Vessel Rupture Database for Transcranial Ultrasound Applications: <i>Vessel Rupture Thresholds for Vessel-Bubble Interactions Using an Earthworm Vasculature Model</i>

<b>OVERALL IDEA FOR VESSEL-RUPTURE DATABASE:</b>The goal of this research was the start of a large scale project - to provide an understanding of the mechanics and safety behind therapeutic ultrasound applications for transcranial procedures, whether Blood-Brain Barrier opening for drug delivery or neuromodulation. The research outcome for this specific project would be a vessel-rupture database consisting of ultrasound alone, and ultrasound with contrast Agents (microbubbles). <br><br>Future databases were to include brain tissue damage based on acoustic parameters, and also for physiology, for instance, what specific acoustic parameters cause seizures by using microelectrode arrays (MEA), that can measure action potentials. These databases would provide holistic views for transcranial applications in terms of safety.A database of vessel ruptures would provide stakeholders a starting point to avoid and understand ruptures in the brain on the transcranial treatment in question. In this specific paper, the goal was that a vessel is targeted with direct ultrasound, but there could also be vasculature in the vicinity that rupture due to the ultrasound field. <br><br><b>DATABASE DESCRIPTION:</b><br><br>Attached are images, that are supplements to the published work: Vessel Rupture Thresholds for Vessel-Bubble Interactions Using an Earthworm Vasculature Model. In the article, there are plots provided, two box plots and two line graphs. The line graphs provides an overview of both frequencies used (0.5 and 1.1 MHz) and the three pulse repetition frequencies (PRF), but the box plot only provides it for a PRF of 1Hz at both 0.5 and 1.1 MHz. If interested in a more granular perspective of the rest of the data, the two figures attached would allow to provide a better visual of the vessel rupture characteristics when plotted as box plots. Or the database itself could serve as a starting point on specific parameters to avoid that cause rupture within a quick period.Descriptions taken from the Publication:<i>Table S1: Data for 0.5 MHz trials, for both ultrasound-only and microbubble-perfused cases. The output for each PRF is displayed as spatial-peak temporal-average Intensity (I</i>_{<em>SPTA</em>}<i>), acoustic pressure (MPa), Mechanical Index (MI), Modified Mechanical Index (MMI), Rupture Time (s), and the Rupture Probability. The “NO” and “YES” corresponds to ultrasound only and perfused vessels with microbubbles, respectively. “NA” or blank are parameters tested in the other frequencies, but not with 0.5MHz due to extreme damage to the earthworm.</i><i>Table S2: Data for 1.1MHz trials, for both ultrasound-only and microbubble-perfused vessels. The output for each PRF is displayed as spatial-peak temporal-average Intensity (I</i>_{<em>SPTA</em>}<i>), acoustic pressure (MPa), Mechanical Index (MI), Modified Mechanical Index (MMI), Rupture Time (s), and the Rupture Probability. The “NO” and “YES” corresponds to ultrasound only and perfused vessels with microbubbles, respectively.</i><b>PUBLICATIONS REFERENCED in </b><b><i>RELATED MATERIALS</i></b><b>:</b><br><br>The first link titled, Vessel-Rupture Database due to Ultrasound Treatment, is the original publication where the vessel-rupture database originates, and describes a modified version of the Mechanical Index.The second link titled, Earthworm, Lumbricus Terrestris: A Novel Microinjection Vasculature In vivo Invertebrate Model, is the publication of the method to inject microbubbles into the earthworm vasculature that produced the vessel rupture experiments and database attached in the images. The third link titled, Microvessel Rupture Induced by High-Intensity Therapeutic Ultrasound — A Study of Parameter Sensitivity in a Simple in vivo Model, is the first publication using the earthworm as a model for understanding vessel-rupture and to determine if earthworms would be a feasible model for understanding a safety perspective on ultrasound treatments on or near the vasculature of the brain. The method in preparing and sonicating the vasculature is optimized in the first link - Vessel Rupture Thresholds for Vessel-Bubble Interactions Using an Earthworm Vasculature Model. An entire new set up was created to capture the smallest ruptures with surgical equipment, a new water tank was created for high-throughout experiments and for the ultrasound focus to be consistent, and it was paired with an injection system for delivering microbubbles into the vasculature.<br><br><b>ABSTRACT FROM THE PUBLICATION:</b><i>Objective:</i><i> </i><i>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.</i><i>Methods:</i><i> </i><i>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.</i><i>Discussion:</i><b><i> </i></b><i>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.</i><i>Conclusion:</i><b><i> </i></b><i>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.</i>