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.

Assessing Pain Intensity Using Photoplethysmography Signals in Chronic Myofascial Pain Syndrome.

BACKGROUND: Efficacy of pain assessment is the basis for effective therapy. Clinically, assessing pain is by subjective scale, but these methods have some shortcomings. Therefore, studies have been conducted on assessment of pain using physiological signals. Photoplethysmography (PPG) signals provide much information about the cardiovascular system. PPG-derived parameters (PPG parameters) reflect nociceptive stimulation, and obtain an approximation of the R-R interval from the PPG period. The aim of this study was to evaluate PPG signals for assessment of pain intensity in chronic myofascial pain syndrome (MPS) patients. METHODS: This study recruited 37 patients with chronic MPS; all of them were treated with electrotherapy and thermotherapy. The difference between pre- and post-therapy PPG parameters, and the correlation between pulse rate variability (PRV) and heart rate variability (HRV) were determined. We also obtained patients' pain intensity scores by visual analog scale, visual rating scale, and Wong-Banker face pain rating scale. RESULTS: Photoplethysmography and PRV/HRV parameters showed significant differences between pre- and post-treatment. The variation trend of PRV was similar with HRV in heart rate, R-R interval, low frequency, high frequency, and LF/HF; in addition, a high correlation between the parameters was observed either in pre- or post-therapy. PPG parameters indicated increased sympathetic tone. CONCLUSION: The results of the study indicated that PRV substituted for HRV in assessment of pain intensity in chronic MPS reflected parasympathetic nervous tone increase, and PPG parameters might reflect stress stimulation on skin.

Observing continuous change in heart rate variability and photoplethysmography-derived parameters during the process of pain production/relief with thermal stimuli.

Continuously monitoring and efficiently managing pain has become an important issue. However, no study has investigated a change in physiological parameters during the process of pain production/relief. This study modeled the process of pain production/relief using ramped thermal stimulation (no pain: 37°C water, process of pain production: a heating rate of 1°C/min, and subject feels pain: water kept at the painful temperature for each subject, with each segment lasting 10 min). In this duration, the variation of the heat rate variability and photoplethysmography-derived parameters was observed. A total of 40 healthy individuals participated: 30 in the trial group (14 males and 16 females with a mean age of 22.5±1.9 years) and 10 in the control group (7 males and 3 females with a mean age of 22.5±1.3 years). The results showed that the numeric rating scale value was 5.03±1.99 when the subjects felt pain, with a temperature of 43.54±1.70°C. Heart rate, R-R interval, low frequency, high frequency, photoplethysmography amplitude, baseline, and autonomic nervous system state showed significant changes during the pain production process, but these changes differed during the period Segment D (painful temperature 10: min). In summary, the study observed that physiological parameters changed qualitatively during the process of pain production and relief and found that the high frequency, low frequency, and photoplethysmography parameters seemed to have different responses in four situations (no pain, pain production, pain experienced, and pain relief). The trends of these variations may be used as references in the clinical setting for continuously observing pain intensity.

Use of Heart Rate Variability and Photoplethysmograph-Derived Parameters as Assessment Signals of Radiofrequency Therapy Efficacy for Chronic Pain.

BACKGROUND: Radiofrequency therapy (RFT) generates molecular motion and produces heat and electromagnetic effects on tissues, which attenuate pain sensation and thereby relieve pain. This study was to observe the altering trend of physiological parameters after RFT for chronic cervical or lumbar pain. METHODS: This study recruited 66 patients with chronic cervical or lumbar pain and recorded their physiological parameters before and after RFT using heart rate variability (HRV) and photoplethysmography (PPG) to explore the feasibility of RFT efficacy assessment. RESULTS: The patients' visual analog scale scores significantly decreased after RFT and the HRV parameters that represented parasympathetic activity significantly changed (HR decreased, and R-R interval and low- and high-frequency power increased significantly). Meanwhile, the PPG parameters that represented sympathetic activity also increased (PPG amplitude and autonomic nervous system state significantly decreased). CONCLUSIONS: This study showed significant efficacy of RFT in patients with chronic cervical or lumbar pain. The changes of HRV and PPG parameters may explain part of the mechanisms of RFT.

Photoplethysmography variability as an alternative approach to obtain heart rate variability information in chronic pain patient.

Heart rate variability (HRV) is a well-known method for the assessment of autonomic nervous function of the heart. Previous study suggested that pulse rate variability (PRV) determined by photoplethysmography could be used instead of HRV to more simply assess autonomic nervous function. However, most research studies included healthy subjects. Thus, the aim of this study was to investigate the feasibility for PRV as a surrogate index for patients with chronic pain. This study investigated the correlation coefficient (by Pearson correlation) and agreement (by Bland-Altman analysis) between PRV and HRV in chronic pain patients in the clinical setting. The results showed high significant correlations (p < 0.001, r > 0.86) between all the HRV and PRV parameters and good agreements (ratio < 0.1) between the parameters in terms of HR, mean RR, VLF, LF, nLF, nHF, and SD1/SD2. Our study suggests that HRV can also be reliably estimated using the photoplethysmography-based PP interval in elderly patients with chronic pain.

Aging-related changes in swallowing, and in the coordination of swallowing and respiration determined by novel non-invasive measurement techniques.

AIM: Previous studies have shown that the process of swallowing changes with aging, a phenomenon known as presbyphagia. These subtle and subclinical age-related changes make older adults more vulnerable to dysphagia during disease insults. However, there are limited studies of the swallowing process in older adults, because measurements are typically invasive or require exposure to X-rays. In the present study, we used integrated non-invasive measurements to determine aging-related changes of swallowing, and in the coordination of swallowing and respiration for a population of healthy participants. METHODS: The non-invasive system provided measurements of larynx movement with piezoelectric sensors, submental muscle activity with surface electromyography and respiration-swallowing coordination by measurement of nasal airflow. We recruited 112 healthy participants from the community, 35 in a young-age group (age 20-30 years), 38 in a middle-age group (age 31-50 years) and 39 in an old-age group (age 51-70 years). RESULTS: The oropharyngeal swallowing parameters of the old-age group had delayed onset latency and longer swallowing apnea duration relative to the other groups, and these differences were greater for larger boluses. The middle- and old-age groups had less expiratory-expiratory respiratory phase pattern than the young-age group. The probability of piecemeal deglutition was highest in the old-age group and lowest in the young-age group. These results show that the phases of oropharyngeal swallowing and the coordination of swallowing with respiration gradually change with aging. CONCLUSIONS: We used integrated non-invasive measurements to document age-related changes in swallowing, and in the coordination of swallowing and respiration in healthy adults.

Study of the trapezius muscle region pressure pain threshold and latency time in young people with and without depressed scapula.

The scapula is stabilized in or moved to a certain position to coordinate shoulder function and achieve shoulder and arm movement during the athletic and daily activities. An alteration in the scapular position both at rest and during arm movements is commonly associated with shoulder injury or dysfunction. The purpose of this study was to assess the influence of the depressed scapular position using pressure pain threshold (PPT) and delayed muscle activation of the upper and middle trapezius muscles. The study included 20 subjects who were divided into normal shoulder (n = 12) and depressed shoulder (n = 8) group. PPT was measured in a relaxed position. Muscle activity was recorded using surface electromyography and by calculating each shrug's muscle latency time (MLT). The results revealed that the healthy young subjects with depressed scapular position had significantly lower PPT levels than those with normal scapular position both in the upper and middle trapezius muscle (P < 0.05). MLT of the upper trapezius was significantly delayed in both sides during the shoulder shrugs (P < 0.05).

Effects of ultrasound on osteotomy healing in a rabbit fracture model.

This study investigated the effects of ultrasound (US) at different frequencies on fracture healing over a three-week period in a rabbit fibular fracture model. Forty-five adult New Zealand White rabbits were divided into five groups: a control group and four groups treated with US frequencies of 0.5, 1.0, 1.5 and 2.0 MHz (0.5 W/cm(2), 200-µs burst, pulsed 1:4). After anesthesia, transverse osteotomy was performed on the fibula bone. This was followed by intravital staining and fluorescence microscopic examination of new bone formation and biomechanical tests of torsional stiffness at the osteotomy site. Results showed that total new bone formation and torsional stiffness of the fibula were greater in all US-treated groups than in the control group. No significant difference was found between any of the four US-treated groups. The US treatment also enhanced bone growth of the sham-treated contralateral fracture site. These results suggest that US treatment at 0.5, 1.0, 1.5 or 2.0 MHz can enhance fracture healing in a rabbit model. Furthermore, the effects of US on fracture healing at present parameters might not be confined locally.

A novel system design for implantable stimulator application.

In this paper, we present a novel and implantable micro-stimulator design. Instead of generating the stimulating pulses by using the conventional computerized controller such as FPGA or MCU, the pulse width modulation (PWM) has been used to control the stimulation. The proposed system need not program the computerized controller, so it simplifies the circuit complexity and achieves the low-cost issue. The proposed micro-stimulator chip has a 5-bits programmable current selectivity and uses pulse width modulation skill to adjust the pulse width. Besides, the system has four different stimulation frequencies to be chosen and provides normal, random, and burst stimulation pulses for the practical situation.