Label-free monitoring of embolotherapy via catheter electrochemical impedance spectroscopy.

Catheter-based embolization has become a widely adopted minimally-invasive treatment for a broad range of applications. However, assessment of embolization endpoints requires x-ray fluoroscopic monitoring, exposing patients and physicians performing embolization procedures to harmful ionizing radiation. Moreover, x-ray fluoroscopy assessment of embolization endpoints is low sensitivity, subjective, and may not reflect the actual physiology of blood flow reduction, thus providing little oversight of the embolization procedure. Inspired by the observation that the dielectric properties of blood differ from those of fluids injected during the embolization procedure, a customized angiographic catheter was created with embedded electrodes for catheter-based electrochemical impedance spectroscopy as a way to monitor embolization. Real-time electrochemical impedance spectroscopy was performed in a phantom and compared to visual and videographic monitoring. Electrochemical impedance spectroscopy was able to sense endpoints of embolization, including stasis, reflux, and persistent flow. This new technique offers a label-free method of sensing embolization progress with potentially higher sensitivity and reproducibility compared to x-ray, as well as offer substantial reduction in x-ray exposure to patients and physicians.

Design and implementation of a cost-effective, open-source, and programmable pulsatile flow system.

The primary objective of this research was to design, implement, and validate a programmable open-source pulsatile flow system to cost-effectively simulate vascular flows. We employed an Arduino-compatible microcontroller combined with a motor driver to control a centrifugal direct current (DC) motor pump. The system was programmed to produce pulsatile flows with an arterial pulse waveform. Validation with Doppler ultrasound and flow measurements confirmed that our Arduino-based system successfully replicated arterial vascular flow. The materials are easily accessible, with a total bill of materials as low as $99. This open-source programmable pulsatile pump platform offers superior cost-effectiveness and adaptability relative to commercial offerings.

Percutaneous Cryoneurolysis for Pain Control After Rib Fractures in Older Adults.

This case series evaluates changes in numeric pain scores, opioid use, and other measures before, during, and 30 days after computed tomography­guided percutaneous cryoneurolysis in patients with rib injury.

The Role of Physician-Driven Device Preference in the Cost Variation of Common Interventional Radiology Procedures.

PURPOSE: To analyze the impact of physician-specific equipment preference on cost variation for procedures typically performed by interventional radiologists at a tertiary care academic hospital. MATERIALS AND METHODS: From October 2017 to October 2019, data on all expendable items used by 9 interventional radiologists for 11 common interventional radiology procedure categories were compiled from the hospital analytics system. This search yielded a final dataset of 44,654 items used in 2,121 procedures of 11 different categories. The mean cost per case for each physician as well as the mean, standard deviation, and coefficient of variation (CV) of the mean cost per case across physicians were calculated. The proportion of spending by item type was compared across physicians for 2 high-variation, high-volume procedures. The relationship between the mean cost per case and case volume was examined using linear regression. RESULTS: There was a high variability within each procedure, with the highest and the lowest CV for radioembolization administration (56.6%) and transjugular liver biopsy (4.9%), respectively. Variation in transarterial chemoembolization cost was mainly driven by microcatheters/microwires, while for nephrostomy, the main drivers were catheters/wires and access sets. Mean spending by physician was not significantly correlated with case volume (P =.584). CONCLUSIONS: Physicians vary in their item selection even for standard procedures. While the financial impact of these differences vary across procedures, these findings suggest that standardization may offer an opportunity for cost savings.

Fluorous-phase iron oxide nanoparticles as enhancers of acoustic droplet vaporization of perfluorocarbons with supra-physiologic boiling point.

Perfluorocarbon emulsion nanodroplets containing iron oxide nanoparticles (IONPs) within their inner perfluorohexane (PFH) core were prepared to investigate potential use as an acoustically activatable ultrasound contrast agent, with the hypothesis that incorporation of IONPs into the fluorous phase of a liquid perfluorocarbon emulsion would potentiate acoustic vaporization. IONPs with an oleic acid (OA) hydrophobic coating were synthesized through chemical co-precipitation. To suspend IONP in PFH, OA was exchanged with perfluorononanoic acid (PFNA) via ligand exchange to yield fluorophilic PFNA-coated IONPs (PFNA-IONPs). Suspensions with various amounts of PFNA-IONPs (0-15% w/v) in PFH were emulsified in saline by sonication, using 5% (w/v) egg yolk phospholipid as an emulsifier. PFNA-IONPs were characterized with transmission electron microscopy (TEM), transmission electron cryomicroscopy (cryoTEM), and thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FTIR). IONP were between 5 and 10 nm in diameter as measured by electron microscopy, and hydrodynamic size of the PFH nanodroplets were 150 to 230 nm as measured by dynamic light scattering (DLS). Acoustic droplet vaporization of PFH nanodroplets (PFH-NDs) was induced using conversion pulses (100 cycle at 1.1 MHz and 50% duty cycle) provided by a focused ultrasound transducer, and formed microbubbles were imaged using a clinical ultrasound scanner. The acoustic pressure threshold needed for PFH-NDs vaporization decreased with increasing temperature and IONP content. PFH-NDs containing 5% w/v IONP converted to microbubbles at 42 °C at 2.18 MI, which is just above the exposure limits of 1.9 MI allowed by the FDA for clinical ultrasound scanners, whereas 10 and 15% emulsion vaporized at 1.87 and 1.24 MI, respectively. Furthermore, 5% IONP-loaded PFH-NDs injected intravenously into melanoma-bearing mice at a dose of 120 mg PFH/kg, converted into detectable microbubbles in vivo 5 h, but not shortly after injection, indicating that this technique detects NDs accumulated in tumors.

Thrombin-Activatable Microbubbles as Potential Ultrasound Contrast Agents for the Detection of Acute Thrombosis.

Acute deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins of the body that can lead to fatal pulmonary embolism. Acute DVT is difficult to distinguish from chronic DVT by ultrasound (US), the imaging modality of choice, and is therefore treated aggressively with anticoagulants, which can lead to internal bleeding. Here we demonstrate that conjugating perfluorobutane-filled (PFB-filled) microbubbles (MBs) with thrombin-sensitive activatable cell-penetrating peptides (ACPPs) could lead to the development of contrast agents that detect acute thrombosis with US imaging. Successful conjugation of ACPP to PFB-filled MBs was confirmed by fluorescence microscopy and flow cytometry. Fluorescein-labeled ACPP was used to evaluate the efficiency of thrombin-triggered cleavage by measuring the mean fluorescence intensity of ACPP-labeled MBs (ACPP-MBs) before and after incubation at 37 °C with thrombin. Lastly, control MBs and ACPP-MBs were infused through a tube containing a clot, and US contrast enhancement was measured with or without the presence of a thrombin inhibitor after washing the clot with saline. With thrombin activity, 91.7 ± 14.2% of the signal was retained after ACPP-MB infusion and washing, whereas only 16.7 ± 4% of the signal was retained when infusing ACPP-MBs in the presence of hirudin, a potent thrombin inhibitor.

Polymer-Stabilized Perfluorobutane Nanodroplets for Ultrasound Imaging Agents.

In this paper, we describe a method for the stabilization of low-boiling point (low-bp) perfluorocarbons (PFCs) at physiological temperatures by an amphiphilic triblock copolymer which can emulsify PFCs and be cross-linked. After UV-induced thiol-ene cross-linking, the core of the PFC emulsion remains in liquid form even at temperatures exceeding their boiling points. Critically, the formulation permits vaporization at rarefactional pressures relevant for clinical ultrasound.

Evaluation of Knee Donor and Elbow Recipient Sites for Osteochondral Autologous Transplantation Surgery in Capitellar Osteochondritis Dissecans.

BACKGROUND: Osteochondral autologous transplantation surgery (OATS) has been advocated for treatment of osteochondritis dissecans (OCD) of the capitellum in adolescents. However, little information is available regarding the optimal knee harvest site to match the contour and cartilage thickness of the recipient elbow lesion. PURPOSE: To characterize the capitellar anatomic structure in adolescents with and without OCD and to compare these measurements to normal adolescent knees to identify the optimal site for osteochondral graft harvest. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-one patients with OCD were analyzed. Twenty-two patients with normal elbows and 25 age-, weight-, and height-matched patients with normal knees were also identified. Cartilage radii of curvatures (ROCs) in the sagittal and coronal-axial planes were measured on magnetic resonance imaging (MRI) of normal capitella and 5 sites (posterior lateral femoral condyle, medial and lateral middle trochlear ridges, and medial and lateral inferior trochlear ridges) in normal knees. Differences in ROC between the knee donor and capitellar recipient sites were calculated based on a 10-mm osteochondral plug diameter. RESULTS: Overall, the mean apex differences between graft and recipient sites ranged from 0.4 to 0.9 mm, and mean edge differences ranged from 0.5 to 1.4 mm in the coronal-axial dimension. Of all knee sites tested, the posterior lateral femoral condyle had average ROCs (19.1 mm sagittal; 14.1 mm axial) most like the capitellum (10.6 mm sagittal, 12.6 mm coronal-axial), resulting in minimal apex and edge differences (apex difference = -0.6 mm; coronal-axial side difference = -0.5 mm; no sagittal side difference). Of the anterior nonweightbearing sites, the inferior medial trochlear ridge (28.3 mm sagittal ROC; 13.2 mm coronal-axial ROC) demonstrated the lowest apex and side differences when compared with the capitellum (apex difference = -0.8 mm; coronal-axial side difference = -0.8 mm; no sagittal side difference). The frequently used middle lateral trochlear ridge (28.8 mm sagittal; 8.7 mm coronal-axial ROCs) had the largest side difference (apex distance = -0.8 mm; coronal-axial side difference = -1.4 mm; no sagittal side difference). CONCLUSION/CLINICAL RELEVANCE: In cases where a large single-plug OATS is considered, a 10-mm plug from the anterior nonweightbearing aspect of the distal femur is calculated to result in ≤1 mm of articular incongruity at the recipient capitellum. The inferior medial trochlear ridge should be considered as a donor site for OATS procedures for OCD given its accessibility and favorable geometry.

Domains of apoE4 required for the biogenesis of apoE-containing HDL.

INTRODUCTION. We have studied the functions of truncated apoE4 forms in vitro and in vivo in order to identify the domains of apoE4 required for the biogenesis of apoE-containing high-density lipoprotein (HDL). RESULTS. We have found that apoE4-185, -202, -229, or -259 could promote ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux in vitro, although less efficiently than Full-length apoE4, and had diminished capacity to activate lecithin cholesterol acyltransferase (LCAT). Formation of HDL in vivo was assessed by various methods following gene transfer in apolipoprotein A-I(-/-) × apoE(-/-) mice. Fast protein liquid chromatography of plasma showed that the truncated apoE forms, except apoE4-185, generated an apoE-containing HDL peak. Two-dimensional gel electrophoresis of plasma and electron microscopy showed that truncated apoE forms generated distinct HDL subpopulations and formed discoidal HDL particles which could be converted to spherical by co-administration of truncated apoE4-202 and LCAT. CONCLUSION. Overall, the in-vivo and in-vitro data are consistent and indicate that apoE4-185 is the shortest truncated form that supports formation of discoidal apoE4-containing HDL particles.

Molecular etiology of a dominant form of type III hyperlipoproteinemia caused by R142C substitution in apoE4.

We have used adenovirus-mediated gene transfer in apolipoprotein (apo)E(-/-) mice to elucidate the molecular etiology of a dominant form of type III hyperlipoproteinemia (HLP) caused by the R142C substitution in apoE4. It was found that low doses of adenovirus expressing apoE4 cleared cholesterol, whereas comparable doses of apoE4[R142C] greatly increased plasma cholesterol, triglyceride, and apoE levels, caused accumulation of apoE in VLDL/IDL/LDL region, and promoted the formation of discoidal HDL. Co-expression of apoE4[R142C] with lecithin cholesterol acyltransferase (LCAT) or lipoprotein lipase (LPL) in apoE(-/-) mice partially corrected the apoE4[R142C]-induced dyslipidemia. High doses of C-terminally truncated apoE4[R142C]-202 partially cleared cholesterol in apoE(-/-) mice and promoted formation of discoidal HDL. The findings establish that apoE4[R142C] causes accumulation of apoE in VLDL/IDL/LDL region and affects in vivo the activity of LCAT and LPL, the maturation of HDL, and the clearance of triglyceride-rich lipoproteins. The prevention of apoE4[R142C]-induced dyslipidemia by deletion of the 203-299 residues suggests that, in the full-length protein, the R142C substitution may have altered the conformation of apoE bound to VLDL/IDL/LDL in ways that prevent triglyceride hydrolysis, cholesterol esterification, and receptor-mediated clearance in vivo.