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As focused ultrasound for blood-brain barrier disruption (FUS-BBBD) has progressed to human application, it has become necessary to consider the potential effects of prior irradiation treatments. Using a murine model, we examined the effects of whole-brain irradiation on FUS-BBBD. We first subjected half of the experimental cohort to daily 3-Gy whole-brain irradiation for 10 consecutive days. Then, microbubble-assisted FUS-BBBD was performed unilaterally while the contralateral sides served as unsonicated controls. FUS-BBBD, as evident by measuring the fluorescence yield of extravasated trypan blue dye, was identified at all sites with minimal or no apparent pathology. The peak fluorescence intensity caused by extravasated dye in the sonicated region was 17.5 ± 12.1% higher after radiation and FUS-BBBD than after FUS-BBBD alone, suggesting that prior radiation of the brain may be a sensitizing factor for FUS-BBBD. Radiation alone-without FUS-BBBD-resulted in mild BBB disruption. Hemorrhagic petechiae were observed in 9 of 12 radiated brains, with 77% of them clearly located outside the sonicated area; no petechiae were found in non-irradiated animals. This radiation protocol did not appear to increase the risk for vascular damage associated with FUS-BBBD.

Intergenerational initiatives in post-secondary settings have demonstrated health and social benefits. However, there is a lack of detail with regard to the process by which such initiatives are conceptualized and the role of older and younger users in their development. Guided by the principles of an Age-Friendly University (AFU) alongside elements from a 'Design Thinking' approach, this project outlines the process undertaken to design a new intergenerational space to promote intergenerational connectivity. An online student survey (n = 504; 72.2% female) and focus groups were conducted with older adults (n = 22; 12 females; aged 70-95), which found similar themes across age groups with respect to: 1) past intergenerational experiences; 2) perceived benefits/challenges of accessing the space, and; 3) activity suggestions. Using these findings, alongside direct stakeholder input, Occupational Therapy students developed programming and design suggestions for the space in question aimed at strengthening interactions across age and ability. Results from this process indicate consulting with older and younger users can circumvent potential challenges and inform the design of campus-based initiatives that can promote intergenerational exchange. yes

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

The development of high-intensity ultrasound technology into a system for performing image-guided noninvasive ultrasound neurosurgery has developed at a relatively rapid pace in the past few years. Magnetic resonance imaging has contributed significantly to this development by providing a modality by which percutaneous ultrasound treatments can be preoperatively planned, intraoperatively guided and postoperatively evaluated for safety and efficacy. Especially in the case of transcranial ultrasound therapies, the structural identification and thermal monitoring of cortical structures is essential to avoid overheating at the skull-brain interface and to avoid the sonication of critical structures. This chapter briefly describes the physics of transmitting ultrasound through the skull and the technological advances that circumvented the physical limits imposed by the skull bone. The integration of magnetic resonance guidance and monitoring is detailed, along with an overview of ongoing studies with a commercially developed magnetic resonance imaging-compatible hemispherical transducer array.

Ultrasound imaging has become a standard method for evaluating patients who have suffered blunt trauma. Specifically, focused assessment with sonography in trauma, commonly known as the “FAST exam,” is regularly employed to detect free intraperitoneal, intrathoracic, and pericardial fluid in the setting of trauma. Currently, evaluation of the intracranial space remains a significant missing component of the FAST exam because the skull bone acts as a physical barrier to ultrasound transmission for existing approaches in pulse-echo ultrasound imaging. To address this shortcoming, we have explored a grounds-up re-evaluation of the way in which ultrasound can be used in neurosonography based on the hypothesis that backscattered signal from the intracranial space can be analyzed to identify the unique signature of pooling and coagulated blood. Preliminary experiments with tissue phantoms, ex vivo animal blood, and ex vivo human calvaria have established the parameters that optimize the SNR of pulse-echo transc...

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6–1.4 MHz through a series of seventeen points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

A ventriculostomy is often performed to relieve symptoms of emergent hydrocephalus. This involves the placement of an external ventricular drain (EVD) into the cerebral ventricles to remove excess cerebrospinal fluid. Free-handed EVD cannulation results in high rates of misplacement (~50%), leading to an increased risk of iatrogenic complications. Extant technical approaches to improve ventriculostomy guidance are either too complex or inaccurate. We have investigated the possibility of a novel device to guide EVD placement using transcranial ultrasound. The device uses three specifically aligned transducers delivering pulse-echo 0.5-MHz ultrasound through the skull bone to detect and localize the targeted ventricle. It also incorporates a cannula guide that is registered with the ultrasound FOV to integrate guidance with surgery. Results from the design, fabrication, and testing of the prototype device with ex vivo human skulls and brain phantoms will be presented.

Malfunction of peritoneal catheters due to mechanical outflow problems is an annoying complication in patients undergoing chronic peritoneal dialysis (PD). Correction often involves catheter replacement or revision via laparotomy.Twenty-five patients undergoing PD who developed mechanical catheter flow restriction underwent 28 laparoscopic procedures. Preoperative diagnoses were made by contrast catheter radiography and were: catheter sequestration (36%), omental wrap (64%). Pneumoperitoneum was induced after general anesthesia and laparoscopy was performed using a Storz laparoscope. The catheter was then identified and manipulation was attempted using instruments placed percutaneously.In 26 cases (93%), the catheter was freed and function restored. In two cases (7%), adhesions were so numerous and dense that the distal catheter could not be visualized. Four episodes of peritonitis developed subcutaneous leakage of peritoneal fluid which responded to cessation of PD for 2 weeks. Four patients had recurrent occlusions; three of these were managed laparoscopically. Two patients developed late hernias at the site of insertion of the laparoscope. Catheter patency averaged 9.2 months postoperatively.Laparoscopic revision is a successful technique for salvage of occluded peritoneal catheters.

High‐intensity focused ultrasound (HIFU) therapy is a non‐invasive treatment method for uterine fibroids patients. However, there exists focal distortion, due to inhomogeneous tissues, that can divert therapeutic dosage to non‐targeted locations. A missing component of current HIFU protocols is a simulated pre‐treatment planning, a procedure that can predict the efficiency of ultrasonic energy delivery pathways based on MRI scans using a simulated propagation model. To conduct this study, a 1.502‐MHz transducer transmitted HIFU through five ex vivo bovine tissue specimens in an MR‐compatible tank setup. A needle hydrophone (aperture = 0.2 mm) scanned the acoustic pressure field orthogonal to the axis of propagation for three different positions of the tissue specimens (0, 4, and 8 deg, about the rotation mounts). To quantify the level of distortion, the distortion index (DI = 1—ratio between local and total acoustic energy fields) were calculated. The data collected confirmed HIFU distortion due to tissue...

For decades, the origin of toxemia of pregnancy was the subject of many more or less poorly founded speculations. Hofbauer (1) was probably the first to suspect an important involvement of the adrenal cortex in its pathogenesis. Finally, the demonstration of an increased corticoid production during pregnancy and of the role played by adrenal corticoids in the formation of edema and in the pathogenesis of arterial hypertension provided some solid footholds from which to attack the problem systematically.