Ultrasound Catheter Research Articles

Interstitial dual-mode ultrasound with a 3-mm MR-compatible catheter for image-guided HIFU and directional in-vitro tissue ablations.

Current interstitial techniques of tumor ablation face challenges that ultrasound technologies could meet. The ablation radius and directionality of the ultrasound beam could improve the efficiency and precision. Here, a 9-gauge MR-compatible dual-mode ultrasound catheter prototype was experimentally evaluated for Ultrasound Image-guided High Intensity Focused Ultrasound (USgHIFU) conformal ablations. The prototype consisted of 64 piezocomposite linear array elements and was driven by an open research programmable dual-mode ultrasound platform. After verifying the US-image guidance capabilities of the prototype, the HIFU output performances (dynamic focusing and HIFU intensities) were quantitatively characterized, together with the associated 3D HIFU-induced thermal heating in tissue phantoms (using MR thermometry). Finally, the ability to produce robustly HIFU-induced thermal ablations in in-vitro liver was studied experimentally and compared to numerical modeling. Investigations of several HIFU dynamic focusing allowed overcoming the challenges of miniaturizing the device: mono-focal focusing maximized deep energy deposition, while multi-focal strategies eliminated grating lobes. The linear-array design of the prototype made it possible to produce interstitial ultrasound images of tissue and tumor mimics in situ. Multi-focal pressure fields were generated without grating lobes and transducer surface intensities reached up to Isapa = 14 W·cm-2. Seventeen elementary thermal ablations were performed in vitro. Rotation of the catheter proved the directionality of ablation, sparing non-targeted tissue. This experimental proof of concept demonstrates the feasibility of treating volumes comparable to those of primary solid tumors with a miniaturized USgHIFU catheter whose dimensions are close to those of tools traditionally used in interventional radiology, while offering new functionalities.

Abstract P191: Progesterone Supplementation Ameliorates the Maternal Syndrome of Preeclampsia in the Dahl Salt-Sensitive Rats

Introduction: Preeclampsia (PreE) is characterized by new onset hypertension after 20 weeks of gestation. PreE is associated with activated CD4+ T cells, inflammation, autoantibodies to angiotensin II type 1 receptor (AT1-AA) and hypertension. To date, the best treatment remains early delivery of the feto-placental unit. Hypothesis: This study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), reduces inflammation and blood pressure in the Dahl Salt-Sensitive (Dahl S) rat model of PreE. Methods: A subset of pregnant Sprague-Dawley (SD) and Dahl S rats were injected with 17-OHPC (3.32mg/kg, human dose equivalent) or vehicle (saline) at day 15 (GD15) of gestation. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Doppler Ultrasound and carotid catheters were inserted for mean arterial blood pressure (MAP) measurement on GD19. Circulating and placental populations of CD4+ T cells were quantified by flow cytometry. TNF-alpha and IL-6 were measured by ELISA and AT1-AA were quantified by the chronotropic responses to angiotensin II type 1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes. Results are reported as means ± standard error means (SEM) and statistically significant when p < 0.05. Results: MAP was 105±5 mmHg in SD+ vehicle rats (n=6), 104±4 in SD+17-OHPC rats (n=6), 136±3 in Dahl S+ saline rats (p <0.05, n=11), which improved to 125±4 in DS+17-OHPC rats (p <0.05, n=7). Pup and Placenta weights were 2.1± 0.1, 0.6 ± 0.1 g in SD+ vehicle rats and reduced to 1.4±0.1 (p<0.05), 0.5±0.1 g in Dahl S +vehicle. UARI was 0.5 ±0.1 in SD+ vehicle rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=6), 0.7±0.1 in Dahl S+ vehicle rats (n=6, p<0.05), which reduced to 0.5±0.1 in Dahl S+17-OHPC (n=7, p<0.05). TNF-alpha and IL-6 levels (n=4-5/group) were 3.0±1.0, 45±11 pg/mL in SD+ vehicle rats, 11.0±1.2, 78±21 in Dahl S+ vehicle rats, which reduced to 4.1±1.6 (p<0.05), 62±12 in Dahl S+17-OHPC. Circulating and placental CD4+ T cells were 9.3±3.7 %, 6.4± 1.6 % gate in SD+ vehicle rats (n=4), 38.9 ±2.9, 33.1±4.3 % gate Dahl S+ Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 %, 3.4±1.2 % gate in DahlS+17-OHPC. AT1-AA were -1 ± 2 ΔBPM (beats per minute) in SD+ vehicle rats, 4 ± 1 in Dahl S+ Saline rats and -0.6±2 Dahl S+17-OHPC rats (n=5, p<0.05). Conclusion: Our findings demonstrate that 17-OHPC ameliorates the maternal syndrome in the Dahl Salt-Sensitive rat model of PreE.

The impact of real-time ultrasound guidance for ventricular catheter placement in cerebrospinal fluid shunts - a single center study.

Purpose Misplacement of ventricular catheters in shunt surgery occurs in 40% with freehand technique and represents therefore a risk for early shunt failure. The goal of this retrospective, single center study is to analyze the impact of real-time ultrasound guidance on ventricular catheter positioning and early outcome of shunt survival. Materials and Methods We analyzed the charts and images of all patients who underwent shunt surgery from 09/2017 to 12/2022 and compared the position of ventricular catheter by using the freehand technique and real-time ultrasound guidance. Central catheter position was graded as grade I (optimal), II (contact with ventricle structures or contralateral) and III (misplacement). Results Ventricular catheter was placed in 244 patients using real-time US-guidance and in 506 patients using freehand technique. The mean age (53.4 and 53.6 years respectively) and the preoperative frontal occipital horn ratio (FOHR; 0.47 versus 0.44) were almost equal in both groups. In the study group, grade I catheter position was achieved in 64%, grade II in 34% and grade III in 2%. The control group showed grade I position in 45%, grade II in 32% and grade III in 23% of cases (p<0.05). Early central catheter failure rate was the highest in grade III (40.5%) compared to 4% in grade I. Conclusion Our data demonstrate that real-time US-guidance lead to a significant improvement of ventricular catheter placement. In consequence early shunt revisions decrease significantly. Further prospective, randomized, and controlled studies comparing standard method to a real-time ultrasound catheter placement are required.

Rotational Intravascular Multidirectional Ultrasound Catheter for Sonothrombolysis of Retracted Clots: An in Vitro and in Vivo Study

Thromboembolism in blood vessels poses a serious risk of stroke, heart attack, and even sudden death if not properly managed. Sonothrombolysis combined with ultrasound contrast agents has emerged as a promising approach for the effective treatment of thromboembolism. Recent reports have highlighted the potential of intravascular sonothrombolysis as a safe and effective treatment modality for deep vein thrombosis (DVT). However, its efficiency has not been validated through in vivo testing of retracted clots. This study aimed to develop a miniaturized multidirectional transducer featuring two 4-layer lead zirconate titanate (PZT-5A) stacks with an aperture size of 1.4 mm × 1.4 mm, enabling both forward- and side-looking treatment. Integrated into a custom two-lumen 10-French (Fr) catheter, the capability of this device for intravascular sonothrombolysis was validated both in vitro and in vivo. With low-dose tissue plasminogen activators and nanodroplets, the rotational multidirectional transducer reduced the retracted clot mass (800 mg) by an average of 52% within 30 min during in vitro testing. The lysis rate was significantly higher by 37% than that in a forward-viewing transducer without rotation. This improvement was particularly noteworthy in the treatment of retracted clots. Notably, a long-retracted clot (> 10 cm) was successfully treated within 40 min in vivo by creating a flow channel with a diameter > 4 mm in a porcine DVT model. In conclusion, these findings strongly suggest the potential of this technique for clinical applications in sonothrombolysis, offering a feasible solution for effectively treating thromboembolism, particularly in challenging cases involving retracted clots.

Progesterone Supplementation Improves the Maternal Syndrome of Superimposed Preeclampsia in the Dahl Salt Sensitive Rats

Introduction: Preeclampsia (PE) is characterized by new onset of hypertension after 20 weeks of gestation. It affects 5-7% of all pregnancies in the U.S., and is associated with reduced fetal weight, inflammation and hypertension (HTN). Importantly, 30% of HTN disorders in pregnancy are caused by chronic HTN that is present prior to pregnancy which increases the risk of superimposed PE (SIPE). The mechanisms responsible for the pathogenesis of PE and SIPE are unclear and currently the only treatment is early delivery of the fetus. Progesterone is important for the establishment and maintenance of pregnancy. We have previously shown that progesterone supplementation with 17-hydroxyprogesterone caproate (17-OHPC) improves inflammation, fetal weight and blood pressure in the preclinical RUPP rat model of PE, however the mechanism for this in SIPE is still unknown. Hypothesis: This study was designed to test the hypothesis that 17-OHPC reduces inflammation while improving maternal blood pressure in the preclinical pregnant Dahl Salt Sensitive (DS) rat model of SIPE. Methods: 17-OHPC (3.32mg/kg) or vehicle (Saline) was administrated intraperitoneally on gestation day (GD) 15 to normal pregnant (NP) Sprague-Dawley (SD) and pregnant Dahl Salt Sensitive (DS) rats. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Vevo Doppler Ultrasound and carotid catheters were inserted. On GD 19, mean arterial blood pressure (MAP) and samples were collected. All data are expressed as mean ± standard error means (SEM). Results: MAP was 105±5 mmHg in SD+ Saline rats (n=7) and 105±4 mmHg in SD+17-OHPC rats (n=4), 137±3 mmHg in DS + Saline rats (p&lt;0.05, n=11), which improved to 125±4 mmHg in DS+17-OHPC rats (p&lt;0.05, n=7). Pup and Placenta weights were 2.1± 0.1 g, 0.6 ± 0.1 g in SD + saline rats and significantly reduced to 1.4±0.1 g, 0.5±0.1 g in DS+ Saline rats (p&lt;0.05). Neither placental weight nor pup weight was affected by 17-OHPC. UARI was 0.5 ±0.1 in SD+ Saline rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=4), 0.7±0.1 in DS+Saline rats (n=6, p&lt;0.05), which reduced to 0.5±0.1 in DS+17-OHPC (n=7, p&lt;0.05). TNF-alpha levels were 3.0±1.0 pg/mL in SD+ Saline rats, 11.0±1.2 in DS + Saline rats, which reduced to 4.1±1.6 in DS+17-OHPC (n=4, p&lt;0.05). Importantly, circulating and placental CD4+ T cells were 9.3±3.7 % Gate and 6.4± 1.6 % Gate in SD+ Saline rats (n=4), 38.9 ±2.9 % Gate and 33.1±4.3 % Gate in DS + Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 % Gate and 3.4±1.2 % Gate in DS + 17-OHPC. Conclusion: Collectively, our findings demonstrate that 17-OHPC reduces inflammation and hypertension in the Dahl Salt Sensitive rat model of SIPE. Supported by NIH P20GM121334. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Remanufacturing as a circular design strategy in healthcare: integrating socio-technical and environmental-economic assessments

AbstractThis paper examines the role of remanufacturing in healthcare as a key circular design strategy, particularly for medical devices, assessing its socio-technical, environmental, and economic dimensions of sustainability. Through a detailed case of ultrasound catheters, it demonstrates how remanufacturing can lead to resource conservation, cost savings, and enhanced product lifecycles in health care without compromising quality and patient safety. The study argues for systemic changes in healthcare practices to fully integrate remanufacturing, underscoring its role beyond a technical solution.

A 1.11 mm2 IVUS SoC with ±50°-Range Plane Wave Transmit Beamforming at 40 MHz.

Intravascular ultrasound (IVUS) imaging catheters are significant tools for cardiovascular interventions, and their use can be expanded by realizing IVUS imaging guidewires and microcatheters. The miniaturization of these devices creates challenges in SNR due to the need for higher frequencies to provide adequate resolution. An integrated IVUS system with transmit beamforming can mitigate these limitations. This work presents the first practical highly integrated system-on-a-chip (SoC) with plane wave transmit beamforming at 40 MHz for IVUS on guidewire or microcatheters. The front-end circuitry has a 20-channel ultrasound transmitter (Tx) and receiver (Rx) array interfaced with a capacitive micromachined ultrasound transducer (CMUT) array. During each firing, all 20 Tx are excited with the same analog delay with respect to each other, which can be continuously adjusted between ~0 and 10 ns in two directions, generating a steerable plane wave in a range of ±/-50° for a phased array at 40 MHz. The unit delays are generated via a voltage-controlled delay line (VCDL), which only needs two external controls, one tuning the unit delay and the other determining the steering direction. The SoC is fabricated using a 180-nm high-voltage (HV) CMOS process and features a slender active area of 0.3 mm × 3.7 mm. The proposed SoC consumes 31.3 mW during the receiving mode. The beamformer's functionality and the SoC's overall performance were validated through acoustic characterization and imaging experiments.

Ultrasound continuous erector spinae catheter versus paravertebral catheter for pain management in modified radical mastectomy for cancer patients: A randomized double-blind

ABSTRACT Background Regional analgesia provides adequate management of pain during mastectomies and early postoperative period. The erector spinae plane block (ESPB) is a promising regional technique. This study compared the efficacy of ESPB versus paravertebral block (PVB) catheters for pain management in modified radical mastectomy (MRM). Methods This randomized, double-blind, non-inferiority study recruited 70 adult female cases planned for MRM. The patients were equally randomized into two groups: group ESPB and group PVB. The blocks were performed before general anesthesia induction with 20 ml bupivacaine 0.25%, then 0.1 ml/kg/hr continuous infusion through a catheter. Results The duration of block performance was significantly lower in the group ESPB than in the group PVB (P < 0.001). The total morphine consumption in 48 h postoperative was 1.54 ± 3.74 mg in group ESPB and 1.68 ± 3.48 mg in group PVB (P = 0.878). Patients required fentanyl and postoperative morphine in the 1st 48 h, time to 1st request analgesia insignificantly differed between groups. Intraoperative and postoperative heart rate, mean arterial pressure and oxygen saturation, and visual analog scale at rest and movement insignificantly differed between groups. Postoperative pneumothorax occurred in one case in group PVB and did not occur in group ESPB. Conclusions In MRM, analgesic efficacy of preoperative ultrasound-guided ESPB and PVB is comparable, and ESPB is an easier technique and more safer to perform when compared to PVB.

Improving Ultrasound Visualization of Catheters During Interstitial Brachytherapy

Interstitial brachytherapy utilizes catheters to deliver high doses of radiation directly to target tissues. Proper catheter placement is vital to successful treatment and patient outcome. To ensure effective internal guidance, catheters are often positioned under real-time ultrasound (US) in the operating room, with post-operative confirmation using axial imaging. However real-time catheter localization is often difficult due to poor catheter visualization, which can result in ineffectual treatment, reduced organ-sparing, or catheter intrusion into surrounding organs. In the current space for this oncological technique, there are no devices or methods that aim to improve the visualization of catheters which leverage the convenience and accessibility of real-time ultrasound, hindering the optimization of procedural outcomes. To address this need, our team designed a piezo material-integrated medical accessory to integrate the qualitative visualization of color Doppler US into interstitial brachytherapy procedures. The device transduces low-magnitude vibration to brachytherapy catheters to be detected in tissue under real-time B-mode US. Upon activation, the device propagates vibrations down the length of brachytherapy catheters, allowing color Doppler to detect and display repeated, internal movements to assist the operator in catheter placement. Active adjustability over the voltage output using a simple circuit with potentiometer control allows the user to directly control the magnitude and frequency of vibration, offering real-time visualization during interstitial brachytherapy. Pivotal elements of this design include a noninvasive integration into existing brachytherapy workflows, a reproducible and low-cost 3D-printed design, compatibility with real-time US catheter visualization, and highly specific control over the magnitude of Doppler visualization with catheter detachability and dial-regulated voltage/vibration adjustment. The device is able to qualitatively increase the visualization of brachytherapy catheters in a simulated brachytherapy procedure using a custom US phantom at moderate to extreme operational depths, while also staying within safety thresholds set by international standards for medical/electronic/handheld accessories in regards to heat generation, housing weight, and vibrational exposure. Results obtained using an obstructive US phantom with 10-15 cm depth, which consists of fruits, airway through the phantom, and multiple catheters in a localized area, allowed us to clearly distinguish the catheter of interest from the rest of the structures, even in the presence of highly intrusive noise and shadowing CONCLUSION: Brachytherapy catheter visualization can be improved using low-magnitude vibration transmitted through the brachytherapy catheter detected under real-time B-mode US. Further research and clinical testing are ongoing.

All-optical ultrasound catheter for rapid B-mode oesophageal imaging.

All-optical ultrasound (OpUS) is an imaging paradigm that uses light to both generate and receive ultrasound, and has progressed from benchtop to in vivo studies in recent years, demonstrating promise for minimally invasive surgical applications. In this work, we present a rapid pullback imaging catheter for side-viewing B-mode ultrasound imaging within the upper gastrointestinal tract. The device comprised an ultrasound transmitter configured to generate ultrasound laterally from the catheter and a plano-concave microresonator for ultrasound reception. This imaging probe was capable of generating ultrasound pressures in excess of 1 MPa with corresponding -6 dB bandwidths > 20 MHz. This enabled imaging resolutions as low as 45 µm and 120 µm in the axial and lateral extent respectively, with a corresponding signal-to-noise ratio (SNR) of 42 dB. To demonstrate the potential of the device for clinical imaging, an ex vivo swine oesophagus was imaged using the working channel of a mock endoscope for device delivery. The full thickness of the oesophagus was resolved and several tissue layers were present in the resulting ultrasound images. This work demonstrates the promise for OpUS to provide rapid diagnostics and guidance alongside conventional endoscopy.

Mortality and bleeding associated with the management of sub-massive pulmonary embolism: a systematic review and Bayesian network meta-analysis

Current guidelines recommend anticoagulation (AC) for low and intermediate-risk pulmonary embolism (PE) and systemic thrombolysis (tPA) for high risk (massive) PE. How these treatment options compare with other modalities of treatment such as catheter directed thrombolysis (CDT), ultrasound assisted catheter thrombolysis (USAT), and administering lower dose of thrombolytics (LDT) is unclear. There is no study that has compared all these treatment options. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials in patients with submassive (intermediate risk) PE. Fourteen randomized controlled trials were included, comprising 2132 patients. On Bayesian network meta-analysis, a significant decrease in mortality was noted in tPA versus AC. There was no significant difference between USAT versus CDT. For risk of major bleeding, there was no significant difference in relative risk of major bleeding between tPA versus AC and USAT versus CDT. tPA was found to have a significantly higher risk of minor bleeding and a lower risk of recurrent PE compared to AC. Systemic thrombolysis is associated with a significant reduction in mortality and recurrent PE compared to anticoagulation but an increased risk of minor bleeding. There was no difference in risk of major bleeding. Our study also shows that while the newer modalities of treatment for pulmonary embolism are promising, there is lack of data to comment on the purported advantages.

Successful ablation of atrial fibrillation in a patient with a highly calcified septum after an atrial septal defect operation.

Successful ablation of atrial fibrillation in a patient with a highly calcified septum after an atrial septal defect operation.

Vortex ultrasound catheter for cerebral intravenous sonothrombolysis

One treatment challenge for cerebral venous sinus thrombosis (CVST) is to achieve recanalization within a short period of time (e.g., 30 min) for significant clinical outcomes. Ultrasound-mediated thrombolysis (sonothrombolysis) presents a promising treatment for venous embolism. In this paper, a miniature vortex ultrasound transducer with frequency of 1.8 MHz was developed for sonothrombolysis. A composite transducer with 2-by-2 sub-aperture piezoelectric elements was assembled into a 9-French catheter to generate a physical helical wavefront. The prototyped vortex ultrasound catheter was characterized by measuring the acoustic pressure amplitude and phases, followed by in-vitro- sonothrombolysis tests. It was found that a vortex ultrasound field can be successfully generated by the prototype. The vortex lytic rate was increased by more than 50% compared with the nonvortex lysis with the same acoustic power input. A long (∼7.5 cm), completely occluded in-vitro- 3D model of acute CVST was fully recanalized within 8 min. The unprecedented sonothrombolysis rate was likely attributed to the vortex ultrasound-induced shear stress, which can effectively disrupt acute blood clots. Furthermore, no vessel wall damage over ex-vivo bovine veins was found after the vortex sonothrombolysis treatment.

Imaging delays among medical inpatients in Toronto, Ontario: A cohort study.

Imaging procedures are commonly performed on hospitalized patients and waiting for these could increase length-of-stay. The study objective was to quantify delays for imaging procedures in General Internal Medicine and identify contributing patient, physician, and system factors. This was a retrospective cohort study of medical inpatients admitted to 5 hospitals in Toronto, Ontario (2010-2019), with at least one imaging procedure (CT, MRI, ultrasound, or peripherally-inserted central catheter [PICC] insertion). The primary outcome was time-to-test, and the secondary outcome was acute length-of-stay after test ordering. The study cohort included 73,107 hospitalizations. Time-to-test was longest for MRI (median 22 hours) and shortest for CT (median 7 hours). The greatest contributors to time-to-test were system factors such as hospital site (up to 22 additional hours), location of test ordering (up to 10 additional hours), the timing of test ordering relative to admission (up to 13 additional hours), and ordering during weekends (up to 21 additional hours). Older patient age, having more comorbidities, and residence in a low-income neighborhood were also associated with testing delays. Each additional hour spent waiting for a test was associated with increased acute length-of-stay after test ordering, ranging from 0.4 additional hours for CT to 1.2 hours for MRI. The greatest contributors to testing delays relate to when and where a test was ordered. Wait times affect length-of-stay and the quality of patient care. Hospitals can apply our novel approach to explore opportunities to decrease testing delays locally.

The Importance of Early Thrombus Removal

Historically, anticoagulation has been the primary treatment for acute lower extremity deep venous thrombosis (DVT) with or without thrombolysis. Despite large amounts of clinical research data supporting an ‘open vein hypothesis’, which favours early thrombus removal, clinicians have been hesitant to take this option due to a historically high risk of major bleeding and a few notable studies that failed to show any meaningful benefit. The ATTRACT trial failed to show the benefit of using pharmacomechanical catheter-directed thrombolysis (PCDT) for iliofemoral and femoropopliteal DVT but did result in more bleeding. However, the CaVent study before it revealed a significant reduction in post-thrombotic syndrome (PTS) for patients with iliofemoral and femoral DVT after long-term follow-up past 24 months that grew over time. Since these trials, there have been significant advancements in magnetic resonance and CT venography, intravascular ultrasound (IVUS), venous stenting and thrombectomy catheters meaning there is little to no need for adjunct thrombolytics. Results from ongoing research such as CLEAR-DVT reflect the advances in modern technology.

Augmentation of Pulmonary Perfusion by Conducted Effects of a Pulmonary Artery Ultrasound Catheter.

Ultrasound (US) generated by catheters used clinically for US-facilitated thrombolysis can release shear-dependent vasodilators from endothelial and red blood cells. We hypothesized that catheter-based US in the pulmonary artery (PA) decreases downstream vascular resistance and increases pulmonary blood flow. In rhesus macaques, a U.S. Food and Drug Administration-approved multi-element US catheter was placed in a pulmonary artery. Comprehensive echocardiography was performed (i) at baseline, (ii) during hypoxemia (12% FIO2) to increase pulmonary vascular resistance (PVR) and (c) 15 min after initiating US during hypoxemia. Reduced FIO2 produced intended reductions in oxygen saturation (69 ± 3%) and PaO2 (34 ± 5 mm Hg), yet on echocardiography, hypoxemia did not create the intended model, with only modest hypoxia-related increases in PA systolic pressure (24 ± 4 to 28 ± 4 mm Hg, p=0.05) and no significant change in PVR or multiparametric right ventricular (RV) function. Although US did not further change total PVR, on 99mTc-macroalbumin aggregate single-photon-emission computed tomography imaging, lung perfusion was significantly higher in the lung ipsilateral to the US catheter versus the contralateral control lung (133 ± 48 cpm vs. 103 ± 43×103 cpm, p=0.01). We conclude that PA catheter-based US increases regional lung perfusion, most likely from vasodilators that are conducted downstream.

The effects of varying ultrasound parameters on oxygen scavenging via acoustic droplet vaporization

Acoustic droplet vaporization (ADV) is a process that phase transitions liquid droplets into gas microbubbles via ultrasound. ADV results in oxygen scavenging from the surrounding fluid into the microbubbles. The objective of this study was to determine the effect of ultrasound parameters on oxygen scavenging. A microfluidic device was used to produce perfluoropentane droplets with a modal diameter of 1.14 ± 0.04 μm and a polydispersity index of 0.08 ± 0.02. Droplets were diluted to a concentration of 4.7 × 10−4 ± 0.4 × 10−5 ml/ml in 95% oxygenated water. The oxygen partial pressure (pO2) of the water was measured before and during ADV. An EkoSonic ultrasound catheter (2.35 MHz, 1.5 MPa peak negative pressure, 47 W pulse average power) nucleated ADV while either varying burst period or pulse duration (n = 5). Pre-ADV pO2 was 558 ± 5 mm Hg for all experiments. Peri-ADV pO2 dropped to 294 ± 6, 316 ± 10, and 356 ± 12 mmHg for a pulse duration of 17 μs and burst periods of 0.450 ms, 0.725 ms, and 1.000 ms, respectively. The peri-ADV pO2 dropped to 331 ± 14, 342 ± 10, 313 ± 10 mmHg for a burst period of 1.000 ms and pulse durations of 17.0, 23.4, and 37.9 μs, respectively. A significant difference was seen between the amount of oxygen scavenging for the lowest and highest burst periods (p = 0.0012) and pulse durations (p = 0.027).

Feasibility of Microbubble-Accelerated Low-Dose Thrombolysis of Peripheral Arterial Occlusions Using an Ultrasound Catheter.

Intra-arterial administration of microbubbles (MBs) through an ultrasound (US) catheter increases the local concentration of MBs into the thrombus and may further enhance outcomes of contrast-enhanced sonothrombolysis (CEST). The objective of this study was to evaluate the feasibility and lytic efficacy of intra-arterial infusion of MBs during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models. SonoVue and Luminity MBs were infused at a flow rate of 20 mL/h through either the drug delivery lumen of the US catheter (DDC, n=20) or through the tube lumen of the vascular phantom (systematic infusion, n=20) during thrombolysis with a low-dose urokinase (UK) protocol (50 000 IU/h) with(out) US application to assess MB survivability and size by pre-treatment and post-treatment measurements. A human thrombus was placed into a vascular phantom of the flow system to examine the lytic effects of CEST by post-treatment D-dimer concentrations measurements of 5 treatment conditions (saline, UK, UK+US, UK+US+SonoVue, and UK+US+Luminity). Thrombolytic efficacy of localized MBs and US delivery was then investigated in vivo in 5 porcine models by arterial blood flow, microcirculation, and postmortem determined thrombus weight and remaining length. US exposure significantly decreased SonoVue (p=0.000) and Luminity (p=0.000) survivability by 37% and 62%, respectively. In vitro CEST treatment resulted in higher median D-dimer concentrations for the SonoVue (0.94 [0.07-7.59] mg/mL, p=0.025) and Luminity (0.83 [0.09-2.53] mg/mL, p=0.048) subgroups when compared with thrombolysis alone (0.36 [0.02-1.00] mg/mL). The lytic efficacy of CEST examined in the porcine model showed an improved median arterial blood flow of 21% (7%-79%), and a median thrombus weight and length of 1.02 (0.96-1.43) g and 2.25 (1.5-4.0) cm, respectively. One allergic reaction and 2 arrhythmias were observed due to the known allergic reaction on lipids in the porcine model. SonoVue and Luminity can be combined with an US catheter and could potentially accelerate thrombolytic treatment of peripheral arterial occlusions. Catheter-directed thrombolysis showed to be an effective alternative to surgery for acute peripheral arterial occlusions, but this technique is still associated with several limb and life-threatening complications. The effects of thrombolysis on clot dissolution may be further enhanced by intra-arterial administration of microbubbles through an ultrasound catheter. This study demonstrates the feasibility and lytic efficacy of intra-arterial infusion of microbubbles during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models.

Hematoporphyrin- mediated focused ultrasound sonodynamic therapy combined with catheter- based rhenium-186 brachytherapy after B- mode ultrasound- guided balloon angioplasty of occluded artery

Background and Aims : Three mechanisms are responsible for the development of restenosis: elastic recoil, intimal hyperplasia and late vascular constriction, all grouped under the catch phrase “negative remodeling”. Neointimal hyperplasia is usually defined in an artery as thickening of the intimal layer after an injury such as balloon angioplasty methods. The aim of this study was to evaluate the effect of combined ultrasound sonodynamic therapy and catheter- based 186Re-mediated beta radiation (β-) brachytherapy on restenosis reduction after balloon angioplasty.

Ultrasound-Guided Intravascular Sonothrombolysis With a Dual Mode Ultrasound Catheter: In Vitro Study.

Thromboembolism in vessels often leads to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis based on ultrasound contrast agents has shown promising outcome in effective treatment of thromboembolism. Intravascular sonothrombolysis transducer was reported recently for unprecedented sonothrombolysis in vitro. However, it is necessary to provide an imaging guide during thrombolysis in clinical applications for optimal treatment efficiency. In this article, a dual mode ultrasound catheter was developed by combining a 16-MHz high-frequency element (imaging transducer) and a 220-kHz low-frequency element (treatment transducer) for sonothrombolysis in vitro. The treatment transducer was designed with a 20-layer PZT-5A stack with the aperture size of 1.2×1.2 mm2, and the imaging transducer with the aperture size of 1.2×1.2 mm2 was attached in front of the treatment transducer. Both transducers were assembled into a customized 2-lm 10-Fr catheter. In vitro experiment was carried out using a bovine blood clot. Imaging tests were conducted, showing that the backscattering signals can be obtained with a high signal-to-noise ratio (SNR) for the 16-MHz imaging transducer. Sonothrombolysis was performed successfully that the volume of clot was reduced significantly after the 30-min treatment. The size changes of clot were observed clearly using the 16-MHz M-mode imaging during the thrombolysis. The findings suggest that the proposed ultrasound-guided intravascular sonothrombolysis can be enhanced since the position of treatment transducer can be adjusted with the target at the clot due to the imaging guide.