Sonic Concepts Research Articles

Real time cavitation monitoring during ultrasound-mediated drug delivery in normothermically perfused human tumour-bearing livers

In the fight against a broad spectrum of human diseases, cavitation techniques show great promise for overcoming physical barriers that lead to suboptimal uptake of passively administered therapeutics. However, small animal testing of candidate therapies remains a poor predictor of clinical success. Here we demonstrate ultrasound-mediated drug delivery in normal and tumour-bearing human livers infused with protein-based cavitation nuclei (PCaN). Whole and partial human livers were obtained immediately from hepatectomy surgeries and were normothermically sustained using a clinically approved perfusion system (OrganOx Metra). Ultrasound was applied using a 0.5 MHz focused source (Sonic Concepts H107) and was monitored with a calibrated linear array (ATS L7-4) for real time structural and cavitational imaging implemented on an array controller (Verasonics Vantage 256). Specifically, the therapy process was monitored using passive acoustic mapping (PAM) of broadband cavitation emissions, employing a non-adaptive beamformer that deconvolves the array point spread function. Levels of fluorescently labelled drugs incorporated in and co-administered with the PCaN were quantified in blood and tissue samples collected during and following treatment, respectively. This presentation highlights PAM observations of broadband cavitation persistence and drug delivery in untargeted and targeted tissues, including the first ever experiments in tumour-bearing human livers.

Assessment of focused ultrasound stimulation to induce peripheral nerve activity and potential damage in vivo.

Peripheral neuroprostheses are aimed to restore loss of sensory and motor functions by interfacing axons in the peripheral nerves. Most common interfaces in neuroprostheses are electrodes that establish electrical connection with peripheral axons. However, some challenges arise related to long-term functionality, durability, and body response. Recently, focused ultrasound stimulation (FUS) has emerged as a non-invasive approach to modulate the nervous system. However, it is controversial whether FUS can induce axon depolarization. We have assessed FUS applied in vivo to the rat peripheral nerve, with two objectives: first, to test whether FUS activates peripheral nerves under different stimulation conditions, and second, to evaluate if FUS inflicts damage to the nerve. FUS was delivered with three ultrasound transducers (Sonic Concept H115, H107, and H102) covering the largest set of parameters examined for FUS of peripheral nerves so far. We did not obtain reliable evoked action potentials in either nerves or muscles, under any FUS condition applied, neither over the skin nor directly to the nerve exposed. Additional experiments ex vivo and in vivo on mice, confirmed this conclusion. When FUS stimulation was applied directly to the exposed sciatic nerve, neuromuscular function decreased significantly, and recovered one week later, except for FUS at 0.25 MHz. Histologically, degenerating nerve fibers were observed, with a tendency to be higher with the lower FUS frequency. Past reports on the ability of ultrasound to stimulate the peripheral nerve are controversial. After testing a wide range of FUS conditions, we conclude that it is not a reliable and safe method for stimulating the peripheral nerve. Special consideration should be taken, especially when low-frequency FUS is applied, as it may lead to nerve damage.

Developing a focused ultrasound treatment for tendinopathies in a large animal model

Current treatments for tendinopathies produce mixed success rates, with 0-84% of patients showing improvement. Our prior work in rats suggests mild microdamage induced by focused ultrasound (fUS) may perform better than traditional treatments for tendinopathies, like dry needling. Here, we work to scale our work in rats to larger animal models and develop treatment monitoring. Ex vivo bovine digital flexor tendons were obtained and injected with collagenase to induce chronic tendinopathy. One day later, tendons were treated with focused ultrasound at 1.1–3.68 MHz, with 1–10ms pulses at pressures up to p + = 127 MPa/p− = 35 MPa repeated at 0.2–1 Hz for up to 20 min. Treatments were monitored with passive cavitation detection (PCD; Sonic Concepts Y-107) and Philips/ATL L7-4 controlled by the Verasonics research ultrasound system in passive cavitation imaging (PCI) mode. Samples were collected for histological analysis. Preliminary results suggest that lower pulse repetition frequencies produce mild mechanical microdamage with no evidence of thermal necrosis. PCI and PCD results show no consistent trends to indicate the intended mechanical microdamage bioeffect has been achieved. Work is continuing to determine the treatment parameters that produce the intended bioeffects in the smallest time and to develop a means to monitor treatment progress. [Work supported by NIHR01EB032860.]

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model

Tumors become inoperable due to their size or location, making neoadjuvant chemotherapy the primary treatment. However, target tissue accumulation of anticancer agents is limited by the physical barriers of the tumor microenvironment. Low-intensity focused ultrasound (FUS) in combination with microbubble (MB) contrast agents can increase microvascular permeability and improve drug delivery to the target tissue after systemic administration. The goal of this research was to investigate image-guided FUS-mediated molecular delivery in volume space. Three-dimensional (3-D) FUS therapy functionality was implemented on a programmable ultrasound scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). FUS treatment was performed on breast cancer-bearing female mice (N = 25). Animals were randomly divided into three groups, namely, 3-D FUS therapy, two-dimensional (2-D) FUS therapy, or sham (control) therapy. Immediately prior to the application of FUS therapy, animals received a slow bolus injection of MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared dye (IR-780, surrogate drug) for optical reporting and quantification of molecular delivery. Dye accumulation was monitored via in vivo optical imaging at 0, 1, 24, and 48 h (Pearl Trilogy, LI-COR). Following the 48 h time point, animals were humanely euthanized and tumors excised for ex vivo analyzes. Optical imaging results revealed that 3-D FUS therapy improved delivery of the IR-780 dye by 66.4% and 168.1% at 48 h compared to 2-D FUS (p = 0.18) and sham (p = 0.047) therapeutic strategies, respectively. Ex vivo analysis revealed similar trends. Overall, 3-D FUS therapy can improve accumulation of a surrogate drug throughout the entire target tumor burden after systemic administration.

Therapeutic ultrasound to market

Therapeutic ultrasound is proving to be viable in the clinic and is producing a high level of commercial activity in Therapeutic Ultrasound Systems globally across a wide variety of clinical indications. Recently there has been an increased level of commercial interest in systems delivering lower intensity ultrasound. Some examples of clinical indications include modulating nerves, sonodynamic therapy, or combining ultrasound with drugs to lower the threshold of required intensities. Regardless of the acoustic intensity required, new product inception will adopt an effective bio-acoustic result to match a clinical indication, creating a gap in product development. Sonic Concepts provides transmit ultrasound development services to fill this gap through a phased development program, accelerating first-in-man and time to market. Sonic Concepts has co-developed 30 + clinical systems, servicing customers with more than 100 years of accumulated experience, creative design techniques, and a spectrum of products and intellectual property to leverage. Examples of co-developed clinical systems will be presented, detailing the process from initial concept to first-in-man while using pre-clinical systems, HIFUPlex™ and NeuroFUS® to fast-track development.

The verasonics platform for ultrasound-guided focused ultrasound preclinical studies

Verasonics, in partnership with Sonic Concepts (Bothell, WA, USA), has developed a turnkey platform for Ultrasound-Guided Focused Ultrasound (USgFUS) therapy with performance over a wide range of acoustic regimes. Built around the Verasonics Vantage HIFU ultrasound research system, it uses a 150 mm diameter, f1 HIFU transducer with 64 (0.5 MHz) or 128 (1.1 and 2 MHz) elements arranged in a spiral pattern that produce a highly focused field with low sidelobes over a 3D steering volume. Guidance and monitoring are provided by a coaxially mounted 128-element broadband phased array imaging transducer that can be rotated about the HIFU axis. Coupling to the subject is achieved by means of a membrane sealed water-filled cone through which degassed and temperature regulated water is circulated. The USgFUS applicator is mounted on an articulated arm that can be mechanically locked with a button actuated servo mechanism. Graphical software enables a conventional therapeutic workflow including imaging with any of several B-Mode and Doppler modalities, positioning of the applicator, focal zone exposure planning, therapy delivery, interleaved ultrasound monitoring using any supplied imaging mode or with Thermal Strain Imaging (TSI), and post-therapy imaging. This talk will describe the platform and provide examples of its capabilities using experiments in scattering phantoms and ex vivo tissues.

Liver Ultrasound Histotripsy: Novel Analysis of the Histotripsy Site Cell Constituents with Implications for Histotripsy Application in Cell Transplantation and Cancer Therapy.

Introduction: Allogenic hepatocyte transplantation is an attractive alternative to whole-organ transplantation, particularly for the treatment of metabolic disorders and acute liver failure. However, the shortage of human donor organs for cell isolation, the low cell yield from decellularisation regimes, and low engraftment rates from portal administration of donor cells have restricted its clinical application. Using ultrasound histotripsy to provide a nidus in the liver for direct cell transplantation offers a new approach to overcoming key limitations in current cell therapy. We have analysed the liver cavity constituents to assess their potential as a site for cell delivery and implantation. Methods: Using human organ retrieval techniques, pig livers were collected from the abattoir and transported in ice-cold storage to the laboratory. Following 2 h of cold storage, the livers were flushed with organ preservation solution and placed on an organ perfusion circuit to maintain viability. Organs were perfused with Soltran™ organ preservation solution via the portal vein at a temperature of 24-30 °C. The perfusion circuit was oxygenated through equilibration with room air. Perfused livers (n=5) were subjected to ultrasound histotripsy, producing a total of 130 lesions. Lesions were generated by applying 50 pulses at 1 Hz pulse repetition frequency and 1% duty cycle using a single element 2 MHz bowl-shaped transducer (Sonic Concepts, H-148). Following histotripsy, a focal liver lesion was produced, which had a liquid centre. The fluid from each lesion was aspirated and cultured in medium (RPMI) at 37 °C in an incubator. Cell cultures were analysed at 1 and 7 days for cell viability and a live-dead assay was performed. The histotripsy sites were excised following aspiration and H&E staining was used to characterise the liver lesions. Cell morphology was determined by histology. Results: Histotripsy created a subcapsular lesion (~5 mm below the liver capsule; size ranging from 3 to 5 mm), which contained a suspension of cells. On average, 61×104 cells per mL were isolated. Hepatocytes were present in the aspirate, were viable at 24 h post isolation and remained viable in culture for up to 1 week, as determined by phalloidin/DAPI cell viability stains. Cultures up to 21 days revealed metabolically active live hepatocyte. Live-dead assays confirmed hepatocyte viability at 1 week (Day 1: 12% to Day 7: 45% live cells; p < 0.0001), which retained metabolic activity and morphology, confirmed on assay and microscopy. Cell Titre-GloTM showed a peak metabolic activity at 1 week (average luminescence 24.6 RLU; p < 0.0001) post-culture compared with the control (culture medium alone), reduced to 1/3 of peak level (7.85 RLU) by day 21. Conclusions: Histotripsy of the liver allows isolation and culture of hepatocytes with a high rate of viability after 1 week in culture. Reproducing these findings using human livers may lead to wide clinical applications in cell therapy.

Reservoir Quality Prediction of Gas-Bearing Carbonate Sediments in the Qadirpur Field: Insights from Advanced Machine Learning Approaches of SOM and Cluster Analysis

The detailed reservoir characterization was examined for the Central Indus Basin (CIB), Pakistan, across Qadirpur Field Eocene rock units. Various petrophysical parameters were analyzed with the integration of various cross-plots, complex water saturation, shale volume, effective porosity, total porosity, hydrocarbon saturation, neutron porosity and sonic concepts, gas effects, and lithology. In total, 8–14% of high effective porosity and 45–62% of hydrocarbon saturation are superbly found in the reservoirs of the Eocene. The Sui Upper Limestone is one of the poorest reservoirs among all these reservoirs. However, this reservoir has few intervals of rich hydrocarbons with highly effective porosity values. The shale volume ranges from 30 to 43%. The reservoir is filled with effective and total porosities along with secondary porosities. Fracture–vuggy, chalky, and intracrystalline reservoirs are the main contributors of porosity. The reservoirs produce hydrocarbon without water and gas-emitting carbonates with an irreducible water saturation rate of 38–55%. In order to evaluate lithotypes, including axial changes in reservoir characterization, self-organizing maps, isoparametersetric maps of the petrophysical parameters, and litho-saturation cross-plots were constructed. Estimating the petrophysical parameters of gas wells and understanding reservoir prospects were both feasible with the methods employed in this study, and could be applied in the Central Indus Basin and anywhere else with comparable basins.

Abstract 2469: Image-guided focused ultrasound-mediated drug delivery for improved cancer treatment

Abstract Introduction: The first option for cancer treatment is often chemotherapy. However, studies have shown that only 1% of the injected dose reaches the target cancer as the tumor microenvironment presents a physical barrier for optimal drug delivery. Focused ultrasound (FUS) in combination with microbubble (MB) contrast agents is an emerging therapy to improve drug delivery by temporarily increasing microvascular permeability. This research details the development and testing of a novel ultrasound (US) image-guided FUS system and method for enhancing drug delivery to tumor tissue and volume space with comparison to a 2-dimensional (2-D) US therapeutic technology. Methods: Real-time US therapy was implemented on a programmable US system (Vantage 256, Verasonics Inc) equipped with a dual US transducer configuration for interleaved anatomical imaging and volumetric treatment delivery (HIFU-Plex, Sonic Concepts Inc). Both US imaging and therapeutic transducers are co-registered 128 element arrays with center frequencies of 3.5 and 2.0 MHz, respectively. The latter is a concentric array that enables beam steering in 3-dimensional (3-D) space. US treatment was performed at a peak negative pressure of 0.7 MPa (mechanical index, MI of 0.45), pulse repetition frequency of 10 Hz, and duty cycle of 10%. BALB/c mice (N = 22, Charles River Laboratory) were implanted with 2.0 × 105 breast cancer cells (4T1, ATCC). Once tumors reached 0.6 cm in size, mice were randomly divided into a 3-D or 2-D US therapy group or sham control. US therapy was performed following an intravascular injection of microbubbles (Definity, Lantheus Medical Imaging) and IR-780 dye. Note microbubbles function as a therapeutic mediator whereas the fluorescent dye represents a surrogate small molecule drug. Live animal fluorescent imaging was performed at baseline before US therapy (0 h) and again at 1, 24, and 48 h. Following the 48 h timepoint, animals were euthanized and tumors surgically excised for ex vivo analysis. Results: 3-D US-mediated therapy improved molecular delivery to tumor tissue by 150 and 180% at 24 and 48 h, respectively, when compared to our previously established 2-D US therapeutic approach (p = 0.22) or sham therapy (p = 0.07). A similar trend was observed during ex vivo imaging of excised tumor samples treated with 3-D US therapy as compared to the 2-D US therapeutic approach (p = 0.41) or sham therapy (p = 0.04). Dye extraction further confirmed these observations (p &amp;gt; 0.12). Conclusions: 3-D US therapy improved molecular delivery to the tumor volume compared to our previously established 2-D US-based method as confirmed by a series of optical imaging studies. Citation Format: Ryan Margolis, Junjie Li, Lokesh Basavarajappa, Kenneth Hoyt. Image-guided focused ultrasound-mediated drug delivery for improved cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2469.

The Soundscapes of the Lower Chuya River Area, Russian Altai: Ethnographic Sources, Indigenous Ontologies and the Archaeoacoustics of Rock Art Sites

The acoustics of the Lower Chuya River area rock art landscape are analyzed through both the exploration of its acoustic properties and the ethnographic information gathered about the region. The results obtained in the acoustics tests undertaken in the area, in particular at the rock art sites of Kalbak-Tash I, Kalbak-Tash II, and Adyr-Kan, are examined. They indicate that the perceived loudness resulting from a natural amplification of sound (strength parameter) and music and speech clarity may have been some of the reasons behind the selection of these locations for rock art production. The ethnographic sources related to the Altai and other Siberian areas are then reviewed as a way of providing an ontological framework for the study of Altaian sonic concepts and behaviors in nature. As the sources indicate, at least for the historical period and presumably earlier, in the prehistoric period, all existing beings are entangled by sound, and they mimic each other in endless ways. We argue that these sites were selected in a non-linear relational ontological framework. It is suggested that the multidisciplinary perspective combining archaeology, physical acoustics, and ethnography has considerable potential for providing a new, richer understanding of rock art landscapes.

Implementation of real-time high-speed ultrasound communications through tissue

In this work, we propose a novel implementation of both a transmitter and receiver with field programmable gate arrays (FPGAs) to achieve real-time continuous high-definition (HD) video transmission through tissue, which can enable HD and higher frame rate wireless capsule endoscopy. We used a Texas Instruments AFE58JD48EVM 16 channel analog front end (AFE) evaluation board as the receiver connected to a Xilinx ZCU106 Zynq Ultrascale MPSoC development board in which we implemented a digital down converter (DDC), OFDM demodulator, maximum ratio combiner and low-density parity-check (LDPC) decoder. For the transmitter, we used an Analog Devices EVAL-AD9166 vector signal generator evaluation board, which has a built-in 4.3 dBm output power amplifier as a transmitter connected to another ZCU106 development board in which we implemented a LDPC encoder, OFDM modulator and digital up converter (DUC). The modulated signal was transmitted through a tissue-mimicking abdominal phantom using a 2-mm microcrystal transducer and received with a Sonic Concepts IP103 64 channel phased array at a center frequency of 3.2 MHz. We achieved the continuous transmission of up to over[OML1] 6 Mbps error free payload data rate after LDPC decoder which is used to carry HD video streams through ultrasound.

Abstract 14111: Feasibility of Therapeutic Ultrasound Delivery for the Treatment of Mitral Stenosis

Introduction: Currently, the only disease-modifying therapy for degenerative mitral stenosis (DMS) due to mitral annular calcification (MAC) is open surgical valve repair or replacement, but it is technically challenging, and patients with DMS are often at elevated risk of surgical complications. As such, there is an unmet need for less-invasive strategies to treat DMS. Given the ability of shock-wave grade therapeutic ultrasound to disrupt calcifications, we set out to determine whether therapeutic ultrasound may be a possible treatment strategy for DMS. Hypothesis: This study aimed to evaluate whether ex vivo histotripsy can produce internal disruption of calcified nodules in the mitral annulus, a precursor to improving valve function in DMS. Methods: All experiments were performed on a formalin-fixed human cadaveric heart with severe MAC (Figure 1 A). Histotripsy cavitation was directed at calcified nodules utilizing a sonic concepts HIFUPlex Focused 128 element,1.1MHz array therapy transducer (Figure 1 E). B-mode ultrasound imaging was used to guide therapy. Transducer settings were PRF: 60 Hz, Duty cycle: 8x10^-4, transmit frequency: 1.1 MHz, HIFU Voltage: 60 V, resulting in an estimated pressure output of 34.6 MPa_pk. Results: A total of three histotripsy experiments were performed on the primary dominant calcium nodule. Visual assessment of treatment X-ray microtomography (Micro-CT) revealed qualitative fracturing of the calcified nodule from baseline (Figure 1 B), after the first treatment (Figure 1 C), and after three treatments (Figure 1 D). Gross visual inspection and Micro-CT demonstrated no changes to the surrounding fibrous annulus. Conclusions: In a feasibility study involving a fixed cadaveric heart, histotripsy therapeutic ultrasound demonstrated the potential to internally disrupt a MAC nodule without injuring the mitral annulus. Further studies are needed to address the ability of histotripsy to improve valve function in DMS.

Multifocused Ultrasound Therapy for Controlled Microvascular Permeabilization and Improved Drug Delivery.

Focused ultrasound (FUS) exposure of micro-bubble (MB) contrast agents can transiently increase microvascular permeability allowing anticancer drugs to extravasate into a targeted tumor tissue. Either fixed or mechanically steered in space, most studies to date have used a single element focused transducer to deliver the ultrasound (US) energy. The goal of this study was to investigate various multi-FUS strategies implemented on a programmable US scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). The multi-FUS strategies include multi-FUS with sequential excitation (multi-FUS-SE) and multi-FUS with temporal sequential excitation (multi-FUS-TSE) and were compared to single-FUS and sham treatment. This study was performed using athymic mice implanted with breast cancer cells ( N = 20 ). FUS therapy experiments were performed for 10 min after a solution containing MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared (NIR, surrogate drug) dye were injected via the tail vein. The fluorescent signal was monitored using an in vivo optical imaging system (Pearl Trilogy, LI-COR) to quantify intratumoral dye accumulation at baseline and again at 0.1, 24, and 48 h after receiving US therapy. Animals were then euthanized for ex vivo dye extraction analysis. At 48 h, fluorescent tracer accumulation within the tumor space for the multi-FUS-TSE therapy group animals was found to be 67.3%, 50.3%, and 36.2% higher when compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. Also, dye extraction and fluorescence measurements from excised tumor tissue found increases of 243.2%, 163.1%, and 68.1% for the multi-FUS-TSE group compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. In summary, experimental results revealed that for a multi-FUS sequence, increased microvascular permeability was considerably influenced by both the spatial and temporal aspects of the applied US therapy.

“The aporia of the veil: the influence of Walter Benjamin’s aura in contemporary sound studies”

ABSTRACT Walter Benjamin’s seminal essay “The Work of Art in the Age of Technological Reproducibility” has recently shaped discussions in sound studies. However, the main theoretical apparatus of the Artwork essay, the aura, lacks sustained attention in sound studies scholarship. While sound studies scholars use analogy to refocus the essay towards sonic reproducibility, they have heretofore missed an important opportunity to analyse Benjamin’s framework for the aura. Reading the etymology of “aura” is a sonic concept at its very foundation shows how it. However, a sonic aura should not be taken as an ending point of this essay, because the auratic structure itself is problematic for sound studies scholars. Pierre Schaeffer’s influential study of the sound object uses a similar framework characterised by the acousmatic. In this framework, Schaeffer claims that the acousmatic veil disconnects sight from sound, producing what he calls the “sound object” (l’objet sonore). Schaeffer argues for both a transcendent and immanent logic of the veil. Transcendence and immanence cannot both underpin experience at the same time and are two philosophically incompatible concepts.

The Art of Theatrical Sound Design: A Practical Guide by Victoria Deiorio

Reviewed by: The Art of Theatrical Sound Design: A Practical Guide by Victoria Deiorio Jessica Greenberg The Art of Theatrical Sound Design: A Practical Guide. By Victoria Deiorio. London: Bloomsbury Methuen Drama, 2018; pp. 240. Victoria Deiorio's The Art of Theatrical Sound Design: A Practical Guide is a useful and accessible introduction to the theory and craft of theatrical sound design that would be an excellent text in a foundational sound-design course. Educators and designers at the college level, and perhaps the high school level, would find this book appropriate for introductory courses or for mentoring young designers. The core goals are well-stated in the introduction: "You will come to understand how what one hears can play into our emotional state and how the physics of sound plays upon our physical bodies … and more importantly, how sound designers use that knowledge to artistically support the visual expression of theatre art" (1). Deiorio draws on her extensive experience as a designer, composer, and educator to provide a foundation in sound theory, real-world production examples, and classroom exercises in her three-part text. Part 1 focuses on the theoretical foundation of sound and lays the ground work for the creative and collaborative processes discussed later in parts 2 and 3. Deiorio begins with an explanation of how humans experience sound and vibrations in the world, influenced by our physiology and our psychology, and then focuses on how an emotional response is evoked through that experience. Learning this context assists in moving previously subconscious impacts of sound to a conscious level, as Deiorio teaches the reader how to analyze and describe sounds in the world with new specificity and awareness. She discusses the physics of sound waves in architectural space and sound technology tools within the context of the choices that designers must make. This section gives an introduction to the qualities and functions of sound that designers can intentionally manipulate to evoke a specific response in their audiences. Part 2 offers exercises for practical classroom activities to help students build creative design skills. Exercises in this section first strengthen aural techniques and vocabulary, including ways to use ambiance, repetition, droning, and punctuation for dramatic effect. As a case study that she returns to throughout part 2 of the book, Deiorio breaks down her sound design for a professional production of the play Dr. Jekyll and Mr. Hyde and uses it to illustrate the sonic concepts presented both succinctly and effectively. Particularly effective is the section on "Theatrical Application of Themes," in which she discusses analyzing themes in a script and then mapping sonic qualities to those themes. The chapter includes a table of contrasting themes, or "Intellectual Dualities" matched to the "Sonic Dualities" one might choose to convey those themes in a sound design. For example, "good vs. evil" could be explored using "organic vs. inorganic" sounds, or "life vs. death" could be explored using "major key vs. minor key" music. After sharing her own process connecting themes to sonic qualities in Dr. Jekyll and Mr. Hyde, Deoirio leads the reader through the creation of a three-part mini soundscape using this process. With the step-by-step instructions and reflection questions provided, instructors could easily adapt this exercise into an in-class activity or assignment. After the artistic sound-design exercises, a section on sound dramaturgy follows. Deiorio argues that "[a]s artists, sound designers must have an understanding of the other artists' work they will be using or emulating, and the culture that evoked the art" (6), and this chapter offers a broad overview of historical trends in music from the 1600s to the present day. It is not meant to be comprehensive, but rather to offer a summary of form, structure, and sonic "special ingredients" featured in these music periods. Here, Deiorio draws connections between the aural techniques learned in the previous chapters and the qualities found in the musical [End Page 220] genres and historical periods. This section can be a helpful starting point for students before they conduct more specific research on their own. Part 3 explores the collaborative artistic process and also the practical responsibilities of being a theatrical sound designer. The...

Real-time imaging of brain displacement during FUS neuromodulation in rodents in vivo

Focused ultrasound (FUS) is capable of modulating the central and peripheral nervous system. Temperature increase, cavitation, and acoustic radiation force have been proposed as potential mechanisms. Thus, tissue displacement imaging during FUS modulation is critical to understanding its physical mechanism. A cranial window was formed to perform imaging during FUS neuromodulation in C57BL/6 mice. FUS sonications were performed with a 4 MHz single-element transducer with a focal volume 0.2 × 0.9 mm (Sonic Concepts, WA), an applied tone burst of 0.5 ms and peak positive pressures varying from 1.9 to 6.7 MPa. Real-time channel data using plane wave sequences were acquired with an 18 MHz linear array (Vermon, France) and axial displacements throughout the entire brain were estimated using 1D cross-correlation (9λ window, 99% overlap) at 1 kHz frame rate. Downward displacements were only detected during FUS within the focal region. During modulation, the cumulative displacement ranged from 0.021 ± 0.017 μm (n = 3) at 3.1 MPa to 0.24 ± 0.004 μm at 6.7 MPa (n = 3). Displacement decreased post-FUS and returned to null within 1–2 ms. Unlike in a preliminary phantom study, no shear waves were detected. Real-time displacement imaging could thus provide effective targeting and monitoring as well as unveil the mechanism during FUS modulation.Focused ultrasound (FUS) is capable of modulating the central and peripheral nervous system. Temperature increase, cavitation, and acoustic radiation force have been proposed as potential mechanisms. Thus, tissue displacement imaging during FUS modulation is critical to understanding its physical mechanism. A cranial window was formed to perform imaging during FUS neuromodulation in C57BL/6 mice. FUS sonications were performed with a 4 MHz single-element transducer with a focal volume 0.2 × 0.9 mm (Sonic Concepts, WA), an applied tone burst of 0.5 ms and peak positive pressures varying from 1.9 to 6.7 MPa. Real-time channel data using plane wave sequences were acquired with an 18 MHz linear array (Vermon, France) and axial displacements throughout the entire brain were estimated using 1D cross-correlation (9λ window, 99% overlap) at 1 kHz frame rate. Downward displacements were only detected during FUS within the focal region. During modulation, the cumulative displacement ranged from 0.021 ± 0.017 μm (n ...

Embodied sound design

Abstract Embodied sound design is a process of sound creation that involves the designer’s vocal apparatus and gestures. The possibilities of vocal sketching were investigated by means of an art installation. An artist–designer interpreted several vocal self-portraits and rendered the corresponding synthetic sketches by using physics-based and concatenative sound synthesis. Both synthesis techniques afforded a broad range of artificial sound objects, from concrete to abstract, all derived from natural vocalisations. The vocal-to-synthetic transformation process was then automated in SEeD, a tool allowing to set and play interactively with physics- or corpus-based sound models. The voice-driven process and tool, developed and evaluated through design exercises, show how an embodied sound sketching system can work in supporting the externalisation of sonic concepts.

Transcranial acoustic cavitation localization with ultrafast power cavitation imaging in non-human primates

Acoustic cavitation-guided blood-brain barrier (BBB) opening with focused ultrasound (FUS) and microbubbles is a promising technique for safe and controlled opening of the BBB. Passive cavitation imaging has the ability to monitor the spatial intensity of acoustic cavitation for targeting verification and treatment monitoring. However, isolating acoustic cavitation emissions from tissue and skull reflections is a major challenge. In this study, we perform transcranial passive cavitation imaging with a 1.5D imaging array (M5Sc-D, bandwidth: 1.5–4 MHz, GE Medical Systems) placed in the central opening of a 0.5 MHz FUS transducer (H204, Sonic Concepts) in non-human primates. Broadband FUS pulses were used along with synchronous transmit and receive sequences to perform delay and sum beamforming with absolute time delays. Image sets were acquired at ultrafast frame rates (>1000 frames per second) for calculation of mean intensity images, i.e., power cavitation images. Spatiotemporal clutter filtering of image...

In Vivo Monitoring of HIFU Induced Temperature Rise in Porcine Liver Using Magnetic Resonance Thermometry1

High intensity focused ultrasound (HIFU) is a noninvasive medical procedure during which a large amount of energy is deposited in a short duration, which causes sudden localized rise in tissue temperature, and ultimately, cell necrosis. In the preclinical characterization of thermal fields generated by HIFU systems, the temperature rise in an ex vivo or an in vivo tissue must be accurately measured. The temperature rise can be measured using thin wire thermocouples or magnetic resonance (MR) thermometry. Among the two methods, thermocouples can be embedded invasively in the animal tissue, and HIFU induced temperature rise can be measured by focusing the beam on the thermocouple junction for the desired sonication time. However, the temperature rise measured using thermocouples is subject to several significant sources of error. One source of error associated with direct HIFU sonication of thermocouples is viscous-heating artifact [1]. Positioning errors represent another challenge in measuring temperature by locating beam atop a thermocouple [2]. Consequently, it has been difficult to accept that the temperature recorded by the thermocouple is the actual temperature at the focus of the HIFU beam. Therefore, there is a need for a method that can address these limitations. Unlike the measurement of temperature using thermocouples, the MR thermometry is a noninvasive method that does not suffer from the problems of positioning error and thermal artifacts. The magnetic resonance imaging (MRI) scanner is capable of assessing the transient temperature rise across the treatment volume, as well as measuring the volume of the thermal lesion [3]. Although the MR temperature monitoring was used to evaluate the feasibility of MR-guided HIFU ablation in the liver and kidney [4], the effect of higher acoustic powers on initiation of cavitation and possible maximum temperature rise in these organs were not assessed using MR thermometry. In this study, MR thermometry was used to monitor HIFU ablations performed on in vivo porcine livers, at elevated acoustic powers of 10 W, 30 W, and 40 W to assess the temperature field where initiation of cavitation is known to occur. Temperature rise during the heating phase as well as the temperature decay during the cooling phase was acquired. The transient temperature profiles measured during the heating and cooling phases for the three powers were compared, in order to check the HIFU induced maximum temperature rise.

876 Development of an EUS-Guided High-Intensity Focused Ultrasound Endoscope

876 Development of an EUS-Guided High-Intensity Focused Ultrasound Endoscope