Distributed Wearable Ultrasound Sensors Predict Isometric Ground Reaction Force.

Rehabilitation from musculoskeletal injuries focuses on reestablishing and monitoring muscle activation patterns to accurately produce force. The aim of this study is to explore the use of a novel low-powered wearable distributed Simultaneous Musculoskeletal Assessment with Real-Time Ultrasound (SMART-US) device to predict force during an isometric squat task. Participants (N = 5) performed maximum isometric squats under two medical imaging techniques; clinical musculoskeletal motion mode (m-mode) ultrasound on the dominant vastus lateralis and SMART-US sensors placed on the rectus femoris, vastus lateralis, medial hamstring, and vastus medialis. Ultrasound features were extracted, and a linear ridge regression model was used to predict ground reaction force. The performance of ultrasound features to predict measured force was tested using either the Clinical M-mode, SMART-US sensors on the vastus lateralis (SMART-US: VL), rectus femoris (SMART-US: RF), medial hamstring (SMART-US: MH), and vastus medialis (SMART-US: VMO) or utilized all four SMART-US sensors (Distributed SMART-US). Model training showed that the Clinical M-mode and the Distributed SMART-US model were both significantly different from the SMART-US: VL, SMART-US: MH, SMART-US: RF, and SMART-US: VMO models (p < 0.05). Model validation showed that the Distributed SMART-US model had an R2 of 0.80 ± 0.04 and was significantly different from SMART-US: VL but not from the Clinical M-mode model. In conclusion, a novel wearable distributed SMART-US system can predict ground reaction force using machine learning, demonstrating the feasibility of wearable ultrasound imaging for ground reaction force estimation.

Ultrasound-Responsive Aqueous Two-Phase Microcapsules for On-Demand Drug Release.

Traditional implanted drug delivery systems cannot easily change their release profile in real time to respond to physiological changes. Here we present a microfluidic aqueous two-phase system to generate microcapsules that can release drugs on demand as triggered by focused ultrasound (FUS). The biphasic microcapsules are made of hydrogels with an outer phase of mixed molecular weight (MW) poly(ethylene glycol) diacrylate that mitigates premature payload release and an inner phase of high MW dextran with payload that breaks down in response to FUS. Compound release from microcapsules could be triggered as desired; 0.4 µg of payload was released across 16 on-demand steps over days. We detected broadband acoustic signals amidst low heating, suggesting inertial cavitation as a key mechanism for payload release. Overall, FUS-responsive microcapsules are a biocompatible and wirelessly triggerable structure for on-demand drug delivery over days to weeks.

Coherence-Weighted Synthetic Focusing Applied to Photoacoustic Imaging Using a High-Frequency Annular-Array Transducer.

This paper presents an adaptive synthetic-focusing scheme that, when applied to photoacoustic (PA) data acquired using an annular array, improves focusing across a greater imaging depth and enhances spatial resolution. The imaging system was based on a 40-MHz, 5-element, annular-array transducer with a focal length of 12 mm and an 800-µm diameter hole through its central element to facilitate coaxial delivery of 532-nm laser. The transducer was raster-scanned to facilitate 3D acquisition of co-registered ultrasound and PA image data. Three synthetic-focusing schemes were compared for obtaining PA A-lines for each scan location: delay-and-sum (DAS), DAS weighted with a coherence factor (DAS + CF), and DAS weighted with a sign-coherence factor (DAS + SCF). Bench-top experiments that used an 80-µm hair were performed to assess the enhancement provided by the two coherence-based schemes. Both coherence-based schemes increased the signal-to-noise ratio by approximately 10 dB. When processed using the DAS-only scheme, the lateral dimension of the hair in a PA image with 20 dB dynamic range was between 300 µm and 1 mm for imaging depth ranging from 8 to 20 mm. In comparison, the DAS + CF scheme resulted in a lateral dimension of 200 to 450 µm over the same range. The DAS + SCF synthetic focusing further improved the smallest-resolvable dimension, which was between 150 and 400 µm over the same range of imaging depth. When used on PA data obtained from a 12-day-old mouse embryo, the DAS + SCF processing improved visualization of neurovasculature.

Wearable Ultrasound System Using Low-Voltage Time Delay Spectrometry for Dynamic Tissue Imaging.

OBJECTIVE: Wearable ultrasound is emerging as a new paradigm of real-time imaging in freely moving humans and has wide applications from cardiovascular health monitoring to human gesture recognition. However, current wearable ultrasound devices have typically employed pulse-echo imaging which requires high excitation voltages and sampling rates, posing safety risks, and requiring specialized hardware. Our objective was to develop and evaluate a wearable ultrasound system based on time delay spectrometry (TDS) that utilizes low-voltage excitation and significantly simplified instrumentation. METHODS: We developed a TDS-based ultrasound system that utilizes continuous, frequency-modulated sweeps at low excitation voltages. By mixing the transmit and receive signals, the system digitizes the ultrasound signal at audio frequency (kHz) sampling rates. Wearable ultrasound transducers were developed, and the system was characterized in terms of imaging performance, acoustic output, thermal characteristics, and applications in musculoskeletal imaging. RESULTS: The prototype TDS system is capable of imaging up to 6 cm of depth with signal-to-noise ratio of up to 42 dB at a spatial resolution of 0.33 mm. Acoustic and thermal radiation measurements were within clinically safe limits for continuous ultrasound imaging. We demonstrated the ability to use a 4-channel wearable system for dynamic imaging of muscle activity. CONCLUSION: We developed a wearable ultrasound imaging system using TDS to mitigate challenges with pulse echo-based wearable ultrasound imaging systems. Our device is capable of high-resolution, dynamic imaging of deep-seated tissue structures and is safe for long-term use. SIGNIFICANCE: This work paves the way for low-voltage wearable ultrasound imaging devices with significantly reduced hardware complexity.

Fast iterative reconstruction for photoacoustic tomography using learned physical model: Theoretical validation.

Iterative reconstruction has demonstrated superior performance in medical imaging under compressed, sparse, and limited-view sensing scenarios. However, iterative reconstruction algorithms are slow to converge and rely heavily on hand-crafted parameters to achieve good performance. Many iterations are usually required to reconstruct a high-quality image, which is computationally expensive due to repeated evaluations of the physical model. While learned iterative reconstruction approaches such as model-based learning (MBLr) can reduce the number of iterations through convolutional neural networks, it still requires repeated evaluations of the physical models at each iteration. Therefore, the goal of this study is to develop a Fast Iterative Reconstruction (FIRe) algorithm that incorporates a learned physical model into the learned iterative reconstruction scheme to further reduce the reconstruction time while maintaining robust reconstruction performance. We also propose an efficient training scheme for FIRe, which releases the enormous memory footprint required by learned iterative reconstruction methods through the concept of recursive training. The results of our proposed method demonstrate comparable reconstruction performance to learned iterative reconstruction methods with a 9x reduction in computation time and a 620x reduction in computation time compared to variational reconstruction.

DNA-Based Near-Infrared Voltage Sensors.

Indocyanine green (ICG) is an FDA approved dye widely used for fluorescence imaging in research, surgical navigation, and medical diagnostics. However, ICG has a few drawbacks, such as concentration-dependent aggregation and absorbance, nonspecific cellular targeting, and rapid photobleaching. Here, we report a novel DNA-based nanosensor platform that utilizes monomers of ICG and cholesterol. Using DNA origami, we can attach ICG to a DNA structure, maintaining its concentration, preserving its near-infrared (NIR) absorbance, and allowing attachment of targeting moieties. We characterized the nanosensors' absorbance, stability in blood, and voltage sensing in vitro. This study presents a novel DNA-based ICG nanosensor platform for cellular voltage sensing for future in vivo applications.

NIR-II Nanoprobes: A Review of Components-Based Approaches to Next-Generation Bioimaging Probes.

Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare.

Size-tunable ICG-based contrast agent platform for targeted near-infrared photoacoustic imaging.

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional information of tissues with high resolution. Although NIR-PAI is promising, its widespread use is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represents an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agents with tunable size down to 230 nm and direct functionalization with targeting moieties. The ICG-JA platform has a detectable PA signal in vitro that is two times stronger than whole blood and high photostability. The targeting ability of ICG-JA was measured in vitro using HeLa cells. The ICG-JA platform was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 min post-injection with a contrast-to-noise ratio of 2.42.

Relationships between surrogate measures of mechanical and psychophysiological load, patellar tendon adaptations, and neuromuscular performance in NCAA division I men's volleyball athletes.

Introduction: Patellar tendon adaptations occur in response to mechanical load. Appropriate loading is necessary to elicit positive adaptations with increased risk of injury and decreased performance likely if loading exceeds the capacity of the tendon. The aim of the current study was to examine intra-individual associations between workloads and patellar tendon properties and neuromuscular performance in collegiate volleyball athletes. Methods: National Collegiate Athletics Association Division I men's volleyball athletes (n = 16, age: 20.33 ± 1.15 years, height: 193.50 ± 6.50 cm, body mass: 84.32 ± 7.99 kg, bodyfat%: 13.18 ± 4.72%) competing across 9 weeks of in-season competition participated. Daily measurements of external workloads (i.e., jump count) and internal workloads [i.e., session rating of perceived exertion (sRPE)] were recorded. Weekly measurements included neuromuscular performance assessments (i.e., countermovement jump, drop jump), and ultrasound images of the patellar tendon to evaluate structural adaptations. Repeated measures correlations (r-rm) assessed intra-individual associations among performance and patellar tendon metrics. Results: Workload measures exhibited significant negative small to moderate (r-rm =-0.26-0.31) associations with neuromuscular performance, negative (r-rm = -0.21-0.30), and positive (r-rm = 0.20-0.32) small to moderate associations with patellar tendon properties. Discussion: Monitoring change in tendon composition and performance adaptations alongside workloads may inform evidence-based frameworks toward managing and reducing the risk of the development of patellar tendinopathy in collegiate men's volleyball athletes.

Deep-Learning-Based Segmentation of Extraocular Muscles from Magnetic Resonance Images.

In this study, we investigated the performance of four deep learning frameworks of U-Net, U-NeXt, DeepLabV3+, and ConResNet in multi-class pixel-based segmentation of the extraocular muscles (EOMs) from coronal MRI. Performances of the four models were evaluated and compared with the standard F-measure-based metrics of intersection over union (IoU) and Dice, where the U-Net achieved the highest overall IoU and Dice scores of 0.77 and 0.85, respectively. Centroid distance offset between identified and ground truth EOM centroids was measured where U-Net and DeepLabV3+ achieved low offsets (p > 0.05) of 0.33 mm and 0.35 mm, respectively. Our results also demonstrated that segmentation accuracy varies in spatially different image planes. This study systematically compared factors that impact the variability of segmentation and morphometric accuracy of the deep learning models when applied to segmenting EOMs from MRI.

Toward a wearable monitor of local muscle fatigue during electrical muscle stimulation using tissue Doppler imaging.

Electrical muscle stimulation (EMS) is widely used in rehabilitation and athletic training to generate involuntary muscle contractions. However, EMS leads to rapid muscle fatigue, limiting the force a muscle can produce during prolonged use. Currently available methods to monitor localized muscle fatigue and recovery are generally not compatible with EMS. The purpose of this study was to examine whether Doppler ultrasound imaging can assess changes in stimulated muscle twitches that are related to muscle fatigue from electrical stimulation. We stimulated five isometric muscle twitches in the medial and lateral gastrocnemius of 13 healthy subjects before and after a fatiguing EMS protocol. Tissue Doppler imaging of the medial gastrocnemius recorded muscle tissue velocities during each twitch. Features of the average muscle tissue velocity waveforms changed immediately after the fatiguing stimulation protocol (peak velocity: -38%, p = .022; time-to-zero velocity: +8%, p = .050). As the fatigued muscle recovered, the features of the average tissue velocity waveforms showed a return towards their baseline values similar to that of the normalized ankle torque. We also found that features of the average tissue velocity waveform could significantly predict the ankle twitch torque for each participant (R2 = 0.255-0.849, p < .001). Our results provide evidence that Doppler ultrasound imaging can detect changes in muscle tissue during isometric muscle twitch that are related to muscle fatigue, fatigue recovery, and the generated joint torque. Tissue Doppler imaging may be a feasible method to monitor localized muscle fatigue during EMS in a wearable device.

Photoacoustic-guided convergence of light through optically diffusive media.

We demonstrate that laser beams can be converged toward a light-absorbing target through optically diffusive media by using photoacoustic-guided interferometric focusing. The convergence of light is achieved by shaping the wavefront of the incident light with a deformable mirror to maximize the photoacoustic signal, which is proportional to the scattered light intensity at the light absorber.

Comparing Deep Learning Frameworks for Photoacoustic Tomography Image Reconstruction.

Conventional reconstruction methods for photoacoustic images are not suitable for the scenario of sparse sensing and geometrical limitation. To overcome these challenges and enhance the quality of reconstruction, several learning-based methods have recently been introduced for photoacoustic tomography reconstruction. The goal of this study is to compare and systematically evaluate the recently proposed learning-based methods and modified networks for photoacoustic image reconstruction. Specifically, learning-based post-processing methods and model-based learned iterative reconstruction methods are investigated. In addition to comparing the differences inherently brought by the models, we also study the impact of different inputs on the reconstruction effect. Our results demonstrate that the reconstruction performance mainly stems from the effective amount of information carried by the input. The inherent difference of the models based on the learning-based post-processing method does not provide a significant difference in photoacoustic image reconstruction. Furthermore, the results indicate that the model-based learned iterative reconstruction method outperforms all other learning-based post-processing methods in terms of generalizability and robustness.

Detecting cavitation in mercury exposed to a high-energy pulsed proton beam.

The Oak Ridge National Laboratory Spallation Neutron Source employs a high-energy pulsed proton beam incident on a mercury target to generate short bursts of neutrons. Absorption of the proton beam produces rapid heating of the mercury, resulting in the formation of acoustic shock waves and the nucleation of cavitation bubbles. The subsequent collapse of these cavitation bubbles promote erosion of the steel target walls. Preliminary measurements using two passive cavitation detectors (megahertz-frequency focused and unfocused piezoelectric transducers) installed in a mercury test target to monitor cavitation generated by proton beams with charges ranging from 0.041 to 4.1 muC will be reported on. Cavitation was initially detected for a beam charge of 0.082 muC by the presence of an acoustic emission approximately 250 mus after arrival of the incident proton beam. This emission was consistent with an inertial cavitation collapse of a bubble with an estimated maximum bubble radius of 0.19 mm, based on collapse time. The peak pressure in the mercury for the initiation of cavitation was predicted to be 0.6 MPa. For a beam charge of 0.41 muC and higher, the lifetimes of the bubbles exceeded the reverberation time of the chamber ( approximately 300 mus), and distinct windows of cavitation activity were detected, a phenomenon that likely resulted from the interaction of the reverberation in the chamber and the cavitation bubbles.

Limited-View and Sparse Photoacoustic Tomography for Neuroimaging with Deep Learning.

Photoacoustic tomography (PAT) is a non-ionizing imaging modality capable of acquiring high contrast and resolution images of optical absorption at depths greater than traditional optical imaging techniques. Practical considerations with instrumentation and geometry limit the number of available acoustic sensors and their "view" of the imaging target, which result in image reconstruction artifacts degrading image quality. Iterative reconstruction methods can be used to reduce artifacts but are computationally expensive. In this work, we propose a novel deep learning approach termed pixel-wise deep learning (Pixel-DL) that first employs pixel-wise interpolation governed by the physics of photoacoustic wave propagation and then uses a convolution neural network to reconstruct an image. Simulated photoacoustic data from synthetic, mouse-brain, lung, and fundus vasculature phantoms were used for training and testing. Results demonstrated that Pixel-DL achieved comparable or better performance to iterative methods and consistently outperformed other CNN-based approaches for correcting artifacts. Pixel-DL is a computationally efficient approach that enables for real-time PAT rendering and improved image reconstruction quality for limited-view and sparse PAT.

Fully Dense UNet for 2-D Sparse Photoacoustic Tomography Artifact Removal.

Photoacoustic imaging is an emerging imaging modality that is based upon the photoacoustic effect. In photoacoustic tomography (PAT), the induced acoustic pressure waves are measured by an array of detectors and used to reconstruct an image of the initial pressure distribution. A common challenge faced in PAT is that the measured acoustic waves can only be sparsely sampled. Reconstructing sparsely sampled data using standard methods results in severe artifacts that obscure information within the image. We propose a modified convolutional neural network (CNN) architecture termed fully dense UNet (FD-UNet) for removing artifacts from two-dimensional PAT images reconstructed from sparse data and compare the proposed CNN with the standard UNet in terms of reconstructed image quality.

SVD-Based Separation of Stable and Inertial Cavitation Signals Applied to Passive Cavitation Mapping During HIFU.

Detection of inertial and stable cavitation is important for guiding high-intensity focused ultrasound (HIFU). Acoustic transducers can passively detect broadband noise from inertial cavitation and the scattering of HIFU harmonics from stable cavitation bubbles. Conventional approaches to cavitation noise diagnostics typically involve computing the Fourier transform of the time-domain noise signal, applying a custom comb filter to isolate the frequency components of interest, followed by an inverse Fourier transform. We present an alternative technique based on singular value decomposition (SVD) that efficiently separates the broadband emissions and HIFU harmonics. Spatiotemporally resolved cavitation detection was achieved using a 128-element, 5-MHz linear-array ultrasound imaging system operating in the receive mode at 15 frames/s. A 1.1-MHz transducer delivered HIFU to tissue-mimicking phantoms and excised liver tissue for a duration of 5 s. Beamformed radio frequency signals corresponding to each scan line in a frame were assembled into a matrix, and SVD was performed. Spectra of the singular vectors obtained from a tissue-mimicking gel phantom were analyzed by computing the peak ratio ( R ), defined as the ratio of the peak of its fifth-order polynomial fit and the maximum spectral peak. Singular vectors that produced an were classified as those representing stable cavitation, i.e., predominantly containing harmonics of HIFU. The projection of data onto this singular base reproduced stable cavitation signals. Similarly, singular vectors that produced an were classified as those predominantly containing broadband noise associated with inertial cavitation. These singular vectors were used to isolate the inertial cavitation signal. The R -value thresholds determined using gel data were then employed to analyze cavitation data obtained from bovine liver ex vivo. The SVD-based method faithfully reproduced the structural details in the spatiotemporal cavitation maps produced using the more cumbersome comb-filter approach with a maximum root-mean-squared error of 10%.

Customization of the acoustic field produced by a piezoelectric array through interelement delays.

A method for producing a prescribed acoustic pressure field from a piezoelectric array was investigated. The array consisted of 170 elements placed on the inner surface of a 15 cm radius spherical cap. Each element was independently driven by using individual pulsers each capable of generating 1.2 kV. Acoustic field customization was achieved by independently controlling the time when each element was excited. The set of time delays necessary to produce a particular acoustic field was determined by using an optimization scheme. The acoustic field at the focal plane was simulated by using the angular spectrum method, and the optimization searched for the time delays that minimized the least squared difference between the magnitudes of the simulated and desired pressure fields. The acoustic field was shaped in two different ways: the -6 dB focal width was increased to different desired widths and the ring-shaped pressure distributions of various prescribed diameters were produced. For both cases, the set of delays resulting from the respective optimization schemes were confirmed to yield the desired pressure distributions by using simulations and measurements. The simulations, however, predicted peak positive pressures roughly half those obtained from the measurements, which was attributed to the exclusion of nonlinearity in the simulations.

A frequency-domain non-contact photoacoustic microscope based on an adaptive interferometer.

A frequency-domain, non-contact approach to photoacoustic microscopy (PAM) that employs amplitude-modulated (0.1-1 MHz) laser for excitation (638-nm pump) in conjunction with a 2-wave mixing interferometer (532-nm probe) for non-contact detection of photoacoustic waves at the specimen surface is presented. A lock-in amplifier is employed to detect the photoacoustic signal. Illustrative images of tissue-mimicking phantoms, red-blood cells and retinal vasculature are presented. Single-frequency modulation of the pump beam directly provides an image that is equivalent to the 2-dimensional projection of the image volume. Targets located superficially produce phase modulations in the surface-reflected probe beam due to surface vibrations as well as direct intensity modulation in the backscattered probe light due to local changes in pressure and/or temperature. In comparison, the observed modulations in the probe beam due to targets located deeper in the specimen, for example, beyond the ballistic photon regime, predominantly consist of phase modulation.

Acoustic field of a ballistic shock wave therapy device.

Shock wave therapy (SWT) refers to the use of focused shock waves for treatment of musculoskeletal indications including plantar fascitis and dystrophic mineralization of tendons and joint capsules. Measurements were made of a SWT device that uses a ballistic source. The ballistic source consists of a handpiece within which compressed air (1-4 bar) is used to fire a projectile that strikes a metal applicator placed on the skin. The projectile generates stress waves in the applicator that transmit as pressure waves into tissue. The acoustic fields from two applicators were measured: one applicator was 15 mm in diameter and the surface slightly convex and the second was 12 mm in diameter the surface was concave. Measurements were made in a water tank and both applicators generated a similar pressure pulse consisting of a rectangular positive phase (4 micros duration and up to 8 MPa peak pressure) followed by a predominantly negative tail (duration of 20 micros and peak negative pressure of -6 MPa), with many oscillations. The rise times of the waveforms were around 1 micros and were shown to be too long for the pulses to be considered shock waves. Measurements of the field indicated that region of high pressure was restricted to the near-field (20-40 mm) of the source and was consistent with the Rayleigh distance. The measured acoustic field did not display focusing supported by calculations, which demonstrated that the radius of curvature of the concave surface was too large to effect a focusing gain. Other SWT devices use electrohydraulic, electromagnetic and piezoelectric sources that do result in focused shock waves. This difference in the acoustic fields means there is potentially a significant mechanistic difference between a ballistic source and other SWT devices.