Microbubble-mediated sonothrombolysis shows great potential for deep vein thrombosis (DVT) treatment, yet its clinical efficacy is often hindered by restricted drug penetration and suboptimal acoustic parameter configurations. While multi-ultrasound systems offer improved thrombolytic performance, acoustic field interactions remain poorly understood. This study developed a multiphysics simulation integrating microbubble dynamics, acoustic streaming, and convection-reaction to investigate the combined effects of an intravascular ultrasound catheter (IVUC) and a semi-flexible wearable ultrasound probe (sf-WUP). Numerical simulations were employed to predict the impact of dual-source configuration on thrombolysis, with validation performed through in vitro phantom experiments. Both approaches demonstrated that the dual-source approach achieves superior thrombolytic efficiency compared to either single mode. Furthermore, by introducing a pulse delay time (DT) between IVUC and sf-WUP, temporal decoupling of the two acoustic fields was achieved. Thrombolytic efficiency was found to increase with DT, exhibiting a negative correlation with temporal overlap between the two acoustic fields. The temporally decoupled dual-source configuration significantly outperformed synchronous excitation (DT = 0 ms). Specifically, in vitro experiments achieved a thrombolysis extent of 62.0% at DT of 3 ms, markedly higher than the 51.0% observed with synchronous excitation at DT = 0 ms. Simulations further revealed that temporal separation enhances acoustic streaming velocity, seepage flow, and clot deformation compared to synchronous excitation. These findings elucidate the crucial role of temporal decoupling in dual-source sonothrombolysis, providing a solid theoretical foundation for optimizing non-invasive therapeutic protocols.

Dexterous hand motor functions are highly flexible and finely controlled by complex neural commands from the motor cortex. However, in patients with brain injuries such as stroke, restoring fine motor control from the perilesional cortex remains extremely challenging. A major obstacle is the absence of appropriate non-human primate models to elucidate the behavioral and neural signatures of hand motor function during recovery following treatments. Here, we present a new non-human primate model that reflects the motor function recovery processes following lesion-induced hand paralysis after contralateral C7 nerve transfer (CC7) surgery, which establishes a new neural pathway from the ipsilateral cortex to control the paralyzed hand. By developing a hand reach-to-pinch task and quantifying finger kinematics, we established systematic, objective profiles of fine motor recovery in human patients and monkey models following CC7 treatment. Furthermore, when considering behavioral aspects, spontaneous recovery of hand motor skills was notably limited in human patients and monkey models, as indicated by the consistently abnormal “thumb-in-palm” patterns observed in finger kinematic analysis. However, the CC7 surgery gradually restored the finger kinematic patterns during hand-pinch actions to nearly identical patterns to those of the healthy hand. In addition, the human functional MRI and macaque electrophysiology results revealed, on a neural level, the emergence of a new command area and its spiking-based motor-command refinements specifically for the paralyzed hand in the contralesional M1 and premotor cortex (PMC) after CC7 treatment. Thus, our findings strongly support the notion that modifying peripheral nerve pathways greatly promotes the recovery of dexterous motor function in a paralyzed hand by reconstructing new motor-control neural mechanisms within the ipsilateral healthy motor cortex.

Catheter-directed thrombolysis (CDT) is a commonly treatment for blood clots, but it requires large urokinase doses and carries bleeding risks. Therapeutic ultrasound has shown ability in enhancing thrombolysis, but existing ultrasound thrombolysis strategy is not suitable for long-term operation. This study had developed a semi-flexible wearable ultrasound probe (sf-WUP) to enhance effectiveness of CDT in heavy thrombus burden with low-dose urokinase. The sf-WUP was bent to focus on the thrombus and transmit either single-frequency ultrasound at 1.8 MHz or dual-frequency ultrasound (1.8 MHz and 1.88 MHz). The catheter was used to deliver low-dose urokinase or a combination of urokinase and microbubbles to the target thrombus. Thrombolysis extent was the thrombus mass reduction percentage. In 50 min, the thrombolysis extent of low-dose urokinase was only 11.40%, while the sf-WUP using single-frequency ultrasound with microbubbles increased to 55.23%. Under constant acoustic power, the dual-frequency ultrasound reached a thrombolysis extent of 63.78%. When the peak-to-peak sound pressure was kept constant, the dual-frequency ultrasound achieved a similar thrombolysis extent but with 9.75%-13.84% lower electrical power compared to single-frequency ultrasound. The sf-WUP using single-frequency ultrasound can significantly improve the thrombolysis extent of low-dose urokinase CDT. The use of dual-frequency ultrasound with constant power can further enhance efficiency, while dual-frequency ultrasound with constant peak-to-peak sound pressure shows better energy efficiency. Both are compatible with wearable devices, laying the foundation for the clinical translation of ultrasound assisted CDT.

The effective radiating area is a crucial parameter in ultrasound applications, particularly for evaluating the therapeutic effect of planar non-focused therapeutic ultrasound transducers. Recent studies, however, reveal significant uncertainty in measuring effective radiating area. Additionally, the high-power input used in the measurement may shorten the lifespan of both the transducer and the hydrophone. These issues undermine the reliability of the effective radiating area measurement results. At present, a definitive and practical method for obtaining a reliable measurement of the effective radiating area safely and conveniently is still lacking. To address these issues, the measurement setup, including the duty cycle, grid accuracy, and hydrophone sensitivity, was discussed in detail in this study. The duty cycles were classified into low-level and high-level categories in consideration of the specific requirements and limitations of the actual experimental setup. The trends revealed by the ideal-field simulation with different grid sizes, in relation to the duty cycles, indicated that the calculated effective radiating area fluctuated within a narrow range, which was far smaller than that specified by the IEC 61689 standard (20%). When the low duty cycles were utilized, the acoustic absorber was omitted. Experimental measurements on a customized ultrasound transducer confirmed that the effective radiating area under high duty cycles can be reliably predicted from that under low duty cycles, with an error range less than 7%. Furthermore, an example is presented to further investigate the predication stability and reliability when different hydrophones are applied to measure the treatment head of a physiotherapy product.

Intravascular shockwave lithotripsy (IVL) is an effective treatment for vascular calcification. Previous studies suggest that ultrasound can enhance the efficiency of extracorporeal shockwave lithotripsy (ESWL) by mitigating the bubble shielding effect. We developed a novel ultrasound-shockwave catheter that combines flowing liquid and ultrasound to suppress bubble shielding and enhance lithotripsy efficiency. Experimental results confirm the bubble shielding effect in IVL, which can be mitigated by flowing liquid or ultrasound. Fracture experiments using Ultracal-30 as phantoms demonstrate the ultrasound emitted after 10 ms of shockwave generation and combines with bubbles can enhance lithotripsy efficiency. Specifically, the addition of ultrasound and bubbles reduced the mass percentage of fragments larger than 4.5 mm by 38.56% compared to the control. Spectrum analysis of ultrasound reveals cavitation's role in improving lithotripsy efficiency. In summary, while bubbles initially attenuate shockwave intensity and reduce lithotripsy efficiency, their combination with ultrasound-induced cavitation enhances treatment outcomes.

Background: The accuracy of pedicle screw fixation is crucial for patient safety. Traditional navigation methods based on computed tomography (CT) imaging have several limitations. Therefore, this study aimed to investigate the ultrasonic propagation characteristics of bone tissue and their relationship with CT imaging results, as well as the potential application of ultrasound navigation in pedicle screw fixation. Methods: The study used three bovine spine specimens (BSSs) and five human vertebral allograft bones (HABs) to progressively decrease the thickness of the cancellous bone layer, simulating the process of pedicle screw perforation. Five unfocused miniature ultrasound probes with frequencies of 2.2, 2.5, 3, 12, and 30 MHz were employed for investigating the ultrasonic propagation characteristics of cancellous and cortical bone through ultrasound transmission and backscatter experiments. The CT features of the bone tissue was obtained with the Skyscan 1174 micro-CT scanner (Bruker, Billerica, MA, USA). Results: The experimental results demonstrated that low-frequency (2-3 MHz) ultrasound effectively penetrated the cancellous bone layer up to a depth of approximately 5 mm, with an attenuation coefficient below 10 dB/cm. Conversely, high-frequency (12 MHz) ultrasound exhibited significant signal attenuation in cancellous bone, reaching up to 55.8 dB/cm. The amplitude of the backscattered signal at the cancellous bone interface exhibited a negative correlation with the bone sample thickness (average r=-0.84), meaning that as the thickness of the cancellous bone layer on the cortical bone decreases, the backscattered signal amplitude gradually increases (P<0.05). Upon reaching the cortical bone interface, there was a rapid surge in echo signal amplitude, up to 8 times higher. Meanwhile, the statistical results indicated a significant correlation between the amplitude of the echo signal and the micro-CT scanning results of bone trabecular structure. Conclusions: Theoretically, using multiple ultrasonic probes (>= 3) >= 3) and regions of interest (ROIs) (>= 5) >= 5) has the potential to provide surgeons with early warning signals for pedicle perforation based on three or more successive increases in echo signal amplitude or a sudden substantial increase. The statistical results indicate a significant correlation between the amplitude of the echo signal and the micro-CT scanning results of bone trabeculae, suggesting the potential use of ultrasound as opposed to CT for real-time intraoperative bone navigation.

Commercialized micro ultrasonic transducer generally adopts thickness mode to produce ultrasound radiation of thickness direction. The miniaturization of low-frequency transducer is a problem due to frequency inversely proportional to thickness of transducer. A new micro contour mode ultrasound transducer is proposed for satisfying miniaturization design. Theory analysis, FEM analysis and experimental investigation are carried out to verify the principle and improve the sound field distribution of contour mode transducer. Three kinds of contour transducers with width 300 mu m, 600 mu m, and 900 mu m are fabricated and the reflecting house is added to improve lateral resolution. The performance is evaluated by electrical impedance, pulse-echo response tests and B-mode imaging tests with a 25 mu m tungsten wire phantom. The corresponding experiment result of center frequency, -6 dB bandwidth and sensitivity are 4.1 MHz@37 %@4.5Vpp, 2.5 MHz@37 %@3.4Vpp, and 1.8 MHz@29 %@2.0Vpp respectively. Wire phantom imaging showed the lateral resolution has been markedly promoted with reflecting house. Compared with traditional thickness mode transducer, the proposed transducer can achieve smaller size with simplifying fabricated structure. It has a good application prospect in the fields of intervention image and therapy.

ABSTRACT Background Post-stroke aphasia is a common but intractable sequela which still needs new and more effective treatments. Evidence from follow-ups after contralateral seventh cervical nerve transfer surgery indicated that nerve transection leads to immediate language improvements in patients with right post-stroke aphasia. Objective Through a prospective cohort design, this study aims to prove that C7 neurotomy at the intervertebral foramen (NC7) combined with a 3-week intensive speech and language therapy (iSLT) can improve the language function in post-stroke aphasia patients. Methods In this study, patients aged over 18 years old and had been diagnosed with post-stroke aphasia for 1 year or longer were included. Primary outcomes were the change in the ability to retrieve personally relevant words in Boston Naming Test (BNT) with follow-up assessment after three-weeks’ iSLT post-operatively. As well as several secondary outcome measures including the Western Aphasia Battery (WAB), daily communication abilities (measured by the Communication Activities of Daily Living Third Edition [CADL-3]) and Fugl-Meyer of upper limb part (UEFM). Results The average increase of BNT score was 11.2 points from baseline to 3 weeks post-operatively (P=0.001, 95%CI: 8.1-14.1). The WAB and CADL-3 assessment showed 9.4, 10.4 points increasing in average (P<0.005, 95%CI: 4.6 to 14.1; P<0.001, 95%CI:6.7 to 14.1) from baseline to 4-week follow-up, respectively. The mean difference from baseline to 3 weeks post-operatively in UEFM score decreased 0.8 points (95% CI: -3.2 to 1.6; p<0.405). Conclusions NC7 plus iSLT significantly improved the language function in patients with post-stroke aphasia, and did not significantly affect the motor function of the right limb. The mechanism of this surgery needs to be further explored.

Due to the small size and proximity to the spinal cord and vertebral artery, the cervical pedicle screw fixation procedure remains to be challenging in clinical practice. The screw misplacement has a high probability of occurrence of severe complications. How to prevent direct injury to the vertebral artery is a vital study focus in cervical spine surgery. In this work, a trans-osseous ultrasound Doppler method is proposed to explore the possibility of detecting blood flow through thin cortical bone. A miniature single-element prototype probe with a center frequency of 2.5 MHz is prepared. With the classical pulse-echo acquisition, a Spectral Power Index (SPI) algorithm based on Spectral Doppler and sliding window traversal is designed to enhance the Doppler signal intensity. In vitro and in vivo experiments were conducted to investigate the feasibility of this method. The results of in vitro experiments suggest that the anticoagulated bovine blood flowing at a mean velocity of 15 cm/s to 80 cm/s is detectable when the thickness of cortical bone is 0.7 +/- 0.1 mm. The in vivo experiment showed that the large blood vessel with a diameter of about 3 mm (radial artery) can be detected through thin cortical bone (thickness of 0.7 +/- 0.1 mm). The proposed trans-osseous Doppler method achieves artery detection through thin cortical bone, which has demonstrated the possibility of intraoperative vessel pre-warning. The present study poses a promising strategy to reduce the risk of vertebral artery injury and misalignment rate in the cervical pedicle screw insertion procedure.

Objective:To understand the acoustic profiles of vertebral cancellous bone in ultrasonography using data of Micro-CT scanning as the reference, so as to lay a theoretical foundation for ultrasound-guided posterior pedicle screw fixation in spinal fusion surgery.Methods:Two cancellous bovine spinal bone blocks and two human cancellous allogeneic spinal bone blocks were used to simulate the cancellous bones along the pedicle screw channel. Each bone specimen was obtained of CT parameters on Micro-CT scanning, then subjected to ultrasound transmission measurement using an unfocused broadband transducer with central frequencies of 2.2 MHz, 2.5 MHz, 3 MHz, and 12 MHz, respectively. The acoustic amplitude, attenuation, and velocity of the ultrasound penetrating each bone specimen were captured by a hydrophone. Then the attenuation and impact on acoustic velocity of ultrasound by the bone specimens under different ultrasonic frequencies were calculated.Results:High-density human allogeneic bone blocks presented higher bone volume fraction (BV/TV) and greater trabecular number (TB. N) (both P<0.05), lower trabecular separation and structural model index (both P<0.05), compared with the low-density human allogeneic ones. For each of the 4 bone specimens under the 4 different frequencies, the ultrasound amplitudes decreased (all P<0.05) and the acoustic attenuation in creased (all P<0.05) with greater bone thickness. With rising frequency, a downward reduction in acoustic attenuation of low-frequency ultrasound (2.2 MHz, 2.5 MHz and 3 MHz) was noted inside the 2 mm thin cancellous bovine bone ( r=0.95 for bovine bone block #1, r=0.89 for bovine bone block #2, both P<0.05), and an upward increase in acoustic velocity was noted inside all of the 4 bone blocks ( r=0.71 for bovine bone block #1, r=0.81 for bovine bone block #2, r=0.35 for the high-density human allogeneic bone block, r=0.61 for the low density human allogeneic bone block, all P<0.05). In cancellous bovine bone blocks tested with any given low frequency of the ultrasound (2.2 MHz, 2.5 MHz, and 3 MHz), the acoustic velocity increased with greater bone thickness (all P<0.05) . Conclusion:There is a correlation between CT parameter features of cancellous bone blocks and their acoustic profiles with ultrasound transmission at varying frequencies. This finding theoretically implies a foundation for development of ultrasound navigation systems.

Structure design of medical ultrasonic transducers is of prime importance, as it not only affects the transducer's imaging performance, but also limits its application scene and scope. In this paper, a single element transducer with subdicing is fabricated and its performance is studied using finite element method. In addition, the comparison transducers (CPTs) are fabricated as well as single element transducers with and without subdicing the element. The experimental results show that by subdicing the element with cut width 120 mu m and cut depth 500 mu m of the single transducer with a center frequency of 8 MHz and dimension of 2 mm x 0.9 mm x 1.2 mm, the center frequency reduced by up to 58.3 %, the -6 dB bandwidth increased by up to 48.7 %, but the echo signal amplitude reduced by 52.4 %. Compared to CPT-5, the volume of the subdicing transducer reduced by 94.6 %, the center frequency reduced by 4.3 %, the -6 dB bandwidth increased by 1.26 times, the transmitted pulse signal length decreased by 50 %, and the echo signal amplitude achieved 28 % of CPT-5. Therefore, the proposed subdicing transducer may have great potential for miniaturization and close-range imaging.

The contour mode is introduced with normal thickness mode to generate dual frequency ultrasonic waves in a single element transducer. The proposed dual frequency transducers are analyzed and designed by finite element analysis. Based on the results of simulation analysis, the four transducers prototypes are fabricated and tested. For dual frequency transducer with optimized matching layer, the pulse echo characteristics of low frequency part are similar with the comparison characteristics of 1-3 composites transducer. The dual frequency transducer still simultaneously owns effective high frequency part. The results demonstrate that the proposed contour vibration mode can work with thickness vibration mode to realize dual frequency with a high performance. (C) 2022 Elsevier Ltd. All rights reserved.

Intravascular lithotripsy (IVL) is an effective method to treat vascular calcification. IVL employs the shockwave generated by the electrohydraulic effect to make calcification fractured without damaging blood vessels. The current commonly used discharge structure is the wire-metal ring structure. However, with the increase in the number of discharges, the burning loss will continue to aggravate, leading to structural failure and seriously limiting the equipment's life at about 80 times. To solve the above problems, this paper proposes parallel wires discharge electrode structure for IVL. The changes of shockwave intensity generated by the electrode are measured with 1.6kV, pulse width of 60μs at PRF 1Hz. Then the gypsum ring is used as the phantom and the fracture ability of the shockwave on phantom is evaluated. The results show that the intensity and fracture ability of the shockwave remain stable over 280 consecutive generations. The discharge electrode can reduce the operation time caused by equipment replacement and relieve the pain of patients

Multifrequency ultrasonic transducers have broad application prospects in the field of biomedical due to their high imaging resolution and detection depth. This paper proposed a design method of triple frequency single-element transducers by finite element method(FEM). The triple frequency transducers are based on contour mode, thickness mode and the third harmonic of thickness mode. Nine micro single element transducers with different widths and matching layers were fabricated and characterized to verify the design method. The traditional 30 MHz single frequency transducer and 2.3 MHz 1-3 piezoelectric composite transducer were used to compare with high frequency part and low frequency part of the triple frequency transducers, respectively. The pulse-echo characteristics of the triple frequency transducers have impressive low and middle frequency part. The high frequency part is similar with traditional transducer except the sensitivity is 0.5 times. The results certify the feasibility of a triple-Frequency transducer based on dual vibration and harmonic modes. (c) 2021 Elsevier B.V. All rights reserved.

Background Double crush syndrome (DCS) of the ulnar nerve, including cubital tunnel syndrome with ulnar tunnel syndrome (UTS), is uncommon. This study compares the postoperative outcomes of patients with isolated ulnar tunnel syndrome versus those with double crush syndrome of the elbow and ulnar tunnel. Methods This study enrolled 22 patients: 12 underwent cubital tunnel surgery and ulnar tunnel surgery (double crush group); and 10 underwent only ulnar tunnel decompression (isolated UTS group). Postoperative effect evaluation of patients in both groups after at least 2.6 years (mean, 5.1 years and 5.7 years, respectively). Statistical analysis compared postoperative function, physical examination, and patient-reported satisfaction between groups. Results In terms of postoperative grip strength, there was no difference between the postoperative states of the two groups (0.88 +/- 0.04 versus 0.87 +/- 0.05), while there was statistical difference in terms of the increment of the grip strength (p = 0.036); the two-point discrimination of isolated UTS group is better than the double crush group (90% versus 83.3%); double crush patients reported lower satisfaction than the UTS group (90% versus 83.3%). Conclusions At a minimum of 2.6 years after the nerve decompression, the patients of isolated UTS group are likely to have superior grip strength increment than patients with a history of double crush surgery, and there is no big difference in the final recovery situation. The sensation and satisfaction of isolated UTS group after nerve release were better compared with patients following double crush surgery.

In this study, a low-frequency(1.1MHz) ultrasonic thrombolytic catheter was designed. In order to evaluate its sonothrombolysis efficacy, the thrombolysis test in different experimental groups were conducted, including ultrasound (US) alone, urokinase (UK) alone, US combined with microbubbles (MB) and US combined with MB and UK. The results showed that the clot lysis rate of the different groups for control, US alone, US+ MB and US+ MB+UK is 28.2%,32.8%, 45.6%, 50.2% and 69.4%, respectively. Under the condition of optimal acoustic parameters (1.1 MHz, 0.4 MPa, 5% duty cycle, 500 Hz PRF), ultrasound combined with microbubble could achieve better thrombolytic effect than urokinase treatment alone.

Intravascular ultrasound has good prospects for clinical applications in sonothrombolysis. The catheter-based side-looking intravascular ultrasound thrombolysis (e.g., Ekosonic catheters) used in clinical studies has a high frequency (2 MHz). The lower-frequency ultrasound requires a larger-diameter transducer. In our study, we designed and manufactured a small ultrasound-based prototype catheter that can emit a lower frequency ultrasound (1.1 MHz). In order to evaluate the safety and efficacy of local low-frequency ultrasound-enhanced thrombolysis, a microbubble (MB) was introduced to augment thrombolysis effect of locally delivered low-intensity ultrasound. The results demonstrated that combination of ultrasound and MB realized higher clot lysis than urokinase-only treatment (17.0% ± 1.2% vs. 14.9% ± 2.7%) under optimal ultrasound settings of 1.1 MHz, 0.414 MPa, 4.89 W/cm2, 5% duty cycle and MB concentration of 60 μg/mL. When urokinase was added, the fibrinolysis accelerated by MB and ultrasound resulted in a further increased thrombolysis rate that was more than two times than that of urokinase alone (36.7% ± 5.5% vs. 14.9% ± 2.7%). However, a great quantity of ultrasound energy was required to achieve substantial clot lysis without MB, leading to the situation that temperature accumulated inside the clot became harmful. We suggest that MB-assisted local sonothrombolysis be considered as adjuvant therapy of thrombolytic agents.

Background: Ultrasound has been proved to be a promising alternative spine navigation method. High frequency ultrasound transducer has the advantage of high resolution on surface structure, but imaging at close range is difficult, especially in narrow space of the pilot-hole in pedicle.Methods: Twenty cortical bone chips were made and different size of hole with diameter of 1mm, 2mm, 3mm or 5mm was randomly carved in each bone chip. A tailored 30MHz high frequency transducer scanned bone samples at the distance of 4mm, 3mm, 2mm and 1mm. Successive transmission ringingeffect elimination, Hilbert transform and Gray-scale mapping method were utilized to process and optimize attained original images.Results: At the distance of 4mm, 3mm, 2mm and 1mm, the holes with diameter of 5mm, 3mm and 2mm could be discerned. At the distance of 1mm, only the holes with 5mm and 3mm could be clearly distinguished and the 2mm hole appeared obscure. The holes with diameter of 1mm could not be detected at any distance. The holes with diameter of 2mm were able to be detected at the distance of 1mm.Conclusions: This study indicated that the high frequency transducer had limited imaging capability at close range on the bony surface. These results lay a foundation for further developing a novel ultrasound-based spinal pedicle interior imaging and navigation system.

Background: The purpose of this study was to understand the acoustic properties of vertebral cancellous bone by combining micro-CT scan data and use this as the theoretical basis for ultrasonic navigation with posterior pedicle screw fixation during spinal fusion surgery. Results: Two bovine spinal cancellous bone blocks and two human spinal allograft bone blocks simulated the condition of cancellous bone in the pedicle screw channel. Transmission experiments were performed on them, including amplitude, attenuation and sound velocity tests. Four unfocused wideband ultrasonic transducers were used for the detection, with the central frequencies of 2.2MHz, 2.5MHz, 3MHz and 12MHz respectively. The results were favorable and stable. The amplitude of the signal decreased with depth penetration (p< 0.05). With the increase of frequency, sound attenuation and sound velocity increased (p< 0.05). Conclusions: In summary, the conclusions lay a theoretical foundation for the ultrasonic navigation system. However, how ultrasound navigation will facilitate pedicle screw insertion in spine surgery remains to be determined. Therefore, ultrasonic guided pedicle screw implantation is effective and promising in theory.