OBJECTIVE:Intravenous microbubble oscillation in the presence of ultrasound has the potential to yield a wide range of therapeutic benefits. However, the likelihood of vessel damage caused by mechanical effects has not been quantified as a function of the numerous important parameters in therapeutic ultrasound procedures. In this study, we examined the effects of microbubbles injected into the vasculature of the earthworm. It was found that the elastic properties of earthworm blood vessels are similar to those of arteries in older humans, and that earthworms are well suited to the large number of experiments necessary to investigate safety of procedures involving microbubble oscillation in sonicated vessels.METHODS:Microbubbles were infused into earthworm vessels, and the rupture time during sonication was recorded as a function of ultrasound frequency, pulse repetition frequency and acoustic pressure.DISCUSSION:A modified mechanical index (MMI) was defined that successfully captured the trends in rupture probability and rupture time for the different parameter values, creating a database of vessel rupture thresholds. In the absence of bubbles, the product of MMI squared and rupture time was approximately constant, indicating a possible radiation-force effect.CONCLUSION:The MMI was an effective correlating parameter in the presence of bubbles, though the mathematical dependence is not yet apparent. The results of the study are expected to be valuable in designing more refined studies in vertebrate models, as well as informing computational models.

A key consideration in ultrasound medical device safety is the potential for cavitation related bioeffects. Device testing should address possible cavitation pathways, such as bubble formation, either in the focal region or at the device-tissue interface along with possible consequences regarding both safety and effectiveness. This has been particularly important in a number of emerging transcranial therapies including ablation, neuromodulation, and targeted opening of the blood-brain barrier (BBB) in conjunction with microbubbles. Subharmonic, and ultraharmonic emissions have been identified as indicators of treatment outcome and are a basis for safety and feedback control in BBB disruption. However, there remains a scarcity of baseline cavitation threshold data in the living mammalian brain, particularly at lower ultrasound frequencies. In our ongoing study, we are measuring and evaluating in vivo cavitation response in mice using a passive cavitation detector (PCD) for ultrasound frequencies as low as 40 kHz. Additional measurements are being carried out using a hydrophone imbedded in the brain tissue of mouse cadavers to characterize absolute pressure values as well as evaluate the sensitivity and reliability of the PCD measurements. Analyzed data will be presented along with detailed methodology and potential implications in future product evaluation will be discussed.

Although vertebrates are indispensable to biomedical research, studies are often limited by factors such as cost, lengthy internal review, and ethical considerations. We present the earthworm as an alternative, low-cost, invertebrate applicable to certain preliminary vasculature studies. Due to the surgical availability of the earthworm's dorsal vessels, ventral vessels, and five pairs of pseudo hearts, earthworms are readily accessible, offer low-cost maintenance, and require administration of only small doses of a given compound. The earthworm model provides a simple closed vascular circulatory system with a hemoglobin structure similar to human blood. A protocol is provided for anaesthetizing the earthworms and performing surgical incisions to expose relevant blood vessels. Micropipettes for compound administration are formed by heating and pulling glass with a pipette puller and using a beveling system to create a micron-scale fine needle tip. The tips are then used with a micropositioner and microinjector to inject arbitrary compounds into the vascular system of an earthworm, repeatably, with the availability of large sample sizes and small compound volumes. Details on the intricacies of injection procedure are provided. The small vessel size of the earthworm is challenging, particularly in the case of the ventral vessel; however, mastery of the techniques presented offers high repeatability as a low-cost solution, making studies of very large sample size practical.

We present the earthworm as a useful model for studying vasculature rupture induced by High-Intensity Therapeutic Ultrasound (HITU) with Microbubbles. Although vertebrates are indispensable to biomedical research, studies are often limited by factors such as cost, lengthy internal review, and ethical considerations. An extensive database of vessel-rupture probabilities and times was created for both HITU and HITU + Microbubbles as a function of critical parameters, including microbubble dosage and size, and ultrasound operating frequency and intensity. The earthworm model allows the large number of trials to be performed that enable identification of the critical characteristics of bubbles, blood vessels, and acoustic fields affecting the threshold for blood-vessel rupture in HITU + Microbubble applications. In the experiments performed, the driving frequencies were 0.5, 1.1, 2.5, and 3.3 MHz, and the pulse repetition frequencies (PRF) were 1, 3 and 10 Hz. The duty factor was held at 0.1%. The outcomes of these in-vivo experiments are expected to assist in predicting the rupture probability for HITU + Microbubble procedures. They will also inform a computational model of bubble-induced vessel rupture.

The blood-brain barrier (BBB) is notoriously difficult to penetrate for the delivery of drugs and therapeutic compounds due to the unique nature of the tight junctions between endothelial cells. Ultrasound in the presence of microbubbles has been discovered to transiently open the BBB, however, little is known about the mechanism and the effects of excitation parameters at a cellular level. In this study, a static vascular lumen in vitro model, LumeNEXT, was utilized to investigate the excitation parameters in a controlled manner. Fibrin lumen hydrogels were lined with human cerebral microvessel endothelial and astrocyte cells. Cells were exposed to ultrasound with and without the presence of microbubbles. The devices were exposed to ultrasound parameters ranging in frequency from 0.5 to 1.55MHz, duty factor from 0.0001–0.001 and pulse repetition frequency of 1–10 Hz. Acoustic and thermal characterization of the device was performed. Effects of microbubble size and composition on the endothelial permeability were also investigated. The transepithelial electrical resistance (TEER) and cell morphology were monitored post-ultrasound exposure to investigate endothelial permeability duration and extent. Understanding the fundamentals of ultrasound-induced permeability in a controlled manner can lead to further investigations and optimization for in vivo and clinical settings.

Controllable, localized permeability of the blood-brain barrier (BBB) has been a goal of health professionals for enhanced delivery of drugs and therapeutic compounds for cancer and other neurological medical conditions. The transient permeability induced by transcranial ultrasound exposure in the presence of microbubbles has been shown to be a promising option, but little is known about the exact mechanism and response on a cellular level. A microfluidic device developed to recreate the in vivo microenvironment, including physiological fluid flow, was seeded with human cerebral microvessel endothelial cells surrounded by a matrix of astrocytes. The devices were exposed to ultrasound with and without the presence of microbubbles. The ultrasound parameters ranged in frequency from 0.5 to 1.55 MHz, duty factor from 0.0001–0.001 and pulse repetition frequency of 1 Hz–10 Hz. Microbubble size, composition, and concentration within the pumped fluid were also varied, along with varied flow rate. The transepithelial electrical resistance (TEER) and cell morphology were monitored throughout and post ultrasound exposure to understand the effects on permeability and cell viability. With this controlled variation of the ultrasound and microbubble parameters, a greater understanding of the induced permeability could lead to more success for clinical utilization.

Background: Safety analyses of transcranial therapeutic ultrasound procedures require knowledge of the dependence of the rupture probability and rupture time upon sonication parameters. As previous vessel-rupture studies have concentrated on a specific set of exposure conditions, there is a need for more comprehensive parametric studies.Methods: Probability of rupture and rupture times were measured by exposing the large blood vessel of a live earthworm to high-intensity focused ultrasound pulse trains of various characteristics. Pressures generated by the ultrasound transducers were estimated through numerical solutions to the KZK ( Khokhlov-Zabolotskaya-Kuznetsov) equation. Three ultrasound frequencies ( 1.1, 2.5, and 3.3 MHz) were considered, as were three pulse repetition frequencies ( 1, 3, and 10 Hz), and two duty factors ( 0.0001, 0.001). The pressures produced ranged from 4 to 18 MPa. Exposures of up to 10 min in duration were employed. Trials were repeated an average of 11 times.Results: No trends as a function of pulse repetition rate were identifiable, for either probability of rupture or rupture time. Rupture time was found to be a strong function of duty factor at the lower pressures; at 1.1 MHz the rupture time was an order of magnitude lower for the 0.001 duty factor than the 0.0001. At moderate pressures, the difference between the duty factors was less, and there was essentially no difference between duty factors at the highest pressure. Probability of rupture was not found to be a strong function of duty factor. Rupture thresholds were about 4 MPa for the 1.1 MHz frequency, 7 MPa at 3.3 MHz, and 11 MPa for the 2.5 MHz, though the pressure value at 2.5 MHz frequency will likely be reduced when steep-angle corrections are accounted for in the KZK model used to estimate pressures. Mechanical index provided a better collapse of the data ( less separation of the curves pertaining to the different frequencies) than peak negative pressure, for both probability of rupture and rupture time.Conclusion: The results provide a database with which investigations in more complex animal models can be compared, potentially establishing trends by which bioeffects in human vessels can be estimated.

An estimated 55M individuals experience spinal cord injuries (SCIs), 230K in the United States. When a nerve is injured, the environment prevents healing of neurons and myelin. This is due to the presence of myelin inhibitors, growth factor not re-expressing, and glial tissue scarring rapidly. In order to bypass this mechanism nerves need to regenerate quickly, and unfortunately, no effective method currently exists to stimulate neurogenesis to the central nervous system. We propose an innovative non-invasive method to stimulate neurogenesis through low-intensity focused or unfocused ultrasound irradiation. We developed an in vitro system integrating unfocused ultrasound (UFUS) with neuron axon dynamics using a 3D microenvironment for neurogenesis. Dorsal root ganglion (DRG) neurons are used for our studies and microsurgically removed at day 15 and E18 Sprague Dawley cortical neurons from BrainBits, LLC. To determine if stimulation of axon growth occurs, we measure density and distance using phase contrast imaging and perform Scholl Method. In parallel, we began an in vivo protocol exposing the spinal cord of mice and using two-photon microscopy. We tested and demonstrated a variety of operating parameters to identify optimal conditions that stimulate axon DRGs by UFUS.

You have accessJournal of UrologySurgical Technology & Simulation: Training & Skills Assessment II1 Apr 2016MP20-17 ACCELEROMETER MEASUREMENT OF HEAD MOVEMENT DURING LAPAROSCOPIC SURGERY: WILL IT HELP OPTIMIZE ERGONOMICS OF SURGERY? Sarayuth Viriyasiripong, Asis Lopez, Weil Lai, Gregory Mitchell, Sree Harsha Mandava, Aaron Boonjindasup, Mary Powers, Jonathan Silberstein, and Benjamin Lee Sarayuth ViriyasiripongSarayuth Viriyasiripong More articles by this author , Asis LopezAsis Lopez More articles by this author , Weil LaiWeil Lai More articles by this author , Gregory MitchellGregory Mitchell More articles by this author , Sree Harsha MandavaSree Harsha Mandava More articles by this author , Aaron BoonjindasupAaron Boonjindasup More articles by this author , Mary PowersMary Powers More articles by this author , Jonathan SilbersteinJonathan Silberstein More articles by this author , and Benjamin LeeBenjamin Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2786AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To detect and measure surgeon head motion during laparoscopic simulator performance to determine whether expert surgeons have higher economy of motion in head movement, including change of direction, compared to intermediate and novice surgeons. We investigated head movement as an objective tool for the assessment of laparoscopic surgical skills and its potential use for assessing novice surgeons’ progress on the learning curve. METHODS After obtaining institutional review board approval, medical students (n=6), urology residents (n=9), and attending staff surgeons (n=4) from one academic institution were recruited. Participants were grouped by level of experience and performed tasks on the EDGE laparoscopic simulator. Surgeons wore a commercially available wireless EEG monitor, as a flexible, adjustable, lightweight headband with 7 sensors: 2 forehead sensors, 2 ear sensors, and 3 reference sensors. The headband incorporates a 3-axis accelerometer, enabling quantification of head movements. A variance analysis was used to compare the average head movement acceleration data among the groups. RESULTS Analysis of the average acceleration rate of head movement showed significant differences among groups on both the vertical and horizontal axes (p=0.006 and 0.018) in the laparoscopic suturing task, demonstrating the ability to distinguish between experts and novices (Table 1). The average acceleration among groups trended towards significance on the vertical and horizontal axes (p=0.078 and 0.077) in the peg transfer task. The analysis of the forward-backward axis showed no significant differences among the groups. CONCLUSIONS Accelerometer-based motion analysis of head movement appears to be a useful tool to evaluate laparoscopic skill development of surgeons in terms of their economy of motion and could potentially be used for ergonomic assessment of training in the future. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e220 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Sarayuth Viriyasiripong More articles by this author Asis Lopez More articles by this author Weil Lai More articles by this author Gregory Mitchell More articles by this author Sree Harsha Mandava More articles by this author Aaron Boonjindasup More articles by this author Mary Powers More articles by this author Jonathan Silberstein More articles by this author Benjamin Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

OBJECTIVE: To detect and measure surgeons' head movement during laparoscopic simulator performance to determine whether expert surgeons have economy of motion in their head movement, including change of direction, compared with intermediate and novice surgeons. We investigated head movement as an objective tool for assessment of laparoscopic surgical skill and its potential use for assessing novice surgeons' progress on the learning curve.DESIGN: After obtaining institutional review board approval, medical students, urology residents, and attending staff surgeons from an academic institution were recruited. Participants were grouped by level of experience and performed tasks on the Electronic Data Generation for Evaluation laparoscopic simulator. Surgeons wore a commercially available wireless electroencephalogram monitor as a flexible, adjustable, and lightweight headband with 7 sensors-2 forehead sensors, 2 ear sensors, and 3 reference sensors. The headband incorporates a 3-axis accelerometer enabling head movement quantification. A variance analysis was used to compare the average head movement acceleration data between each group.SETTING: Tulane University Medical Center, New Orleans, LA, an academic medical center and the principal teaching hospital for Tulane University School of Medicine.PARTICIPANTS: A total of following 19 participants were recruited for the study and stratified by surgical experience into novice (n = 6), intermediate (n = 9), and expert (n = 4) laparoscopy groups: 6 medical students, 9 urology residents (postgraduate years 1 to 5), and 4 attending urologists, respectively.RESULTS: Analysis of the average acceleration rate of head movement showed statistically significant differences among groups on both the vertical axis (p = 0.006) and horizontal axis (p = 0.018) in the laparoscopic suturing task. This demonstrated the ability to distinguish between experts and novice laparoscopic surgeons. The average acceleration among groups did not demonstrate statistical significance on the vertical axis (p = 0.078) and horizontal axis (p = 0.077) in the peg transfer task. This may be in response to the ease of the task. The analysis of the forward-backward axis or depth perception also showed no significant differences between groups.CONCLUSION: Accelerometer-based motion analysis of head movement appears to be a useful tool to evaluate laparoscopic skill development of surgeons in terms of their economy of motion, and it could potentially be used for ergonomic assessment of training in the future, and progression on the learning curve. (c) 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

PURPOSE To measure gamma and alpha brain wave activity as a measurement of concentration and stress levels during surgical simulator performance of laparoscopic tasks to determine if expert surgeons have different brain activity patterns compared with intermediate and novice surgeons. MATERIALS AND METHODS After obtaining Institutional Review Board approval, 1st and 2nd year medical students, urology residents (PGY2-PGY5), and attending urologists from one institution were recruited. Participants were stratified by level of experience and performed laparoscopic tasks on the EDGE laparoscopic simulator. Subjects were evaluated for concentration and stress levels using the electroencephalography (EEG) data extracted from the MUSE(™) headband. The MUSE software developer kit (SDK) allowed quantification of gamma and alpha waves during each task. An analysis of variance was used to compare concentration and stress levels between groups. RESULTS A total of 19 participants were recruited for the study and stratified by surgical experience into novice, intermediate, and expert laparoscopy groups: 6 medical students, 9 urology residents, and 4 attending urologists, respectively. Concentration and stress were quantified by calculating the area under the curve of the gamma and alpha EEG wave tracings. Stress was significantly lower in the attending urologists compared with the residents and medical students during the laparoscopic suturing and trended toward significance in the peg transfer task (P = 0.0003, P = 0.069). Concentration was significantly higher in the expert group compared with the less experienced groups during both the peg and suture tasks (P = 0.036, P = 0.0039). CONCLUSIONS EEG brain activity in more experienced surgeons reveals a significant increase in concentration levels with a decrease in stress during simulated laparoscopic tasks compared with novices. This information may correlate with increased proficiency as well as provide objective feedback of progress along the learning curve with the MUSE SDK.