Spatially controlled diffusion range of tumor-associated angiogenic factors to develop a tumor model using a microfluidic resistive circuit.

Developing a tumor model with vessels has been a challenge in microfluidics. This difficulty is because cancer cells can overgrow in a co-culture system. The up-regulation of anti-angiogenic factors during the initial tumor development can hinder neovascularization. The standard method is to develop a quiescent vessel network before loading a tumor construct in an adjacent chamber, which simulates the interaction between a tumor and its surrounding vessels. Here, we present a new method that allows a vessel network and a tumor to develop simultaneously in two linked chambers. The physiological environment of these two chambers is controlled by a microfluidic resistive circuit using two symmetric long microchannels. Applying the resistive circuit, a diffusion-dominated environment with a small 2-D pressure gradient is created across the two chambers with velocity <10.9 nm s-1 and Péclet number <6.3 × 10-5. This 2-D pressure gradient creates a V-shaped velocity clamp to confine the tumor-associated angiogenic factors at pores between the two chambers, and it has two functions. At the early stage, vasculogenesis is stimulated to grow a vessel network in the vessel chamber with minimal influence from the tumor that is still developed in the adjacent chamber. At the post-tumor-development stage, the induced steep concentration gradient at pores mimics vessel-tumor interactions to stimulate angiogenesis to grow vessels toward the tumor. Applying this method, we demonstrate that vasculogenic vessels can grow first, followed by stimulating angiogenesis. Angiogenic vessels can grow into stroma tissue up to 1.3 mm long, and vessels can also grow into or wrap around a 625 µm tumor spheroid or a tumor tissue developed from a cell suspension. In summary, our study suggests that the interactions between a developing vasculature and a growing tumor must be controlled differently throughout the tissue development process, including at the early stage when vessels are still forming and at the later stage when the tumor needs to interact with the vessels.

Ultrafast Doppler Imaging for Early Detection of Synovitis in Rheumatoid Arthritis.

OBJECTIVE: Current medical ultrasound systems possess limited sensitivity in detecting slow and weak blood flow during the early stages of rheumatoid arthritis (RA), leading to potential misdiagnosis. Ultrafast Doppler is capable of detecting slow and weak flow. This study was aimed at evaluating the diagnostic value of ultrafast Doppler for RA. METHODS: Thirty-three RA patients (19 established, 14 early stage) and 15 healthy participants were enrolled. A programmable imaging platform with ultrafast Doppler capability was used. The benchmark was a clinical system with conventional Doppler imaging. Standardized dorsal long-axis scanning of both wrists was performed. Both ultrafast and conventional power Doppler (PD) images were quantitatively analyzed with computer assistance and semiquantitatively scored with the Outcome Measures in Rheumatology (OMERACT) scoring system. RESULTS: Ultrafast PD revealed more blood area than conventional PD in both RA wrists and healthy wrists. Ultrafast PD OMERACT was positive in 65 of 66 RA wrists and 26 of 30 healthy wrists (sensitivity [SEN] = 0.985, accuracy [ACC] = 0.719), while conventional PD OMERACT was positive in 28 of 66 RA wrists and 0 of 30 healthy wrists (SEN = 0.424, ACC = 0.604). Ultrafast PD revealed a higher synovial PD area, dilated vessels and PD brightness in RA wrists. Peak synovial PD brightness had the best diagnostic value for RA (area under the receiver operating characteristic curve = 0.802, SEN = 0.909, ACC = 0.813). For early-stage RA patients, ultrafast peak synovial PD brightness had higher sensitivity and accuracy than conventional PD indexes. CONCLUSION: Ultrafast PD had an increase of 0.561 in sensitivity and 0.209 in accuracy when compared with conventional PD. With its high sensitivity, ultrafast PD can detect early synovitis and identify RA patients during the early phase.

Fourier-Based Fast 3-D Ultrasound Imaging Using Row-Column-Addressed 2-D Arrays.

A Fourier-based fast 3-D ultrasound imaging method using row-column-addressed (RCA) 2-D arrays is presented. The row elements in an RCA array are activated sequentially, and all the column elements are used to receive. The obtained dataset is adapted to approximate to that obtained using a fully sampled array after a plane wave at a given incident angle is transmitted. In this way, the fast algorithm in plane-wave Fourier imaging (PWFI) can be applied to the adapted dataset. In addition, synthesizing multiple datasets based on multiple incident angles enables angular compounding, which improves the image quality. The proposed method was validated using computer simulations and physical-phantom experiments. The results show that the spatial resolution and contrast of the proposed method are comparable with those of its PWFI counterpart without requiring a fully sampled (FS) array. Compared with the delay-and-sum (DAS) method using the RCA array, the proposed method provides comparable spatial resolution but lower contrast; however, the computational complexity is significantly reduced from O(N4Nz) to O(WN2Nz log2(N2Nz)) , where N is the number of elements on each side of the RCA array, Nz is the number of voxels in the axial direction in the output image, and W is the number of compounding angles. For example, in the simulated results when the maximum compounding angle M is 5°, at a given point the lateral - 6-dB width provided by the proposed method is 0.241 mm (0.267 mm for DAS), the contrast ratio of a hyperechoic cyst is 8.87 dB (9.10 dB for DAS), the number of real number operations is reduced by a factor of 20.62, and the number of memory accesses is reduced by a factor of 47.21, both compared with DAS. This novel fast algorithm could facilitate the development of compact real-time 3-D imaging systems, especially when the channel count is high and a large field of view (FOV) is required.

Longitudinal shear wave elasticity measurements of millimeter-sized biomaterials using a single-element transducer platform.

Temporal variations of the extracellular matrix (ECM) stiffness profoundly impact cellular behaviors, possibly more significantly than the influence of static stiffness. Three-dimensional (3D) cell cultures with tunable matrix stiffness have been utilized to characterize the mechanobiological interactions of elasticity-mediated cellular behaviors. Conventional studies usually perform static interrogations of elasticity at micro-scale resolution. While such studies are essential for investigations of cellular mechanotransduction, few tools are available for depicting the temporal dynamics of the stiffness of the cellular environment, especially for optically turbid millimeter-sized biomaterials. We present a single-element transducer shear wave (SW) elasticity imaging system that is applied to a millimeter-sized, ECM-based cell-laden hydrogel. The single-element ultrasound transducer is used both to generate SWs and to detect their arrival times after being reflected from the side boundaries of the sample. The sample's shear wave speed (SWS) is calculated by applying a time-of-flight algorithm to the reflected SWs. We use this noninvasive and technically straightforward approach to demonstrate that exposing 3D cancer cell cultures to X-ray irradiation induces a temporal change in the SWS. The proposed platform is appropriate for investigating in vitro how a group of cells remodels their surrounding matrix and how changes to their mechanical properties could affect the embedded cells in optically turbid millimeter-sized biomaterials.

Sonoporation based on repeated vaporization of gold nanodroplets.

BACKGROUND: Gold nanodroplets (AuNDs) have been proposed as agents for photothermal therapy and photoacoustic imaging. Previously, we demonstrated that the sonoporation can be more effectively achieved with synchronized optical and acoustic droplet vaporization. By applying a laser pulse at the rarefactional phase of the ultrasound (US) pulse, the vaporization threshold can be reached at a considerably lower laser average power. However, a large loading quantity of the AuNDs may increase the risk of air embolism. The destruction of phase-shifted AuNDs at the inertial cavitation stage leads to a reduced drug delivery performance. And it also causes instability of echogenicity during therapeutic monitoring. PURPOSE: In this study, we propose to further improve the sonoporation effectiveness with repeated vaporization. In other words, the AuNDs repeatedly undergo vaporization and recondensation so that sonoporation effects are accumulated over time at lower energy requirements. Previously, repeated vaporization has been demonstrated as an imaging contrast agent. In this study, we aim to adopt this repeated vaporization scheme for sonoporation. METHODS: Perfluoropentane NDs with a shell made of human serum albumin were used as the US contrast agents. Laser pulses at 808 nm and US pulses of 1 MHz were delivered for triggering vaporization and inertial cavitation of NDs. We detected the vaporization and cavitation effects under different activation firings, US peak negative pressures (PNPs), and laser fluences using 5- and 10-MHz focused US receivers. Numbers of calcein-AM and propidium iodide signals uptake by BNL hepatocarcinoma cancer cells were used to evaluate the sonoporation and cell death rate of the cells. RESULTS: We demonstrate that sonoporation can be realized based on repeatable vaporization instead of the commonly adopted inertial cavitation effects. In addition, it is found that the laser fluence and the acoustic pressure can be reduced. As an example, we demonstrate that the acoustic and optical energy for achieving a similar level of sonoporation rate can be as low as 0.44 MPa for the US PNP and 4.01 mJ/cm2 for the laser fluence, which are lower than those with our previous approach (0.53 MPa and 4.95 mJ/cm2 , respectively). CONCLUSION: We demonstrated the feasibility of vaporization-based sonoporation at a lower optical and acoustic energy. It is an advantageous method that can enhance drug delivery efficiency, therapeutic safety and potentially deliver an upgraded gene therapy strategy for improved theragnosis.

Development and validation of a deep learning-based algorithm for colonoscopy quality assessment.

BACKGROUND: Quality indicators should be assessed and monitored to improve colonoscopy quality in clinical practice. Endoscopists must enter relevant information in the endoscopy reporting system to facilitate data collection, which may be inaccurate. The current study aimed to develop a full deep learning-based algorithm to identify and analyze intra-procedural colonoscopy quality indicators based on endoscopy images obtained during the procedure. METHODS: A deep learning system for classifying colonoscopy images for quality assurance purposes was developed and its performance was assessed with an independent dataset. The system was utilized to analyze captured images and results were compared with those of real-world reports. RESULTS: In total, 10,417 images from the hospital endoscopy database and 3157 from Hyper-Kvasir open dataset were utilized to develop the quality assurance algorithm. The overall accuracy of the algorithm was 96.72% and that of the independent test dataset was 94.71%. Moreover, 761 real-world reports and colonoscopy images were analyzed. The accuracy of electronic reports about cecal intubation rate was 99.34% and that of the algorithm was 98.95%. The agreement rate for the assessment of polypectomy rates using the electronic reports and the algorithm was 0.87 (95% confidence interval 0.83-0.90). A good correlation was found between the withdrawal time calculated using the algorithm and that entered by the physician (correlation coefficient r = 0.959, p < 0.0001). CONCLUSION: We proposed a novel deep learning-based algorithm that used colonoscopy images for quality assurance purposes. This model can be used to automatically assess intra-procedural colonoscopy quality indicators in clinical practice.

Upper endoscopy photodocumentation quality evaluation with novel deep learning system.

OBJECTIVES: Visualization and photodocumentation during endoscopy procedures are suggested to be one indicator for endoscopy performance quality. However, this indicator is difficult to measure and audit manually in clinical practice. Artificial intelligence (AI) is an emerging technology that may solve this problem. METHODS: A deep learning model with an accuracy of 96.64% was developed from 15,305 images for upper endoscopy anatomy classification in the unit. Endoscopy images for asymptomatic patients receiving screening endoscopy were evaluated with this model to assess the completeness of photodocumentation rate. RESULTS: A total of 15,723 images from 472 upper endoscopies performed by 12 endoscopists were enrolled. The complete photodocumentation rate from the pharynx to the duodenum was 53.8% and from the esophagus to the duodenum was 78.0% in this study. Endoscopists with a higher adenoma detection rate had a higher complete examination rate from the pharynx to duodenum (60.0% vs. 38.7%, P < 0.0001) and from esophagus to duodenum (83.0% vs. 65.7%, P < 0.0001) compared with endoscopists with lower adenoma detection rate. The pharynx, gastric angle, gastric retroflex view, gastric antrum, and the first portion of duodenum are likely to be missed by endoscopists with lower adenoma detection rates. CONCLUSIONS: We report the use of a deep learning model to audit endoscopy photodocumentation quality in our unit. Endoscopists with better performance in colonoscopy had a better performance for this quality indicator. The use of such an AI system may help the endoscopy unit audit endoscopy performance.

Deep learning-based endoscopic anatomy classification: an accelerated approach for data preparation and model validation.

BACKGROUND: Photodocumentation during endoscopy procedures is one of the indicators for endoscopy performance quality; however, this indicator is difficult to measure and audit in the endoscopy unit. Emerging artificial intelligence technology may solve this problem, which requires a large amount of material for model development. We developed a deep learning-based endoscopic anatomy classification system through convolutional neural networks with an accelerated data preparation approach. PATIENTS AND METHODS: We retrospectively collected 8,041 images from esophagogastroduodenoscopy (EGD) procedures and labeled them using two experts for nine anatomical locations of the upper gastrointestinal tract. A base model for EGD image multiclass classification was first developed, and an additional 6,091 images were enrolled and classified by the base model. A total of 5,963 images were manually confirmed and added to develop the subsequent enhanced model. Additional internal and external endoscopy image datasets were used to test the model performance. RESULTS: The base model achieved total accuracy of 96.29%. For the enhanced model, the total accuracy was 96.64%. The overall accuracy improved with the enhanced model compared with the base model for the internal test dataset without narrowband images (93.05% vs. 91.25%, p < 0.01) or with narrowband images (92.74% vs. 90.46%, p < 0.01). The total accuracy was 92.56% of the enhanced model on the external test dataset. CONCLUSIONS: We constructed a deep learning-based model with an accelerated approach that can be used for quality control in endoscopy units. The model was also validated with both internal and external datasets with high accuracy.

Laser-Generated Leaky Acoustic Wave Imaging for Interventional Guidewire Guidance.

Ultrasound (US) is widely used to visualize both tissue and the positions of surgical instruments in real time during surgery. Previously we proposed a new method to exploit US imaging and laser-generated leaky acoustic waves (LAWs) for needle visualization. Although successful, that method only detects the position of a needle tip, with the location of the entire needle deduced from knowing that the needle is straight. The purpose of the current study was to develop a beamforming-based method for the direct visualization of objects. The approach can be applied to objects with arbitrary shapes, such as the guidewires that are commonly used in interventional guidance. With this method, illumination by a short laser pulse generates photoacoustic waves at the top of the guidewire that propagate down its metal surface. These waves then leak into the surrounding tissue, which can be detected by a US array transducer. The time of flight consists of two parts: 1) the propagation time of the guided waves on the guidewire and 2) the propagation time of the US that leaks into the tissue. In principle, an image of the guidewire can be formed based on array beamforming by taking the propagation time on the metal into consideration. Furthermore, we introduced directional filtering and a matched filter to compress the dispersion signal associated with long propagation times. The results showed that guidewires could be detected at depths of at least 70 mm. The maximum detectable angle was 56.3°. LAW imaging with a 1268-mm-long guidewire was also demonstrated. The proposed method has considerable potential in new clinical applications.

Functional photoacoustic calcium imaging using chlorophosphonazo III in a 3D tumor cell culture.

This study demonstrates that chlorophosphonazo III (CPZ III) can be used as a contrast agent for photoacoustic calcium imaging. CPZ III can pass across the plasma membrane for labeling intracellular Ca2+ without cytotoxicity. In optical-resolution photoacoustic microscopy (OR-PAM), the photoacoustic (PA) signal intensity was strongly correlated with the presence of CPZ III and Ca2+ at various concentrations. The sensitivity of PA signal reception was enhanced by using an 8 MHz single-element focused ultrasound detector due to their matched frequency characteristics. Differences in the PA signal intensity were successfully found between the core and margin areas of tumorspheres in three-dimensional cell cultures. These findings indicate that CPZ III can serve as a novel PA contrast agent for functional Ca2+ imaging using OR-PAM.

Enhanced Radiosensitization for Cancer Treatment with Gold Nanoparticles through Sonoporation.

We demonstrate the megavoltage (MV) radiosensitization of a human liver cancer line by combining gold-nanoparticle-encapsulated microbubbles (AuMBs) with ultrasound. Microbubbles-mediated sonoporation was administered for 5 min, at 2 h prior to applying radiotherapy. The intracellular concentration of gold nanoparticles (AuNPs) increased with the inertial cavitation of AuMBs in a dose-dependent manner. A higher inertial cavitation dose was also associated with more DNA damage, higher levels of apoptosis markers, and inferior cell surviving fractions after MV X-ray irradiation. The dose-modifying ratio in a clonogenic assay was 1.56 ± 0.45 for a 10% surviving fraction. In a xenograft mouse model, combining vascular endothelial growth factor receptor 2 (VEGFR2)-targeted AuMBs with sonoporation significantly delayed tumor regrowth. A strategy involving the spatially and temporally controlled release of AuNPs followed by clinically utilized MV irradiation shows promising results that make it worthy of further translational investigations.

Photoacoustic imaging of cells in a three-dimensional microenvironment.

Imaging live cells in a three-dimensional (3D) culture system yields more accurate information and spatial visualization of the interplay of cells and the surrounding matrix components compared to using a two-dimensional (2D) cell culture system. However, the thickness of 3D cultures results in a high degree of scattering that makes it difficult for the light to penetrate deeply to allow clear optical imaging. Photoacoustic (PA) imaging is a powerful imaging modality that relies on a PA effect generated when light is absorbed by exogenous contrast agents or endogenous molecules in a medium. It combines a high optical contrast with a high acoustic spatiotemporal resolution, allowing the noninvasive visualization of 3D cellular scaffolds at considerable depths with a high resolution and no image distortion. Moreover, advances in targeted contrast agents have also made PA imaging capable of molecular and cellular characterization for use in preclinical personalized diagnostics or PA imaging-guided therapeutics. Here we review the applications and challenges of PA imaging in a 3D cellular microenvironment. Potential future developments of PA imaging in preclinical applications are also discussed.

Laser-speckle-contrast projection tomography for three-dimensional shear wave imaging.

Laser-speckle-contrast shear wave (LSC-SW) imaging is an optical method for tracking the propagation of a transient shear wave. With high spatial resolution and sensitivity in detecting displacements, this method is suitable for performing mechanical measurements in vitro. Here, we present a LSC-SW tomographic imaging system for visualizing the propagating shear wave wavefront in four dimensions [i.e., three-dimensional (3D) space plus time]. The volumetric elasticity distribution of a sample is constructed by estimating the speeds of the shear waves propagating along multiple paths at different angles. The proposed method enables multidirectional estimations of the shear wave speed. The capabilities of the imaging system are demonstrated by evaluating isotropy (both homogeneous and heterogeneous) and anisotropy in semiturbid phantoms. The proposed system is suitable for the mechanical characterization of a 3D cell culture system, such as monitoring changes in fiber orientation during the remodeling of the extracellular matrix that is known to be strongly associated with the progression and characterization of tumors.

Synchronized Optical and Acoustic Droplet Vaporization for Effective Sonoporation.

Inertial cavitation-based sonoporation has been utilized to enhance treatment delivery efficacy. In our previous study, we demonstrated that tumor therapeutic efficacy can be enhanced through vaporization-assisted sonoporation with gold nanodroplets (AuNDs). Specifically, the AuNDs were vaporized both acoustically (i.e., acoustic droplet vaporization, ADV) and optically (i.e., optical droplet vaporization, ODV). A continuous wave (CW) laser was used for ODV in combination with an ultrasound pulse for ADV. Although effective for vaporization, the use of a CW laser is not energy efficient and may create unwanted heating and concomitant tissue damage. In this study, we propose the use of a pulsed wave (PW) laser to replace the CW laser. In addition, the PW laser was applied at the rarefaction phase of the ultrasound pulse so that the synergistic effects of ADV and ODV can be expected. Therefore, a significantly lower laser average power can be expected to achieve the vaporization threshold. Compared to the CW laser power at 2 W/cm2 from the previous approach, the PW laser power was reduced to only 0.2404 W/cm2. Furthermore, we also demonstrate in vitro that the sonoporation rate was increased when the PW laser was applied at the rarefaction phase. Specifically, the vaporization signal, the inertial cavitation signal, and the sonoporation rate all displayed a 1-µs period, which corresponded to the period of the 1-MHz acoustic wave used for ADV, as a function of the relative laser delay. The increased sonoporation rate indicates that this technique has the potential to enhance sonoporation-directed drug delivery and tumor therapy with a lower laser power while keeping the cell death rate at the minimum. Photoacoustic imaging can also be performed at the same time since a PW laser is used for the ODV.

Study of diffusive- and convective-transport mediated microtumor growth in a controlled microchamber.

In this paper, we report on using mass transport to control nutrition supply of colorectal cancer cells for developing a microtumor in a confined microchamber. To mimic the spatial heterogeneity of a tumor, two microfluidic configurations based on resistive circuits are designed. One has a convection-dominated microchamber to simulate the tumor region proximal to leaky blood vessels. The other has a diffusion-dominated microchamber to mimic the tumor core that lacks blood vessels and nutrient supply. Thus, the time for nutrition to fill the microchamber can vary from tens of minutes to several hours. Results show that cells cultured under a diffusive supply of nutrition have a high glycolytic rate and a nearly constant oxygen consumption rate. In contrast, cells cultured under convective supply of nutrition have a gradual increase of oxygen consumption rate with a low glycolytic rate. This suggests that cancer cells have distinct reactions under different mass transport and nutrition supply. Using these two microfluidic platforms to create different rate of nutrition supply, it is found that a continuous microtumor that almost fills the mm-size microchamber can be developed under a low-nutrient supply environment, but not for the convective condition. It also is demonstrated that microchannels can simulate the delivery of anti-cancer drugs to the microtumor under controlled mass-transport. This method provides a means to develop a larger scale microtumor in a lab-on-a-Chip system for post development and stimulations, and microchannels can be applied to control the physical and chemical environment for anti-cancer drug screening.

Shear Wave Elasticity Measurements of Three-Dimensional Cancer Cell Cultures Using Laser Speckle Contrast Imaging.

Shear wave elastography (SWE) has been widely adopted for clinical in vivo imaging of tissue elasticity for disease diagnosis, and this modality can be a valuable tool for in vitro mechanobiology studies but its full potential has yet to be explored. Here we present a laser speckle contrast SWE system for noncontact monitoring the spatiotemporal changes of the extracellular matrix (ECM) stiffness in three-dimensional cancer cell culture system while providing submillimeter spatial resolution and temporal resolution of 10 s. The shear modulus measured was found to be strongly correlated with the ECM fiber density in two types of cell culture system (r = 0.832 with P < 0.001, and r = 0.642 with P = 0.024 for cell culture systems containing 4 mg/ml Matrigel with 1 mg/ml and 2 mg/ml collagen type I hydrogel, respectively). Cell migration along the stiffness gradient in the cell culture system and an association between cell proliferation and the local ECM stiffness was observed. As the elasticity measurement is performed without the need of exogenous probes, the proposed method can be used to study how the microenvironmental stiffness interacts with cancer cell behaviors without possible adverse effects of the exogenous particles, and could potentially be an effective screening tool when developing new treatment strategies.

Microbeamforming With Error Compensation.

One of the main issues in the development of 2-D arrays is the high system complexity due to the requirement for a large number of elements. The 2-D array systems suffer from high system complexity. The microbeamforming (MBF) method has been proposed to reduce the system complexity; however, distortions of MBF approach such as focusing errors of postbeamforming process result in broadening the main lobe and increasing the sidelobe and grating-lobe levels, which together degrade the image quality. As the presteered radio frequency (RF) data can be estimated from MBF data at the digital back end, better postbeamforming can be performed and higher image quality can be achieved. In this paper, a compensation approach is proposed to estimate the presteered RF data from MBF data by utilizing additional headers and compensation factors. The compensation factors and headers are estimated at the probe front end and then applied to the back-end digital system to reconstruct the required presteered RF data. As the absolute values of the MBF errors are modeled as a single-sided Gaussian distribution, the theoretical mean square error with the proposed method is approximately 2.75 times lower than that of its counterpart without compensation; this implies better reconstruction of presteered RF data can be achieved with the proposed method. The simulation results showed that the main lobe is improved, and the sidelobe and grating-lobe levels in both the lateral and elevation directions were improved by 11.73 and 19.12 dB, respectively, while the peak signal-to-noise ratios improved by 6-9 dB with the proposed method. The contrast-to-noise ratios also are enhanced by 0.5 dB when using the proposed method. Analog circuits are presented to demonstrate that this novel compensation method can be realized in practice. The reduction of cables and analog-to-digital converters are about seven-fold compared to fully sampled 2-D array systems as 4 by 4 channels are grouped for the proposed method as well.

Micro-beamforming with Error Compensation.

One of the main issues in the development of 2D arrays is the high system complexity due to the requirement for a large number of elements. 2D array systems suffer from high system complexity. Micro-beamforming (MBF) method has been proposed to reduce the system complexity; however, distortions of MBF approach such as focusing errors of post-beamforming process results in broadening the main lobe and increasing the side-lobe and grating-lobe levels, which together degrade the image quality. As the pre-steered radio-frequency (RF) data can be estimated from MBF data at the digital back end, better post-beamforming can be performed and higher image quality can be achieved. In this study, a compensation approach is proposed to estimate the pre-steered RF data from MBF data by utilizing additional headers and compensation factors. The compensation factors and headers are estimated at the probe front end and then applied to the back-end digital system to reconstruct the required pre-steered RF data. As the absolute values of the MBF errors are modeled as a single-sided Gaussian distribution, the theoretical mean square error (MSE) with the proposed method is approximately 2.75 times lower than that of its counterpart without compensation; this implies better reconstruction of pre-steered RF data can be achieved with the proposed method. The simulation results showed that the main lobe is improved, and the side-lobe and grating-lobe levels in both the lateral and elevation directions were improved by 11.73 dB and 19.12 dB, respectively, while the peak signal-to-noise ratios improved by 6-9 dB with the proposed method. The contrast-to-noise ratios also are enhanced by 0.5 dB when using the proposed method. Analog circuits are presented to demonstrate that this novel compensation method can be realized in practice. The reduction of cables and analog-to-digital converters (ADCs) are about 7-fold compared to fully-sampled 2D array systems as 4 by 4 channels are grouped for the proposed method as well.

Laser Generated Leaky Acoustic Waves for Needle Visualization.

Ultrasound (US)-guided needle operation is usually used to visualize both tissue and needle position such as tissue biopsy and localized drug delivery. However, the transducer-needle orientation is limited due to reflection of the acoustic waves. We proposed a leaky acoustic wave method to visualize the needle position and orientation. Laser pulses are emitted on top of the needle to generate acoustic waves; then, these acoustic waves propagate along the needle surface. Leaky wave signals are detected by the US array transducer. The needle position can be calculated by phase velocities of two different wave modes and their corresponding emission angles. In our experiments, a series of needles was inserted into a tissue mimicking phantom and porcine tissue to evaluate the accuracy of the proposed method. The results show that the detection depth is up to 51 mm and the insertion angle is up to 40° with needles of different diameters. It is demonstrated that the proposed approach outperforms the conventional B-mode US-guided needle operation in terms of the detection range while achieving similar accuracy. The proposed method reveals the potentials for further clinical applications.

Ultrasound Strain Imaging to Assess the Biceps Brachii Muscle in Chronic Poststroke Spasticity.

OBJECTIVES: The aim of the study was to assess the feasibility of ultrasound strain imaging in characterizing the biceps brachii muscle in chronic poststroke spasticity. METHODS: We prospectively analyzed strain imaging data from bilateral biceps brachii muscles in 8 healthy volunteers and 7 patients with poststroke chronic spasticity. Axial deformations of the biceps brachii muscle and overlying subcutaneous tissue were produced by external compression using a sandbag (1.0 kg) attached to a transducer. The lengthening and shortening of the biceps brachii muscle and subcutaneous tissue were produced by manual passive elbow extension (from 90° to 0°) and flexion (from 0° to 90°), respectively. We used offline 2-dimensional speckle tracking to estimate axial and longitudinal strain ratios (biceps brachii strain/subcutaneous tissue strain), and the longitudinal tissue velocity of the biceps brachii muscle. Statistical analyses included analysis of variance for testing differences in strain imaging parameters among healthy, nonspastic, and spastic biceps brachii muscles, the Bonferroni correction for further testing differences in US strain imaging among paired groups (healthy versus spastic, nonspastic versus spastic, and healthy versus nonspastic), and the Pearson correlation coefficient for assessing the intraobserver reliability of performing strain imaging in stroke survivors. RESULTS: The differences in strain imaging parameters between healthy and spastic and between nonspastic and spastic biceps brachii muscles were significant at both 90° elbow flexion and maximal elbow extension (P < .01). There was no significant difference in axial strain ratios at 90° of elbow flexion or longitudinal tissue velocities between healthy and nonspastic muscles (P > .05). The intraobserver reliability of performing strain imaging in stroke survivors was good (r = 0.85; P < .01). CONCLUSIONS: Ultrasound strain imaging seems to be feasible for characterizing the biceps brachii muscle in chronic poststroke spasticity.