Focused Ultrasound Research Articles

Stable acoustic levitation based on coaxial confocal dual-frequency focused ultrasound and vortex beams.

Objective: Low-intensity, pulsed, focused ultrasound (FUS) combined with the local injection of phase-change perfluorocarbon droplets can mechanically disrupt the canine prostate; however, long-term observation of prostate shrinkage is lacking. This study aimed to develop an acoustic-responsive scaffold (ARS) to limit the washing out of droplets and achieve long-term observation of treated prostates. Method: A spherical single-element FUS transducer provided therapeutic ultrasound (US). The ARS consisted of sodium alginate and perfluoropentane emulsion. Subsequently, 18 male beagles were treated with FUS and local prostate injection of the ARS at different levels of peak negative pressure (PNP) (1.5–4.1 MPa). The long-term observation was a 1-month follow-up. US imaging and pathological examination were used to assess treatment. Results: US imaging showed that the bubble cloud produced in the P4.1 (PNP = 4.1 MPa) group exhibited stronger echoes and a larger range compared with the other groups, and it persisted for > 72 h. Gross and hematoxylin and eosin (H&E) staining showed that the total area of prostate damage was significantly larger and the damage ratio was significantly higher in the P4.1 group than in the other groups. Prostate volumes significantly decreased 1 month after FUS treatment, from 6.57 ± 0.92 cm³ to 4.84 ± 0.15 cm³. H&E staining revealed atrophy of the prostate tissue in the target area, reduced glandular cavities, and decreased glandular cells. Conclusion: In conclusion, at a PNP of 4.1 MPa, FUS and ARS not only cause mechanical damage to prostate tissues but also lead to a significant 20.8% reduction in prostate volume at the 1-month follow-up.

Paclitaxel (PTX), a widely-used chemotherapeutic agent, exhibits a high rate of plasma protein binding, which severely limits its bioavailability and reduces therapeutic efficacy. This study explored a novel strategy using low-intensity, non-thermal focused ultrasound (FUS) to locally disrupt PTX-albumin binding, thereby enhancing drug delivery and tumoricidal efficacy at tumor sites without increasing systemic toxicity. We applied sonication (600 kHz) with varying pulse durations and duty cycles to OVCAR3 cell constructs in vitro and identified the parameters that maximally enhanced PTX uptake and induced tumor cell death. Intracellular PTX concentrations and cell viability were quantified across the conditions. The optimized FUS parameters were then applied to a mouse xenograft model of ovarian cancer using athymic nu/nu mice. Luciferase-expressing OVCAR3 tumor growth was longitudinally monitored using bioluminescence imaging. The sonication parameters (70% duty cycle and 100 ms pulse duration), applied using 3 W/cm2 spatial peak temporal average intensity, optimally enhanced intracellular PTX uptake and increased cell death, independent of thermal or flow-related effects. In vivo, a single FUS treatment nearly doubled intratumoral PTX levels, without altering serum concentration. Repeated FUS sessions combined with PTX treatments over two weeks significantly suppressed tumor growth, compared to no treatment, PTX alone, or FUS alone. Histological analysis in PTX-treated groups showed that FUS did not cause additional damage to the liver, kidney, or surrounding tissues, nor did it affect peripheral blood markers of liver and kidney function. FUS can reversibly unbind PTX from albumin, increasing its bioavailability specifically at tumor sites. This targeted approach enhances chemotherapeutic effectiveness without elevating systemic toxicity or causing off-target damage, highlighting FUS as a promising adjuvant strategy for improving anticancer drug delivery in solid tumors.

Malignant brain tumors remain a major therapeutic challenge due to poor intracellular delivery of therapeutics. Radiopharmaceuticals such as Technetium-99m (^99mTc) are valuable for imaging and therapy but suffer from limited tumor uptake caused by cellular and membrane barriers. Focused ultrasound (FUS) offers a noninvasive strategy to transiently enhance membrane permeability through sonoporation. Unlike prior studies largely focused on blood-brain barrier disruption, this work specifically investigates direct tumor cell sonoporation as an independent uptake mechanism. This study evaluates FUS-mediated enhancement of ^99mTc radiopharmaceutical uptake in brain tumor cells and determines optimal acoustic parameters balancing efficacy and safety. Human glioblastoma (U87-MG) and astrocytoma (A172) cells were cultured and exposed to FUS at intensities of 0.3, 0.5, and 0.7 W/cm2 for 30-120 s. Radiopharmaceutical uptake was quantified using γ-scintillation counting. Membrane integrity was assessed by live/dead fluorescence microscopy and lactate dehydrogenase release, while cell viability was evaluated via medical training therapy (MTT) assays. U87-MG cells exhibited up to a 3.1-fold increase at 0.7 W/cm2 for 120 s, with a 2.3-fold enhancement at the clinically relevant 0.5 W/cm2 for 60 s while maintaining >92% viability. A172 cells showed similar trends with slightly lower magnitudes. Safety assays confirmed reversible membrane permeabilization at ≤0.5 W/cm2. The temporal uptake kinetics aligned with established membrane pore resealing dynamics, supporting reversible sonoporation as the uptake mechanism. Importantly, while ^99mTc complexes are primarily diagnostic, enhanced intracellular delivery achieved by optimized FUS may also support future theranostic strategies, including radionuclide therapy. These findings underscore the translational potential of FUS in neuro-oncology, where tumor heterogeneity necessitates parameter optimization to maximize radiopharmaceutical delivery, improve imaging contrast, and overcome therapeutic resistance.

Background:Minimally invasive facial laxity treatments, such as thread lifts and high-intensity focused ultrasound (HIFU), are increasingly popular in Asia, but standardized guidelines are lacking. Treatment outcomes are often subjective and heavily dependent on the physician’s expertise. Earlier studies indicate that facial soft tissue shifts significantly between supine and seated positions in cases of laxity. This study aimed to objectively evaluate facial laxity improvements after thread lift and HIFU treatments in Asians.Methods:Photographs of 143 Japanese individuals (mean age, 41.0 ± 15.5 y; mean body mass index, 21.2 ± 3.2 kg/m2) taken between February and May 2024 were analyzed. Frontal and lateral facial measurements in both seated and supine positions were compared across untreated, HIFU, and thread lift groups using ImageJ software. Statistical significance was determined using t tests with a threshold value of P less than 0.05.Results:The soft tissue shifts were measured as 20.8% (SD = 19.4) in untreated, 20.7% (SD = 14.1) in HIFU, and 14.1% (SD = 11.6) in thread lift groups for frontal views. Lateral views showed shifts of 41.4% (SD = 20.9), 38.2% (SD = 20.7), and 33.4% (SD = 23.2), respectively. Significant reductions in tissue movement were observed in the thread lift group (frontal, P = 0.0092; lateral, P = 0.02) but not in the HIFU treatment group.Conclusions:Thread lifting significantly reduces facial tissue movement between seated and supine positions, indicating superior efficacy in preventing facial laxity. This study underscored the importance of assessing facial laxity in the seated position to accurately gauge treatment effects.

Focused ultrasound (FUS) combined with microbubbles (MBs) represents a noninvasive, targeted approach for transiently opening the blood–brain barrier (BBB). While higher MB concentrations can enhance BBB permeability, they also raise the risk of adverse effects such as erythrocyte extravasation. In this study, acoustic vortex (AV) manipulation of MBs was integrated with FUS-mediated BBB opening. The results demonstrated that dispersed MBs could be effectively clustered by an AV tweezer in multi-well plates. Compared with FUS applied to dispersed MBs, the combination of AV, FUS, and MBs required lower acoustic pressure, achieved higher BBB opening efficiency, and elicited significantly stronger stable cavitation. In addition, both pore density and size on cell membranes were greater in the AV + FUS + MB group relative to the FUS + MB group. Importantly, temperature elevation was minimal and cell viability was preserved. These findings suggest that combining FUS with MB clusters trapped by an AV tweezer offers a promising and efficient strategy for BBB opening.

Achieving reliable, on‐demand targeted drug release in dynamic environments such as the gastrointestinal tract remains a critical challenge. Here, we introduce a hollow two‐photon polymerized microrobot whose ports are sealed by a mechanically interlocked heneicosane wax cap within a suspended microgrid, retaining seal integrity during locomotion in biologically relevant environments. In vitro, microrobots loaded with doxorubicin remained stable at body temperature (37°C) and exhibited complete, step‐like discharge within 1 min once the bath temperature crossed the 40–42°C threshold. Guided by an integrated magnetic and robotic ultrasound system, microrobots were introduced rectally and navigated in vivo to the distal colon of anesthetized rats and visualized in real time. Focused ultrasound (FUS) heating to 42°C triggered on‐demand release of an echogenic nanoparticle tracer, producing a distinct contrast plume. No release occurred before reaching the targeted release temperature, underscoring the design's high thermal specificity and leakage‐free performance at body temperature. Therapeutic relevance was demonstrated in an inflammatory‐bowel‐disease cell model: doxorubicin‐filled microrobots reduced MDA‐MB‐231 viability below the projected LC50 value after 72 h. Together, the heneicosane cap and the noninvasive FUS thermal trigger enable leakage‐free storage, real‐time navigation, and spatially confined drug release in vivo, advancing untethered microrobotic delivery toward clinically actionable, colon‐targeted therapies.

Perfluorocarbon nanotechnologies for blood-brain barrier modulation: Enhancing drug delivery and neuroprotection.

Objective.Although less established than transcranial focused ultrasound (FUS), transvertebral FUS is being developed to treat spinal cord pathologies. Transvertebral sonication of the spinal cord for microbubble-mediated drug delivery generates cavitation at the target in the spinal canal, and outside the spinal canal due to reflection off the posterior surface of the spinal column. In these two regions, circulating microbubbles are excited by local foci to generate acoustic emissions that are used to monitor FUS treatments. When trying to localize acoustic emissions generated from cavitation in the spinal cord, prefocal cavitation emissions emanating from paraspinal regions can dwarf signals originating in the canal and compromising monitoring capabilities. This paper evaluates alternative reconstruction algorithms to delay-sum-and-integrate (DAS)in-silicoandex-vivoto more reliably map intra-spinal canal sources in the face of interference.Approach.A proof-of-concept 400/800 kHz (transmit/receive) spine-specific array prototype was used to generate intracanal cavitation through intact human vertebrae and passively monitor the corresponding acoustic emissions. Delay-multiply-sum-and-integrate (DMAS) beamforming was compared to DAS in two different implementations, full array (DMAS) and half-array multiplicative compounding (DMASMu), in the modeled cavitation scenarios where paraspinal cavitation is present.Main results.Both DMAS and DMASMu improved image quality by reducing peak sidelobes and increasing image signal-to-noise ratio. Aberration corrections further improved image quality metrics and, when applied selectively to voxels co-registered to the canal, assisted localization when prefocal sources were presentin-silico. When localizing canal sources in the presence of paraspinal cavitation, a switch to DMAS/DMASMu offered a more consistent localization ratein-silicoandex-vivo, thoughex-vivophase and amplitude corrections failed to replicatein-silicofindings.Significance.DMAS or DMASMu reconstruction with multiple dynamic ranges and sub-image integration timings can provide more reliable mapping of cavitation in the canal in the presence of interference from paraspinal cavitation.

Volumetric printing is an emerging additive manufacturing technique that builds 3D constructs with enhanced printing speed and surface quality by forgoing the stepwise ink renewal. Existing volumetric printing techniques almost exclusively rely on light energy to trigger photopolymerization in transparent inks, limiting the material choice, build size, cell density and in vivo printability. Sonicated ink (or sono-ink) and focused-ultrasound (FUS) writing have been developed for deep-penetration acoustic volumetric printing (DAVP) within optically scattering media and beneath soft tissues. This technology uses rapid sono-thermal heating to induce material solidification at the FUS focal region, constructing 3D objects without the need for a build platform. Here, we describe two procedures necessary to achieve DAVP. First, we provide a step-by-step guide for preparing and characterizing multicomponent viscoelastic self-enhancing sono-inks. The lower critical solution temperature polymers are synthesized as a phase-transition reversible acoustic absorber to formulate the sono-inks. We characterize the rheological, acoustic and cytocompatibility properties of the sono-inks. We then detail the procedure for building a 3D FUS printer by integrating an FUS transducer with a 3D printing platform. The development of the 3D FUS printer needs basic knowledge of the ultrasound system, FUS physics and volumetric printing. Using the sono-inks and the 3D FUS printer, we further provide guidance to evaluate the sono-thermal heating effect and characterize the volumetric printing resolutions. We demonstrate the printing of volumetric constructs through optically scattering materials such as centimeter-thick biological tissues. The procedures require ~470 h to complete.

Objective To compare the effects of focused ultrasound (FUS) and loop electrosurgical excision procedure (LEEP) on cervical morphology and elasticity after treatment of cervical squamous intraepithelial lesions (SILs). Methods Eighty-one patients with histologically confirmed SILs (42 FUS vs. 39 LEEP) were prospectively evaluated. FUS ablation was performed using the CZF-2 device (Haifu® Medical, 3.5 MHz). LEEP followed ASCCP guidelines with resection margins ≥5 mm beyond lesions. Serial transvaginal ultrasound measurements (cervical length/width/volume) were conducted at baseline and 3/6 months postoperatively. Results At 3–6 months after surgery, the high-risk human papilloma virus (HR-HPV) clearance rate and high-grade SIL cure rate were similar in the FUS and LEEP groups (p > 0.05). Cervical length, width, anterior-posterior diameter, and volume did not significantly change after FUS (p > 0.003125). All 4 dimensions were significantly reduced after LEEP (p < 0.003125). These morphological alterations were greater in the LEEP group (p < 0.05). Strain rates at the internal and external os, and anterior-posterior lips did not significantly change after FUS (p > 0.05). After LEEP, strain rates slightly decreased at the internal and external os (1.02 ± 1.00 vs. 0.79 ± 0.69, p > 0.05) and significantly decreased at the anterior-posterior lips (1.43 ± 1.34 vs. 0.97 ± 0.93; p < 0.05). Conclusion FUS and LEEP demonstrate comparable efficacy in treating HR-HPV-associated SILs. Initial observations suggest that FUS impacts cervical morphology and elasticity less than does LEEP, implying an advantage of FUS for fertility preservation, although the long-term fertility outcomes require further investigation.

Microvascular and astrocytic responses to repeated magnetic resonance-guided focused ultrasound.

Comparison of mechanical and thermal effects of focused ultrasound on drug delivery efficiency and toxicity for pancreatic cancer treatment.

Study of heat transfer and flow within atherosclerotic plaques in a focused ultrasound field.

A multifunctional theranostic ultrasound platform for remote magnetogenetics and expanded blood-brain barrier opening.

Brain thermal response to low intensity focused ultrasound at the action potential level and neuron response to various stimulus.

While passive acoustic mapping (PAM) has been advanced for monitoring acoustic cavitation activity in focused ultrasound (FUS) therapy, achieving both real-time and high-quality imaging capabilities is still challenging. The angular spectrum (AS) method presents the most efficient algorithm for PAM, but it suffers from artifacts and low resolution due to the diffraction pattern of the imaging array. Data-adaptive beamformers suppress artifacts well, but their overwhelming computational complexity, more than two orders of magnitude higher than the classical time exposure acoustic (TEA) method, hinders their application in real time. In this work, we introduce the cross-correlated AS method to address the challenge. This method is based on cross-correlating the AS back-propagated wave fields, in the frequency domain (FD), measured by different apodized subapertures of the transducer array to provide the normalized cross-correlation coefficient (NCC) matrix for artifacts suppression. We observed that the spatial pattern of NCC matrix is variable, which can be utilized by the triple apodization with cross correlation (TAX) with AS scheme, namely, the AS-TAX method, for optimal artifacts suppression outcomes. Both the phantom and mouse tumor experiments showed that: 1) the AS-TAX method has comparable image quality as the data-adaptive beamformers, reducing the energy spread area (ESA) by 34.8%-65.0% and improving image signal-to-noise ratio (ISNR) by 10.6-14.4 dB compared to TEA; 2) it reduces the computational complexity by two orders of magnitude compared to TEA allowing millisecond-level image reconstruction speed with a parallel implementation; and 3) it can well map microbubble cavitation activity of different status (stable or inertial). The AS-TAX method represents a real-time approach to monitor cavitation-based FUS therapy with high image quality.

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignances with a 5-year survival rate at around 13%. This dismal prognosis is, in part, due to the dense desmoplastic stroma and low vascularity of PDAC tumors, leading to inefficient uptake of therapeutics. The combination of FDA-approved ultrasound contrast agents called microbubbles (MBs), and focused ultrasound (FUS) has the potential to increase drug uptake in PDAC tumors. Our team has developed a novel therapeutic that loads antisense oligonucleotides (ASOs) onto MBs for targeted drug delivery in vivo. The ASOs have been designed to target the pre-mRNA transcript of Negative Elongation Factor E (NELFE), a protein that is upregulated in multiple tumor types, including PDAC. In vitro ASO-only treatment was sufficient in significantly reducing cell proliferation, cell migration, and colony formation in three PDAC cell lines. To investigate the effects of ASO+MBs+FUS treatment in vivo, we performed intrapancreatic orthotopic injections of KPC-4662 cells derived from the KPC mouse model (LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre) into C57BL/6 mice and recorded tumor growth over time using bioluminescence imaging. Once tumors were established, we performed 6 rounds of ASO+MBs+FUS treatment across a 2-week timespan. Mice treated with ASO+MBs+FUS had a significant reduction in tumor burden and increased overall survival compared to mice treated with MBs+FUS alone. In conclusion, targeting NELFE using ASO+MBs+FUS can be a potential therapeutic strategy for PDAC patients. Citation Format: Brittany N. Ruiz, Alvaro Lucci, Laura M. Reynolds, Pongsakorn Choochuen, Corinne Wessner, Christine Wiktor, Sarah Hynd, Christoph Eckert, Meghan Grim, Avinoam Nevler, Harish Lavu, Charles Yeo, Matthias M. Gaida, Elda Grabocka, John Eisenbrey, Hien Dang. Targeting NELFE using antisense oligonucelotides reduces tumor burden and increases overall survival in vivo [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B033.

Accurate targeting during MR-guided focused ultrasound (FUS) procedures is essential for effective treatment to be achieved. However, spatial discrepancies frequently arise between the planned target and the observed thermal hotspot on proton resonance frequency (PRF)-based MR thermometry because of temperature-induced artifacts. This study aims to correct such displacements caused by chemical shift and k-space center offset. Spatial misregistration was addressed using a two-step correction approach. The first step corrected pixel-wise displacements attributed to temperature-dependent resonance frequency shifts (chemical shift), based on local frequency offset maps. The second step compensated for TE errors induced by asymmetric phase gradients near the thermal focus, restoring accuracy in hotspot localization. Validation was performed in controlled phantom experiments, and the approach was retrospectively tested in vivo, in 121 sonications across seven essential tremor (ET) patients. Phantom experiments demonstrated that spatial shifts up to approximately 1.5 mm could be effectively corrected. Clinical analysis showed a strong correlation (R2 = 0.852) between temperature rise and spatial displacement, with a mean shift of 0.5 Mm per 10°C. Combined correction significantly reduced temperature estimation bias, with the mean error decreasing from -0.11°C to -0.05°C, as evaluated by Bland-Altman analysis. Temperature-related chemical shift and k-space offset substantially impact the spatial fidelity of PRF-based MR thermometry. The proposed correction framework improves thermal hotspot localization, enabling more accurate lesion targeting during FUS procedures.

Focused ultrasound (FUS) is currently in the limelight of veterinary medicine as a novel treatment modality for companion animals, offering significant benefits over traditional techniques. In this study, the safety, feasibility, and efficacy of FUS for the treatment of various spontaneous canine and feline tumours was investigated. Dogs and cats diagnosed with naturally occurring tumours were recruited in the study based on certain eligibility criteria. Fifteen dogs and cats with superficial tumours at various anatomical locations including the belly, chest, shoulder, rump, and neck were enrolled. Treated tumours in pets were mammary, sarcoma, pressure-point comedones and lipoma. Tumours in enrolled pets were treated using an in-house Magnetic Resonance Imaging guided FUS (MRgFUS) robotic system integrating a 2.75MHz single-element spherically focused transducer. Partial FUS ablations were delivered to targeted tumours using sonication protocols tailored to tumour volume and location. Following FUS, the tumours were surgically excised and sent for histological examination. FUS treatments were well-tolerated with no significant adverse events or off-target damages, with only one canine case experiencing mild erythema and superficial skin ulceration at the treated site. Haematoxylin and Eosin (H&E)-stained slides revealed that well-demarcated areas of coagulative necrosis were effectively achieved at the targeted FUS regions in all treated cases. Study findings demonstrate that FUS can be safely used for the management of various types of spontaneous canine and feline tumours, highlighting the promising potential of the technology as a valuable and versatile therapeutic approach for veterinary cancer patients.