Advancements in drug delivery methods for the treatment of brain disease.

The blood-brain barrier (BBB) presents a formidable obstacle to the effective delivery of systemically administered pharmacological agents to the brain, with ~5% of candidate drugs capable of effectively penetrating the BBB. A variety of biomaterials and therapeutic delivery devices have recently been developed that facilitate drug delivery to the brain. These technologies have addressed many of the limitations imposed by the BBB by: (1) designing or modifying the physiochemical properties of therapeutic compounds to allow for transport across the BBB; (2) bypassing the BBB by administration of drugs alternative routes; and (3) transiently disrupting the BBB (BBBD) using biophysical therapies.

An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields.

The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing.

Assessment of Hindfoot Alignment Comparing Weightbearing Radiography to Weightbearing Computed Tomography.

Background: Hindfoot alignment view (HAV) radiographs are widely utilized for 2-dimensional (2D) radiographic assessment of hindfoot alignment; however, the development of weightbearing computed tomography (WBCT) may provide more accurate methods of quantifying 3-dimensional (3D) hindfoot alignment. The aim of this study was to compare the 2D calcaneal moment arm measurements on HAV radiographs with WBCT.

Methods: This retrospective cohort study included 375 consecutive patients with both HAV radiographs and WBCT imaging.

Web Conferencing Facilitation Within Problem-Based Learning Biomedical Engineering Courses.

Problem-based learning (PBL) has been effectively used within BME education, though there are several challenges in its implementation within courses with larger enrollments. Furthermore, the sudden transition to online learning from the COVID-19 pandemic introduced additional challenges in creating a similar PBL experience in an online environment. Online constrained PBL was implemented through asynchronous modules and synchronous web conferencing with rotating facilitators.

Rapid Impedance Spectroscopy for Monitoring Tissue Impedance, Temperature, and Treatment Outcome During Electroporation-Based Therapies.

Objective: Electroporation-based therapies (EBTs) employ high voltage pulsed electric fields (PEFs) to permeabilize tumor tissue; this results in changes in electrical properties detectable using electrical impedance spectroscopy (EIS). Currently, commercial potentiostats for EIS are limited by impedance spectrum acquisition time (  ∼ 10 s); this timeframe is much larger than pulse periods used with EBTs (  ∼ 1 s). In this study, we utilize rapid EIS techniques to develop a methodology for characterizing electroporation (EP) and thermal effects associated with high-frequency irreversible EP (H-FIRE) in real-time by monitoring inter-burst impedance changes.

What Is the Definition of Acute and Chronic Periprosthetic Joint Infection (PJI) of Total Ankle Arthroplasty (TAA)?

Recommendation: There is a paucity of data for defining acute or chronic periprosthetic joint infection (PJI) following total ankle arthroplasty (TAA) in the literature. Any discussion of PJI after ankle replacement is entirely reliant on the literature surrounding knee and hip arthroplasty.

Level Of Evidence: Consensus.

Numerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences.

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue with IRE.

Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy.

Diagnostic Criteria and Treatment of Acute and Chronic Periprosthetic Joint Infection of Total Ankle Arthroplasty.

Background: Prosthetic joint infection (PJI) after total ankle arthroplasty (TAA) is a serious complication that results in significant consequences to the patient and threatens the survival of the ankle replacement. PJI in TAA may require debridement, placement of antibiotic spacer, revision arthroplasty, conversion to arthrodesis, or potentially below the knee amputation. While the practice of TAA has gained popularity in recent years, there is some minimal data regarding wound complications in acute or chronic PJI of TAA.

Distal fibula osteotomies improve tibiotalar joint compression: A biomechanical study in a cadaveric model.

Background: Successful tibiotalar joint fusion relies on adequate compression. Compression following joint preparation may be affected by the extent to which the fibula holds the joint out to anatomical length. The purpose of this study was to evaluate the effect of various distal fibula osteotomies on tibiotalar joint compression.

High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model.

High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death.

Focused ultrasound-facilitated brain drug delivery using optimized nanodroplets: vaporization efficiency dictates large molecular delivery.

Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization with potentially improved in vivo stability, drug payload, and minimal interference outside of the focal zone compared with microbubbles. While the feasibility of blood-brain barrier (BBB) opening using nanodroplets has been previously reported, characterization of the associated delivery has not been achieved. It was hypothesized that the outcome of drug delivery was associated with the droplet's sensitivity to acoustic energy, and can be modulated with the boiling point of the liquid core.

An evaluation of irreversible electroporation thresholds in human prostate cancer and potential correlations to physiological measurements.

Irreversible electroporation (IRE) is an emerging cancer treatment that utilizes non-thermal electric pulses for tumor ablation. The pulses are delivered through minimally invasive needle electrodes inserted into the target tissue and lead to cell death through the creation of nanoscale membrane defects. IRE has been shown to be safe and effective when performed on tumors in the brain, liver, kidneys, pancreas, and prostate that are located near critical blood vessels and nerves.

Avoiding nerve stimulation in irreversible electroporation: a numerical modeling study.

Electroporation based treatments consist in applying one or multiple high voltage pulses to the tissues to be treated. As an undesired side effect, these pulses cause electrical stimulation of excitable tissues such as nerves and muscles. This increases the complexity of the treatments and may pose a risk to the patient.

An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro.

Background: Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro.

Methods: Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy.

Wideband acoustic activation and detection of droplet vaporization events using a capacitive micromachined ultrasonic transducer.

An ongoing challenge exists in understanding and optimizing the acoustic droplet vaporization (ADV) process to enhance contrast agent effectiveness for biomedical applications. Acoustic signatures from vaporization events can be identified and differentiated from microbubble or tissue signals based on their frequency content. The present study exploited the wide bandwidth of a 128-element capacitive micromachined ultrasonic transducer (CMUT) array for activation (8 MHz) and real-time imaging (1 MHz) of ADV events from droplets circulating in a tube.

Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth.

Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions.

Dual-frequency acoustic droplet vaporization detection for medical imaging.

Liquid-filled perfluorocarbon droplets emit a unique acoustic signature when vaporized into gas-filled microbubbles using ultrasound. Here, we conducted a pilot study in a tissue-mimicking flow phantom to explore the spatial aspects of droplet vaporization and investigate the effects of applied pressure and droplet concentration on image contrast and axial and lateral resolution. Control microbubble contrast agents were used for comparison.

Mitigation of impedance changes due to electroporation therapy using bursts of high-frequency bipolar pulses.

Background: For electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume. In response to conventional, unipolar pulses, the electrical impedance of a tissue varies as a function of the local electric field, leading to a redistribution of the field. These dynamic impedance changes, which depend on the tissue type and the applied electric field, need to be quantified a priori, making mathematical modeling complicated.

Optimization of multi-pulse sequences for nonlinear contrast agent imaging using a cMUT array.

Capacitive micromachined ultrasonic transducer (cMUT) technology provides advantages such as wide frequency bandwidth, which can be exploited for contrast agent imaging. Nevertheless, the efficiency of traditional multi-pulse imaging schemes, such as pulse inversion (PI), remains limited because of the intrinsic nonlinear character of cMUTs. Recently, a new contrast imaging sequence, called bias voltage modulation sequence (BVM), has been specifically developed for cMUTs to suppress their unwanted nonlinear behavior.

Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents.

Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties.

In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible electroporation therapies.

Under the influence of external electric fields, cells experience a rapid potential buildup across the cell membrane. Above a critical threshold of electric field strength, permanent cell damage can occur, resulting in cell death. Typical investigations of electroporation effects focus on two distinct regimes.

Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation-induced Cytotoxicity for the Selective Treatment of Cancer Cells.

Cellulose nanocrystals are rod-shaped, crystalline nanoparticles that have shown prom-ise in a number of industrial applications for their unique chemical and physical properties. However, investigations of their abilities in the biomedical field are limited. The goal of this study is to show the potential use of folic acid-conjugated cellulose nanocrystals in the potentiation of irreversible electroporation-induced cell death in folate receptor (FR)-positive cancers.