Sensing of triglyceride concentration in blood solution using photoacoustic microscopy.

The level of triglyceride (TG) in blood is essential to human health, and hypertriglyceridemia (TG level > 150 mg/dL) would lead to cardiovascular disease and acute pancreatitis that threaten human life. Routine methods for measuring the TG level in blood depend on a lipid panel blood test, which is invasive and not convenient. Here, we use photoacoustic (PA) microscopy to test the PA amplitude of blood solutions (based on hemoglobin powder as well as flowing sheep blood) with different TG concentrations. Interestingly, we observe that the PA amplitude increases with increasing TG concentration in blood solutions, which is attributed to the increase of the Grüneisen coefficient. The preliminary in vitro study shows that the PA methodology is able to detect the TG level down to 450 mg/dL. This finding provides an opportunity for using photoacoustics to noninvasively diagnose hypertriglyceridemia.

Photoacoustic-fluorescence microendoscopy in vivo.

A miniature endoscope capable of imaging multiple tissue contrasts in high resolution is highly attractive, because it can provide complementary and detailed tissue information of internal organs. Here we present a photoacoustic (PA)-fluorescence (FL) endoscope for optical-resolution PA microscopy (PAM) and FL microscopy (FLM). The endoscope with a diameter of 2.8 mm achieves high lateral resolutions of 5.5 and 6.3 µm for PAM and FLM modes, respectively. In vivo imaging of zebrafish larvae and a mouse ear is conducted, and high-quality images are obtained. Additionally, in vivo endoscopic imaging of a rat rectum is demonstrated, showing the endoscopic imaging capability of our endoscope. By providing dual contrasts with high resolution, the endoscope may open up new opportunities for clinical endoscopic imaging applications.

Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe.

INTRODUCTION: Female sexual arousal disorder (FSAD) can be caused by the change in vaginal structure due to the decline of estrogen and one of the main symptoms is vaginal dryness. FSAD is a prevalent problem afflicting women all over the world and thus the interest is growing on the matter, but related studies of monitoring FSAD using a non-invasive optical method barely have been carried out. AIM: This study aims to investigate the longitudinal changes in female sexual arousal response induced by apomorphine (APO) administration in the ovariectomized rat using near-infrared spectroscopy (NIRS) probe. METHODS: To elicit sexual arousal, APO was administered subcutaneously to animals (n = 6) before and after ovariectomy, and the changes in oxyhemoglobin (OHb), deoxyhemoglobin (RHb), total hemoglobin (THb) concentration, and temperature on the vaginal wall after APO administration were monitored bi-weekly for 8 weeks. Furthermore, estradiol hormone, vaginal secretion, and body weight have been measured for comparison with the results from vaginal hemodynamics. RESULTS: APO administration caused the increase of vaginal OHb and RHb concentration but a decrease in temperature. The amplitude of OHb, RHb, and THb increase induced by APO gradually decreased over 8 weeks after ovariectomy while the decrease in vaginal temperature became profound. The level of estradiol and vaginal secretions also decreased over 8 weeks after ovariectomy, but bodyweight showed an increasing trend. CONCLUSIONS: A comparison between the parameters measured from the NIRS probe and the others (estradiol level, amount of vaginal secretion, and body weight) proved that the NIRS has the potential as a monitoring tool to evaluate female sexual arousal response. Jeong H, Lee HS, Seong M, et al. Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe. J Sex Med 2021;18:1328-1336.

Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China.

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM2.5 and NO2 were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08-1.19) at lag 18 day and 1.19 (95% CI, 1.12-1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM2.5 and NO2, respectively. This positive association between LN and NO2 was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O3 was not generally associated with LN. Finally, the negative associations of LN with SO2 were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.

Design of an Optical Probe to Monitor Vaginal Hemodynamics during Sexual Arousal.

An optical probe was developed to measure the change of oxy-hemoglobin (OHb), deoxy- hemoglobin (RHb), and total hemoglobin (THb) along with temperature from the vaginal wall of female rats. Apomorphine (APO, 80 µg/kg) was administered to elicit sexual arousal in female Sprague Dawley rats (SD, 180-200 g). The behavior changes caused by APO administration were checked before monitoring vaginal responses. The changes of oxy-, deoxy-, and total hemoglobin concentration and the temperature from the vaginal wall were monitored before, during, and after APO administration. Animals were under anesthesia during the measurement. After APO administration, the concentration of OHb (55 ± 29 µM/DPF), RHb (33 ± 25 µM/DPF), and THb (83 ± 59 µM/DPF) in the vaginal wall increased in a few min, while saline administration did not cause any significant change. In case of the vaginal temperature change, APO decreased the temperature slightly in the vaginal wall while saline administration did not show any temperature change in the vaginal wall. As the outcomes demonstrated, the developed probe can detect hemodynamic and temperature variation in the vaginal wall. The hemodynamic information acquired by the probe can be utilized to establish an objective and accurate standard of female sexual disorders.

Comparison of numerical-integration-based methods for blood flow estimation in diffuse correlation spectroscopy.

BACKGROUND AND OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical blood flow monitoring technology that has been utilized in various biomedical applications. In signal processing of DCS, nonlinear fitting of the experimental data and the theoretical model can be a hindrance in real-time blood flow monitoring. As one of the approaches to resolve the issue, INISg1, the inverse of numerical integration of squared g1 (a normalized electric field autocorrelation function), that could surpass the state-of-the-art technique at the time in terms of signal processing speed, has been introduced. While it is possible to implement INISg1 using various numerical integration methods, no relevant studies have been performed. Meanwhile, INISg1 was only tested within limited experimental conditions, which cannot guarantee the robustness of INISg1 in various experimental conditions. Thus, this study aims to introduce variants of INISg1 and perform a thorough comparison of the original INISg1 and its variants. METHODS: In this study, based on the right Riemann sum (RR) and trapezoid rule (TR) of numerical integration, INISg1_RR and INISg1_TR are suggested. They are thoroughly compared with the original INISg1 using model-based simulations that offer us control of most of the experimental conditions, including integration time, ß, and photon count rate. RESULTS: Except for some extreme cases, INISg1 performed more robustly than INISg1_RR and INISg1_TR. However, in extreme conditions, variants of INISg1 performed better than INISg1. With the same condition, the signal processing speed of INISg1 was 1.63 and 1.98 times faster than INISg1_RR and INISg1_TR, respectively. CONCLUSION: This study shows that INISg1 is robust in most cases and the study can be a guide for researchers using INISg1 and its variants in different types of DCS applications.

Implantable QR code subcutaneous microchip using photoacoustic and ultrasound microscopy for secure and convenient individual identification and authentication.

Individual identification and authentication techniques are merged into many aspects of human life with various applications, including access control, payment or banking transfer, and healthcare. Yet conventional identification and authentication methods such as passwords, biometrics, tokens, and smart cards suffer from inconvenience and/or insecurity. Here, inspired by quick response (QR) code and implantable microdevices, implantable and minimally-invasive QR code subcutaneous microchips (QRC-SMs) are proposed to be an effective approach to carry useful and private information, thus enabling individual identification and authentication. Two types of QRC-SMs, QRC-SMs with "hole" and "flat" elements and QRC-SMs with "titanium-coated" and "non-coated" elements, are designed and fabricated to store personal information. Corresponding ultrasound microscopy and photoacoustic microscopy are used for imaging the QR code pattern underneath skin, and open-source artificial intelligence algorithm is applied for QR code detection and recognition. Ex vivo experiments under tissue and in vivo experiments with QRC-SMs implanted in live mice have been performed, demonstrating successful information retrieval from implanted QRC-SMs. QRC-SMs are hidden subcutaneously and invisible to the eyes. They cannot be forgotten, misplaced or lost, and can always be ready for timely medical identification, access control, and payment or banking transfer. Hence, QRC-SMs provide promising routes towards private, secure, and convenient individual identification and authentication.

Blood flow estimation via numerical integration of temporal autocorrelation function in diffuse correlation spectroscopy.

BACKGROUND AND OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique widely used to monitor blood flow. Recently, efforts have been made to derive new signal processing methods to minimize the systems used and shorten the signal processing time. Herein, we propose alternative approaches to obtain blood flow information via DCS by numerically integrating the temporal autocorrelation curves. METHODS: We use the following methods: the inverse of K2 (IK2)-based on the framework of diffuse speckle contrast analysis-and the inverse of the numerical integration of squared g1 (INISg1) which, based on the normalized electric field autocorrelation curve, is more simplified than IK2. In addition, g1 thresholding is introduced to further reduce computational time and make the suggested methods comparable to the conventional nonlinear fitting approach. To validate the feasibility of the suggested methods, studies using simulation, liquid phantom, and in vivo settings were performed. In the meantime, the suggested methods were implemented and tested on three types of Arduino (Arduino Due, Arduino Nano 33 BLE Sense, and Portenta H7) to demonstrate the possibility of miniaturizing the DCS systems using microcotrollers for signal processing. RESULTS: The simulation and experimental results confirm that both IK2 and INISg1 are sufficiently relevant to capture the changes in blood flow information. More interestingly, when g1 thresholding was applied, our results showed that INISg1 outperformed IK2. It was further confirmed that INISg1 with g1 thresholding implemented on a PC and Portenta H7, an advanced Arduino board, performed faster than did the deep learning-based, state-of-the-art processing method. CONCLUSION: Our findings strongly indicate that INISg1 with g1 thresholding could be an alternative approach to derive relative blood flow information via DCS, which may contribute to the simplification of DCS methodologies.

Investigation of nonlinear photoacoustic microscopy using a low-cost infrared lamp.

Nonlinear photoacoustic microscopy (PAM) is a novel approach to enhance contrast and resolution. In this study, a low-cost infrared (IR) lamp as a simple approach for nonlinear PAM is demonstrated. Numerical simulations are first performed to verify the nonlinear photoacoustic effect under steady heating for two cases: (a) Differentiation of absorbers with different Grüneisen coefficients; (b) enhancement of photoacoustic amplitude. Then, sets of experiments are conducted to experimentally demonstrate our proposed approach: (a) Longitudinal monitoring of photoacoustic A-line signals from two samples, porcine tissue ex vivo and hemoglobin and indocyanine green (ICG) solutions in tubes in vitro for demonstrating the above-mentioned two cases; (b) PAM imaging of hemoglobin and ICG solutions in tubes before and after IR lamp heating. Different signal change and amplitude enhancement are observed in different demonstrations, showing the efficacy of the proposed approach. By virtue of cost-effectiveness and decent performance, our work facilitates nonlinear PAM studies.

Use of Hypoxic Respiratory Challenge for Differentiating Alzheimer's Disease and Wild-Type Mice Non-Invasively: A Diffuse Optical Spectroscopy Study.

Alzheimer's disease is one of the most critical brain diseases. The prevalence of the disease keeps rising due to increasing life spans. This study aims to examine the use of hemodynamic signals during hypoxic respiratory challenge for the differentiation of Alzheimer's disease (AD) and wild-type (WT) mice. Diffuse optical spectroscopy, an optical system that can non-invasively monitor transient changes in deoxygenated (ΔRHb) and oxygenated (ΔOHb) hemoglobin concentrations, was used to monitor hemodynamic reactivity during hypoxic respiratory challenges in an animal model. From the acquired signals, 13 hemodynamic features were extracted from each of ΔRHb and -ΔOHb (26 features total) for more in-depth analyses of the differences between AD and WT. The hemodynamic features were statistically analyzed and tested to explore the possibility of using machine learning (ML) to differentiate AD and WT. Among the twenty-six features, two features of ΔRHb and one feature of -ΔOHb showed statistically significant differences between AD and WT. Among ML techniques, a naive Bayes algorithm achieved the best accuracy of 84.3% when whole hemodynamic features were used for differentiation. While further works are required to improve the approach, the suggested approach has the potential to be an alternative method for the differentiation of AD and WT.

Recent advances toward clinical applications of photoacoustic microscopy: a review.

Photoacoustic imaging (PAI) is an emerging technology that has been dramatically developed in the last decade. PAI, a combination of optical illumination and ultrasound detection, allows us to achieve fine resolution and obtain fruitful information of endogenous and exogenous chromophores. Among PAI imaging techniques, photoacoustic computed tomography (PACT) has been extensively used in human studies due to its deep tissue penetration (several centimeters). Alternatively, photoacoustic microscopy (PAM) offers higher resolution at the expense of penetration depth, which can also be advantageous in clinics. Recently, there has been increasing attention and studies on PAM of human tissues. In this paper, we will review principles of PAM and its applications to human tissues, including the breast tissue, carotid atheroma tissue, eye, gastrointestinal tissue, ovarian tissue and tooth ex vivo as well as the oral cavity and dermatological tissue in vivo. The paper is closed with the outlook regarding the potential applications of PAM in clinics.

Change of tumor vascular reactivity during tumor growth and postchemotherapy observed by near-infrared spectroscopy.

Breast cancer is one of the most common cancers in females. To monitor chemotherapeutic efficacy for breast cancer, medical imaging systems such as x-ray mammography, computed tomography, magnetic resonance imaging, and ultrasound imaging have been used. Currently, it can take up to 3 to 6 weeks to see the tumor response from chemotherapy by monitoring tumor volume changes. We used near-infrared spectroscopy (NIRS) to predict breast cancer treatment efficacy earlier than tumor volume changes by monitoring tumor vascular reactivity during inhalational gas interventions. The results show that the amplitude of oxy-hemoglobin changes (vascular reactivity) during hyperoxic gas inhalation is well correlated with tumor growth and responded one day earlier than tumor volume changes after chemotherapy. These results may imply that NIRS with respiratory challenges can be useful in early detection of tumor and in the prediction of tumor response to chemotherapy.

Low-cost compact diffuse speckle contrast flowmeter using small laser diode and bare charge-coupled-device.

We report a low-cost compact diffuse speckle contrast flowmeter (DSCF) consisting of a small laser diode and a bare charge-coupled-device (CCD) chip, which can be used for contact measurements of blood flow variations in relatively deep tissues (up to ∼ 8 mm). Measurements of large flow variations by the contact DSCF probe are compared to a noncontact CCD-based diffuse speckle contrast spectroscopy and a standard contact diffuse correlation spectroscopy in tissue phantoms and a human forearm. Bland­Altman analysis shows no significant bias with good limits of agreement among these measurements: 96.5%±2.2% (94.4% to 100.0%) in phantom experiments and 92.8% in the forearm test. The relatively lower limit of agreement observed in the in vivo measurements (92.8%) is likely due to heterogeneous reactive responses of blood flow in different regions/volumes of the forearm tissues measured by different probes. The low-cost compact DSCF device holds great potential to be broadly used for continuous and longitudinal monitoring of blood flow alterations in ischemic/hypoxic tissues, which are usually associated with various vascular diseases.

Simultaneous blood flow and blood oxygenation measurements using a combination of diffuse speckle contrast analysis and near-infrared spectroscopy.

A combined diffuse speckle contrast analysis (DSCA)-near-infrared spectroscopy (NIRS) system is proposed to simultaneously measure qualitative blood flow and blood oxygenation changes in human tissue. The system employs an optical switch to alternate two laser sources at two different wavelengths and a CCD camera to capture the speckle image. Therefore, an optical density can be measured from two wavelengths for NIRS measurements and a speckle contrast can be calculated for DSCA measurements. In order to validate the system, a flow phantom test and an arm occlusion protocol for arterial and venous occlusion were performed. Shorter exposure times (<1 ms ) show a higher drop (between 50% and 66%) and recovery of 1/K²S values after occlusion (approximately 150%), but longer exposure time (3 ms) shows more consistent hemodynamic changes. For four subjects, the 1/K²S values dropped to an average of 82.1±4.0% during the occlusion period and the average recovery of 1/K²S values after occlusion was 109.1±0.8% . There was also an approximately equivalent amplitude change in oxyhemoglobin (OHb) and deoxyhemoglobin (RHb) during arterial occlusion (max RHb=0.0085±0.0024 mM/DPF, min OHb=-0.0057±0.0044 mM/DPF). The sensitivity of the system makes it a suitable modality to observe qualitative hemodynamic trends during induced physiological changes.