An Adjustable Dark-Field Acoustic-Resolution Photoacoustic Imaging System with Fiber Bundle-Based Illumination.

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.

In Vivo Assessment of Hypoxia Levels in Pancreatic Tumors Using a Dual-Modality Ultrasound/Photoacoustic Imaging System.

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.

Design and Implementation of a Multifunction Wearable Device to Monitor Sleep Physiological Signals.

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-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.

Characterization of a Fiber Bundle-Based Real-Time Ultrasound/Photoacoustic Imaging System and Its In Vivo Functional Imaging Applications.

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.