Ultrasound Energy Research Articles

Part III - Ultrasound assisted processes, sonochemical reactors and energy efficiency

Part III - Ultrasound assisted processes, sonochemical reactors and energy efficiency

Multifunctional theragnostic ultrasmall gold nanodot-encapsuled perfluorocarbon nanodroplets for laser-focused ultrasound sequence irradiation (LFSI)-based enhanced tumor ablation.

Despite the substantial potential of focused ultrasound therapy, its efficacy in cancer therapy has been limited due to the high cavitation threshold and safety concerns regarding the use of high-intensity energy pulses. Here, ultrasmall Au nanodot-loaded PEG-modified perfluorocarbon nanodroplets (Au-PFCnDs) were prepared and used as a therapeutic enhancer. A LFSI method was designed to achieve enhanced tumor ablation at a mild focused ultrasound (FUS) energy pulse with the assistance of the instinct photothermal effect of intratumor-permeable ultrasmall Au nanodots under 808 nm NIR laser irradiation. In addition to their therapeutic function, Au-PFCnDs can also generate multimodal images to provide information for tumor surveillance and treatment guidance. The experimental results also showed that the cRGD-targeted Au-PFCnDs could be more efficiently delivered into the tumor and selectively destroy tumors with no observable side effects on normal tissue under LFSI treatment.

Sonicated chemical synthesis for energy efficient production of Hexahydro-1H-quinazolin-2-thiones

We have reported here the potential of ultrasound energy for the construction of quinazoline ring in the presence of TBASH and L-Proline in multicomponent fashion using diethylene glycol. The complete methodology comes out as green synthetic protocol. This catalytic system is found to be useful, inexpensive and effective non-toxic catalysts for a smooth one pot multicomponent synthesis of hexahydro-1H-quinazoline-2-thiones. Synthesis proceeds via condensation of aromatic aldehydes, cyclohexanone and thiourea in excellent yields. The thiourea results exclusively the hexahydro-1H-quinazolin-2-thiones, in excellent yields. The easy handling of reaction, reduced reaction times, easy isolation method and clean product formation are the additional advantages associated with this sonication green synthetic method.

Focused Ultrasound-Mediated Intranasal Brain Drug Delivery Technique (FUSIN).

The blood-brain barrier (BBB) is the major barrier for brain drug delivery and limits the treatment options for central nervous system diseases. To circumvent the BBB, we introduced the focused ultrasound-mediated intranasal brain drug delivery (FUSIN) technique. FUSIN utilizes the nasal route for direct nose-to-brain drug administration, bypassing the BBB and minimizing systemic exposure. It also uses the transcranial application of ultrasound energy focused at a targeted brain region to induce microbubble cavitation, which enhances the transport of intranasally administered agents at the FUS-targeted brain location. FUSIN is unique in that it can achieve noninvasive and localized brain drug delivery with minimized systemic toxicity. The goal of this chapter is to provide a detailed protocol for FUSIN delivery to the mouse brain.

Sonoprocessing of freshly squeezed orange juice: Ascorbic acid content, pectin methylesterase activity, rheological properties and cloud stability

Ultrasound performance at low energy densities (9–86 J/mL) on the quality attributes of freshly squeezed orange juice was compared to heat treatment (90 °C/1 min). Mild sonoprocessing improved orange juice's kinetic stability preserving its ascorbic acid (vitamin C) content. The ultrasound energy densities could not promote the inactivation of pectin methylesterase (PME) in the orange juice samples. However, higher energy densities contributed to their cloud stability along cold storage. In contrast, the heat processing inactivated 96.3% of PME, but thermally treated samples lost their cloudiness and had their ascorbic acid content reduced by 7%. Cloud stabilization after sonoprocessing was mainly attributed to acoustic cavitation performance to modulate particle size distribution. Ultrasound processing is a promising technique to solve one of the main technological issues of the freshly squeezed orange juice. However, mild sonoprocessing must be combined with other innovative non-thermal technologies to provide a safe and high-quality orange juice.

Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound.

Brain tumors are particularly challenging malignancies, due to their location in a structurally and functionally distinct part of the human body - the central nervous system (CNS). The CNS is separated and protected by a unique system of brain and blood vessel cells which together prevent most bloodborne therapeutics from entering the brain tumor microenvironment (TME). Recently, great strides have been made through microbubble (MB) ultrasound contrast agents in conjunction with ultrasound energy to locally increase the permeability of brain vessels and modulate the brain TME. As we elaborate in this review, this physical method can effectively deliver a wide range of anticancer agents, including chemotherapeutics, antibodies, and nanoparticle drug conjugates across a range of preclinical brain tumors, including high grade glioma (glioblastoma), diffuse intrinsic pontine gliomas, and brain metastasis. Moreover, recent evidence suggests that this technology can promote the effective delivery of novel immunotherapeutic agents, including immune check-point inhibitors and chimeric antigen receptor T cells, among others. With early clinical studies demonstrating safety, and several Phase I/II trials testing the preclinical findings underway, this technology is making firm steps towards shaping the future treatments of primary and metastatic brain cancer. By elaborating on its key components, including ultrasound systems and MB technology, along with methods for closed-loop spatial and temporal control of MB activity, we highlight how this technology can be tuned to enable new, personalized treatment strategies for primary brain malignancies and brain metastases.

Disordered Protein Stabilization by Co-Assembly of Short Peptides Enables Formation of Robust Membranes

Molecular self-assembly is a spontaneous natural process resulting in highly ordered nano to microarchitectures. We report temperature-independent formation of robust stable membranes obtained by the spontaneous interaction of intrinsically disordered elastin-like polypeptides (ELPs) with short aromatic peptides at temperatures both below and above the conformational transition temperature of the ELPs. The membranes are stable over time and display durability over a wide range of parameters including temperature, pH, and ultrasound energy. The morphology and composition of the membranes were analyzed using microscopy. These robust structures support preosteoblast cell adhesion and proliferation as well as pH-dependent cargo release. Simple noncovalent interactions with short aromatic peptides can overcome conformational restrictions due to the phase transition to facilitate the formation of complex bioactive scaffolds that are stable over a wide range of environmental parameters. This approach offers novel possibilities for controlling the conformational restriction of intrinsically disordered proteins and using them in the design of new materials.

Effects of focused ultrasound and dry needling on tendon mechanical properties

Tendon injuries are extremely common, resulting in mechanically weaker tendons that could lead to tendon rupture. Dry needling (DN) is widely used to manage pain and function after injury. However, DN is invasive and high inter-practitioner variability has led to mixed success rates. Focused ultrasound (fUS) is a non-invasive medical technology that directs ultrasound energy into a well-defined focal volume. fUS can induce thermal ablation or mechanical fractionation, with bioeffect type controlled through ultrasound parameters. Tendons must withstand high physiological loads, thus treatments maintaining tendon mechanical properties while promoting healing are needed. Our objective was to evaluate mechanical effects of DN and 3 fUS parameter sets, chosen to prioritize mechanical fractionation, on Achilles and supraspinatus tendons. Ex vivo rat Achilles and supraspinatus tendons (50 each) were divided into sham, DN, fUS-1, fUS-2, and fUS-3 (n = 10/group). Following treatment, tendons were mechanically tested. Elastic modulus of supraspinatus tendons treated with DN (126.64 ± 28.1 MPa) was lower than sham (153.02 ± 29.3 MPa; p = 0.0280). Stiffness and percent relaxation of tendons treated with DN (Achilles: 114.40 ± 31.6 N/mm; 49.10 ± 6.1%; supraspinatus: 109.53 ± 30.8 N/mm; 50.17 ± 7.6%) were lower (all p < 0.0334) than sham (Achilles: 141.34 ± 20.9 N/mm; 60.30 ± 7.7%; supraspinatus: 135.14 ± 30.2 N/mm; 60.85 ± 15.4%). Modulus of Achilles and supraspinatus tendons treated with fUS-1 (159.88 ± 25.7 MPa; 150.12 ± 22.0 MPa, respectively) were similar to sham (156.35 ± 23.0 MPa; 153.02 ± 29.3 MPa, respectively). These results suggest that fUS preserves mechanical properties better than DN, with fUS-1 performing better than fUS-2 and fUS-3. fUS should be studied further to fully understand its mechanical and healing effects to help evaluate fUS as an alternative, non-invasive treatment for tendon injuries.

The Evolving Role of Ultrasound in Therapy

This study highlights the role of ultrasound in therapy and to be a step toward of further development. When an ultrasound wave moves through a tissue it will raise the temperature of that tissue. This effect is beneficial in the treatment of some acute and chronic diseases. A special device used in this study. the device is designed to provide ultrasound waves with frequencies of 1 MHz and 3 MHz which are used in therapy. The frequency of ultrasound is inversely proportional to the depth of the tissues which have to be treated, 1 MHz frequency was used to treat deep body structures reaching 5 cm depth, while 3 MHz used to treat superficial structures. The increase in tissue temperature was measured when: First, by fixing the time and gradually increasing intensity and it is noticed that there is an increase in tissue temperature 0.16-3.04 °C for 1 MHz, and 0.3-3 °C for 3 MHz. Secondly, by fixing the intensity and gradually increasing time, also it is shown that there is an increase in tissue temperature of 0.3-3 °C for 1 MHz and 0.24-2.4 °C for 3 MHz. This rise in tissue temperature is due to the absorption of ultrasound energy in tissues and this effect is used in therapy. So, in a limited time larger number of patients can be treated by reducing the period of treatment with increased intensity of the ultrasound.

Luting indirect restorations with resin cements versus composite resins: Effects of preheating and ultrasound energy on film thickness.

This study aims to evaluate and compare the film thickness obtained with a resin cement and two composite resins, preheated and/or ultrasonically vibrated, as luting agents. One hundred and twenty-six (126) pairs of resin discs were randomly assigned to six experimental groups (n= 21) according to luting agent (Variolink Esthetic LC, IPS Empress Direct or Estelite Omega) and cementation technique (preheating at 68°C and/or ultrasonic vibration). Specimens were luted by applying a controlled force. Following sectioning and film thickness measurement through field emission gun scanning electron microscopy, statistical analysis was carried out considering a 5% significance level. Statistically significant lower film thickness was observed in Variolink Esthetic LC group when compared to all composite resin groups (p< 0.001), except IPS Empress Direct preheated and ultrasonically vibrated group (p = 0.073). IPS Empress Direct with ultrasonic vibration yielded statistically lower film thickness values than Estelite Omega groups, regardless of luting technique (p< 0.05). Ultrasonically vibrated Estelite Omega groups showed statistically lower film thickness values than solely preheated groups (p< 0.05). Both Variolink Esthetic LC and IPS Empress Direct preheated and ultrasonically vibrated provided the lowest film thickness. The addition of ultrasonic vibration during cementation proved to be effective in reducing film thickness of both tested composite resins. The cementation technique will have variable results depending on the luting material. Adhesive cementation protocols with composite resins should mainly consider ultrasonic vibration, but also preheating, as strategies for reducing film thickness. The tested resin cement, alongside with IPS Empress Direct composite resin preheated and ultrasonically vibrated, provided the lowest film thickness among the tested materials and techniques.

Factors Associated with Energy Efficiency of Focused Ultrasound Through the Skull: A Study of 3D-Printed Skull Phantoms and Its Comparison with Clinical Experiences.

While focused ultrasound (FUS) is non-invasive, the ultrasound energy is attenuated by the skull which results in differences in energy efficiency among patients. In this study, we investigated the effect of skull variables on the energy efficiency of FUS. The thickness and density of the skull and proportion of the trabecular bone were selected as factors that could affect ultrasound energy transmittance. Sixteen 3D-printed skull models were designed and fabricated to reflect the three factors. The energy of each phantom was measured using an ultrasonic sound field energy measurement system. The thickness and proportion of trabecular bone affected the attenuation of transmitted energy. There was no difference in the density of the trabecular bone. In clinical data, the trabecular bone ratio showed a significantly greater correlation with dose/delivered energy than that of thickness and the skull density ratio. Currently, for clinical non-thermal FUS, the data are not sufficient, but we believe that the results of this study will be helpful in selecting patients and appropriate parameters for FUS treatment.

Low-frequency acoustic generation and nonreciprocal transmission device

The acoustic nonreciprocal device has attracted the attention of some researchers because of the potential practical applications, for example, biomedical ultrasound applications, energy saving, and harvesting. We propose a low-frequency acoustic generation and nonreciprocal transmission device inspired by the previous studies and nature of the vibro-acoustic propagation. We utilize ultrasonic transducer to form acoustic radiation pressure on the water surface, which can vibrate water to produce low-frequency sound. Meanwhile, an ultrasonic metamaterial is designed based on our previous research. The metamaterial is placed under the metal sink to obstruct the 20 kHz ultrasonic waves and pass through the frequency sound waves. With that, the low-frequency acoustic sound is generated and pass through the metamaterial when the proposed device is in the forward configuration. When the device is in the backward configuration, the ultrasonic wave is obstructed by the metamaterials and metal sink bottom. Thus, no vibration is excited in the water, and therefore, no acoustic sound is generated. With the above-mentioned mechanism, the device can obtain the acoustic nonreciprocity in the very low-frequency range.

A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound

Nanosizing is an approach to improve the dissolution rate of poorly soluble drugs. The first aim of this work was to develop nanosuspension of cilostazol with liquid antisolvent precipitation (LASP) and its combination with ultrasound. Second, to systematically study the effect of bottom-up processing factors on precipitated particles’ size and identify the optimal settings for the best reduction. After solvent and stabilizer screening, in-depth process characterization and optimization was performed using Design of Experiments. The work discusses the influence of critical factors found with statistical analysis: feed concentration, stabilizer amount, stirring speed and ultrasound energy governed by time and amplitude. LASP alone only generated particle size of a few microns, but combination with ultrasound was successful in nanosizing (d10 = 0.06, d50 = 0.33, d90 = 1.45 µm). Micro- and nanosuspension’s stability, particle morphology and solid state were studied. Nanosuspension displayed higher apparent solubility than equilibrium and superior dissolution rate over coarse cilostazol and microsuspension. A bottom-up method of precipitation-sonication was demonstrated to be a successful approach to improve the dissolution characteristics of poorly soluble, BCS class II drug cilostazol by reducing its particle size below micron scale, while retaining nanosuspension stability and unchanged crystalline form.

EXTH-49. FOCUSED ULTRASOUND AND 5-ALA MEDIATED ELIMINATION OF DIFFUSE MIDLINE GLIOMA

Abstract Diffuse midline glioma (DMG) is a devastating and incurable childhood brain cancer. With a median survival of only 9 to 11 months, over 90% of children affected by DMG die within two years of diagnosis. Despite decades of research and a growing understanding of the biology of these tumors, there have been no advancements in therapies for DMGs. Tumor heterogeneity and diffuse infiltration in inoperable brain regions make these tumors uniquely difficult to manage both surgically and pharmacologically. Therefore, there is an urgent need for the exploration of novel treatment regimens. Focused Ultrasound (FUS) is an emerging technology with significant clinical potentials. Sonodynamic therapy (SDT) is an up-and-coming treatment strategy aiming to non-invasively eliminate tumor cells by acting through compounds known as sonosensitizers, which render tumor cells sensitive to ultrasound energy. Recently, 5-Aminolevulinic acid (5-ALA), an FDA-approved molecule, has been proposed as a sono-sensitizing agent. 5-ALA mediated SDT prolonged survival in C6 rat glioma models by selective elimination of tumor cells upon sonication. Mechanistically, it is thought that 5-ALA uptake and metabolic conversion into Protoporphyrin IX (PpIX) occurs preferentially in tumor cells due to differential activity of enzymes involved in heme metabolism. Here, we investigated SDT in DMG cells treated with 5-ALA. PpIX fluorescence increased linearly up to 24 h upon 5-ALA treatment and accumulated significantly more (1.6-fold, p &amp;lt; 0.01) when compared to C6 cells. Consequently, FUS sonication of 5-ALA treated DMG cells at 250 kHz significantly (p &amp;lt; 0.05) decreased DMG cell viability compared to treatment with 5-ALA or FUS alone. Here, we show the first 5-ALA mediated sonodynamic effect in DMG cells, leading to enhanced cell death. Our findings provide a rationale for considering clinical investigation of 5-ALA mediated sonodynamic therapy in DMG.

On dissection of the uterine wall during laparoscopic myomectomy

BACKGROUND: Laparoscopic myomectomy is becoming the leading method of surgical treatment of uterine fibroids while preserving reproductive and menstrual functions. Increasingly, ultrasound energy is used to dissect the myometrium. Meanwhile, the mode and direction of the ultrasound energy supply to minimize damage to the underlying tissues have not been specified.&#x0D; AIM: The aim of this study was to perform a comparative analysis of the myometrium and the fibroid pseudocapsule in the projection of the myoma nodule after dissection using ultrasound energy with different initial characteristics of the surgical instrument.&#x0D; MATERIALS AND METHODS: For comparison, we selected two instruments with a longitudinal ultrasound energy supply with an output frequency of 80 MHz ... 2.5 GHz and 47 kHz at intermittent operating mode of 5/10 sec and one torsion instrument with a transverse ultrasound energy supply with an output frequency of 36 kHz at intermittent operating mode of 3/30 sec.&#x0D; RESULTS: Our study has shown that the smallest zone of irreversible changes is formed when using ultrasound energy with an output frequency of 36 kHz at intermittent operating mode of 3/30 sec with its transverse feed at 90 degrees to the blade, and the largest zone of irreversible changes is formed when using ultrasound energy with an output frequency of 47 kHz at intermittent operating mode of 5/10 sec with its longitudinal feed.&#x0D; CONCLUSIONS: Morphometric studies with an analysis of the depth of necrotic and necrobiotic changes in the myometrial tissue showed that from the standpoint of reproductive surgery, it is preferable to use USE with an output frequency of 36 kHz at intermittent operating mode of 3/30 sec with its transverse feed.

A High Sensitivity Transparent Ultrasound Transducer based on PMN-PT for Ultrasound and Photoacoustic Imaging.

We recently introduced piezoelectric lithium niobate (LN) based transparent ultrasound transducers (TUT) as a new platform for developing multimodal optical, ultrasound and photoacoustic imaging systems. However, LN based TUT is limited in its signal-to-noise ratio due to material's low piezoelectricity (d 33). In this paper, we report, for the first time, a 0.2 mm thick transparent lead magnesium niobate-lead titanate (PMN-PT) based TUT (PMN-PT-TUT) for ultrasound and photoacoustic applications and compared its performance with a 0.25 mm thick transparent LN based TUT (LN-TUT). To improve the ultrasound energy transmission efficiency, TUTs were fabricated with a two-matching-layer design. This resulted in a dual frequency response with center frequencies of 7.8 MHz/13.2 MHz and corresponding bandwidths of 28.2%/66.67% for PMN-PT-TUT, and center frequencies of 7.2 MHz/11.8 MHz and bandwidths of 36.1%/62.7% for LN-TUT. The optical transmission rate of PMN-PT-TUTs and LN-TUTs are measured as ~73% and ~91% respectively at 532 nm optical wavelength. The PMN-PT-TUT exhibited higher sensitivity compared to LN-TUT with a nearly three-fold higher pulse echo amplitude and more than two-fold higher photoacoustic amplitude. Furthermore, optical resolution photoacoustic microscopy (ORPAM) experiments on phantom targets demonstrated lateral resolutions of 7 μm and 5.1 μm, and axial resolutions of 285.6 μm and 375.9 μm for PMN-PT-TUT and LN-TUT respectively. These results indicated that PMN-PT is a viable alternative to LN for developing TUT based multimodal ultrasound and photoacoustic imaging systems.

Computational investigation of ultrasound induced electricity generation via a triboelectric nanogenerator

The efficient conversion of ultrasound into electrical energy remains a highly desirable wireless powering solution, with potentially profound ramifications in energy transfer across virtually all industrial fields, especially for implantable medical devices. Triboelectric nanogenerators have been shown to effectively carry out ultrasound energy transduction, though efficiency remains poor. Here, we devise a computational model to investigate the optimal triboelectric nanogenerator irradiation conditions, including frequency, probe distance, size, and design, as represented by irradiated triboelectric surface area displacement. Our investigation may set the foundations for the establishment of a standardized protocol for efficient ultrasound mechanical energy harvesting. This holds considerable significance and could be paramount in designing an ever-growing number of applicative solutions in wireless energy transfer, providing a scalable, cost effective and time saving solution in the development of implantable medical devices.

Current state of therapeutic focused ultrasound applications in neuro-oncology.

Despite manifold advances in oncology, cancers of the central nervous system remain among the most lethal. Unique features of the brain, including distinct cellular composition, immunological privilege, and physical barriers to therapeutic delivery, likely contribute to the poor prognosis of patients with neuro-oncological disease. Focused ultrasound is an emerging technology that allows transcranial delivery of ultrasound energy to focal brain targets with great precision. A review of the clinical and preclinical focused ultrasound literature was performed to obtain data regarding the current state of the focused ultrasound in context of neuro-oncology. A narrative review was then constructed to provide an overview of current and future applications of this technology. Focused ultrasound can facilitate direct control of tumors by thermal or mechanical ablation, as well as enhance delivery of diverse therapeutics by disruption of the blood-brain barrier without local tissue damage. Indeed, ultrasound-sensitive drug formulations or sonosensitizers may be combined with ultrasound blood-brain barrier disruption to achieve high local drug concentration while limiting systemic exposure to therapeutics. Furthermore, focused ultrasound can induce radiosensitization, immunomodulation, and neuromodulation. Here we review applications of focused ultrasound with a focus on approaches currently under clinical investigation for the treatment of neuro-oncological disease, such as blood-brain barrier disruption for drug delivery and thermal ablation. We also discuss design of clinical trials, selection of patient cohorts, and emerging approaches to improve the efficacy of transcranial ultrasound, such as histotripsy, as well as combinatorial strategies to exploit synergistic biological effects of existing cancer therapies and ultrasound. Focused ultrasound is a promising and actively expanding therapeutic modality for diverse neuro-oncological diseases.

Rapid in-syringe-based ultrasonic-energy assisted salt-enhanced homogeneous liquid-liquid microextraction technique coupled with HPLC/low-temperature evaporative light-scattering detector for quantification of sodium hyaluronate in food products

Sodium-hyaluronate (Na-HA) is a biopolymer-based active ingredient in various dietary and beauty care supplements. However, the existing analytical methods for Na-HA analysis are laborious, less sensitive, and time-consuming. This study demonstrates a simple, low-cost, and green rapid analytical methodology using a novel in-syringe-based ultrasonic energy-assisted salt-enhanced homogeneous liquid-liquid microextraction (IS-USE-SE-HLLME) technique coupled with HPLC/low-temperature evaporative light scattering detector (LT-ELSD) for the sensitive quantification of Na-HA in nutraceutical products. This method utilizes ultrasound energy to extract Na-HA from an aqueous sample solution using a low volume water-miscible extraction solvent with a high salt concentration. Size-exclusion column-based HPLC was applied to separate target Na-HA from co-matrices and quantified using LT-ELSD for sensitive analysis. Under optimal conditions, excellent linearity was observed between 1 and 500 ng mL−1 with a correlation coefficient of 0.9974. Detection and quantification limits were 0.5 ng mL−1 and 1.0 ng mL−1, respectively. The developed (IS-USA-SE-HLLME/HPLC-LT-ESLD) method was applied to analyze Na-HA in commercial nutraceutical and beauty care products. Spiked recoveries of real samples showed between 96.1 and 105.9%, with the precision <7.52%, indicating no matrices influence and good accuracy of the method. These results proved that the developed method is a fast, inexpensive, sensitive, and eco-friendly method for quantifying Na-HA in nutraceutical products. Therefore, the presented method can be applied as an alternative standard analytical method to monitor Na-HA concentrations in food products for food safety regulatory purposes.

Babies, bubbles, and brain disease: An introduction to the Biomedical Acoustics Technical Committee

For most folks, ultrasound in medicine is associated with fetal imaging, and it remains among the most widely available and frequently used imaging modalities in the clinic. Recent advances have expanded the capacity of ultrasound imaging to include the ability to quantify mechanical properties of tissue (elastography), microvascular structure (super resolution imaging), perfusion (contrast imaging), and molecular expression such as oxygenation (photo-acoustic imaging). Effective diagnostic information is now possible for targets traditionally avoided by ultrasound imaging, such as lung for COVID-19 diagnoses. Ultrasound energy can also be harnessed for therapeutic purposes. Focused sources enable us to ablate malignancies through thermal or mechanical-based mechanisms. A strong tumor immune response has been observed for histotripsy, a bubble-based ablation method, potentiating a means to treat multi-focal disease. Ultrasound-mediated bubble activity enhances drug delivery to improve treatment for thrombo occlusive disease (e.g., heart attack, stroke, venous thrombosis), cancer, and tissue regeneration. Improved drug delivery is also possible in the brain via ultrasound-mediated opening of the blood brain barrier. Separate from drug delivery, ultrasound can induce neuromodulation for the treatment of essential tremor, neuropathic pain, and Parkinson’s disease. Diagnostic and therapeutic ultrasound continues to advance the field of medicine, and are integral for improving the outcomes for debilitating diseases.