A Portable and a Scalable Multi-Channel Wireless Recording System for Wearable Electromyometrial Imaging.

Electromyometrial imaging (EMMI) technology has emerged as one of the promising technology that can be used for non-invasive pregnancy risk stratification and for preventing complications due to pre-term birth. Current EMMI systems are bulky and require a tethered connection to desktop instrumentation, as a result, the system cannot be used in non-clinical and ambulatory settings. In this article, we propose an approach for designing a scalable, portable wireless EMMI recording system that can be used for in-home and remote monitoring. The wearable system uses a non-equilibrium differential electrode multiplexing approach to enhance signal acquisition bandwidth and to reduce the artifacts due to electrode drifts, amplifier 1/f noise, and bio-potential amplifier saturation. A combination of active shielding, a passive filter network, and a high-end instrumentation amplifier ensures sufficient input dynamic range ([Formula: see text]) such that the system can simultaneously acquire different bio-potential signals like maternal electrocardiogram (ECG) in addition to the EMMI electromyogram (EMG) signals. We show that the switching artifacts and the channel cross-talk introduced due to non-equilibrium sampling can be reduced using a compensation technique. This enables the system to be potentially scaled to a large number of channels without significantly increasing the system power dissipation. We demonstrate the feasibility of the proposed approach in a clinical setting using an 8-channel battery-powered prototype which dissipates less than 8 µW per channel for a signal bandwidth of 1 KHz.

Noninvasive electrophysiological imaging identifies 4D uterine peristalsis patterns in subjects with normal menstrual cycles and patients with endometriosis.

Throughout the menstrual cycle, spontaneous mild contractions in the inner layer of the uterine smooth muscle cause uterine peristalsis, which plays a critical role in normal menstruation and fertility. Disruptions in peristalsis patterns may occur in women experiencing subfertility, abnormal uterine bleeding, ovulatory dysfunction, endometriosis, and other disorders. However, current tools to measure uterine peristalsis in humans have limitations that hamper their research or clinical utilities. Here, we describe an electrophysiological imaging system to noninvasively quantify the four-dimensional (4D) electrical activation pattern during human uterine peristalsis with high spatial and temporal resolution and coverage. We longitudinally imaged 4968 uterine peristalses in 17 participants with normal gynecologic anatomy and physiology over 34 hours and 679 peristalses in 5 participants with endometriosis over 12.5 hours throughout the menstrual cycle. Our data provide quantitative evidence that uterine peristalsis changes in frequency, direction, duration, magnitude, and power throughout the menstrual cycle and is disrupted in endometriosis patients. Moreover, our data suggest that disrupted uterine peristalsis contributes to excess retrograde menstruation and infertility in patients with endometriosis and potentially contributes to infertility in this cohort.

Stretchable Sponge Electrodes for Long-Term and Motion-Artifact-Tolerant Recording of High-Quality Electrophysiologic Signals.

Soft electronic devices and sensors have shown great potential for wearable and ambulatory electrophysiologic signal monitoring applications due to their light weight, ability to conform to human skin, and improved wearing comfort, and they may replace the conventional rigid electrodes and bulky recording devices widely used nowadays in clinical settings. Herein, we report an elastomeric sponge electrode that offers greatly reduced electrode-skin contact impedance, an improved signal-to-noise ratio (SNR), and is ideally suited for long-term and motion-artifact-tolerant recording of high-quality biopotential signals. The sponge electrode utilizes a porous polydimethylsiloxane sponge made from a sacrificial template of sugar cubes, and it is subsequently coated with a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) conductive polymer using a simple dip-coating process. The sponge electrode contains numerous micropores that greatly increase the skin-electrode contact area and help lower the contact impedance by a factor of 5.25 or 6.7 compared to planar PEDOT:PSS electrodes or gold-standard Ag/AgCl electrodes, respectively. The lowering of contact impedance resulted in high-quality electrocardiogram (ECG) and electromyogram (EMG) recordings with improved SNR. Furthermore, the porous structure also allows the sponge electrode to hold significantly more conductive gel compared to conventional planar electrodes, thereby allowing them to be used for long recording sessions with minimal signal degradation. The conductive gel absorbed into the micropores also serves as a buffer layer to help mitigate motion artifacts, which is crucial for recording on ambulatory patients. Lastly, to demonstrate its feasibility and potential for clinical usage, we have shown that the sponge electrode can be used to monitor uterine contraction activities from a patient in labor. With its low-cost fabrication, softness, and ability to record high SNR biopotential signals, the sponge electrode is a promising platform for long-term wearable health monitoring applications.

Reduced expression in preterm birth of sFLT-1 and PlGF with a high sFLT-1/PlGF ratio in extracellular vesicles suggests a potential biomarker.

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases of preterm birth and 38 control cases. Our results showed that both sFLT-1 (P=0.0014) and PlGF (P=0.0032) were significantly downregulated in cases of preterm birth compared to controls, while the sFLT-1/PIGF ratio was significantly (P=0.0008) increased in EVs-EXs, but not in maternal plasma. Our results suggest that this reduced expression of sFLT-1 and PlGF with an elevated sFLT-1/PlGF ratio in EVs-EXs may represent a potential biomarker for prediction of PTB.

Evolving cervical imaging technologies to predict preterm birth.

Preterm birth, defined as delivery at less than 37 weeks' gestation, increases maternal-fetal morbidity and mortality and places heavy financial and emotional burdens on families and society. Although premature cervical remodeling is a major factor in many preterm deliveries, how and why this occurs is poorly understood. This review describes existing and emerging imaging techniques and their advantages and disadvantages in assessing cervical remodeling. Brightness mode (B-mode) ultrasound is used to measure the cervical length, currently the gold standard for determining risk of preterm birth. Several new B-mode ultrasound techniques are being developed, including measuring attenuation, cervical gland area, and the cervical consistency index. Shear wave speed can differentiate between soft (ripe) and firm (unripe) cervices by measuring the speed of ultrasound through a tissue. Elastography provides qualitative information regarding cervical stiffness by compressing the tissue with the ultrasound probe. Raman spectroscopy uses a fiber optic probe to assess the biochemical composition of the cervix throughout pregnancy. Second harmonic generation microscopy uses light to quantify changes in collagen fiber structure and size during cervical maturation. Finally, photoacoustic endoscopy records light-induced sound to determine optical characteristics of cervical tissue. In the long term, a combination of several imaging approaches, combined with consideration of clinical epidemiologic characteristics, will likely be required to accurately predict preterm birth.

In vivo characterization of connective tissue remodeling using infrared photoacoustic spectra.

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth.

Transvaginal fast-scanning optical-resolution photoacoustic endoscopy.

Photoacoustic endoscopy offers in vivo examination of the visceral tissue using endogenous contrast, but its typical B-scan rate is ∼10 Hz, restricted by the speed of the scanning unit and the laser pulse repetition rate. Here, we present a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250-Hz B-scan rate over a 3-mm scanning range. Using this modality, we not only illustrated the morphological differences of vasculatures among the human ectocervix, uterine body, and sublingual mucosa but also showed the longitudinal and cross-sectional differences of cervical vasculatures in pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.