In-Vitro Measurement of Forces During Debridement with a Piezoelectric Ultrasonic Periodontal Scaler.

PURPOSE: This study investigated the magnitude, direction, and temporal aspects of the force applied during instrumentation with a piezoelectric ultrasonic periodontal scaler, compared this force with recommendations in the literature, and assessed the influence of the profession (dentist or dental hygienist) and calculus hardness. MATERIALS AND METHODS: The force applied by ten dental hygienists and six dentists during debridement of comparatively soft and hard artificial dental calculus with a piezoelectric ultrasonic scaler was recorded in-vitro. The total force and its components in three axes were statistically analysed. RESULTS: During debridement of soft artificial dental calculus, the mean total force applied by dental hygienists was 0.34 N (± 0.18 N, range: 0.13 N to 0.59 N) and by dentists 0.28 N (± 0.33 N, range: 0.06 N to 0.95 N), and the total force exceeded 0.5 N approximately 23% and 14% of the time for dental hygienists and dentists, respectively. During debridement of hard artificial dental calculus, the mean total force applied by dental hygienists was 0.63 N (± 0.40 N, range: 0.28 N to 1.64 N) and by dentists 0.57 N (± 0.17 N, range: 0.34 N to 0.76 N); the total force exceeded 0.5 N more than half of the time for both professions. On average, dental hygienists applied 1.85x (p = 0.04) and dentists 2.04x (p = 0.06) higher force on hard than on soft artificial calculus. However, dental hygienists and dentists used similar forces during the debridement of both hard (p = 1.00) and soft (p = 0.26) calculus. CONCLUSION: The force applied during the debridement of hard artificial dental calculus was statistically significantly higher than during the debridement of soft artificial dental calculus. No statistically significant difference between dentists and dental hygienists was found. The force applied by both groups on soft and hard artificial dental calculus frequently exceeded recommended values.

In-vitro effects of novel periodontal scalers with a planar ultrasonic piezoelectric transducer on periodontal biofilm removal, dentine surface roughness, and periodontal ligament fibroblasts adhesion.

OBJECTIVES: To compare ultrasonic scaler prototypes based on a planar piezoelectric transducer with different working frequencies featuring a titanium (Ti-20, Ti-28, and Ti-40) or stainless steel (SS-28) instrument, with a commercially available scaler (com-29) in terms of biofilm removal and reformation, dentine surface roughness and adhesion of periodontal fibroblasts. MATERIALS AND METHODS: A periodontal multi-species biofilm was formed on specimens with dentine slices. Thereafter specimens were instrumented with scalers in a periodontal pocket model or left untreated (control). The remaining biofilms were quantified and allowed to reform on instrumented dentine slices. In addition, fibroblasts were seeded for attachment evaluation after 72 h of incubation. Dentine surface roughness was analyzed before and after instrumentation. RESULTS: All tested instruments reduced the colony-forming unit (cfu) counts by about 3 to 4 log10 and the biofilm quantity (each p < 0.01 vs. control), but with no statistically significant difference between the instrumented groups. After 24-hour biofilm reformation, no differences in cfu counts were observed between any groups, but the biofilm quantity was about 50% in all instrumented groups compared to the control. The attachment of fibroblasts on instrumented dentine was significantly higher than on untreated dentine (p < 0.05), with the exception of Ti-20. The dentine surface roughness was not affected by any instrumentation. CONCLUSIONS: The planar piezoelectric scaler prototypes are able to efficiently remove biofilm without dentine surface alterations, regardless of the operating frequency or instrument material. CLINICAL RELEVANCE: Ultrasonic scalers based on a planar piezoelectric transducer might be an alternative to currently available ultrasonic scalers.

High-spatial-resolution transcranial focused ultrasound neuromodulation using frequency-modulated pattern interference radiation force.

Stimulating the brain in a precise location is crucial in ultrasound neuromodulation. However, improving the resolution proves a challenge owing to the characteristics of transcranial focused ultrasound. In this paper, we present a new neuromodulation system that overcomes the existing limitations based on an acoustic radiation force with a frequency-modulated waveform and standing waves. By using the frequency-modulated pattern interference radiation force (FM-PIRF), the axial spatial resolution can be reduced to a single wavelength level and the target location can be controlled in axial direction electronically. A linear frequency-modulated chirp waveform used in the experiment was designed based on the simulation results. The displacement of the polydimethylsiloxane (PDMS) cantilever was measured at intervals of 0.1 mm to visualize the distribution of radiation force. These results and methods experimentally show that FM-PIRF has improved spatial resolution and capability of electrical movement.

Speed of sound in the IEC tissue-mimicking material and its maintenance solution as a function of temperature.

Tissue-Mimicking Material (TMM) is defined on IEC International Standards and applied in assessing ultrasonic diagnostic and therapeutic equipment's basic safety and essential performance. One of the TMM that fits IEC standards specification has its recipe described at IEC 60601-2-37, and it is fabricated using glycerol (11.21 %), deionized water (82.95%), benzalkonium chloride (0.47 %), silicon carbide (0.53 %), aluminum oxide 0.3 µm (0.88%), aluminum oxide 3.0 µm (0.94 %), and agar (3.08 %). Glycerol is the component responsible for adjusting the TMM's speed of sound. Moreover, it is recommended to store TMM in a closed container immersed in a mixture of water (88.1 %)/glycerol (11.9 %) to prevent it from drying out and avoiding air contact. The literature points out TMM measurements underwater can alter the speed of sound property as TMM tends to lose glycerol. Herein, the authors proposed to assess the viability of measuring the TMM speed of sound in the water/glycerol maintenance solution. First, the authors characterized the maintenance solution's speed of sound for a temperature range of 20 °C to 45 °C. Then, the group velocity of a set of TMM was measured underwater and in the maintenance solution for the same temperature range. The respective group velocity expanded uncertainty was calculated. The results indicate it is feasible to measure TMM in the maintenance solution, achieving group velocity values with no statistical difference from the ones measured underwater in the temperature range of 20 °C to 40 °C.

Design and Challenges of Sonodynamic Therapy System for Cancer Theranostics: From Equipment to Sensitizers.

As a novel noninvasive therapeutic modality combining low-intensity ultrasound and sonosensitizers, sonodynamic therapy (SDT) is promising for clinical translation due to its high tissue-penetrating capability to treat deeper lesions intractable by photodynamic therapy (PDT), which suffers from the major limitation of low tissue penetration depth of light. The effectiveness and feasibility of SDT are regarded to rely on not only the development of stable and flexible SDT apparatus, but also the screening of sonosensitizers with good specificity and safety. To give an outlook of the development of SDT equipment, the key technologies are discussed according to five aspects including ultrasonic dose settings, sonosensitizer screening, tumor positioning, temperature monitoring, and reactive oxygen species (ROS) detection. In addition, some state-of-the-art SDT multifunctional equipment integrating diagnosis and treatment for accurate SDT are introduced. Further, an overview of the development of sonosensitizers is provided from small molecular sensitizers to nano/microenhanced sensitizers. Several types of nanomaterial-augmented SDT are in discussion, including porphyrin-based nanomaterials, porphyrin-like nanomaterials, inorganic nanomaterials, and organic-inorganic hybrid nanomaterials with different strategies to improve SDT therapeutic efficacy. There is no doubt that the rapid development and clinical translation of sonodynamic therapy will be promoted by advanced equipment, smart nanomaterial-based sonosensitizer, and multidisciplinary collaboration.

Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications.

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.

Inorganic chemoreactive nanosonosensitzers with unique physiochemical properties and structural features for versatile sonodynamic nanotherapies.

The fast development of nanomedicine and nanobiotechnology has enabled the emerging of versatile therapeutic modalities with high therapeutic efficiency and biosafety, among which nanosonosensitizer-involved sonodynamic therapy (SDT) employs ultrasound (US) as the exogenous activation source for inducing the production of reactive oxygen species (ROS) and disease therapy. The chemoreactive nanosonosensitizers are the critical components participating in the SDT process, which generally determine the SDT efficiency and therapeutic outcome. Compared to the traditional and mostly explored organic sonosensitizers, the recently developed inorganic chemoreactive nanosonosensitizers feature the distinct high stability, multifunctionality and significantly different SDT mechanism. This review dominantly discusses and highlights two types of inorganic nanosensitizers in sonodynamic treatments of various diseases and their underlying therapeutic mechanism, including US-activated generation of electrons (e-) and holes (h+) for facilitating the following ROS production and delivery of organic molecular sonosensitizers. Especially, this review proposes four strategies aiming for augmenting the SDT efficiency on antitumor and antibacterial applications based on inorganic sonosensitizers, including defect engineering, novel metal coupling, increasing electric conductivity and alleviating tumor hypoxia. The encountered challenges and critical issues facing these inorganic nanosonosensitzers are also highlighted and discussed for advancing their clinical translations.

Proposal for a novel elliptical ultrasonic aspirator and its fundamental performance in cartilage removal.

An ultrasonic aspirator with elliptical vibration on the end face is presented in this paper. The ultrasonic vibration relied on a specially designed Langevin transducer. The end face of the transducer was screwed into a surgical tool capable of changing amplitude, which requires resonance to provide sufficient vibration amplitude for cutting cartilage or other biological tissues. Based on the coupling of two vertical bending vibrations, the new design produced the elliptical ultrasonic vibration on the end face of the surgical tool, which differed from the axial vibration of a traditional ultrasonic aspirator. The design greatly increased the mechanical effect of the aspirator. A specially designed blade was employed to remove the cartilage tissue. A prototype device was designed to operate at 20 kHz with a displacement amplitude of 150 µm at 200 V. The measurements of the vibrational and impedance responses showed the mechanical and electrical characteristics of the aspirator. Cutting tests on mice costal cartilage were subsequently conducted. Histological analysis displayed a higher proportion of live cells in the region around the cut site, which exhibited a higher removal efficiency.

Therapeutic Ultrasound Parameter Optimization for Drug Delivery Applied to a Murine Model of Hepatocellular Carcinoma.

Ultrasound and microbubble (USMB)-mediated drug delivery is a valuable tool for increasing the efficiency of the delivery of therapeutic agents to cancer while maintaining low systemic toxicity. Typically, selection of USMB drug delivery parameters used in current research settings are either based on previous studies described in the literature or optimized using tissue-mimicking phantoms. However, phantoms rarely mimic in vivo tumor environments, and the selection of parameters should be based on the application or experiment. In the following study, we optimized the therapeutic parameters of the ultrasound drug delivery system to achieve the most efficient in vivo drug delivery using fluorescent semiconducting polymer nanoparticles as a model nanocarrier. We illustrate that voltage, pulse repetition frequency and treatment time (i.e., number of ultrasound pulses per therapy area) delivered to the tumor can successfully be optimized in vivo to ensure effective delivery of the semiconducting polymer nanoparticles to models of hepatocellular carcinoma. The optimal in vivo parameters for USMB drug delivery in this study were 70 V (peak negative pressure = 3.4 MPa, mechanical index = 1.22), 1-Hz pulse repetition frequency and 100-s therapy time. USMB-mediated drug delivery using in vivo optimized ultrasound parameters caused an up to 2.2-fold (p < 0.01) increase in drug delivery to solid tumors compared with that using phantom-optimized ultrasound parameters.

Quantitative measurements of aerosols from air-polishing and ultrasonic devices: (How) can we protect ourselves?

AIM: To assess the distribution and deposition of aerosols during simulated periodontal therapy. METHODS: A manikin with simulated fluorescein salivation was treated by four experienced dentists applying two different periodontal treatment options, i.e. air-polishing with an airflow device or ultrasonic scaling in the upper and lower anterior front for 5 minutes, respectively. Aerosol deposition was quantitatively measured on 21 pre-defined locations with varying distances to the manikins mouth in triplicates using absorbent filter papers. RESULTS: The selected periodontal interventions resulted in different contamination levels around the patient's mouth. The highest contamination could be measured on probes on the patient's chest and forehead but also on the practitioner's glove. With increasing distance to the working site contamination of the probes decreased with both devices. Air-polishing led to greater contamination than ultrasonic. CONCLUSION: Both devices showed contamination of the nearby structures, less contamination was detected when using the ultrasonic. Affirming the value of wearing protective equipment we support the need for universal barrier precautions and effective routine infection control in dental practice.

Amelioration of cyclophosphamide-induced myelosuppression during treatment to rats with breast cancer through low-intensity pulsed ultrasound.

To investigate the alleviating effects of low-intensity pulsed ultrasound (LIPUS) on myelosuppression of Sprague-Dawley rats with breast cancer induced by cyclophosphamide (CTX). Breast cancer in rats was triggered by intragastric gavage with 7,12-dimethylbenz[a]anthracene (150 mg/kg). Then, the rats with breast cancer were randomly allocated to the LIPUS group (n=50) and the control group (n=50). The LIPUS group was injected intraperitoneally with CTX (50 mg/kg) for 4 consecutive days and underwent LIPUS treatment at femoral metaphysis 20 min per day from the first day of injection for 7 consecutive days. The control group was injected with CTX (50 mg/kg) and treated with LIPUS without energy output. Blood, enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction, Hematoxylin and Eosin (H&E) staining, and scanning electron microscopy were applied to detect the changes. The results indicated that LIPUS significantly promoted the proliferation of bone marrow nucleated cells, white blood cells (WBCs), IgA, IgG, and IgM in the peripheral blood (P<0.05) without the damage to liver and kidney function simultaneously. The mechanisms may result from the LIPUS alleviation effect on bone marrow hematopoietic function through regulating cytokines such as LIPUS can increase the expression of granulocyte colony-stimulating factor (G-CSF), stem cell factor, transforming growth factor-ß, and intercellular cell adhesion molecule-1, meanwhile LIPUS will decrease the expression of interleukin-6, tumor necrosis factor-α, and vascular cell adhesion molecule-1. LIPUS has potential to be a new adjuvant therapy method in clinic for ameliorating chemotherapy-induced myelosuppression.

Efficacy of Endoactivator, CanalBrush, and passive ultrasonic irrigation in the removal of calcium hydroxide paste with iodoform and p-chlorophenol from root canals.

AIMS: We evaluated and compared EndoActivator, CanalBrush, and passive ultrasonic irrigation (PUI) in the removal of calcium hydroxide and calcium hydroxide with iodoform and p-chlorophenol paste (Calcipast Forte) from artificial standardized grooves in the apical third of root canals. MATERIALS AND METHODS: A total of 34 mandibular premolars were prepared and then split longitudinally. A standardized groove was prepared in the apical part of both segments. The grooves were filled with either calcium hydroxide or Calcipast Forte, and the segments were reassembled. CanalBrush, EndoActivator, or PUI were used. The amount of remaining medicament was evaluated using a four-grade scoring system. RESULTS: None of the irrigation methods could completely remove the pastes from the grooves. More Calcipast Forte paste was detected compared with calcium hydroxide (P < 0.01). PUI was the least effective method in removing Calcipast Forte. CONCLUSIONS: It was more difficult to remove Calcipast Forte than a water-based calcium hydroxide paste.

Noninvasive acoustic manipulation of objects in a living body.

In certain medical applications, transmitting an ultrasound beam through the skin to manipulate a solid object within the human body would be beneficial. Such applications include, for example, controlling an ingestible camera or expelling a kidney stone. In this paper, ultrasound beams of specific shapes were designed by numerical modeling and produced using a phased array. These beams were shown to levitate and electronically steer solid objects (3-mm-diameter glass spheres), along preprogrammed paths, in a water bath, and in the urinary bladders of live pigs. Deviation from the intended path was on average <10%. No injury was found on the bladder wall or intervening tissue.

Dual-sectored transurethral ultrasound for thermal treatment of stress urinary incontinence: in silico studies in 3D anatomical models.

The purpose of this study is to investigate the feasibility and performance of a stationary, non-focused dual-sectored tubular transurethral ultrasound applicator for thermal exposure of tissue regions adjacent to the urethra for treatment of stress urinary incontinence (SUI) through acoustic and biothermal simulations on 3D anatomical models. Parametric studies in a generalized tissue model over dual-sectored ultrasound applicator configurations (acoustic surface intensities, lateral active acoustic output sector angles, and durations) were performed. Selected configurations and delivery strategies were applied on 3D pelvic anatomical models. Temperature and thermal dose distributions on the target region and surrounding tissues were calculated. Endovaginal cooling was explored as a strategy to mitigate vaginal heating. The 75-90° dual-sectored transurethral tubular transducer (3.5 mm outer diameter (OD), 14 mm length, 6.5 MHz, 8.8-10.2 W/cm2) and 2-3-min sonication duration were selected from the parametric study for acoustic and biothermal simulations on anatomical models. The transurethral applicator with two opposing 75-90° active lateral tubular sectors can create two heated volumes for a total of up to 1.8 cm3 over 60 EM43 °C, with at least 10 mm radial penetration depth, 1.2 mm urethral sparing, and no lethal damage to the vagina and adjacent bone (< 60 EM43 °C). Endovaginal cooling can be applied to further reduce the vaginal wall exposure (< 15 EM43 °C). Simulations on 3D anatomical models indicate that dual-sectored transurethral ultrasound applicators can selectively heat pelvic floor tissue lateral to the mid-urethra in short treatment durations, without damaging adjacent vaginal and bone tissues, as a potential alternative treatment option for stress urinary incontinence. Graphical abstract Schema for in silico investigation of transurethral ultrasound thermal therapy applicator for minimally invasive treatment of SUI.

Antitumor effect of VEGFR2-targeted microbubble destruction with gemcitabine using an endoscopic ultrasound probe: In vivo mouse pancreatic ductal adenocarcinoma model.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) induces cellular inflow of drugs at low intensity, while high intensity eradicates tumor vessels. Since vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), VEGFR2-targeted microbubble (MB) might additionally increase the tissue specificity of drugs and thus improve antitumor effects. In addition, fixing the dual pulse intensity could maximize MB properties. This study evaluated the one-off (experiment 1) and cumulative (experiment 2) treatment effect of UTMD by regulating the dual pulse output applied to PDAC using VEGFR2-targeted MB. METHODS: C57BL/6 mice inoculated with Pan-02 cells were allocated to five groups: VEGFR2-targeted MB+ gemcitabine (GEM), VEGFR2-targeted MB, non-targeted MB+GEM, GEM, and control groups. After injection of GEM or GEM and either VEGFR2-targeted or non-targeted MB, UTMD was applied for several minutes at low intensity followed by high intensity application. In experiment 1, mice were treated by the protocol described above and then euthanized immediately or at the tumor diameter doubling time (TDT). In experiment 2, the same protocol was repeated weekly and mice were euthanized at TDT regardless of protocol completion. Histological analysis by CD31 and VEGFR2 staining provided microvascular density (MVD) and VEGFR2 expression along vessels (VEGFR2v) or intra/peripheral cells (VEGFR2c). RESULTS: In experiment 1, TDT was significantly longer in the VEGFR2-targeted MB+GEM group compared to the non-targeted MB+GEM, GEM, and control groups, while the VEGFR2-targeted MB group showed no statistical significance. MVD and VEGFR2v in the immediate euthanasia was significantly lower in the VEGFR2-targeted MB+GEM and VEGFR2-targeted MB groups than other conditions. In experiment 2, the VEGFR2-targeted MB+GEM group produced significantly longer TDT than the GEM or control groups, whereas the VEGFR2-targeted MB group showed no significant difference. Histology revealed significantly reduced VEGFR2v and VEGFR2c in the VEGFR2-targeted and non-targeted MB+GEM groups, while only VEGFR2v was significantly less in the VEGFR2-targeted MB group. CONCLUSIONS: UTMD-mediated GEM therapy with the dual pulse application using VEGFR2-targeted MB substantially suppresses PDCA growth.

New Sm-PMN-PT Ceramic-Based 2-D Array for Low-Intensity Ultrasound Therapy Application.

A two-dimensional (2-D) array with a small pitch (approximately 0.5λ in medium) can achieve complete 3-D control of ultrasound beams without grating lobes and enable the generation of multiple focal spots simultaneously, which is a desired tool for noninvasive therapy. However, the large electrical impedance of 2-D array elements owing to their small size results in a low energy transfer efficiency between a 2-D array and an electrical system, thereby limiting their practical applications. This article presents the development of a 1-MHz 256-element 2-D array ultrasonic transducer of low electrical impedance based on a new Sm-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 (Sm-PMN-PT) piezoceramic with ultrahigh dielectric permittivity. The electrical impedance of the array element is decreased by 3.4 times as the Sm-PMN-PT replacing commercial PZT-5H. Consequently, the output acoustic pressure of the 2-D array made of Sm-PMN-PT ceramic is approximately twice that of the 2-D array made of PZT-5H ceramic under the same excitation conditions. Array elements are spaced at a 1.1-mm pitch ( 0.71λ in water), enabling a large steering range of the ultrasound beam. A multiple-target blood-brain barrier opening in vivo is demonstrated using the proposed 2-D array with electronic focusing and steering. The obtained results indicate that the 2-D array made of Sm-PMN-PT ceramic is promising for practical use in low-intensity ultrasound therapy applications.

Piezoelectric and Inversely Piezoelectric Responses of Bone Tissue Plates in the Megahertz Range.

Piezoelectricity in bone is thought to be a mechanism by which ultrasound promotes the healing of bone fractures. However, a few studies have been conducted in the more clinically relevant megahertz range. To understand the piezoelectricity in bone, we fabricated ultrasound transducers using bone samples as piezoelectric materials and identified the longitudinal ultrasound radiation and reception in the megahertz range. The maximum transmitting sensitivity of the bone transducer was 140 mPa/V, which was nearly 1/1000 of a polyvinylidene difluoride (PVDF) transducer that has better electrical properties and piezoelectricity. The resonance frequencies of the transducer depend on the plate thickness and angle between the bone axis (alignment direction of the hydroxyapatite crystallites) and ultrasound propagation direction, reflecting the anisotropic character of the bone. The reception and transmission sensitivities of the bone transducers also depend on the plate thickness and angle, showing maximum values at off-axis angles. These results indicate the existence of both piezoelectricity and inverse piezoelectricity in bone, which may be key factors in understanding the bone healing by low-intensity biophysical (electrical or mechanical) stimulation.

Intense focused ultrasound for neck and lower face skin tightening a prospective study.

BACKGROUND: Intense focused ultrasound (IFUS) is a Nonablative skin tightening technology with good safety profile, but limited efficacy. Most clinical studies have been performed to evaluate the efficacy of the Ulthera IFUS (Ulthera, Mesa, AZ) in treating redundant skin. OBJECTIVE: To report our experience with Doublo IFUS (Doublo™, HIRONIC Co.) for treating neck and lower face laxity. METHODS: This is a prospective study of 43 patients with neck and lower facial laxity treated using IFUS. Response was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 5 (75%-100% improvement). Patient's level of "sagging" and "volume loss", satisfaction and tolerance were documented. RESULTS: Nine subjects (52.9%) mentioned some improvement. Erythema and edema were acute and transient responses. CONCLUSION: Ultrasound appears to be a safe modality for facial skin tightening in selected patients with minor skin sagging and no volume discrepancy.

Real-Time Transcranial Histotripsy Treatment Localization and Mapping Using Acoustic Cavitation Emission Feedback.

Cavitation events generated during histotripsy therapy generate large acoustic cavitation emission (ACE) signals that can be detected through the skull. This article investigates the feasibility of using these ACE signals, acquired using the elements of a 500-kHz, 256-element hemispherical histotripsy transducer as receivers, to localize and map the cavitation activity in real time through the human skullcap during transcranial histotripsy therapy. The locations of the generated cavitation events predicted using the ACE feedback signals in this study were found to be accurate to within <1.5 mm of the centers of masses detected by optical imaging and found to lie to within the measured volumes of the generated cavitation events in >~80 % of cases. Localization results were observed to be biased in the prefocal direction of the histotripsy array and toward its transverse origin but were only weakly affected by focal steering location. The choice of skullcap and treatment pulse repetition frequency (PRF) were both observed to affect the accuracy of the localization results in the low PRF regime (1-10 Hz), but the localization accuracy was seen to stabilize at higher PRFs (≥10 Hz). Tests of the localization algorithm in vitro, for treatment delivered to a bovine brain sample mounted within the skullcap, revealed good agreement between the ACE feedback-generated treatment map and the morphological characteristics of the treated volume of the brain sample. Localization during experiments was achieved in real time for pulses delivered at rates up to 70 Hz, but benchmark tests indicate that the localization algorithm is scalable, indicating that higher rates are possible with more powerful hardware. The results of this article demonstrate the feasibility of using ACE feedback signals to localize and map transcranially generated cavitation events during histotripsy. Such capability has the potential to greatly simplify transcranial histotripsy treatments, as it may provide a non-MRI-based method for monitoring and localizing transcranial histotripsy treatments in real time.

Burst wave lithotripsy and acoustic manipulation of stones.

PURPOSE OF REVIEW: Burst wave lithotripsy and ultrasonic propulsion of kidney stones are novel, noninvasive emerging technologies to separately or synergistically fragment and reposition stones in an office setting. The purpose of this review is to discuss the latest refinements in technology, to update on testing of safety and efficacy, and to review future applications. RECENT FINDINGS: Burst wave lithotripsy produced consistent, small passable fragments through transcutaneous applications in a porcine model, while producing minimal injury and clinical trials are now underway. A more efficient ultrasonic propulsion design that can also deliver burst wave lithotripsy effectively repositioned 95% of stones in 18 human participants (18 of 19 kidneys) and clinical trials continue. Acoustic tractor beam technology is an emerging technology with promising clinical applications through the manipulation of macroscopic objects. SUMMARY: The goal of the reviewed work is an office-based system to image, fragment, and reposition urinary stones to facilitate their natural passage. The review highlights progress in establishing safety, effectiveness, and clinical benefit of these new technologies. The work is also anticipating challenges in clinical trials and developing the next generation of technology to improve on the technology as it is being commercialized today.