Prototype 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.

AI-aided geometric design of anti-infection catheters.

Bacteria can swim upstream in a narrow tube and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed to repel bacteria, but no such approach thoroughly addresses the contamination problem in catheters. Here, on the basis of the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an artificial intelligence model. Using Escherichia coli, we demonstrate the anti-infection mechanism in microfluidic experiments and evaluate the effectiveness of the design in three-dimensionally printed prototype catheters under clinical flow rates. Our catheter design shows that one to two orders of magnitude improved suppression of bacterial contamination at the upstream end, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infection.

Determination of online thin film buckling configuration by parametric optimization for flexible sensor application

A mini basket type mapping catheter consists of thin film flexible sensors and is applied in the medical field to measure the electrocardiography (ECG) signals in order to localize and quantize the physiological condition/status of heart. The flexible nature of the thin film changes the configuration with respect to the contact boundary conditions when it contacts a target surface. Therefore, to accurately localize the flexible sensor, the thin film flexible sensor’s configuration must be determined accurately in an on-line fashion. As a study of localizing the thin film flexible sensor, this study proposes an on-line thin film buckling configuration determination method using parametric optimization and interpolation technique. With the specific modulus of elasticity and dimensions of the thin film flexible sensor of the mapping catheter prototype, the buckling configuration with two point boundary condition under axial load can be calculated in desktop environment. The proposed calculation method is validated by mapping catheter sensor prototype test. The calculation/test results showed that the maximum overall length L, x_{a}, and y_{a} value error between the calculation and experiment are approximately 0.16 mm, − 0.12 mm. − 0.10 mm in 50 ms calculation time. The calculation result of the proposed method is also compared with that of the numerical simulation by FEM, which has approximately 0.44 mm y_{a} value error compared with that of the experiment.

Design of Thermoplastic Polyurethanes with Conferred Antibacterial, Mechanical, and Cytotoxic Properties for Catheter Application.

Thermoplastic polyurethanes (TPUs) are proposed as suitable solution for the fabrication of biocompatible catheters with appropriate mechanical parameters and confirmed antibacterial and cytocompatible properties. For this purpose, a series of quaternary ammonium salts (QASs) and quaternary phosphonium salts (QPSs) based monomers were prepared followed by the determination of their minimal inhibitory concentrations (MICs) against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa). A combination of the most active ammonium (QAS-C14) and phosphonium (QPS-TOP) salts led to a MIC down to 2.4 μg/mL against S. aureus and 9 μg/mL against P. aeruginosa, corroborating the existence of a synergistic effect. These quaternary onium salt (QOS) units were successfully incorporated along the polymer chain, as part of a two-step synthesis approach. The resulting TPU-QOS materials were subsequently characterized through thermal, mechanical, and surface analyses. TPU-Mix (combining the most active QAS-C14 and QPS-TOP units) showed the highest antibacterial efficiency, confirming the synergistic effect between both QOS groups. Finally, an MTT assay on the SiHa cell line revealed the low cytotoxicity level of these polymeric films, making these materials suitable for biomedical application. To go one step further in the preindustrialization approach, proof of concept regarding the catheter prototype fabrication based on TPU-QAS/QPS was validated by extrusion.

Effects of Electrode-Tissue Proximity on Cardiac Lesion Formation Using Pulsed Field Ablation.

Background:Pulsed field ablation (PFA) is a novel energy modality for treatment of cardiac arrhythmias. The impact of electrode-tissue proximity on lesion formation by PFA has not been conclusively assessed. The objective of this investigation was to evaluate the effects of electrode-tissue proximity on cardiac lesion formation with a biphasic, bipolar PFA system.Methods:PFA was delivered on the ventricular epicardial surface in an isolated porcine heart model (n=8) via a 4-electrode prototype catheter. An offset tool was designed to control the distance between electrodes and target tissue; deliveries were placed 0 mm (0 mm offset), 2 mm (2 mm offset), and 4 mm away from the tissue (4 mm offset). Lesions were assessed using tetrazolium chloride staining. Numerical models for the experimental setup with and without the offset tool validated and supported results.Results:Cardiac lesion dimensions decreased proportional to the distance between epicardial surface and electrodes. Lesion depth averaged 4.3±0.4 mm, 2.7±0.4 mm, and 1.3±0.4 mm for the 0, 2, and 4 mm and lesion width averaged 9.4±1.1 mm, 7.5±0.8 mm and 5.8±1.4 mm for the 0, 2, and 4 mm offset distances, respectively. Numerical modeling matched ex vivo results well and predicted lesion creation with and without the offset tool.Conclusions:Using a biphasic, bipolar PFA system resulted in cardiac lesions even in the 0 mm offset distance case. The relationship between lesion depth and offset distance was linear, and the deepest lesions were created with 0 mm offset distance, that is, with electrodes in contact with tissue. Therefore, close electrode-tissue proximity increases the likelihood of achieving transmural lesions by maximizing the electric field penetration into the target tissue.

A light-guiding urinary catheter for the inhibition of Proteus mirabilis biofilm formation.

Catheter-associated urinary tract infection (CAUTI) is a leading cause of hospital-acquired infections worldwide causing debilitating illness for patients as well as a significant financial and treatment burden on health services. CAUTI is linked with the build-up of biofilms on catheter surfaces which act as a reservoir for infection. Additionally, urease-producing bacteria such as Gram-negative Proteus mirabilis (PM), can form crystalline biofilms which encrust catheter surfaces ultimately leading to blockages which require immediate removal of the catheter. Currently there are limited treatments available to prevent the formation of biofilms by PM as well as other urinary tract infection causing bacteria. A novel concept for a light-guiding urinary catheter is presented where a silicone elastomer waveguide incorporated along the length of the catheter is used to irradiate the catheter surfaces with antimicrobial blue light (405 nm) to prevent biofilm formation in situ. The prototype device is mass producible while also easy to fabricate in a lab setting for research studies. The inhibitory effect of blue light on PM biofilm formation over a range of irradiances is described for the first time showing an LD90 at 192–345 J/cm2 and total inhibition at 1,700 J/cm2 In vitro studies show that the light-guiding catheter (LGC) prototypes exhibit a 98% inhibition in PM biofilm formation inside the catheter lumen at an average estimated irradiance of 30–50 mW/cm2 (324–540 J/cm2 fluence) showing that the concept is highly effective, promising to be a powerful and economical antimicrobial approach to prevent catheter associated biofilm development and blockage.

A new catheter-integrated drug-delivery system for controlled intravesical mitomycin C release

Intravesical treatment of bladder cancer is preferred over systemic administration. However, the efficacy of intravesical instillations is challenged by the periodic voiding that flushes out the instilled drug and ultimately reduces drug exposure to the bladder epithelium. Here, we demonstrate a new catheter-integrated drug-delivery concept that utilizes a silicone-based interpenetrating polymer network (IPN) as material for the catheter balloon, to facilitate continuous release of the bladder cancer adjuvant, Mitomycin C, from a balloon-reservoir to the urinary bladder. Long-term release properties and anti-carcinoma cell efficacy of released drug was investigated in vitro. Short-term release experiments were performed in live pigs to evaluate the IPN prototype catheter in a physiological relevant environment in vivo. Sustained zero-order release of Mitomycin C was achieved for 12 days in vitro without refilling the balloon. Mitomycin C was released from the IPN-balloons into the urinary bladder of live pigs in concentrations adequate to inhibit carcinoma cell growth. The IPN catheter represents a new drug-delivery concept for prolonged Mitomycin C delivery to the urinary bladder.

Development of a novel low-background noise blood loop model for testing blood-contacting biomaterials and medical devices in fresh human blood.

A novel low volume blood loop model (Ension Triad System [ETS]) incorporating pulsatile flow and a proprietary low-activation blood-contacting surface (Ension bioactive surface [EBS]) enabling high signal-to-noise performance is described. The ETS system incorporates a test chamber that allows direct comparison of material samples or finished medical devices such as catheters with varying compositions and/or surface treatments. ETS performance is presented from two independent organizations (Medtronic and MLM Labs) and includes results for hemolysis (pfHgb), platelet count, platelet activation (βTG), coagulation (TAT), inflammation (PMN Elastase, PMN CD112b, and monocyte CD112b) and immune response (SC5b-9) were made on: (1) the EBS-treated system itself without a test material (No Material, NM); (2) the EBS-treated system with an idealized untreated catheter (UC); and (3) the EBS-treated system with the prototype catheter treated with the EBS surface treatment (CC). The untreated catheter (UC) was associated with significant elevation of all activation marker levels (pfHgb excluded). The EBS-treated catheter, in direct comparison to the UC and NM catheters, appeared invisible with respect to the activation markers (all markers statistically different than the UC and equivalent to the NM control). Based on these data, we conclude that using a relatively small surface area test sample and a small volume of fresh human blood, the high signal-to-noise performance of the ETS system demonstrates comprehensive and statistically significant material differences in the major ISO 10993-4 categories of blood interaction. These data underscore the important benefit of minimal confounding of test/device responses with non-test-material/model-related responses. ETS offers a practical alternative to the common one-test-category-at-a-time approach when assessing blood/medical device interactions.

Alternatingly Amphiphilic Antimicrobial Oligoguanidines: Structure–Property Relationship and Usage as the Coating Material with Unprecedented Hemocompatibility

With the emergence of antibiotic resistance in recent years, the combat against bacteria is becoming more difficult and critical in human healthcare. In addition to the development of new chemical entities and derivatives of antibiotics and disinfectants, the antimicrobial surface is recognized as a potential way to prevent healthcare-associated infections, particularly those caused by medical devices such as implants and various catheters. However, traditional ways of engineering antimicrobial surfaces using coated metal nanostructures or blended-in antibiotics inevitably face the problem of metal ion or antibiotic leakage, leading to surface deactivation, toxicity, and antibiotic resistance. A new strategy developed in recent years involves the use of coated cationic antimicrobial polymers, which serve as resistance-resistant, surface-anchored antibacterial agents, but they also usually come with hemolytic activity resulting from their membrane-disrupting-type mechanism of action. In this report, we show that the combinatorial approach can be highly useful for the selection of alternatingly amphiphilic oligomers, which are essentially molecular nanorods as revealed by molecular dynamic simulations. The combinatorial process allowed the structure–property relationship of these molecular nanorods to be revealed and yielded oligoguanidine hit with high antimicrobial activity, fast killing kinetics, and extremely low hemolytic activity through assay screening. We demonstrate that the covalent conjugation of such a prescreened oligoguanidine nanorod to glass slides or polycaprolactone films could produce antimicrobial surfaces with excellent performance. A catheter prototype made using such a modified polycaprolactone film could transport bacteria-contaminated liquid, efficiently removing all bacteria without causing lysis of red blood cells.

Towards catheter steering using magnetic tractor beam coupling.

Catheters are used in various clinical applications, and the ability to direct the catheter to the desired location is critical for clinical outcomes. Steerable catheters assist clinicians to access targeted areas, notably the vascular bundles and major vessels, while causing no damage to the surrounding tissue. A novel catheter actuation technology for catheter steering is presented in this study. The technique is simple and relies on three magnetic couples interacting with one another to generate steering motions. A proof-of-concept catheter prototype demonstrated the capacity to remotely steer a catheter over 100 mm of distance and ±45° of angular positioning, showing the potential manoeuvrability for clinical applications. It is feasible to steer a catheter using this three-magnet pair approach with the great potential to be used for catheterisation procedures. The presented mechanism’s kinematics and a near-form solution for catheter steering regardless of design factors will be studied in the future.

773. Hypochlorous Acid Generating Electrochemical Catheter Prototype for Prevention of Intraluminal Infections

BackgroundCentral-line associated bloodstream infection (CLABSI) contributes to mortality and cost. While aseptic dressings and antibiotic-impregnated catheters can prevent extraluminal infections, intraluminal infections remain a source of CLABSIs with limited prevention options. MethodsIn this proof-of-concept study, an electrochemical intravascular catheter (e-catheter) prototype capable of electrochemically generating hypochlorous acid intraluminally on the surface of platinum electrodes polarized at a constant potential of 1.5 VAg/AgCl was developed. After 24h of pre-polarization at 1.5 VAg/AgCl, their activity was tested by inoculating four clinical isolates derived from catheter-related infections, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium and Escherichia coli. Figure 1. In vitro catheter and e-catheter models. ResultsE-catheters generated a mean HOCl concentration of 15.86±4.03 μM and had a mean pH of 6.14±0.79. e-catheters prevented infections with all four species, with an average reduction of 8.41±0.61 log10 CFU/mL at 48h compared to controls. Figure 3. Measurement of pH and HOCl at 48 hours in polarized e-catheters. Each dot represents a replicate; bars represent means.Figure 4. Prevention of infection after 48 hours of polarization (24 hours of infections) using e-catheters (polarized and non-polarized) compared to blank catheters. * indicates statistically significant reduction of cell counts in polarized e-catheter compared to blank catheter (p <0.05).ConclusionPolarized e-catheters which generate low amounts of HOCl continuously should be further developed to prevent intraluminal infection.Disclosures Haluk Beyenal, Ph.D, patent (Other Financial or Material Support, HB holds a patent: Beyenal H CD, Fransson BA, Sultana ST. . 2018. Electrochemical reduction or prevention of infections. U.S. patent 20180207301A1, international patent WO/2017/011635.) Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor's Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor's stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant

The End of Wire Wrapping: A Technique to Avoid Intertwining Preloaded Guidewires for Endovascular Aortic Arch Repair

Purpose: The purpose of this study was to present a new technique for endovascular aortic arch repair for 1, 2, or 3 vessels using preloaded wires and precannulated target vessels without wire wrapping. Technique: This technique uses a prototype catheter with 2 parallel lumens to position through-and-through guidewires in the supra-aortic branches and an extra-stiff guidewire in the ascending aorta with no wrapping. This allows the introduction and advancement of the device with the already precannulated target vessels. The endograft is advanced to the aortic arch without twisting or wrapping. Covered stents are deployed to align the graft and target vessels. Conclusion: To our knowledge, a technique that avoids wire wrapping has not been previously described. This technique allows safer and faster endovascular arch procedures and opens up new possibilities by enabling multi-vessel endovascular aortic arch repair with all precannulated target vessels.

Hypochlorous Acid-Generating Electrochemical Catheter Prototype for Prevention of Intraluminal Infection.

ABSTRACTCentral line-associated bloodstream infection (CLABSI) contributes to mortality and cost. While aseptic dressings and antibiotic-impregnated catheters prevent some extraluminal infections, intraluminal infections remain a source of CLABSIs. In this proof-of-concept study, an electrochemical intravascular catheter (e-catheter) prototype capable of electrochemically generating hypochlorous acid intraluminally using platinum electrodes polarized at a constant potential of 1.5 electrode potential relative to saturated silver/silver chloride reference electrode measured in volts (VAg/AgCl) was developed. After 24 h of prepolarization at 1.5 VAg/AgCl, their activity was tested against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, and Escherichia coli derived from catheter-related infections. e-catheters generated a mean HOCl concentration of 15.86 ± 4.03 μM and had a mean pH of 6.14 ± 0.79. E-catheters prevented infections of all four species, with an average reduction of 8.41 ± 0.61 log10 CFU/ml at 48 h compared to controls. Polarized e-catheters which generate low amounts of HOCl continuously should be further developed to prevent intraluminal infection.IMPORTANCE Catheter-related infections constitute an economic and mortality burden in health care. Several options are available to reduce the risk of infection, but only a few focus on preventing intraluminal infection, which occurs in long-term catheters, most often used for dialysis, prolonged treatment, or chemotherapy. A prototype of a catheter called an “e-catheter” composed of three electrodes, capable of producing hypochlorous acid (HOCl) electrochemically in its lumen, was developed. When polarized at 1.5 V, chloride ions in the solution are oxidized to continuously produce low amounts of HOCl, which exhibits antibacterial activity in the lumen of the catheter. Here, this prototype was shown to be able to generate HOCl as well as prevent infection in a preliminary in vitro catheter model. This approach is a potential strategy for catheter infection prevention.

A novel flow and pressure catheter for complete interventional cardiology physiology management

Abstract Ischemia with No Obstructive Coronary Artery (INOCA) in angina patients increases the risk of major cardiac events, with a 1.5x increased mortality rate. There is a link between COVID-19 infection and impairment in the myocardial micro-vasculation which may cause an increase of INOCA patients. Fractional Flow Reserve (FFR), is the standard of care in cardiology but its diagnostic function is only related to Obstructive Coronary Artery disease (or epicardial) and it is ineffective with INOCA. The lack of effective and accurate tools for timely evaluation of coronary impairments creates a clinical unmet need. The PhysioCath catheter was developed within the Eurostars project “FP-Catheter, E!113577” aims to resolve this need a provide an effective tool to interventional cardiologists. The main project outcome is a catheter prototype equipped with a blood flow velocity sensor based on a thermo-convection principle, and a fiber optic pressure sensor (based on Fabry-Perot principle). While the use of Fabry-Perot type of sensor is already standard in the industry, the use of a thermo-convection sensor represents a progress with respect the state of the art. The sensor creates an overheat of 7°C above the physiological blood's temperature (considered as being within the safety limits), and it exchanges thermal power with the blood stream. The power is then measured and converted to velocity by means of a calibration curve. The project encompassed interviews with 14 clinical experts, the summary of the interviews indicated that the preferred form of the device is an over the wire microcatheter, with rapid exchange. Within the project then, it was developed a 3Fr microcatheter, with a rapid exchange section of 24cm. Both pressure sensor and flow velocity sensor were integrated in this embodiment. Finally, the PhysioCath prototype was evaluated in a bench test study. The test setup was composed by an anatomical silicone phantom of the aortic root and the coronaries (Elastrat, Geneva, Switzerland), perfused with a peristaltic pump (Harvard Apparatus, Holliston MA, US). The measurements performed by the flow velocity sensor were compared against and external doppler flow velocity sensor. While the pressure measurement was assessed for stability and presence of drift. The data processing revealed and extreme accuracy in the measurement of flow based indexes like CFR (±6% variability), accuracy of the blood flow velocity measurement (±10%), and extreme stability in the measurement of both pressure and flow velocity. In the second part of the project (that is currently ongoing), it will be studied the performance of the device within an animal setting. In conclusion, the PhysioCath device is a microcatheter integrating bot pressure measurement and blood flow velocity measurement. Its performance is of very high accuracy and stability, that represent a main step ahead with respect the current state of the art, based mainly on thermodilution. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Eureka-Eurostars Test benchMicrocatheter prototype

Thermoplastic polyurethanes for biomedical application: A synthetic, mechanical, antibacterial, and cytotoxic study

AbstractThermoplastic polyurethanes (TPUs) bear tunable chemistry offering the possibility to develop a rich palette of physio‐mechanical properties, making the materials suitable for various fields of application. The great variety in TPUs properties comes from the choices of the monomers and the reaction conditions. Herein, the mechanical properties of the developed TPUs are tailored, while fine‐tuning the hard and soft segment molar ratio, as well as the reaction conditions. TPUs are synthesized from 4,4′‐methylenebis(phenyl isocyanate), poly(tetrahydrofuran), and 1,4‐butanediol, and their thermal and mechanical properties are fully characterized. The sample with the most appropriate mechanical properties that are suitable for catheter fabrication, is selected for the biomedical application. Quaternary ammonium salt is synthesized, and 0.5 mol% is incorporated in the TPU to confer antibacterial properties to the material while preserving its mechanical strength. The microbiological tests reveal the antibacterial effect of the developed materials against Staphylococcus aureus and Pseudomonas aeruginosa, as well as 80% SiHa cell viability, after 72 h of exposure, as part of the performed cytotoxicity studies. Finally, TPUs catheter prototypes fabrication is also proposed, applying an extrusion or injection molding approach for the production of biomedical devices with desirable mechanical properties.

Efficacy Estimation of Microbubble-Assisted Local Sonothrombolysis Using a Catheter with a Series of Miniature Transducers.

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.

A multipurpose brachytherapy catheter to enable intratumoral injection

PurposeTo create and test a multipurpose brachytherapy catheter prototype enabling intratumoral injection and brachytherapy after a single catheter insertion. Methods and MaterialsThe design of the prototype consists of an outer tube and an inner syringe tube that can be filled with injectable agent. The outer sheath and inner syringe tube were constructed using polytetrafluoroethylene tubing, and the other components were 3D printed using dental resin and polylactic acid material. To demonstrate functionality, we injected in vitro phantoms with dyed saline. For proof of concept, we demonstrated the potential for the prototype to deliver cell therapy, enhance tumor delineation, deliver tattoo ink for pathology marking, avoid toxicity through local delivery of chemotherapy, and facilitate combination brachytherapy and immunotherapy. ResultsThe prototype enables accurate injection in vitro and in vivo without altering dosimetry. To illustrate the potential for delivery of cell therapies, we injected luciferase-expressing splenocytes and confirmed their delivery with bioluminescence imaging. To demonstrate feasibility of radiographically visualizing injected material, we delivered iohexol contrast intratumorally and confirmed tumor retention using Faxitron x-ray imaging. In addition, we show the potential of intratumoral administration to reduce toxicity associated with cyclophosphamide compared with systemic administration. To demonstrate feasibility, we treated tumor-bearing mice with brachytherapy (192Ir source, 2 Gy to 5 mm) in combination with intratumoral injection of 375,000 U of interleukin 2 and observed no increased toxicity. ConclusionsThese results demonstrate that a prototype multipurpose brachytherapy catheter enables accurate intratumoral injection and support the feasibility of combining intratumoral injection with brachytherapy.

Novel Dual-Lumen Drainage Catheter to Enhance the Active Evacuation of Complex Fluid Collections

PurposeTo compare the performance of a dual-lumen flushable drainage catheter to a conventional catheter for complex fluid collection drainage. MethodsTwo prototype catheters (20- and 28-F) were created by incorporating a customized infusion lumen within the wall of a large-bore conventional drainage catheter, which facilitated simultaneous irrigation of the drainage lumen and the targeted collection via inward- and outward-facing infusion side holes. These were tested against unaltered 20- and 28-F conventional catheters to determine if the injection of a dedicated flush lumen improved rapidity and completeness of gravity drainage. In vitro models were created to simulate serous fluid, purulent/exudative fluid, particulate debris, and acute hematoma. ResultsIn the purulent model, mean drainage rate was 19.9 ± 8.0 and 9.5±1.4 mL/min for the 20-F prototype and control (P < .001) and 63.9 ± 4.3 and 35.4 ± 3.4 mL/min for the 28-F prototype and control (P = .006), respectively, with complete drainage achieved in all trials. In the particulate model, mean drainage rate was 24.5 ± 9.7 and 12.0 ± 12.5 mL/min for the 28-F prototype and control (P = .003), respectively, with 69.0% versus 41.1% total drainage achieved over 24 minutes (P = .029). In the hematoma model, mean drainage rate was 22.7 ± 4.6 and 4.8 ± 4.3 mL/min for the 28-F prototype and control (P = .022), respectively, with 80.3% versus 20.1% drainage achieved over 15 minutes (P = .003). Particulate and hematoma 20-F prototypes and conventional trials failed due to immediate occlusion. ConclusionsThe proposed dual-lumen drainage catheter with irrigation of a dedicated flush lumen improved evacuation of complex fluid collections in vitro.

A "Smart" Biosensor-Enabled Intravascular Catheter and Platform for Dynamic Delivery of Propofol to "Close the Loop" for Total Intravenous Anesthesia.

Target-controlled infusion anesthesia is used worldwide to provide user-defined, stable, blood concentrations of propofol for sedation and anesthesia. The drug infusion is controlled by a microprocessor that uses population-based pharmacokinetic data and patient biometrics to estimate the required infusion rate to replace losses from the blood compartment due to drug distribution and metabolism. The objective of the research was to develop and validate a method to detect and quantify propofol levels in the blood, to improve the safety of propofol use, and to demonstrate a pathway for regulatory approval for its use in the USA. We conceptualized and prototyped a novel "smart" biosensor-enabled intravenous catheter capable of quantifying propofol at physiologic levels in the blood, in real time. The clinical embodiment of the platform is comprised of a "smart" biosensor-enabled catheter prototype, a signal generation/detection readout display, and a driving electronics software. The biosensor was validated in vitro using a variety of electrochemical methods in both static and flow systems with biofluids, including blood. We present data demonstrating the experimental detection and quantification of propofol at sub-micromolar concentrations using this biosensor and method. Detection of the drug is rapid and stable with negligible biofouling due to the sensor coating. It shows a linear correlation with mass spectroscopy methods. An intuitive graphical user interface was developed to: (1) detect and quantify the propofol sensor signal, (2) determine the difference between targeted and actual propofol concentration, (3) communicate the variance in real time, and (4) use the output of the controller to drive drug delivery from an in-line syringe pump. The automated delivery and maintenance of propofol levels was demonstrated in a modeled benchtop "patient" applying the known pharmacokinetics of the drug using published algorithms. We present a proof-of-concept and in vitro validation of accurate electrochemical quantification of propofol directly from the blood and the design and prototyping of a "smart," indwelling, biosensor-enabled catheter and demonstrate feedback hardware and software architecture permitting accurate measurement of propofol in blood in real time. The controller platform is shown to permit autonomous, "closed-loop" delivery of the drug and maintenance of user-defined propofol levels in a dynamic flow model.

New Biparietal Bipolar Catheter Prototype for Hybrid Atrial Fibrillation Ablation.

ObjectiveTo evaluate the size and depth of linear lesions by in vitro testing with a custom-made radio frequency biparietal bipolar ablation catheter in a single-stage setting.MethodsA custom-made catheter was created to generate linear lesions around the left atrium and pulmonary veins of an ex vivo pig. Two frames were made, 1 epicardial and 1 endocardial. A continuous copper braid electrode and an alignment system consisting of 2 parallel rows of neodymium magnets were embedded in a flexible plastic support. After 24 hours of formalin conservation, samples of the left atrium of a freshly slaughtered pig were sliced in a cryotome, thus obtaining a sequence of 100-µm thick layers extending from the endocardial to the epicardial side. After being digitized through a scanner, these layers were evaluated using morphometric computer software. For each slice, we evaluated the maximum length of the lesions, the maximum epicardial length, the maximum endocardial length, the total area of the lesion, and the total volume.ResultsForty transmural lesions from 40 specimens were obtained. The results were the following (the number in parenthesis is the interquartile range in mm): lesion maximum length (L MAX) was 7.297 mm (0.006), epicardial maximum length (L EPI) was 7.291 mm (0.014), and endocardial maximum length was 7.291 mm (0.018). The total area and total volume were 1018.50 ± 36.51 mm2 and 101.85 ± 3.65 mm3, respectively.ConclusionsOur prototype showed very promising results. The next step will be to enhance the design for clinical application.