was closer to the actual trajectories compared with those predicted by PVA (30.41 ± 11.73 mm), OLE (20.17 ± 6.43 mm), PCA (19.13 ± 0.75 mm), SFS (22.75 ± 2.01 mm), and NN (16.75 ± 2.02 mm). The superiority of SIR was most obvious when the sample size of neurons was small. We concluded that SIR sorted the input data to obtain the effective transform matrices for movement prediction, making it a robust decoding method for conditions with sparse neuronal information.

Electrooculography (EOG) signals can be used to control human-computer interface (HCI) systems, if properly classified. The ability to measure and process these signals may help HCI users to overcome many of the physical limitations and inconveniences in daily life. However, there are currently no effective multidirectional classification methods for monitoring eye movements. Here, we describe a classification method used in a wireless EOG-based HCI device for detecting eye movements in eight directions. This device includes wireless EOG signal acquisition components, wet electrodes and an EOG signal classification algorithm. The EOG classification algorithm is based on extracting features from the electrical signals corresponding to eight directions of eye movement (up, down, left, right, up-left, down-left, up-right, and down-right) and blinking. The recognition and processing of these eight different features were achieved in real-life conditions, demonstrating that this device can reliably measure the features of EOG signals. This system and its classification procedure provide an effective method for identifying eye movements. Additionally, it may be applied to study eye functions in real-life conditions in the near future.

This study aimed to develop a low-cost multichannel neural recording system and multi-electrode array (MEA)chip for a number of research laboratories. Because these elaborate systems may be cost-prohibitive for manylaboratories, the simple fabrication of the MEA chip and the construction of the low-cost recording systemwith cellular image acquisition is presented in this study. The MEA chip is a polyimide-based microelectrodearray with 60 electrodes (5 m thick, 30 m in radius and with 200 m spacing) and is based on the semi-conductor process and advanced microelectro-mechanical system (MEMS) technology. The three-dimensional(3D) structure of the electrodes is fabricated by electroplating, which produces rough textures that increasedthe effective surface area. The

Brain ischemia is a neurological deficit caused by a reduction in the blood supply to tissue, and one of the leading causes of disability in the world. Currently, the most well-known therapeutic agent for ischemia recovery is recombinant tissue plasminogen activator (rtPA), but it is viable for only a small portion (approximately 3.6%) of ischemic patients and may cause side effects such as tissue damage. Thus, introducing a new therapeutic concept for ischemia, we proposed an integrated intervention combining global and focal stimulations in this article. To investigate the potential therapeutic effect of cathodal-transcranial direct current stimulation (C-tDCS) with peripheral sensory stimulation (PSS) during the hyperacute phase of stroke, the present study evaluated neurovascular and neuroprotective responses of the rat cortex following ischemic insult. A hybrid, dual-modality system, including electrocorticography (ECoG) and functional photoacoustic microscopy (fPAM), termed ECoG-fPAM, was used to image cortical functional responses pre- and post-ischemia. Using ECoG-fPAM, results showed that cerebral blood volume (CBV) was able to be recovered during the intervention. In addition, neural activity including somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were restored and greater than the baseline value when the integrated intervention was administered. The results of NeuN/ED-1 immunohistochemical staining and TTC staining also supported the neuroprotective effect of this intervention, protecting more neurons and decreasing the infarct size. Overall, the results acquired from the ECoG-fPAM system demonstrated that C-tDCS + PSS administered immediately following ischemia induction can significantly promote neuroprotection via inhibition of ischemia expansion and reversed cortical neurovascular functions, suggesting effective recovery.

Ischemic stroke is one of the leading causes of death and disability in the world. Thrombolytic therapy using recombinant tissue plasminogen activator (rtPA), the only FDA-approved drug for acute ischemia, is limited by a narrow therapeutic time window and risk of hemorrhage. There is a serious need for a neuroprotective therapy which is clinically viable. We earlier demonstrated that peripheral sensory stimulation (PSS) is a potential therapeutic intervention for hyperacute ischemia resulting in recovery of neurovascular functions when administered immediately following ischemia onset in a rat model. Here, we investigated the potential neuroprotective effect of PSS during the hyperacute phase of stroke in a rat photothrombotic ischemia (PTI) model. We employed electrocorticography (ECoG) to image cortical neural activity responses pre-and post-ischemia. Results showed that the neural activity including somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were restored following administration of PSS. Further, immunohistochemistry and TTC staining also indicated the neuroprotective effect of PSS intervention, protecting more neurons and reduced infarct. Overall, the study demonstrated that PSS administered immediately following ischemia induction in a rat PTI model can significantly promote neuroprotection via inhibition of peri-infarct expansion and enhanced cortical neural activity functions, suggesting effective recovery. Future work utilizing multimodal imaging to probe changes in neurovascular functions, will explore application of PSS as an adjuvant intervention for improving rtPA thrombolysis therapy.

This study aims to achieve high directionality and large extraction of light emission from polymer light-emitting diodes via optimizing photonic crystals (PCs). The optimization is achieved through the optical modeling using a 3D finite-difference time-domain (FDTD) method and the intelligent numerical optimization technique, genetic algorithm (GA). In results, the PC period, depth and filling factor can be found. The FDTD method has been proven very effective for modeling complex multilayer PLED devices in which the electron-transporting layer is only a few tens of nanometers away from a metallic layer. On the other hand, GA is a powerful tool to cope with a complicated optimization problem with multiple variables to optimize. The optimized PCs are later fabricated by focused ion beams (FIB) for the PLED. With desired PCs, an increase of the extraction efficiency in excess of 46% is achieved experimentally and the 3D FDTD calculation explains this result faithfully.

This study presents design, analysis and experiment of a miniaturized rotary generator in size of 10 times 10 times 2 mm3 and its compact energy harvest circuit chip. The designed generator consists of patterned planar copper coils and a multipolar hard magnet ring made of NdFeB. To perform modeling, a harmonic-like magnetic field model along the circumferential path of each magnetic pole is assumed with the assistance from measured peak magnetic flux densities. This is followed by the application of Faraday's law to predict generated electromotive forces (EMFs) in terms of the relative rotational speed between the magnet ring and coils. The genetic algorithm (GA) is next applied to optimize the critical dimensions of the miniaturized generator. The theoretical model of this power microgenerator is evaluated and compared with experimental results, and it is found that the analytical simulation shows a good agreement with the experimental results. The optimized generator offers 4.5 V and 7.23 mW in root mean square (rms) at 10 000 r/min. With microgenerator successfully fabricated, a novel energy harvest circuit employing Dickson charge pump is designed and fabricated via the 0.35-mum process offered by National Chip Implementation Center (CIC) of Taiwan. This charge pump circuit owns the merit of almost-zero thresholds of employed metal-oxide-semiconductor (MOS) transistors, enabling the conversion of low-power alternating current (ac) signals by the microgenerator to direct current (dc) ones.

This study proposes a dual-stage lens actuator used for optical disc drives, which includes a piezoceramic parallel-beam as a fine actuator and a voice coil motor (VCM) as the coarse one. The positioning algorithm of the objective lens is comprised of robust H ∞ fine/coarse controllers designed based on μ synthesis and a repetitive controller to further reduce effects of disturbance. To these ends, the dynamic model of the piezoceramic parallel-beam and VCM are first established and then identified by experiments. Based on these identified models, the system dynamics is represented as a standard form, which is ready for μ synthesis to design robust controller. Performing optimization, the desired robust H ∞ controller used for conducting fine/coarse positioning is obtained. In addition to H ∞ control design, the repetitive controller is further forged to reduce the effect of disturbance based on the periodic nature of the disturbance. Simulations and experiments are conducted to validate the performance expected by previously designed controllers. The experiment shows that the fine piezo-actuator bears the responsibilities of compensating in-precision positioning of the coarse VCM actuator and external small level periodic disturbance.

This study aims to perform the micro-/nano-machining with an atomic force microscopy (AFM) tip in a scanning electron microscope (SEM) via run-to-run (R2R) controller and digital image feedbacks. The R2R is assisted by the technique of exponentially weighted moving average (EWMA). This ''EWMA feedback'' controller is a popular R2R control scheme, which primarily uses data from past process runs to adjust settings for the next run. On the other hand, the digital images are obtained by using the wavelet transform and binarization in order to recognize machining results, and then return feedback of the digital image information to the controller; finally obtain the next input data for the actuating controller to achieve the targeted machining precision. The experimental results for preliminary machining in micro-level indicate that the EWMA controller based on image feedbacks performs with satisfactory results at reducing the process variation, particularly at the first few production runs, thereby making it possible to further reduce the bias and bring the process output closer to its target as soon as the process begins to operate. It is seen that the proposed EWMA controller with digital image feedbacks is easy to implement and provides a good approximation to the optimal variable discount factor, which can reduce the error of the machining process from initial 40% without control to 0.7% with the proposed R2R. More importantly, such a reduction can be achieved at no loss of long-term stability. With sure precision of AFM, the aforementioned resulted micro-machining precision can easily be extended to nano-levels. Therefore, this study demonstrates a successful micro-/nano-machining operation in the environment of a SEM, by employing the designed R2R controller with digital image feedbacks.

This study develops a highly-efficient light-guide plate for edge lighting backlight module that has no optical films. The light guide plate is designed to control the angle of the incident rays to the top surface from light source, to get the highest uniformity of intensity for thin edge lighting backlight system applications. The micro-prisms of pyramidal shape on the top surface can highly-efficient collimate with the light rays. Another micro-prism of v-cut shape on the bottom surface can reflect the incident light into the front direction and mixing the rays in the lightguide plate with the high uniformity. A novel design concept of the v-cut is the regular density varies of the cut in the LGP. The modeling simulation program, employing a Monte Carlo method based on TracePro software, has optimized the shape of the pyramidal micro-prisms on the top surface and the density distribution condition of the v-cut micro-prisms on the bottom surface, also the multiple scattering characteristics. The two types of the micro-prisms at the top and bottom surface can be highly recommended for the uniformity of the brightness via the optimal design process. Future work is warranted on improving the optical efficiency by using light-emitting diodes as a light source. The backlight module will allow us to increase the optical efficiency and to lower the total cost in portable LCD applications. The study confirms that a uniformity of brightness can be achieved without using any optical films, resulting in a high uniformity of 84%.

The paper proposes a novel time based brightness compensation circuit for LED back light modules. The brightness of LED decays while running under constant current driven condition. We have designed a suitable controller to compensate the driving currents to maintain the brightness. The compensation data were calculated from the relative luminous efficiency – time curve provided by the LED manufacturer and were stored in the microprocessor. -The embedded system used the running time of the LED in the back light module as an independent variable for tuning the driving current. The experiment results showed that the brightness of different operating times’ LED arrays can be held almost the same as the new ones.

Using TracePro® Monte-Carlo ray-tracing simulations, this paper investigates the improved light extraction efficiency (LEE) obtained by patterning the surface and/or substrate of GaN LEDs with unique three-dimensional micro-cavity patterns. The simulations commence by considering the case of a sapphire-based GaN LED. The effects on the LEE of the micro-cavity dimensions, the absorption coefficient of the active layer, the point source location, and the chip dimensions are systematically examined. Subsequently, the LEE performance of the sapphire-based GaN LED is compared with that of a thin-GaN LED for various surface texturing strategies. In general, the results show that patterning either the surface or the substrate of the LED structure provides an effective improvement in the LEE of both the sapphire-based GaN LED and the thin- GaN LED. For both LED structures, the maximum LEE enhancement is obtained by patterning both the upper surface of the LED and the substrate surface. However, the simulation results indicate that the improvement obtained in the LEE is the result primarily of pattering the upper surface of the LED.

A novel dual-cone-shaped side-emitting lens cap for High Brightness Light Emitting Diodes (HB-LEDs) is proposed for improving brightness and high uniformity of the direct LED backlight Units (BLUs) for large-sized LCD-TVs. Combining the designed lens cap with red, green and blue (RGB) chips on a Metal Core Printed Circuit Board (MCPCB), the LED module with the proposed cap is able to provide a compact white light source with unique features such as instant color variability and lower power usage, etc. The dual-cone-shaped of the proposed lens cap is designed to emit most of the light rays to the sides, only a small portion of light upward along the optical axis of the lens, providing a uniform luminance distribution and the high brightness on the backlight. In addition, a small reflective surface in semi-circular shape is designed and placed upon the proposed LED module about 10mm, the surfaces of which are attached with reflective films to increase the level of light mixing in the larger, global reflector optical box. With the structure of the LED module well designed, the LED backlight Module would be designed for the large-sized LCDTV using the fewer number of LEDs to lead to lower power consumption. The results indeed identify the attributes of the BLU, which make it possible to achieve excellent backlight performance using a direct illumination approach from the light source of “Dual-Cone-Shaped Side- Emitting Lens Cap of LEDs.”

Functional Electrical Stimulation (FES) has been explored in order to restore the capabilities of the nervous system in patients that suffer from paralysis. This area of research and of clinical practice greatly benefits from any technological improvement yielding miniaturization. In this regard, we recently proposed and demonstrated an innovative electrical stimulation method based on implanted microstimulators that operate as rectifiers of bursts of innocu-ous high frequency current supplied by skin electrodes, gener-ating low frequency currents that are capable of stimulating excitable tissues. We envision flexible ultrathin implants (di-ameters < 300 μm) containing ASICs that have advanced ca-pabilities, such as addressability and current control. As min-iaturization is the main aim of this method, the use of bulky DC-blocking capacitors (e.g. 10 μF) to accomplish zero net charge injection and avoid electrochemical tissue and electrode damage is highly inconvenient. As an alternative, here we present an active charge-balance method based on the use of a digital charge quantifier, whose operation is inspired in the functioning of the tipping bucket rain gauge. The system moni-tors the charge injection, matching the charge injected in the cathodal phase, with the charge injected in the anodal phase, generating a biphasic current waveform that adapts itself to possible current source mismatches. We have implemented a prototype built with discrete components which uses a capaci-tor of only 100 pF for the charge counter. AI’s research is supported by a Ramón y Cajal fellowship/nfrom the Spanish government and a Marie Curie grant/n(IRG 256376) from the European Commission. LBF’s research/nis supported by a scholarship from the UPF.

The narrow 3h therapeutic time window for recombinant tissue-type plasminogen activator (rt-PA) thrombolysis is a challenging limitation in acute ischemic stroke treatment. Intense research focus is being laid on developing novel therapeutic interventions for extending the thrombolysis time window using animal stroke models. However, these animal models are anatomically and physiologically different. Here, we assess the effective time window of rt-PA thrombolysis in the photothrombotic ischemic (PTI) stroke model using the electrocorticography (ECoG) system and histology study. Our results indicate that rt-PA provides effective thrombolysis when administered in the initial 1 to 3 hours post-ischemia, beyond which it does not facilitate recovery. This complements the FDA-approved rt-PA time window in humans. However, it is interesting to note that the trend of neural activity did not strictly correspond to infarct volume changes, indicating the importance of multimodal imaging for holistic assessment of therapeutic efficacy. Therefore, in the future, this ECoG setup will be integrated with the functional photoacoustic microscopy (fPAM) system to jointly evaluate neural activity and cerebral hemodynamics to probe neurovascular function changes effective with thrombolysis.

Study of cerebral cortical functions affected by ischemic stroke explicates post-stroke brain plasticity. We report an innovative combination of electrocorticography (ECoG) recordings and functional photoacoustic microscopy (fPAM) imaging to investigate cortical functions after photothrombotic ischemia (PTI) in rat brain, with electrical forepaw stimulation applied as treatment. The cortical functions were assessed over a chosen ischemic region via somatosensoryevoked potential (SSEP), resting-state ECoG signals and evoked hemodynamic response. Two-phased experimental protocols based on sensory stimulation treatment are proposed and performed in this study. In the phase 1, the treatment is applied to the left forepaw, contralateral to the ischemic hemisphere, with 2 mA pulses initiated 0, 1, or 2 hours postischemia to determine optimal onset timing. After determining the optimal time window, in the phase 2, the treatment was delivered unilaterally or bilaterally using 2 or 4 mA pulses for validating if bilateral peripheral electrical stimulation with different current intensities could improve cerebral perfusion and restore cortical neurovascular response. Overall, the results demonstrated that our treatment administered bilaterally at 2 mA within 2 hours of ischemia can promote neuroprotection significantly via reversed cortical functions, suggesting effective recovery.

Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation ([Formula: see text]) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the [Formula: see text] ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.

Voltage-sensitive dye imaging (VSDi) enables visualization of information processing in different areas of the brain with reasonable spatial and temporal resolution. VSDi employs different chemical compounds to transduce neural activity directly into the changes in intrinsic optical signal. Physically, voltage-sensitive dyes (VSDs) are chemical probes that reside in the neural membrane and change their fluorescence or absorbance in response to membrane potential changes. Based on these features, VSDs can be divided into two groups-absorbance and fluorescence. The spatial and temporal resolution of the VSDi is limited mainly by the technical characteristics of the optical imaging setup (e.g., computer and light-sensitive device-charge-coupled device (CCD) camera or photodiode array). In this article, we briefly review the development of the VSD, technique of VSDi and applications in functional brain imaging.

Restoring perfusion to the penumbra during the hyperacute phase of ischemic stroke is a key goal of neuroprotection. Thrombolysis is currently the only approved treatment for ischemic stroke. However, its use is limited by the narrow therapeutic window and side effect of bleeding. Therefore, other interventions are desired that could potentially increase the perfusion of the penumbra. Here, we hypothesized that bilateral peripheral electrical stimulation will improve cerebral perfusion and restore cortical neurovascular response. We assess the outcomes of bilateral forepaw electrical stimulation at intensities of 2 and 4 mA, administered either unilaterally or bilaterally. We developed a combined electrocorticogram (ECoG)-functional photoacoustic microscopy (fPAM) system to evaluate the relative changes in cerebral hemodynamic function and electrophysiologic response to acute, focal stroke. The fPAM system is used for cerebral blood volume (CBV) and hemoglobin oxygen saturation ([Formula: see text]) and the ECoG for neural activity, namely somatosensory-evoked potential (SSEP), interhemispheric coherence, and alpha-delta ratio (ADR) in response to forepaw stimulation. Our results confirmed the neuroprotective effect of bilateral forepaw stimulation at 2 mA as indicated by the 82% recovery of ADR and 95% improvement in perfusion into the region of penumbra. This experimental model can be used to study other potential interventions such as therapeutic hypertension and hypercarbia.

Recently, the functional photoacoustic microscopy (fPAM) system has been proven to be a reliable imaging technique for measuring the total hemoglobin concentration (HbT), cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) in single cerebral blood vessels of rats. In this study, we report for the first time the combination of electrocorticography (ECoG) recordings and fPAM (ECoG-fPAM) to investigate functional hemodynamic changes and neuro-vascular coupling in single cortical arterioles of rats with electrical forepaw stimulation after photothrombotic stroke. Because of the optical focusing nature of our fPAM system, photo-induced ischemic stroke targeting on single cortical arterioles can be easily conducted with simple adaptation. Functional cerebral HbT, CBV and SO2 changes associated with the induced stroke in selected arterioles from the anterior cerebral artery system were imaged with a 36 × 65-µm spatial resolution. The ECoG-fPAM system complements existing imaging techniques and has the potential to offer a favorable tool for explicitly studying cerebral hemodynamics and neuro-vascular coupling in small animal models of photo-induced ischemic stroke.

The traditional brain-computer interface (BCI) system measures the electroencephalography (EEG) signals by the wet sensors with the conductive gel and skin preparation processes. To overcome the limitations of traditional BCI system with conventional wet sensors, a wireless and wearable multi-channel EEG-based BCI system is proposed in this study, including the wireless EEG data acquisition device, dry spring-loaded sensors, a size-adjustable soft cap. The dry spring-loaded sensors are made of metal conductors, which can measure the EEG signals without skin preparation and conductive gel. In addition, the proposed system provides a size-adjustable soft cap that can be used to fit user's head properly. Indeed, the results are shown that the proposed system can properly and effectively measure the EEG signals with the developed cap and sensors, even under movement. In words, the developed wireless and wearable BCI system is able to be used in cognitive neuroscience applications.

Monitoring the neurophysiological activities of human brain dynamics in an operational environment poses a severe measurement challenge using current laboratory-oriented biosensor technology. The goal of this research is to design, develop and test the wearable and wireless dry-electrode EEG human-computer interface (HCI) that can allow assessment of brain activities of participants actively performing ordinary tasks in natural body positions and situations within a real operational environment. Its implications in HCI were demonstrated through a sample application: vigilance-state prediction of participants performing a realistic sustained-attention driving task. Besides, this study further developed an online signal processing for extracting EEG features and assessing cognitive performance. We demonstrated the feasibility of using dry EEG sensors and miniaturized supporting hardware/software to continuously collect EEG data recorded from hairy sites (i.e., occipital region) in a realistic VR-based dynamic driving simulator.

e21696Background: Severe peripheral neuropathy (PN) can occur in up to 20% of patients treated with paclitaxel, with no effective prevention or treatment. We hypothesize that continuous-flow limb h...

Optical imaging of changes in total hemoglobin concentration ( HbT), cerebral blood volume ( CBV), and hemoglobin oxygen saturation ( SO 2) provides a means to investigate brain hemodynamic regulation. However, high-resolution transcranial imaging remains challenging. In this study, we applied a novel functional photoacoustic microscopy technique to probe the responses of single cortical vessels to left forepaw electrical stimulation in mice with intact skulls. Functional changes in HbT, CBV, and SO 2 in the superior sagittal sinus and different-sized arterioles from the anterior cerebral artery system were bilaterally imaged with unambiguous 36 × 65- μm2 spatial resolution. In addition, an early decrease of SO 2 in single blood vessels during activation (i.e., ‘the initial dip’) was observed. Our results indicate that the initial dip occurred specifically in small arterioles of activated regions but not in large veins. This technique complements other existing imaging approaches for the investigation of the hemodynamic responses in single cerebral blood vessels.

Most researchers acquired EEG by using standard measurement system like NeuroScan system, which includes AgCl electrode cap, SynAmps Amplifier and Scan software to provide good reliability for the acquisition of EEG data. However, it is still not convenient for Brain Computer Interface (BCI) application in daily life because of needing conduction gels to contact skins and being wired, expensive and heavy. Moreover, the conduction gel will trend to be drying, so it does not suitable for long-term monitoring. In this study, we developed a mobile and wireless EEG system. The system consists of frond-end 16-channel dry electrode cap, a miniature low-power wireless portable circuitry, and a back-end program receiving events and digital EEG data simultaneously. We demonstrate the recorded EEG data have high correlations between from our system and from NeuroScan system.

A Wearable Mobile Electrocardiogram Monitoring System (WMEMS), which mainly consists of a wearable Electrocardiogram (ECG) acquisition device, a mobile phone with global positioning system, and a healthcare server, was developed in this study. Most of telemedicine systems for long-term ECG monitoring focus on the application of communication techniques. However, how to monitor long-term ECG state more comfortably in daily life is also an important issue. In this study, a novel dry foam electrode was designed and applied for the wearable ECG acquisition device in our WMEMS. These novel dry foam electrodes without conduction gels can provide good conductivity to acquire ECG signal effectively, and can adapt to irregular skin surface to maintain low skin-electrode impedance and reduce motion artifacts under movement. Therefore, the wearable ECG acquisition device is suitable for long-term ECG monitoring in daily life. Moreover, by combining with wireless communication technique, our WMEMS can monitor patient's heart rate continuously anywhere in the globe if they are under the coverage of GSM cellular network. Experiment results showed that our WMEMS really provides a good system prototype for ECG telemedicine applications.

In this study, a optimization process was performed for the developed dry electroencephalography (EEG) electrodes by using the Non-dominated Sorting Genetic Algorithm II (NSGA-II) to minima the skin-electrode impedance. The developed dry EEG electrodes can measure the EEG signals without any gels applied and no skin preparation. However, how to find a proper skin-electrode contact area is an important issue. The contact area is directly related to the electrodes impedance and fabrication cost. Therefore, the NSGA-II is used to searching the suitable contact area and other design parameters. NSGA-II is a wieldy used optimization method, especially for the multi-objectives issues like this case. Finally, we compare the results of the simulation and experiments for ensuring the optimal process. The experiment results show that using the optimal values provided from NSGA-II can achieve the minima skin-electrode impedance. It confirms the dry electrode can be effectively used for the cognitive or other applications in the future.

In this study, we demonstrated a Wearable Mobile Electroencephalogram (EEG)-based Brain Computer Interface System (WMEBCIS) with foam-based dry electrodes embedded. According to the previous studies, many kinds of BCI systems have been proposed and target the applications on sensors and information techniques. For daily life EEG monitoring by using the BCI systems, the sensors have employ a key technique for ensuring the data quality. In view of this, a novel dry foam electrode was designed and applied for the wearable EEG acquisition device in our WMEBCIS. The developed dry electrodes can achieve the quick-placement and high signals quality under no skin preparation and without gels applied. Most importantly, due to its softness advantage, the developed electrodes can fit properly on the skin surface to maintain low skin-electrode impedance and reduce motion artifacts under movement. By using the specific mechanism of our wearable EEG acquisition device, it can be worn conveniently and can maintain the electrode-scalp contact area to acquire good EEG signal quality effectively. Therefore, the wearable EEG acquisition device is suitable for long-term EEG monitoring in daily life. In words, our WMEBCIS was also demonstrated for a cognitive application on drowsiness detection.

This paper discusses a novel hybrid EEG biosensor module that measures through-hair EEG with zero preparation of the scalp. The biosensors can be donned or doffed quickly by the wearer, requiring no skin preparation, produce no skin irritation, and be comfortably worn for an extended period. The proposed EEG sensor is fabricated by the injection molding process with a flexible base and biofriendly materials. The noninvasive nature of BRCNCTU's EEG system [1] (i.e. zero skin preparation, minimal wiring) permits greater subject freedom of motion and considerably improves user compliance for such systems. This effort culminates in a biomonitoring system, measuring EEG, EOG, ECG and EMG signals for real time monitoring of human-computer interactions.