Yuhling Wang's research while affiliated with National Institutes of Health and other places

Clinical and preclinical studies on epileptic seizures are closely linked to the study of neurovascular coupling. Obtaining reliable information about cerebral blood flow (CBF) in the area of epileptic activity through minimally invasive techniques is crucial for research in this field. In our studies, we used laser speckle contrast imaging (LSCI) to gather information about the local blood circulation in the area of epileptic activity. We used two models of epileptic seizures: one based on 4-aminopyridine (4-AP) and another based on pentylenetetrazole (PTZ). We verified the duration of an epileptic seizure using electrocorticography (ECoG). We applied the antiepileptic drug topiramate (TPM) to both models, but its effect was different in each case. However, in both models, TPM had an effect on neurovascular coupling in the area of epileptic activity, as shown by both LSCI and ECoG data. We demonstrated that TPM significantly reduced the amplitude of 4-AP-induced epileptic seizures (4-AP+TPM: 0.61 ± 0.13 mV vs 4-AP: 1.08 ± 0.19 mV; p < 0.05), and it also reduced gamma power in ECoG in PTZ-induced epileptic seizures (PTZ+TPM: 38.5% ± 11.9% of the peak value vs PTZ: 59.2% ± 3.0% of peak value; p < 0.05). We also captured the pattern of CBF changes during focal epileptic seizures induced by 4-AP. Our data confirm that the system of simultaneous cortical LSCI and registration of ECoG makes it possible to evaluate the effectiveness of pharmacological agents in various types of epileptic seizures in in vivo models and provides spatial and temporal information on the process of ictogenesis.

Brain–computer interfaces (BCIs) allow communication between the brain and the external world. This type of technology has been extensively studied. However, BCI instruments with high signal quality are typically heavy and large. Thus, recording electroencephalography (EEG) signals is an inconvenient task. In recent years, system-on-chip (SoC) approaches have been integrated into BCI research, and sensors for wireless portable devices have been developed; however, there is still considerable work to be done. As neuroscience research has advanced, EEG signal analyses have come to require more accurate data. Due to the limited bandwidth of Bluetooth wireless transmission technology, EEG measurement systems with more than 16 channels must be used to reduce the sampling rate and prevent data loss. Therefore, the goal of this study was to develop a multichannel, high-resolution (24-bit), high-sampling-rate EEG BCI device that transmits signals via Wi-Fi. We believe that this system can be used in neuroscience research. The EEG acquisition system proposed in this work is based on a Cortex-M4 microcontroller with a Wi-Fi subsystem, providing a multichannel design and improved signal quality. This system is compatible with wet sensors, Ag/AgCl electrodes, and dry sensors. A LabVIEW-based user interface receives EEG data via Wi-Fi transmission and saves the raw data for offline analysis. In previous cognitive experiments, event tags have been communicated using Recommended Standard 232 (RS-232). The developed system was validated through event-related potential (ERP) and steady-state visually evoked potential (SSVEP) experiments. Our experimental results demonstrate that this system is suitable for recording EEG measurements and has potential in practical applications. The advantages of the developed system include its high sampling rate and high amplification. Additionally, in the future, Internet of Things (IoT) technology can be integrated into the system for remote real-time analysis or edge computing.Graphical Abstract

Zebrafish have become a widely accepted model organism for biomedical research due to their strong cortisol stress response, behavioral strain differences, and sensitivity to both drug treatments and predators. However, experimental zebrafish studies generate substantial data that must be analyzed through objective, accurate, and repeatable analysis methods. Recently, advancements in artificial intelligence (AI) have enabled automated tracking, image recognition, and data analysis, leading to more efficient and insightful investigations. In this review, we examine key AI applications in zebrafish research, including behavior analysis, genomics, and neuroscience. With the development of deep learning technology, AI algorithms have been used to precisely analyze and identify images of zebrafish, enabling automated testing and analysis. By applying AI algorithms in genomics research, researchers have elucidated the relationship between genes and biology, providing a better basis for the development of disease treatments and gene therapies. Additionally, the development of more effective neuroscience tools could help researchers better understand the complex neural networks in the zebrafish brain. In the future, further advancements in AI technology are expected to enable more extensive and in-depth medical research applications in zebrafish, improving our understanding of this important animal model. This review highlights the potential of AI technology in achieving the full potential of zebrafish research by enabling researchers to efficiently track, process, and visualize the outcomes of their experiments.Graphical Abstract

The COVID-19 pandemic brought the world to a standstill, posing unprecedented challenges for healthcare systems worldwide. The overwhelming number of patients infected with the virus placed an enormous burden on healthcare providers, who struggled to cope with the sheer volume of cases. Furthermore, the lack of effective treatments or vaccines means that quarantining has become a necessary measure to slow the spread of the virus. However, quarantining places a significant burden on healthcare providers, who often lack the resources to monitor patients with mild symptoms or asymptomatic patients. In this study, we propose an Internet of Things (IoT)-based wearable health monitoring system that can remotely monitor the exact locations and physiological parameters of quarantined individuals in real time. The system utilizes a combination of highly miniaturized optoelectronic and electronic technologies, an anti-epidemic watch, a mini-computer, and a monitor terminal to provide real-time updates on physiological parameters. Body temperature, peripheral oxygen saturation (SpO2), and heart rate are recorded as the most important measurements for critical care. If these three physiological parameters are aberrant, then it could represent a life-endangering situation and/or a short period over which irreversible damage may occur. Therefore, these parameters are automatically uploaded to a cloud database for remote monitoring by healthcare providers. The monitor terminal can display real-time health data for multiple patients and provide early warning functions for medical staff. The system significantly reduces the burden on healthcare providers, as it eliminates the need for manual monitoring of patients in quarantine. Moreover, it can help healthcare providers manage the COVID-19 pandemic more effectively by identifying patients who require medical attention in real time. We have validated the system and demonstrated that it is well suited to practical application, making it a promising solution for managing future pandemics. In summary, our IoT-based wearable health monitoring system has the potential to revolutionize healthcare by providing a cost-effective, remote monitoring solution for patients in quarantine. By allowing healthcare providers to monitor patients remotely in real time, the burden on medical resources is reduced, and more efficient use of limited resources is achieved. Furthermore, the system can be easily scaled to manage future pandemics, making it an ideal solution for managing the health challenges of the future.

Sonodynamic therapy (SDT) is a promising approach for cancer treatment that uses sonosensitizers (SNSs) to generate reactive oxygen species (ROS) in the presence of ultrasound. However, SDT is oxygen-dependent and requires an imaging tool to monitor the tumor microenvironment and guide treatment. Photoacoustic imaging (PAI) is a noninvasive and powerful imaging tool that offers high spatial resolution and deep tissue penetration. PAI can quantitatively assess tumor oxygen saturation (sO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) and guide SDT by monitoring time-dependent sO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> changes in the tumor microenvironment. Here, we discuss recent advances in PAI-guided SDT for cancer therapy. We discuss various exogenous contrast agents and nanomaterial-based SNSs developed for PAI-guided SDT. Additionally, combining SDT with other therapies, including photothermal therapy, can enhance its therapeutic effect. However, the application of nanomaterial-based contrast agents in PAI-guided SDT for cancer therapy remains challenging due to the lack of simple designs, the need for extensive pharmacokinetic studies, and high production costs. Integrated efforts from researchers, clinicians, and industry consortia are necessary for the successful clinical translation of these agents and SDT for personalized cancer therapy. PAI-guided SDT shows the potential to revolutionize cancer therapy and improve patient outcomes, but further research is necessary to realize its full potential.

Physical activity in the form of aerobic exercise has many beneficial effects on brain function. Here, we aim to revisit the effects of exercise on brain morphology and neurovascular organization using a rat running model. Electrocorticography (ECoG) was integrated with laser speckle contrast imaging (LSCI) and applied to simultaneously detect CSD propagation and the corresponding neurovascular function. In addition, blood oxygenation level–dependent (BOLD) signal in fMRI was used to observe cerebral utilization of oxygen. Results showed significant decrease in somatosensory evoked potentials (SSEPs) and deceleration of CSD propagation in the EXE group. Western blot results in the EXE group showed significant increases in BDNF, GFAP, and NeuN levels and significant decreases in neurodegenerative disease markers. Decreases in SSEP and CSD parameters may result from exercise-induced increases in cerebrovascular system function and increases in the stability and buffering of extracellular ion concentrations and cortical excitability.

An essential aspect of controlling and preventing mosquito-borne diseases is to reduce mosquitoes that carry viruses. We designed a smart mosquito trap system to reduce the density of mosquito vectors and the spread of mosquito-borne diseases. This smart trap uses computer vision technology and deep learning networks to identify features of live Aedes aegypti and Culex quinquefasciatus in real-time. A unique mechanical design based on the rotation concept is also proposed and implemented to capture specific living mosquitoes into the corresponding chambers successfully. Moreover, this system is equipped with sensors to detect environmental data, such as CO2 concentration, temperature, and humidity. We successfully demonstrated the implementation of such a tool and paired it with a reliable capture mechanism for live mosquitos without destroying important morphological features. The neural network achieved 91.57% accuracy with test set images. When the trap prototype was applied in a tent, the accuracy rate in distinguishing live Ae. aegypti was 92%, with a capture rate reaching 44%. When the prototype was placed into a BG trap to produce a smart mosquito trap, it achieved a 97% recognition rate and a 67% catch rate when placed in the tent. In a simulated living room, the recognition and capture rates were 90% and 49%, respectively. This smart trap correctly differentiated between Cx. quinquefasciatus and Ae. aegypti mosquitoes, and may also help control mosquito-borne diseases and predict their possible outbreak.

In photoacoustic (PA) imaging, tissue absorbs specific wavelengths of light. The absorbed energy results in thermal expansion that generates ultrasound waves that are reconstructed into images. Existing commercial PA imaging systems for preclinical brain imaging are limited by imprecise positioning capabilities and inflexible user interfaces. We introduce a new visible charge-coupled device (CCD) camera-guided photoacoustic imaging (ViCPAI) system that integrates an ultrasound (US) transducer and a data acquisition platform with a CCD camera for positioning. The CCD camera accurately positions the US probe at the measurement location. The programmable MATLAB-based platform has an intuitive user interface. In vitro carbon fiber and in vivo animal experiments were performed to investigate the precise positioning and imaging capabilities of the ViCPAI system. We demonstrated real-time capturing of bilateral cerebral hemodynamic changes during (1) forelimb electrical stimulation under normal conditions, (2) forelimb stimulation after right brain focal photothrombotic ischemia (PTI) stroke, and (3) progression of KCl-induced cortical spreading depression (CSD). The ViCPAI system accurately located target areas and achieved reproducible positioning, which is crucial in animal and clinical experiments. In animal experiments, the ViCPAI system was used to investigate bilateral cerebral cortex responses to left forelimb electrical stimulation before and after stroke, showing that the CBV and SO2 in the right primary somatosensory cortex of the forelimb (S1FL) region were significantly changed by left forelimb electrical stimulation before stroke. No CBV or SO2 changes were observed in the bilateral cortex in the S1FL area in response to left forelimb electrical stimulation after stroke. While monitoring CSD progression, the ViCPAI system accurately locates the S1FL area and returns to the same position after the probe moves, demonstrating reproducible positioning and reducing positioning errors. The ViCPAI system utilizes the real-time precise positioning capability of CCD cameras to overcome various challenges in preclinical and clinical studies.