High-spatial-resolution transcranial focused ultrasound neuromodulation using frequency-modulated pattern interference radiation force.

Stimulating the brain in a precise location is crucial in ultrasound neuromodulation. However, improving the resolution proves a challenge owing to the characteristics of transcranial focused ultrasound. In this paper, we present a new neuromodulation system that overcomes the existing limitations based on an acoustic radiation force with a frequency-modulated waveform and standing waves. By using the frequency-modulated pattern interference radiation force (FM-PIRF), the axial spatial resolution can be reduced to a single wavelength level and the target location can be controlled in axial direction electronically. A linear frequency-modulated chirp waveform used in the experiment was designed based on the simulation results. The displacement of the polydimethylsiloxane (PDMS) cantilever was measured at intervals of 0.1 mm to visualize the distribution of radiation force. These results and methods experimentally show that FM-PIRF has improved spatial resolution and capability of electrical movement.

Speed of sound in the IEC tissue-mimicking material and its maintenance solution as a function of temperature.

Tissue-Mimicking Material (TMM) is defined on IEC International Standards and applied in assessing ultrasonic diagnostic and therapeutic equipment's basic safety and essential performance. One of the TMM that fits IEC standards specification has its recipe described at IEC 60601-2-37, and it is fabricated using glycerol (11.21 %), deionized water (82.95%), benzalkonium chloride (0.47 %), silicon carbide (0.53 %), aluminum oxide 0.3 µm (0.88%), aluminum oxide 3.0 µm (0.94 %), and agar (3.08 %). Glycerol is the component responsible for adjusting the TMM's speed of sound. Moreover, it is recommended to store TMM in a closed container immersed in a mixture of water (88.1 %)/glycerol (11.9 %) to prevent it from drying out and avoiding air contact. The literature points out TMM measurements underwater can alter the speed of sound property as TMM tends to lose glycerol. Herein, the authors proposed to assess the viability of measuring the TMM speed of sound in the water/glycerol maintenance solution. First, the authors characterized the maintenance solution's speed of sound for a temperature range of 20 °C to 45 °C. Then, the group velocity of a set of TMM was measured underwater and in the maintenance solution for the same temperature range. The respective group velocity expanded uncertainty was calculated. The results indicate it is feasible to measure TMM in the maintenance solution, achieving group velocity values with no statistical difference from the ones measured underwater in the temperature range of 20 °C to 40 °C.

Design and Challenges of Sonodynamic Therapy System for Cancer Theranostics: From Equipment to Sensitizers.

As a novel noninvasive therapeutic modality combining low-intensity ultrasound and sonosensitizers, sonodynamic therapy (SDT) is promising for clinical translation due to its high tissue-penetrating capability to treat deeper lesions intractable by photodynamic therapy (PDT), which suffers from the major limitation of low tissue penetration depth of light. The effectiveness and feasibility of SDT are regarded to rely on not only the development of stable and flexible SDT apparatus, but also the screening of sonosensitizers with good specificity and safety. To give an outlook of the development of SDT equipment, the key technologies are discussed according to five aspects including ultrasonic dose settings, sonosensitizer screening, tumor positioning, temperature monitoring, and reactive oxygen species (ROS) detection. In addition, some state-of-the-art SDT multifunctional equipment integrating diagnosis and treatment for accurate SDT are introduced. Further, an overview of the development of sonosensitizers is provided from small molecular sensitizers to nano/microenhanced sensitizers. Several types of nanomaterial-augmented SDT are in discussion, including porphyrin-based nanomaterials, porphyrin-like nanomaterials, inorganic nanomaterials, and organic-inorganic hybrid nanomaterials with different strategies to improve SDT therapeutic efficacy. There is no doubt that the rapid development and clinical translation of sonodynamic therapy will be promoted by advanced equipment, smart nanomaterial-based sonosensitizer, and multidisciplinary collaboration.

Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications.

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.

Inorganic chemoreactive nanosonosensitzers with unique physiochemical properties and structural features for versatile sonodynamic nanotherapies.

The fast development of nanomedicine and nanobiotechnology has enabled the emerging of versatile therapeutic modalities with high therapeutic efficiency and biosafety, among which nanosonosensitizer-involved sonodynamic therapy (SDT) employs ultrasound (US) as the exogenous activation source for inducing the production of reactive oxygen species (ROS) and disease therapy. The chemoreactive nanosonosensitizers are the critical components participating in the SDT process, which generally determine the SDT efficiency and therapeutic outcome. Compared to the traditional and mostly explored organic sonosensitizers, the recently developed inorganic chemoreactive nanosonosensitizers feature the distinct high stability, multifunctionality and significantly different SDT mechanism. This review dominantly discusses and highlights two types of inorganic nanosensitizers in sonodynamic treatments of various diseases and their underlying therapeutic mechanism, including US-activated generation of electrons (e-) and holes (h+) for facilitating the following ROS production and delivery of organic molecular sonosensitizers. Especially, this review proposes four strategies aiming for augmenting the SDT efficiency on antitumor and antibacterial applications based on inorganic sonosensitizers, including defect engineering, novel metal coupling, increasing electric conductivity and alleviating tumor hypoxia. The encountered challenges and critical issues facing these inorganic nanosonosensitzers are also highlighted and discussed for advancing their clinical translations.

Therapeutic Ultrasound Parameter Optimization for Drug Delivery Applied to a Murine Model of Hepatocellular Carcinoma.

Ultrasound and microbubble (USMB)-mediated drug delivery is a valuable tool for increasing the efficiency of the delivery of therapeutic agents to cancer while maintaining low systemic toxicity. Typically, selection of USMB drug delivery parameters used in current research settings are either based on previous studies described in the literature or optimized using tissue-mimicking phantoms. However, phantoms rarely mimic in vivo tumor environments, and the selection of parameters should be based on the application or experiment. In the following study, we optimized the therapeutic parameters of the ultrasound drug delivery system to achieve the most efficient in vivo drug delivery using fluorescent semiconducting polymer nanoparticles as a model nanocarrier. We illustrate that voltage, pulse repetition frequency and treatment time (i.e., number of ultrasound pulses per therapy area) delivered to the tumor can successfully be optimized in vivo to ensure effective delivery of the semiconducting polymer nanoparticles to models of hepatocellular carcinoma. The optimal in vivo parameters for USMB drug delivery in this study were 70 V (peak negative pressure = 3.4 MPa, mechanical index = 1.22), 1-Hz pulse repetition frequency and 100-s therapy time. USMB-mediated drug delivery using in vivo optimized ultrasound parameters caused an up to 2.2-fold (p < 0.01) increase in drug delivery to solid tumors compared with that using phantom-optimized ultrasound parameters.

Amelioration of cyclophosphamide-induced myelosuppression during treatment to rats with breast cancer through low-intensity pulsed ultrasound.

To investigate the alleviating effects of low-intensity pulsed ultrasound (LIPUS) on myelosuppression of Sprague-Dawley rats with breast cancer induced by cyclophosphamide (CTX). Breast cancer in rats was triggered by intragastric gavage with 7,12-dimethylbenz[a]anthracene (150 mg/kg). Then, the rats with breast cancer were randomly allocated to the LIPUS group (n=50) and the control group (n=50). The LIPUS group was injected intraperitoneally with CTX (50 mg/kg) for 4 consecutive days and underwent LIPUS treatment at femoral metaphysis 20 min per day from the first day of injection for 7 consecutive days. The control group was injected with CTX (50 mg/kg) and treated with LIPUS without energy output. Blood, enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction, Hematoxylin and Eosin (H&E) staining, and scanning electron microscopy were applied to detect the changes. The results indicated that LIPUS significantly promoted the proliferation of bone marrow nucleated cells, white blood cells (WBCs), IgA, IgG, and IgM in the peripheral blood (P<0.05) without the damage to liver and kidney function simultaneously. The mechanisms may result from the LIPUS alleviation effect on bone marrow hematopoietic function through regulating cytokines such as LIPUS can increase the expression of granulocyte colony-stimulating factor (G-CSF), stem cell factor, transforming growth factor-ß, and intercellular cell adhesion molecule-1, meanwhile LIPUS will decrease the expression of interleukin-6, tumor necrosis factor-α, and vascular cell adhesion molecule-1. LIPUS has potential to be a new adjuvant therapy method in clinic for ameliorating chemotherapy-induced myelosuppression.

Noninvasive acoustic manipulation of objects in a living body.

In certain medical applications, transmitting an ultrasound beam through the skin to manipulate a solid object within the human body would be beneficial. Such applications include, for example, controlling an ingestible camera or expelling a kidney stone. In this paper, ultrasound beams of specific shapes were designed by numerical modeling and produced using a phased array. These beams were shown to levitate and electronically steer solid objects (3-mm-diameter glass spheres), along preprogrammed paths, in a water bath, and in the urinary bladders of live pigs. Deviation from the intended path was on average <10%. No injury was found on the bladder wall or intervening tissue.

Antitumor effect of VEGFR2-targeted microbubble destruction with gemcitabine using an endoscopic ultrasound probe: In vivo mouse pancreatic ductal adenocarcinoma model.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) induces cellular inflow of drugs at low intensity, while high intensity eradicates tumor vessels. Since vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), VEGFR2-targeted microbubble (MB) might additionally increase the tissue specificity of drugs and thus improve antitumor effects. In addition, fixing the dual pulse intensity could maximize MB properties. This study evaluated the one-off (experiment 1) and cumulative (experiment 2) treatment effect of UTMD by regulating the dual pulse output applied to PDAC using VEGFR2-targeted MB. METHODS: C57BL/6 mice inoculated with Pan-02 cells were allocated to five groups: VEGFR2-targeted MB+ gemcitabine (GEM), VEGFR2-targeted MB, non-targeted MB+GEM, GEM, and control groups. After injection of GEM or GEM and either VEGFR2-targeted or non-targeted MB, UTMD was applied for several minutes at low intensity followed by high intensity application. In experiment 1, mice were treated by the protocol described above and then euthanized immediately or at the tumor diameter doubling time (TDT). In experiment 2, the same protocol was repeated weekly and mice were euthanized at TDT regardless of protocol completion. Histological analysis by CD31 and VEGFR2 staining provided microvascular density (MVD) and VEGFR2 expression along vessels (VEGFR2v) or intra/peripheral cells (VEGFR2c). RESULTS: In experiment 1, TDT was significantly longer in the VEGFR2-targeted MB+GEM group compared to the non-targeted MB+GEM, GEM, and control groups, while the VEGFR2-targeted MB group showed no statistical significance. MVD and VEGFR2v in the immediate euthanasia was significantly lower in the VEGFR2-targeted MB+GEM and VEGFR2-targeted MB groups than other conditions. In experiment 2, the VEGFR2-targeted MB+GEM group produced significantly longer TDT than the GEM or control groups, whereas the VEGFR2-targeted MB group showed no significant difference. Histology revealed significantly reduced VEGFR2v and VEGFR2c in the VEGFR2-targeted and non-targeted MB+GEM groups, while only VEGFR2v was significantly less in the VEGFR2-targeted MB group. CONCLUSIONS: UTMD-mediated GEM therapy with the dual pulse application using VEGFR2-targeted MB substantially suppresses PDCA growth.

Piezoelectric and Inversely Piezoelectric Responses of Bone Tissue Plates in the Megahertz Range.

Piezoelectricity in bone is thought to be a mechanism by which ultrasound promotes the healing of bone fractures. However, a few studies have been conducted in the more clinically relevant megahertz range. To understand the piezoelectricity in bone, we fabricated ultrasound transducers using bone samples as piezoelectric materials and identified the longitudinal ultrasound radiation and reception in the megahertz range. The maximum transmitting sensitivity of the bone transducer was 140 mPa/V, which was nearly 1/1000 of a polyvinylidene difluoride (PVDF) transducer that has better electrical properties and piezoelectricity. The resonance frequencies of the transducer depend on the plate thickness and angle between the bone axis (alignment direction of the hydroxyapatite crystallites) and ultrasound propagation direction, reflecting the anisotropic character of the bone. The reception and transmission sensitivities of the bone transducers also depend on the plate thickness and angle, showing maximum values at off-axis angles. These results indicate the existence of both piezoelectricity and inverse piezoelectricity in bone, which may be key factors in understanding the bone healing by low-intensity biophysical (electrical or mechanical) stimulation.

Profilometric Analysis of Periodontally Diseased Root Surfaces After Application of Different Instrumentation Tools: An In Vitro Study.

Objective: The topography of the root surface plays an important role in plaque accumulation, cell adhesion, and periodontal healing. The aim of this study is to profilometrically evaluate the root surface changes following the instrumentation using different tools. Methods: Forty dentin blocks of buccal and lingual root surfaces were obtained from 20 single-rooted periodontally diseased hopeless teeth and randomly divided into 4 groups. Each group was subjected to different root instrumentation tools such as stainless steel (SS) Gracey curette (Group 1); titanium nitride (TIN) Gracey curette (Group 2); ultrasonic piezoelectric device with a special tip designed for root surfaces (H3) (Group 3); and Er:YAG laser (Er:YAG tip) chisel (Group 4). A calibrated clinician instrumented all surfaces in each group. The root surfaces were profilometrically evaluated before and after instrumentations. Results: There were no statistical differences between the initial roughness levels of the groups. TIN curettes revealed the most prominent effect on smoothing the surface, whereas the Er:YAG tip showed the highest roughness in comparison with the other root surface instrumentation tools. Conclusions: Considering the importance of root surface roughness after treatment for the success of periodontal therapy, the TIN curette was the most periodontally appealing tool followed by H3, SS curette, and Er:YAG tip.

Burst wave lithotripsy and acoustic manipulation of stones.

PURPOSE OF REVIEW: Burst wave lithotripsy and ultrasonic propulsion of kidney stones are novel, noninvasive emerging technologies to separately or synergistically fragment and reposition stones in an office setting. The purpose of this review is to discuss the latest refinements in technology, to update on testing of safety and efficacy, and to review future applications. RECENT FINDINGS: Burst wave lithotripsy produced consistent, small passable fragments through transcutaneous applications in a porcine model, while producing minimal injury and clinical trials are now underway. A more efficient ultrasonic propulsion design that can also deliver burst wave lithotripsy effectively repositioned 95% of stones in 18 human participants (18 of 19 kidneys) and clinical trials continue. Acoustic tractor beam technology is an emerging technology with promising clinical applications through the manipulation of macroscopic objects. SUMMARY: The goal of the reviewed work is an office-based system to image, fragment, and reposition urinary stones to facilitate their natural passage. The review highlights progress in establishing safety, effectiveness, and clinical benefit of these new technologies. The work is also anticipating challenges in clinical trials and developing the next generation of technology to improve on the technology as it is being commercialized today.

Real-World Outcomes of EKOS Ultrasound-Enhanced Catheter-Directed Thrombolysis for Acute Limb Ischemia.

BACKGROUND: Ultrasound-enhanced catheter-directed thrombolysis (UET) using the Ekosonic® Endovascular System device for acute, peripheral arterial ischemia has been purported in clinical trials to accelerate the fibrinolytic process to reduce treatment time and lytic dosage. We aim to describe outcomes of UET in a real-world clinical setting. METHODS: We performed a retrospective review of all patients undergoing UET for acute limb ischemia at a single institution. Data collected included patient demographics, procedural details, and 30-day and 1-year outcomes. The primary endpoints for analysis were major adverse limb events (MALEs; reintervention and/or amputation) and mortality within 30-days and 1-year. Secondary endpoints included technical success, use of adjunctive therapies, and postoperative complications. RESULTS: A total of 32 patients (mean age 67.4 ± 14.9 years; 25% women) underwent UET for acute limb ischemia between 2014 and 2018. The Rutherford Acute Limb Ischemia Classification was Rutherford (R) 1 in 56.3%, R2a in 31.3%, and R2b in 12.5%. Etiology was thrombosis of native artery in 12.5% of patients, prosthetic bypass in 31.3%, autogenous bypass in 6.3%, and stented native vessel in 50.0%. Mean duration of thrombolytic therapy was 22.2 ± 11.3 hr, and mean tissue plasminogen activator dose was 24.5 ± 15.3 mg. MALEs occurred in 16.7% of patients within the first 30 days and 38.9% experienced a MALE by 1 year. Limb salvage at 30 days and 1 year was 93.8% and 87.5%, respectively. Ipsilateral reintervention was required in 12.5% of patients within 30 days and 37.5% of patients within 1 year. Overall mortality was 6.2% at 30 days and 13.5% at 1 year. In-line flow to the foot was re-established in 90.6% of patients, with a significant improvement in preoperative to postoperative ankle-brachial index (0.31 ± 0.29 vs. 0.78 ± 0.34, P < 0.001) and number of patent tibial runoff vessels (1.31 ± 1.20 vs. 1.96 ± 0.86, P < 0.001). There was no significant difference in revascularization success between occluded vessel types. All but one patient required adjunctive therapy such as further thromboaspiration, stenting, or balloon angioplasty. Major bleeding complications occurred in 3 patients (9.4%), including 1 intracranial hemorrhage (3.1%). CONCLUSIONS: UET with the EKOS device demonstrates acceptable real-world outcomes in the treatment of acute limb ischemia. UET is generally safe and effective at re-establishing in-line flow to yield high limb salvage rates. However, UET is associated with a high rate of reintervention. Further investigation is needed into specific predictors of limb salvage and need for reintervention, as well as cost-efficacy of this technology compared with that of traditional methods.

Cold knife dissection and bipolar diathermy Vs harmonic scalpel in parotid gland surgery for benign tumours. / Disección fría y coagulación bipolar versus disección con bisturí armónico en la cirugía de los tumores benignos de la glándula parótida.

INTRODUCTION: Surgical techniques for extirpation of tumours of the parotid gland have evolved significantly in recent years. Previous data suggest the use of Harmonic Scalpel reduced operative time, intraoperative blood loss, postoperative drain production, and incidence of facial nerve injury, in comparison to cold scalpel dissection MATERIAL AND METHODS: retrospective analysis of 2group of patients operated using harmonic scalpel versus cold knife dissection and bipolar diathermy and compare operative time and post-surgical complication rate:, facial nerve injury, sialocele or salivary fístula formation, after parotidectomy for benign parotid tumours. RESULTS: 108 patients were included. Regarding surgical time, the mean time to using Harmonic Scalpel was 114±39 (Min: 60/Max: 240), and the mean time using bipolar diathermy was 135±38 (Min: 90/Max: 285) and this was the only significant difference between the 2techniques (p=.049). CONCLUSIONS: Harmonic scalpel is a safe and effective tool to perform parotid surgery in benign tumours. However, a shorter surgical time was the only advantage found over the traditional cold dissection and bipolar dissection method.

The Efficacy of Ultrasonic Bone Scalpel for Unilateral Cervical Open-Door Laminoplasty: A Randomized Controlled Trial.

BACKGROUND: In cervical open-door laminoplasty for cervical myelopathy, a high-speed rotatory drill and rongeurs are used to make unicortical troughs and bicortical openings in the laminae. The lamina is reflected at the trough to enlarge the spinal canal, followed by bone healing on the hinge side to stabilize laminoplasty. The ultrasonic bone scalpel (UBS) has been used due to theoretical advantages including a better hinge union rate, less soft tissue trauma, less neurological injury, and shorter operative time. OBJECTIVE: To assess the superiority of UBS for hinge union compared to the drill through randomized controlled trial. METHODS: In 190 randomly allocated cervical myelopathy patients, the trough and opening at the lamina were made using either the drill (n = 95) or UBS (n = 95) during 2015 to 2018. The primary outcome was the hinge union rate on 6-mo postoperative computed tomography. Secondary outcomes included the hinge union rate at 12 mo, the operative time, intraoperative/postoperative bleeding, neurological injury, complications, and clinical outcomes over a 24-mo follow-up. RESULTS: Hinge union in all laminae was achieved in 60.0% (drill) and 43.9% (UBS) of patients at 6 mo (intention-to-treat analysis; P = .02; odds ratio, 2.1) and in 91.9% (drill) and 86.5% (UBS) at 12 mo. Dural injury only occurred in the drill group (2.1%), and the UBS group showed significantly less intraoperative bleeding (P < .01). The other secondary outcomes did not differ between groups. CONCLUSION: The hinge union rate was inferior in the UBS group at 6 mo postoperatively, but UBS was efficacious in reducing dural injuries and bleeding.

Scan Parameter Optimization for Histotripsy Treatment of S. Aureus Biofilms on Surgical Mesh.

There is a critical need to develop new noninvasive therapies to treat bacteria biofilms. Previous studies have demonstrated the effectiveness of cavitation-based ultrasound histotripsy to destroy these biofilms. In this study, the dependence of biofilm destruction on multiple scan parameters was assessed by conducting exposures at different scan speeds (0.3-1.4 beamwidths/s), step sizes (0.25-0.5 beamwidths), and the number of passes of the focus across the mesh (2-6). For each of the exposure conditions, the number of colony-forming units (CFUs) remaining on the mesh was quantified. A regression analysis was then conducted, revealing that the scan speed was the most critical parameter for biofilm destruction. Reducing the number of passes and the scan speed should allow for more efficient biofilm destruction in the future, reducing the treatment time.

Effect of passive ultrasonic activation on microorganisms in primary root canal infection: a randomized clinical trial

Abstract Objective: This clinical study sought to evaluate the effectiveness of passive ultrasonic activation (PUA) in eliminating microorganisms in primary endodontic infection (PEI) after instrumentation of root canals using microbiological culture and checkerboard DNA-DNA hybridization. Methodology: Twenty root canals with PEI and apical periodontitis were selected. The root canals were instrumented and then randomly divided into 2 groups, according to the irrigation method: PUA and conventional needle irrigation (CNI). Microbiological samples were collected before instrumentation (S1), after instrumentation (S2) and after irrigation with 17% EDTA (S3). The samples were subjected to anaerobic culture technique and checkerboard DNA-DNA hybridization analysis. Results: A statistically significant difference was found between CNI (23.56%) and PUA (98.37%) regarding the median percentage values for culturable bacteria reduction (p<0.05). In the initial samples, the most frequently detected species was S. constellatus (50%), and after root canal treatment was E. faecalis (50%). Conclusion: Both treatments significantly decreased the number of bacterial species compared with the initial sample. However, no statistical difference in the total microbial load between PUA and CNI groups was detected. The number of cultivable anaerobic bacteria reduced significantly using PUA, and the bacterial composition and number of bacterial species after using either CNI or PUA was similar.

Comparing the Utility and Surgical Outcomes of Harmonic Focus Ultrasonic Scalpel with Ligasure Small Jaw Bipolar Device in Thyroidectomies: A Prospective Randomized Controlled Trial.

BACKGROUND: Ultrasonic or bipolar radiofrequency energy devices are routinely used for dissection and hemostasis during thyroidectomy. We report a single-center, prospective, randomized controlled trial comparing the utility and outcomes of Harmonic Focus, an ultrasonic coagulating shear device (UCSD), versus Ligasure Small Jaw, an electrothermal bipolar vessel sealer (EBVS) in thyroidectomy (NCT01765686). METHODS: Between December 2012 to January 2016, eligible patients were randomized to undergo hemithyroidectomy using either a UCSD or an EBVS. The primary outcome was duration of surgery. Secondary outcomes included blood loss, postoperative complications, ease of device use, ease of device set-up, vocal cord function, postoperative wound drainage, pain score, and adverse events. RESULTS: Of 110 patients assessed for eligibility, 100 were randomly allocated (UCSD: 49 patients; EBVS: 51 patients) and analyzed by intention-to-treat. There were no differences in specimen delivery time, total duration of surgery, wound drainage, and adverse events between the two groups. The UCSD group had a greater proportion of patients with higher postoperative pain scores in the first 72 h (8.1% vs. 2.0%, p = 0.043). Surgeons reported greater ease of use for the UCSD (49% vs. 27%; p = 0.005), while operating room staff favored the EBVS (60% vs. 33%, p = 0.005). CONCLUSIONS: Energy devices are equally effective in reducing thyroidectomy operative times, with no differences in the duration of surgery, drainage, or adverse events. Use of the UCSD was associated with higher postoperative pain scores, but was favored by the surgeons, likely due to the ability to perform fine dissection with the device itself.

Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs.

In this study, we designed and validated a platform for ultrasound and microbubble-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have been shown to reprogram tumor cells and sensitize them to clinically used chemotherapy. To overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into nanocarriers. Focused ultrasound combined with gas-filled microbubbles provides a noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded particles. A single handheld, curvilinear ultrasound array was used in this study for image-guided therapy with clinical-grade SonoVue contrast agent. First, we validated the platform on phantoms to optimize the microbubble cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA nanoparticles co-loaded with antisense-miRNA-21 and antisense-miRNA-10b to pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the ultrasound treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles to visually assess nanoparticle extravasation. Fluorescent microscopy suggested the presence of nanoparticles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that the proposed platform may be used to safely and noninvasively enhance the delivery of miRNA-loaded nanoparticles to target regions in deep organs in large animal models.

Comparison of Ultrasound-Accelerated Versus Multi-Hole Infusion Catheter-Directed Thrombolysis for the Treatment of Acute Limb Ischemia.

OBJECTIVE: Thrombolytic therapy is widely used in the treatment of arterial occlusions causing acute limb ischemia (ALI); however, knowledge regarding the efficacy of the different catheter systems available is scarce. The objective of this study was to compare the safety and efficacy of 2 catheter-directed infusion systems for intra-arterial thrombolysis in the setting of ALI. METHODS: A retrospective analysis was conducted to study all catheter-directed thrombolysis procedures performed over 32 months in patients diagnosed with ALI. Patients with thrombosis in both native arteries and bypass grafts were included. Patients with contraindications to thrombolysis, or those receiving thrombolysis for deep venous thrombosis, were excluded. The duration of thrombolysis, amount of thrombolytic agent, and technical success rate were recorded. Technical success was defined as complete or near-complete resolution of thrombus burden, allowing for further intervention. Data were stratified to include location of thrombus, procedural complications, mortality, and rates of limb loss. RESULTS: Ninety-one patients met inclusion criteria. Among them, Uni-Fuse and EKOS catheters were used in 69 and 22 patients, respectively. The mean age of the population was 71 (standard deviation [SD]: ±1.5) for patients treated with the EKOS catheter and 70 years (SD: ±2.6) for patients receiving thrombolysis with Uni-Fuse. There was no significant difference in the mean infusion duration (1.65 vs 1.9 days), volume of tissue plasminogen activator (44.6 vs 48.2 mg), or technical success rate (72% vs 86%) between the Uni-Fuse and EKOS cohorts (P > .3). Furthermore, there was no difference in major limb loss or compartment syndrome between each group (P > .4). The overall complication rate was 14% in both groups, with a 30-day mortality rate of 4% when treated with either catheter system. CONCLUSION: This study suggests that a standard multi-hole infusion catheter demonstrates similar clinical safety and efficacy as the ultrasound-accelerated EKOS system in the treatment of ALI.