This review resulted from a conference on the pathological role of arterial chemoreflex and carotid bodies in cardiometabolic diseases held at the 27th Congress of the Polish Cardiac Society in September 2023 in Poznan, Poland. It reflects the contribution of Polish researchers and their international collaborations, which have been fundamental in the development of the field. Aberrant activity of the carotid bodies leads to both high tonicity and increased sensitivity of the arterial chemoreflex with resultant sympathoexcitation in chronic heart failure, resistant hypertension and obstructive sleep apnoea. This observation has led to several successful attempts of removing or denervating the carotid bodies as a therapeutic option in humans. Regrettably, such interventions are accompanied by serious respiratory and acid-base balance side-effects. Rather than a single stereotyped reaction, arterial chemoreflex comprises an integrative multi-system response to a variety of stimulants and its specific reflex components may be individually conveyed at varying intensities. Recent research has revealed that carotid bodies express diverse receptors, synthesize a cocktail of mediators, and respond to a plethora of metabolic, hormonal and autonomic nervous stimuli. This state-of-the-art summary discusses exciting new discoveries regarding GLP-1 receptors, purinergic receptors, the glutamate-GABA system, efferent innervation and regulation of blood flow in the carotid body and how they open new avenues for novel pharmacological treatments selectively targeting specific receptors, mediators and neural pathways to correct distinct responses of the carotid body-evoked arterial chemoreflex in cardiometabolic diseases. The carotid body offers novel and advantageous therapeutic opportunities for future consideration by trialists.

Sonodynamic therapy, which combines a tumor cell-selective sonosensitizer with ultrasound, is gaining attention as a promising new treatment approach for glioblastoma. The objective of this case study is to report on the first applications of 5-aminolevulinic acid (5-ALA) in combination with low-intensity, non-targeted ultrasound as neo-adjuvant treatment in therapy naïve glioblastoma.

Three patients with therapy naïve newly diagnosed glioblastoma were treated once before cytoreductive surgery with 5-ALA in combination with hemispheric, low-intensity, non-targeted ultrasound, assuming cell death to be triggered by non-ablative activation of 5-ALA-induced, tumor selective porphyrins.

No adverse effects were noted. Post-procedural MRI indicated a decrease in apparent diffusion coefficient values in tumors, suggesting cytotoxic effects. Relative cerebral blood volumes and leakage were increased for two patients with available perfusion imaging. Tissue obtained during surgery suggested increased cleaved-caspase III expression, a marker of apoptosis.

We saw an immediate marked imaging response indicating cytotoxic edema and indications of a histopathology response from just a single treatment. Correlation to clinical outcomes and extension of overall survival remains to be seen. A Phase 1 safety study has been submitted for regulatory approval.

Acoustic metasurfaces are two-dimensional architected materials designed to enable non-trivial control of waves, with a thickness that is either thinner than or comparable to the wavelength. However, most metasurfaces today have a fixed geometry and lack the ability to tune acoustic waves on command. This limits their ability to perform multiple functions, such as beam steering and dynamic focusing. This study introduces inflatable acoustic metasurface (IAM) lenses that enable tunable focusing. The IAMs feature two-dimensional diffractive focusing patterns embedded in a membrane that can be inflated nonplanarly through hydraulic control. It is experimentally demonstrated that inflation allows continuous focal length adjustment from -2.49λ to +3.17λ. To characterize the lens performance, changes in focal characteristics, including peak pressure, full width at half-maximum, and full length at half-maximum, are tracked at different levels of inflation. Furthermore, it is shown that IAMs can correct aberrations that occur as the angle of incidence increases in conventional planar lenses. To validate this, IAMs were tested in a concave configuration at a 20° oblique incidence angle. The results of this study may be applicable to fields requiring continuous and real-time response in tunable focusing, including acoustic imaging and communication, ultrasound surgery, and neuromodulation.

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is involved in motor abnormality, primarily arising from the degeneration of dopaminergic neurons. Previous studies have examined the electrotherapeutic effects of PD using various methodological contexts, including live conditions, wireless control, diagnostic/therapeutic aspects, removable interfaces, or biocompatible materials, each of which is separately utilized for testing the diagnosis or alleviation of various brain diseases. Here, a cortical surface implant designed to improve motor function in freely moving PD animals is presented. This implant, a minimally invasive system equipped with a graphene electrode array, is the first integrated system to exhibit biocompatibility, wearability, removability, target specificity, and wireless control. The implant positioned at the motor cortical surface activates the motor cortex to maximize therapeutic effects and minimize off-target effects while monitoring motor activities. In PD animals, cortical motor surface stimulation restores motor function and brain waves, which corresponds to potentiated synaptic responses. Furthermore, these changes are associated with the upregulation of metabotropic glutamate receptor 5 (mGluR5, Grm5) and D5 dopamine receptor (D5R, Drd5) genes in the glutamatergic synapse. The newly designed wireless neural implant demonstrates capabilities in both real-time diagnostics and targeted therapeutics, suggesting its potential as a wireless system for biomedical devices for patients with PD and other neurodegenerative diseases.

Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, affects millions worldwide, with a significant proportion resistant to pharmacological treatments. Surgical interventions have emerged as pivotal in managing drug-resistant epilepsy (DRE), aiming to reduce seizure frequency or achieve seizure freedom. Traditional resective surgeries have evolved with technological advances, enhancing precision and safety. Neurostimulation techniques, such as responsive neurostimulation (RNS) and deep brain stimulation (DBS), now provide personalized, real-time seizure management, offering alternatives to traditional surgery. Minimally invasive ablative methods, such as laser interstitial thermal therapy (LITT) and Magnetic Resonance-guided Focused Ultrasound (MRgFUS), allow for targeted destruction of epileptogenic tissue with reduced risks and faster recovery times. The use of stereo-electroencephalography (SEEG) and robotic assistance has further refined surgical precision, enhancing outcomes. These advancements mark a paradigm shift towards precision medicine in epilepsy care, promising improved seizure management and quality of life for patients globally. This review outlines the latest innovations in epilepsy surgery, emphasizing their mechanisms and clinical implications to improve outcomes for patients with DRE.

Invasive open surgery used to be compulsory to access tumor mass to perform excision or resection. Development of minimally invasive laparoscopic procedures followed, as well as catheter-based approaches, such as stenting, endovascular surgery, chemoembolization, brachytherapy, which minimize side effects and reduce the risks to patients. Completely noninvasive procedures bring further benefits in terms of reducing risk, procedure time, recovery time, potential of infection, or other side effects. Focusing ultrasound waves from the outside of the body specifically at the disease site has proven to be a safe noninvasive approach to localized ablative hyperthermia, mechanical ablation, and targeted drug delivery. Focused ultrasound as a medical intervention was proposed decades ago, but it only became feasible to plan, guide, monitor, and control the treatment procedures with advanced radiological imaging capabilities. The purpose of this review is to describe the imaging capabilities and approaches to perform these tasks, with the emphasis on magnetic resonance imaging and ultrasound. Some procedures already are in clinical practice, with more at the clinical trial stage. Imaging is fully integrated in the workflow and includes the following: (1) planning, with definition of the target regions and adjacent organs at risk; (2) real-time treatment monitoring via thermometry imaging, cavitation feedback, and motion control, to assure targeting and safety to adjacent normal tissues; and (3) evaluation of treatment efficacy, via assessment of ablation and physiological parameters, such as blood supply. This review also focuses on sonosensitive microparticles and nanoparticles, such as microbubbles injected in the bloodstream. They enable ultrasound energy deposition down to the microvascular level, induce vascular inflammation and shutdown, accelerate clot dissolution, and perform targeted drug delivery interventions, including focal gene delivery. Especially exciting is the ability to perform noninvasive drug delivery via opening of the blood-brain barrier at the desired areas within the brain. Overall, focused ultrasound under image guidance is rapidly developing, to become a choice noninvasive interventional radiology tool to treat disease and cure patients.

Drug-resistant epilepsy (DRE) secondary to hypothalamic hamartoma (HH) often requires surgical resection or stereotactic radiosurgery, which frequently fail to provide satisfactory outcomes and are associated with severe side effects. Magnetic resonance-guided focused ultrasound (MRgFUS) may represent a minimally invasive surgical approach to HH by offering precise thermal ablation of sub-millimetric brain targets while sparing surrounding structures.

We present the case of a 19-year-old man with HH-associated DRE, who was successfully treated with MRgFUS. The procedure resulted in effective ablation of the hypothalamic interface of the HH, disconnecting the epileptogenic lesion from the surrounding brain tissue. We also reviewed the literature on MRgFUS for DRE.

The patient experienced a complete resolution of seizures and significant improvements in social and occupational functioning over an 18-month follow-up period. No neurological, cognitive, or endocrinological adverse effects were observed.

Our case report and literature review suggest that MRgFUS may achieve adequate seizure control in DRE associated with HH without adverse effects. While MRgFUS shows promise for other forms of DRE, data remain preliminary, and some safety concerns persist. Further studies with long-term follow-up are warranted to better support the use of MRgFUS in DRE.

Background/Objectives: Combining radiation therapy with mild hyperthermia, especially via magnetic resonance-guided focused ultrasound (MRgFUS), holds promise for enhancing tumor control and alleviating symptoms in cancer patients. However, current clinical applications of MRgFUS focus primarily on ablative treatments, and using MRI guidance for each radiation session increases treatment costs and logistical demands. This study aimed to test a streamlined workflow for repeated hyperthermia treatments that reduces the need for continuous MRI monitoring, using an approach based on impulse response function (Green's function) to optimize acoustic power settings in advance. Methods: We implemented the Green's function approach in a perfused, tissue-mimicking phantom, conducting 30 experiments to simulate hyperthermia delivery via MRgFUS. Pre-calculated acoustic power settings were applied to maintain a stable hyperthermia target without the need for real-time feedback control from MRI thermometry. Additionally, a retrospective analysis of patient thermometry data from MRgFUS sonications was performed to assess feasibility in clinical contexts. Results: Our experiments demonstrated consistent, stable hyperthermia (+7 °C) for 15 min across varying perfusion rates, outperforming conventional closed-loop MRI feedback methods in maintaining temperature stability. The retrospective analysis confirmed that this method is noise-robust and clinically applicable. Conclusions: This off-line approach to hyperthermia control could simplify the integration of MRgFUS hyperthermia in cancer treatment, reducing costs and logistical barriers. These findings suggest that our method may enable the broader adoption of hyperthermia in radiation therapy, supporting its role as a viable adjuvant treatment in oncology.

Precise and individualized targeting of the ventral intermediate thalamic nucleus for the MR-guided focused ultrasound is crucial for enhancing treatment efficacy and avoiding undesirable side effects. In this study, we tested the hypothesis that the spatial relationships between Thalamus Optimized Multi Atlas Segmentation derived segmentations and the post-focused ultrasound lesion can predict post-operative side effects in patients treated with MR-guided focused ultrasound.

We retrospectively analyzed 30 patients (essential tremor, n = 26; tremor-dominant Parkinson's disease, n = 4) who underwent unilateral ventral intermediate thalamic nucleus focused ultrasound treatment. We created ROIs of coordinate-based indirect treatment target, focused ultrasound-induced lesion, and thalamus and ventral intermediate thalamic nucleus segmentations. We extracted imaging features including 1) focused ultrasound-induced lesion volumes, 2) overlap between lesions and thalamus and ventral intermediate thalamic nucleus segmentations, 3) distance between lesions and ventral intermediate thalamic nucleus segmentation and 4) distance between lesions and the indirect standard target. These imaging features were compared between patients with and without post-operative gait/balance side effects using Wilcoxon rank-sum test. Multivariate prediction models of side effects based on the imaging features were evaluated using the receiver operating characteristic analyses.

Patients with self-reported gait/balance side effects had a significantly larger extent of focused ultrasound-induced edema, a smaller fraction of the lesion within the ventral intermediate thalamic nucleus segmentation, a larger fraction of the off-target lesion outside the thalamus segmentation, a more inferior centroid of the lesion from the ventral intermediate thalamic nucleus segmentation, and a larger distance between the centroid of the lesion and ventral intermediate thalamic nucleus segmentation (p < 0.05). Similar results were found for exam-based side effects. Multivariate regression models based on the imaging features achieved areas under the curve of 0.99 (95% CI: 0.88 to 1.00) and 0.96 (95% CI: 0.73 to 1.00) for predicting self-reported and exam-based side effects, respectively.

Thalamus Optimized Multi Atlas Segmentation-based patient-specific segmentation of the ventral intermediate thalamic nucleus can predict post-operative side effects, which has implications for aiding the direct targeting of MR-guided focused ultrasound and reducing side effects.

Ultrasound is well-perceived for its diagnostic application. Meanwhile, ultrasound, especially focused ultrasound (FUS), has also demonstrated therapeutic capabilities, such as thermal tissue ablation, hyperthermia, and mechanical tissue ablation, making it a viable therapeutic approach for cancer treatment. Cancer immunotherapy is an emerging cancer treatment approach that boosts the immune system to fight cancer, and it has also exhibited enhanced effectiveness in treating previously considered untreatable conditions. Currently, cancer immunotherapy is regarded as one of the four pillars of cancer treatment because it has fewer adverse effects than radiation and chemotherapy. In recent years, the unique capabilities of FUS in ablating tumors, regulating the immune system, and enhancing anti-tumor responses have resulted in a new field of research known as FUS-induced/assisted cancer immunotherapy. In this work, we provide a comprehensive overview of this new research field by introducing the basics of focused ultrasound and cancer immunotherapy and providing the state-of-the-art applications of FUS in cancer immunotherapy: the mechanisms and preclinical and clinical studies. This review aims to offer the scientific community a reliable reference to the exciting field of FUS-induced/assisted cancer immunotherapy, hoping to foster the further development of related technology and expand its medical applications.

Within medical imaging, ultrasound serves as a crucial tool, particularly in the realms of brain imaging and disease diagnosis. It offers superior safety, speed, and wider applicability compared to Magnetic Resonance Imaging (MRI) and X-ray Computed Tomography (CT). Nonetheless, conventional transcranial ultrasound applications in adult brain imaging face challenges stemming from the significant acoustic impedance contrast between the skull bone and soft tissues. Recent strides in ultrasound technology encompass a spectrum of advancements spanning tissue structural imaging, blood flow imaging, functional imaging, and image enhancement techniques. Structural imaging methods include traditional transcranial ultrasound techniques and ultrasound elastography. Transcranial ultrasound assesses the structure and function of the skull and brain, while ultrasound elastography evaluates the elasticity of brain tissue. Blood flow imaging includes traditional transcranial Doppler (TCD), ultrafast Doppler (UfD), contrast-enhanced ultrasound (CEUS), and ultrasound localization microscopy (ULM), which can be used to evaluate the velocity, direction, and perfusion of cerebral blood flow. Functional ultrasound imaging (fUS) detects changes in cerebral blood flow to create images of brain activity. Image enhancement techniques include full waveform inversion (FWI) and phase aberration correction techniques, focusing on more accurate localization and analysis of brain structures, achieving more precise and reliable brain imaging results. These methods have been extensively studied in clinical animal models, neonates, and adults, showing significant potential in brain tissue structural imaging, cerebral hemodynamics monitoring, and brain disease diagnosis. They represent current hotspots and focal points of ultrasound medical research. This review provides a comprehensive summary of recent developments in brain imaging technologies and methods, discussing their advantages, limitations, and future trends, offering insights into their prospects.

Brain tumor treatment presents challenges for patients and clinicians, with prognosis for many of the most common brain tumors being poor. Focused ultrasound (FUS) can be deployed in several ways to circumvent these challenges, including the need to penetrate the blood-brain barrier and spare healthy brain tissue. This article reviews current FUS applications within neuro-oncology, emphasizing ongoing or recently completed clinical trials.

Most clinical interest in FUS for neuro-oncology remains focused on exploring BBB disruption to enhance the delivery of standard-of-care therapeutics. More recently, the application of FUS for radiosensitization, liquid biopsy, and sonodynamic therapy is garnering increased clinical attention to assist in tumor ablation, early detection, and phenotypic diagnosis. Preclinical studies show encouraging data for the immunomodulatory effects of FUS, but these findings have yet to be tested clinically.

FUS is a burgeoning area of neuro-oncology research. Data from several forthcoming large clinical trials should help clarify its role in neuro-oncology care.

In the realm of high-intensity focused ultrasound (HIFU) therapy, the precise prediction of lesion size during treatment planning remains a challenge, primarily due to the difficulty in quantitatively assessing energy deposition at the target site and the acoustic properties of the tissue through which the ultrasound wave propagates. This study investigates the hypothesis that the echo amplitude originating from the focus is indicative of acoustic attenuation and is directly related to the resultant lesion size. Echoes from multi-layered tissues, specifically porcine tenderloin and bovine livers, with varying fat thickness from 0 mm to 35 mm were collected using a focused ultrasound (FUS) transducer operated at a low power output and short duration. Subsequent to HIFU treatment under clinical conditions, the resulting lesion areas in the ex vivo tissues were meticulously quantified. A novel treatment strategy that prioritizes treatment spots based on descending echo amplitudes was proposed and compared with the conventional raster scan approach. Our findings reveal a consistent trend of decreasing echo amplitudes and HIFU-induced lesion areas with the increasing fat thickness. For porcine tenderloin, the values decreased from 2541.7 ± 641.9 mV and 94.4 ± 17.9 mm2 to 385(342.5) mV and 24.9 ± 18.7 mm2, and for bovine liver, from 1406(1202.5) mV and 94.4 ± 17.9 mm2 to 502.1 ± 225.7 mV and 9.4 ± 6.3 mm2, respectively, as the fat thickness increases from 0 mm to 35 mm. Significant correlations were identified between preoperative echo amplitudes and the HIFU-induced lesion areas (R = 0.833 and 0.784 for the porcine tenderloin and bovine liver, respectively). These correlations underscore the potential for an accurate and dependable prediction of treatment outcomes. Employing the proposed treatment strategy, the ex vivo experiment yielded larger lesion areas in bovine liver at a penetration depth of 8 cm compared to the conventional approach (58.84 ± 17.16 mm2 vs. 44.28 ± 15.37 mm2, p < 0.05). The preoperative echo amplitude from the FUS transducer is shown to be a reflective measure of acoustic attenuation within the wave propagation window and is closely correlated with the induced lesion areas. The proposed treatment strategy demonstrated enhanced efficiency in ex vivo settings, affirming the feasibility and accuracy of predicting HIFU-induced lesion size based on echo amplitude.

High intensity focused ultrasound (HIFU) is a non-invasive therapy that induces heat in a small, localized volume of cancerous tissue without damaging neighbouring vital structures and cells. Precise targeting and treatment monitoring is typically achieved by pairing HIFU with an imaging modality such as magnetic resonance imaging (MRI). The most commonly used MRI pulse sequence for detecting HIFU thermal lesions is the T2-weighted fast spin echo (T2W-FSE) pulse sequence as it provides good contrast between normal and coagulated tissue. The drawbacks of the T2W-FSE pulse sequence are the manifestation of ringing artifacts and the loss of spatial resolution due to the signal modulation in k-space caused by the T2 decay. The inverse Fourier transform (IFT) multiplication scheme aims to remove the signal modulation by incorporating an inverse filter, which is an inverse of the signal modulation trend present in the k-space, to reduce the effects of T2 decay and improve image quality. In this study, four inverse filters (named as regular, narrow, wide, and compound) were developed and implemented on T2W-FSE MR images of ex vivo porcine muscle tissue with HIFU induced thermal lesion using a 0.55 T benchtop MRI research system (Pure Devices, Rimpar, Germany). Offline processing and enhancement of MR images of ex vivo porcine muscle tissue with HIFU induced thermal lesion using the narrow filter yielded the largest improvements of 13.8 ± 2.5 %, 17.0 ± 2.3 %, and 14.4 ± 1.1 % in lateral and axial spatial resolutions, and lesion signal-to-noise ratio (SNR), respectively, compared to the original images. Our results indicate an amplification of the signals in k-space and a reduction in the exponential signal modulation caused by T2 decay. These results also indicate the potential of the IFT multiplication scheme as an image processing method to improve thermal lesion detectability in MR-guided HIFU procedures.

Prostate cancer (PCa) is a prevalent malignancy in men, and the management of localized disease has evolved significantly in recent years. Focal therapy, wherein the biopsy confirmed site of tumor with margins is treated leaving the remaining gland intact, has emerged as a promising strategy for treating localized clinically significant PCa, minimizing side effects associated with radical therapies. We present the technical aspects, a summary of the most relevant evidence to date on the performance and safety of this technique, and the characteristic MR imaging findings during treatment, in the early posttreatment period and in the long term.

Proton resonance frequency shift (PRFS) MR thermometry is the most common method used in clinical thermal treatments because of its fast acquisition and high sensitivity to temperature. However, motion is the biggest obstacle in PRFS MR thermometry for monitoring thermal treatment in moving organs. This challenge arises because of the introduction of phase errors into the PRFS calculation through multiple methods, such as image misregistration, susceptibility changes in the magnetic field, and intraframe motion during MRI acquisition. Various approaches for motion correction have been developed for real-time, motion-robust, and volumetric MR thermometry. However, current technologies have inherent trade-offs among volume coverage, processing time, and temperature accuracy. These tradeoffs should be considered and chosen according to the thermal treatment application. In hyperthermia treatment, precise temperature measurements are of increased importance rather than the requirement for exceedingly high temporal resolution. In contrast, ablation procedures require robust temporal resolution to accurately capture a rapid temperature rise. This paper presents a comprehensive review of current cutting-edge MRI techniques for motion-robust MR thermometry, and recommends which techniques are better suited for each thermal treatment. We expect that this study will help discern the selection of motion-robust MR thermometry strategies and inspire the development of motion-robust volumetric MR thermometry for practical use in clinics.

Artificial intelligence (AI) has emerged as a powerful tool in the field of neurology, significantly impacting the diagnosis and treatment of neurological disorders. Recent technological breakthroughs have given us access to a plethora of information relevant to many aspects of neurology. Neuroscience and AI share a long history of collaboration. Along with great potential, we encounter obstacles relating to data quality, ethics, and inherent difficulty in applying data science in healthcare. Neurological disorders pose intricate challenges due to their complex manifestations and variability. Automating image interpretation tasks, AI algorithms accurately identify brain structures and detect abnormalities. This accelerates diagnosis and reduces the workload on medical professionals. Treatment optimization benefits from AI simulations that model different scenarios and predict outcomes. These AI systems can currently perform many of the sophisticated perceptual and cognitive capacities of biological systems, such as object identification and decision making. Furthermore, AI is rapidly being used as a tool in neuroscience research, altering our understanding of brain functioning. It has the ability to revolutionize healthcare as we know it into a system in which humans and robots collaborate to deliver better care for our patients. Image analysis activities such as recognizing particular brain regions, calculating changes in brain volume over time, and detecting abnormalities in brain scans can be automated by AI systems. This lessens the strain on radiologists and neurologists while improving diagnostic accuracy and efficiency. It is now obvious that cutting-edge artificial intelligence models combined with high-quality clinical data will lead to enhanced prognostic and diagnostic models in neurological illness, permitting expert-level clinical decision aids across healthcare settings. In conclusion, AI's integration into neurology has revolutionized diagnosis, treatment, and research. As AI technologies advance, they promise to unravel the complexities of neurological disorders further, leading to improved patient care and quality of life. The symbiosis of AI and neurology offers a glimpse into a future where innovation and compassion converge to reshape neurological healthcare. This abstract provides a concise overview of the role of AI in neurology and its transformative potential.

High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement.

The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging.

Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%.

The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.

Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax, etc.) at the bedside. Over the past decade, advancements in technology have led to the use of ultrasound waves in treating many neurological conditions, such as essential tremor and Parkinson's disease, with high specificity. The convergence of ultrasound waves at a specific region of interest/target while avoiding surrounding tissue has led to the coined term "focused ultrasound (FUS)." In tumor research, ultrasound technology was initially used as an intraoperative guidance tool for tumor resection. However, in recent years, there has been growing interest in utilizing FUS as a therapeutic tool in the management of brain tumors such as gliomas. This mini-review highlights the current knowledge surrounding using FUS as a treatment modality for gliomas. Furthermore, we discuss the utility of FUS in enhanced drug delivery to the central nervous system (CNS) and highlight promising clinical trials that utilize FUS as a treatment modality for gliomas.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an "incisionless" treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data.

A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018-December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review.

The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature.

We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years.

Focused ultrasound (FUS) is a minimally invasive treatment that utilizes high-energy ultrasound waves to thermally ablate tissue. Magnetic resonance imaging (MRI) guidance may be combined with FUS (MRgFUS) to increase its accuracy and has been proposed for lung tumor ablation/debulking. However, the lungs are predominantly filled with air, which attenuates the strength of the FUS beam. This investigation aimed to test the feasibility of a new approach using an intentional lung collapse to reduce the amount of air inside the lung and a controlled hydrothorax to create an acoustic window for transcutaneous MRgFUS lung ablation. Eleven pigs had one lung mechanically ventilated while the other lung underwent a controlled collapse and subsequent hydrothorax of that hemisphere. The MRgFUS lung ablations were then conducted via the intercostal space. All the animals recovered well and remained healthy in the week following the FUS treatment. The location and size of the ablations were confirmed one week post-treatment via MRI, necropsy, and histological analysis. The animals had almost no side effects and the skin burns were completely eliminated after the first two animal studies, following technique refinement. This study introduces a novel methodology of MRgFUS that can be used to treat deep lung parenchyma in a safe and viable manner.

Ablative surgery using bilateral anterior capsulotomy (BAC) is an option for treatment resistant depression (TRD) and obsessive-compulsive disorder (TROCD). The location and extent of the lesion within anterior limb of the internal capsule (ALIC) remains uncertain. Accumulating evidence has suggested that the lesion should be located ventrally while limiting the dorsal extent. Our center is now targeting specific fiber tracts within the lower half of the ALIC.

Presurgical diffusion tensor Magnetic Resonance Imaging (MRI) was used to identify individual fibre tracts within the ventral aspect of the ALIC in the last two patients who underwent BAC at our center. One patient had TRD and the other had both TROCD and TRD. Radiofrequency-induced thermal lesions were created in the identified targets with lesion volumes between 20 and 229 mm3 (average 95 mm3).

Both patients were responders with neither experiencing significant side effects including compromised executive functions.

The generalizability of our findings is limited because the outcome is based on two subjects.

This work suggests that BAC can be individually tailored and more limited to the ventral aspect of the ALIC and is effective and safe for TRD and TROCD. Accumulating data also suggests that to be clinically effective the length of the capsulotomy should be about 10mm. BAC's use may increase with the growing utilization and mastery of magnetic resonance guided focused ultrasound.

Tissue-mimicking phantoms (TMPs) have been used extensively in clinical and nonclinical settings to simulate the thermal effects of focus ultrasound (FUS) technology in real tissue or organs. With recent technological developments in the FUS technology and its monitoring/guided techniques such as ultrasound-guided FUS and magnetic resonance-guided FUS (MRgFUS) the need for TMPs are more important than ever to ensure the safety of the patients before being treated with FUS for a variety of diseases (e.g., cancer or neurological). The purpose of this study was to prepare a tumor-mimicking phantom (TUMP) model that can simulate competently a tumor that is surrounded by healthy tissue.

The TUMP models were prepared using polyacrylamide (PAA) and agar solutions enriched with MR contrast agents (silicon dioxide and glycerol), and the thermosensitive component bovine serum albumin (BSA) that can alter its physical properties once thermal change is detected, therefore offering real-time visualization of the applied FUS ablation in the TUMPs models. To establish if these TUMPs are good candidates to be used in thermoablation, their thermal properties were characterized with a custom-made FUS system in the laboratory and a magnetic resonance imaging (MRI) setup with MR-thermometry. The BSA protein's coagulation temperature was adjusted at 55°C by setting the pH of the PAA solution to 4.5, therefore simulating the necrosis temperature of the tissue.

The experiments carried out showed that the TUMP models prepared by PAA can change color from transparent to cream-white due to the BSA protein coagulation caused by the thermal stress applied. The TUMP models offered a good MRI contrast between the TMPs and the TUMPs including real-time visualization of the ablation area due to the BSA protein coagulation. Furthermore, the T2-weighted MR images obtained showed a significant change in T2 when the BSA protein is thermally coagulated. MR thermometry maps demonstrated that the suggested TUMP models may successfully imitate a tumor that is present in soft tissue.

The TUMP models developed in this study have numerous uses in the testing and calibration of FUS equipment including the simulation and validation of thermal therapy treatment plans with FUS or MRgFUS in oncology applications.

Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

Harmonic motion imaging (HMI) is an acoustic radiation force-based elasticity imaging technique, which can be used to monitor changes in tissue mechanical properties caused by focused ultrasound (FUS)-induced thermal ablation. In conventional HMI, the amplitude-modulated FUS sequence and imaging pulse are transmitted simultaneously. With this method, the high-amplitude FUS signal must be separated from the imaging data for tissue displacement estimation. Frequency domain notch filtering and bandpass filtering were previously used to filter FUS interference from imaging data. However, FUS interference becomes more pronounced at the increased intensities and durations necessary for thermal ablation, rendering frequency domain filtering challenging. In this study, three methods for FUS interference filtering during HMI-guided FUS ablation (HMIgFUS) were compared. The methods were notch filtering; interleaved HMIgFUS, with interleaved FUS and imaging pulses; and FUS-net, a convolutional neural network-based U-Net autoencoder developed by our group for FUS interference filtering in radiofrequency data. FUS-net was applied here for the first time for the purpose of ablation displacement monitoring.

The three filtering methods were tested during 20 HMIgFUS acquisitions in an ex vivo canine liver using a range of peak positive pressures from 11 to 18 MPa and durations ranging from 60 to 180 seconds. The B-mode mean squared errors (MSEs) and displacement amplitude contrast-to-noise ratios (CNRs) of the three methods were calculated and compared.

The interleaved method for HMIgFUS was found to be significantly robust in avoiding FUS interference in all tested cases for FUS ablation monitoring, especially cases with high FUS pressure and long durations, as opposed to traditional notch filtering and FUS-net filtering. CNRs obtained from displacement amplitude maps in the interleaved data set were significantly higher in all cases than those obtained from the notch filtered and FUS-net data sets. There was not a significant trend in displacement CNR between the FUS-net and notch filtered data sets. However, B-mode MSE was found to be significantly higher when comparing the FUS-net and interleaved data sets as opposed to the notch filtered and interleaved data sets, suggesting further potential of FUS-net as an FUS interference filtering method.

These findings indicate the robustness of interleaved HMIgFUS in avoiding FUS interference during HMIgFUS monitoring and the advantages, limitations and future potential of FUS-net and notch filtering.

Focused ultrasound (FUS) is emerging as one of the most promising, non-invasive treatment techniques. The advancement of transducer technology has paved the way for dermatological applications. A comprehensive review is presented for healthcare practitioners and researchers, summarizing the effect of various operational parameters on the injury zone produced by ultrasound beams for various dermatological applications, which include skin tightening, fat reduction, hyperpigmentation and cancer treatment. In this article, we aim to highlight the efficient operational parameters of FUS to enhance pain relief during surgery and its affordability for skin treatment. Finally, a prospective future technique for efficient FUS is discussed.

The potential improvement in sonication efficiency achieved by tilting the focused ultrasound (FUS) transducer of the transcranial MR-guided FUS system is presented. A total of 56 cases of patient treatment data were used. The relative position of the clinical FUS transducer to the patient's head was reconstructed, and region-specific skull density and porosity were calculated based on the patient's CT volume image. The total transmission coefficient of acoustic waves emitted from each channel was calculated. Then, the total energy penetrating the human skull-which represents the sonication efficiency-was estimated. As a result, improved sonication efficiency was by titling the FUS transducer to a more appropriate angle achieved in all 56 treatment cases. This simulation result suggests the potential improvement in transcranial-focused ultrasound treatment by simply adjusting the transducer angle.

Ultrasonic therapy is an increasingly promising approach for the treatment of seizures and drug-resistant epilepsy (DRE). Therapeutic focused ultrasound (FUS) uses thermal or nonthermal energy to either ablate neural tissue or modulate neural activity through high- or low-intensity FUS (HIFU, LIFU), respectively. Both HIFU and LIFU approaches have been investigated for reducing seizure activity in DRE, and additional FUS applications include disrupting the blood-brain barrier in the presence of microbubbles for targeted-drug delivery to the seizure foci. Here, we review the preclinical and clinical studies that have used FUS to treat seizures. Additionally, we review effective FUS parameters and consider limitations and future directions of FUS with respect to the treatment of DRE. While detailed studies to optimize FUS applications are ongoing, FUS has established itself as a potential noninvasive alternative for the treatment of DRE and other neurological disorders.

One big challenge with high intensity focused ultrasound (HIFU) is the difficulty in accurate prediction of focal location due to the complex wave propagation in heterogeneous medium even with imaging guidance. This study aims to overcome this by combining therapy and imaging guidance with one single HIFU transducer using the vibro-acoustography (VA) strategy.

Based on the VA imaging method, a HIFU transducer consisting of 8 transmitting elements was proposed for therapy planning, treatment and evaluation. Inherent registration between the therapy and imaging created unique spatial consistence in HIFU transducer's focal region in the above three procedures. Performance of this imaging modality was first evaluated through in-vitro phantoms. In-vitro and ex-vivo experiments were then designed to demonstrate the proposed dual-mode system's ability in conducting accurate thermal ablation.

Point spread function of the HIFU-converted imaging system had a full wave half maximum of about 1.2 mm in both directions at a transmitting frequency of 1.2 MHz, which outperformed the conventional ultrasound imaging (3.15 MHz) in in-vitro situation. Image contrast was also tested on the in-vitro phantom. Various geometric patterns could be accurately 'burned out' on the testing objects by the proposed system both in vitro and ex vivo.

Implementation of imaging and therapy with one HIFU transducer in this manner is feasible and it has potential as a novel strategy for addressing the long-standing problem in the HIFU therapy, possibly pushing this non-invasive technique forward towards wider clinical applications.

Two cases involving patients diagnosed with localized prostate cancer and treated with MRI-guided focal therapies are presented. Patient selection procedures, techniques, outcomes, challenges, and future directions of MRI-guided focal therapies, as well as their role in the treatment of low- to intermediate-risk localized prostate cancer, are summarized.

High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement.

The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging.

Comparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

We introduce a non-invasive MR-Acoustic Radiation Force Imaging (ARFI)-based elastography method that provides both the local shear modulus and temperature maps for the monitoring of High Intensity Focused Ultrasound (HIFU) therapy.

To take tissue anisotropy into account, the local shear modulus μ is determined in selected radial directions around the focal spot by fitting the phase profiles to a linear viscoelastic model, including tissue-specific mechanical relaxation time τ. MR-ARFI was evaluated on a calibrated phantom, then applied to the monitoring of HIFU in a gel phantom, ex vivo and in vivo porcine muscle tissue, in parallel with MR-thermometry.

As expected, the shear modulus polar maps reflected the isotropy of phantoms and the anisotropy of muscle. In the HIFU monitoring experiments, both the shear modulus polar map and the thermometry map were updated with every pair of MR-ARFI phase images acquired with opposite MR-ARFI-encoding. The shear modulus was found to decrease (phantom and ex vivo) or increase (in vivo) during heating, before remaining steady during the cooling phase. The mechanical relaxation time, estimated pre- and post-HIFU, was found to vary in muscle tissue.

MR-ARFI allowed for monitoring of viscoelasticity changes around the HIFU focal spot even in anisotropic muscle tissue.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies.

This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging.

The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure.

The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel noninvasive interventional technique for osteoid osteoma (OO). The purpose of this study was to evaluate the efficacy and safety of MRgFUS in the treatment of OO through a systematic review and meta-analysis of pain scores and post-treatment adverse events before and after MRgFUS treatment.

A comprehensive literature search of PubMed, Embase, Web of science, and Cochrane Library databases was conducted to screen the study literature based on inclusion and exclusion criteria to extract and analyze pre- and post-treatment pain score data, success rates (complete pain relief with no recurrence until the last follow-up), recurrence rates, secondary intervention rates, and complications to evaluate the efficacy and/or safety of MRgFUS for OO.

A total of 113 studies published between 2012 and 2022were collected, resulting in a total sample size of 353 patients. The majority of the studies were prospective and had a follow-up period of 4 weeks or more, and overall, the quality of evidence ranged from low to high. Pain scores at 1 week and 1 month after the merger were 0.62 (9.5% CI:0.28-0.96) and 0.37 (9.5% CI:0.07-0.68), respectively. The success rate of the combination was 92.8% (95% CI: 89.8%-95.7%), the incidence of minor complications (thermal injury at the ablation site) was 0.85%, and no major complications were recorded in any of the included literature.

MRgFUS is an effective procedure that is able to treat pain for patients with OO with satisfying efficacy and safety.

No.CRD42023415573.

Transcranial focused ultrasound (tFUS) is a therapeutic ultrasound method that focuses sound through the skull to a small region noninvasively and often under magnetic resonance imaging (MRI) guidance. CT imaging is used to estimate the acoustic properties that vary between individual skulls to enable effective focusing during tFUS procedures, exposing patients to potentially harmful radiation. A method to estimate acoustic parameters in the skull without the need for CT is desirable.

We synthesized CT images from routinely acquired T1-weighted MRI using a 3D patch-based conditional generative adversarial network and evaluated the performance of synthesized CT (sCT) images for treatment planning with tFUS. We compared the performance of sCT with real CT (rCT) images for tFUS planning using Kranion and simulations using the acoustic toolbox, k-Wave. Simulations were performed for 3 tFUS scenarios: (1) no aberration correction, (2) correction with phases calculated from Kranion, and (3) phase shifts calculated from time reversal.

From Kranion, the skull density ratio, skull thickness, and number of active elements between rCT and sCT had Pearson's correlation coefficients of 0.94, 0.92, and 0.98, respectively. Among 20 targets, differences in simulated peak pressure between rCT and sCT were largest without phase correction (12.4 % ± 8.1 % ) and smallest with Kranion phases (7.3 % ± 6.0 % ). The distance between peak focal locations between rCT and sCT was < 1.3    mm for all simulation cases.

Real and synthetically generated skulls had comparable image similarity, skull measurements, and acoustic simulation metrics. Our work demonstrated similar results for 10 testing cases comparing MR-sCTs and rCTs for tFUS planning. Source code and a docker image with the trained model are available at https://github.com/han-liu/SynCT_TcMRgFUS.

Leiomyomas, or uterine fibroids, are growths consisting of muscle and tissue that develop in or on the uterine wall. The most frequent benign uterine tumours in women of reproductive age are thought to be fibroids. Dysmenorrhea, spotting, hypermenorrhoea, abdominal pain, pressure on surrounding organs, and issues with micturition and defecation are among the symptoms that are often present. Fibroids can form as a single nodule or as a cluster. Uterine fibroids, especially large submucosal and intramural uterine fibroids, can cause obstacles to implantation and lead to pregnancy loss. Uterine fibroids can be treated without surgery and with little downtime using focused ultrasound. There is published research showing that women can conceive and have healthy children after therapy, thus protecting fertility. The ablation of uterine fibroids by high-intensity focused ultrasound (HIFU) is successful since the volume of the fibroids is significantly reduced.

Essential Tremor (ET) is one of the most common tremor syndromes typically presented as action tremor, affecting mainly the upper limbs. In at least 30-50% of patients, tremor interferes with quality of life, does not respond to first-line therapies and/or intolerable adverse effects may occur. Therefore, surgery may be considered.

In this review, the authors discuss and compare unilateral ventral intermedius nucleus deep brain stimulation (VIM DBS) and bilateral DBS with Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy, which comprises focused acoustic energy generating ablation under real-time MRI guidance. Discussion includes their impact on tremor reduction and their potential complications. Finally, the authors provide their expert opinion.

DBS is adjustable, potentially reversible and allows bilateral treatments; however, it is invasive requires hardware implantation, and has higher surgical risks. Instead, MRgFUS is less invasive, less expensive, and requires no hardware maintenance. Beyond these technical differences, the decision should also involve the patient, family, and caregivers.

Sonosensitive high-boiling point perfluorocarbon F₈TAC₁₈-PFOB emulsions previously exhibited thermal enhancement during focused ultrasound heating in ex vivo pig livers, kidneys and a laminar flow phantom. The main objectives of this study were to evaluate heating under turbulent conditions, observe perfusion effects, quantify heating in terms of acoustic absorption and model the experimental data.

In this study, similar perfluorocarbon emulsions were circulated at incremental concentrations of 0.07, 0.13, 0.19 and 0.25% v:v through a percolated turbulent flow phantom, more representative of the biological tissue than a laminar flow phantom. The concentrations represent the droplet content in only the perfused fluid, rather than the droplet concentration throughout the entire cross-section. The temperature was measured with magnetic resonance thermometry, during focused ultrasound sonications of 67 W, 95% duty cycle and 33 s duration. These were used in Bioheat equation simulations to investigate in silico the thermal phenomena. The temperature change was compared with the control condition by circulating de-gassed and de-ionized water through the flow phantom without droplets.

With these 1.24 µm diameter droplets at 0.25% v:v, the acoustic absorption coefficient increased from 0.93 ± 0.05 at 0.0% v:v to 1.82 ± 0.22 m^-1 at 0.25% v:v using a 0.1 mL s^-1 flow rate. Without perfusion at 0.25% v:v, an increase was observed from 1.23 ± 0.07 m^-1 at 0.0% v:v to 1.65 ± 0.17 m^-1.

The results further support previously reported thermal enhancement with F₈TAC₁₈-PFOB emulsion, quantified the increased absorption at small concentration intervals, illustrated that the effects can be observed in a variety of visceral tissue models and provided a method to simulate untested scenarios.

To facilitate practical medical applications such as cancer treatment utilizing focused ultrasound and bubbles, a mathematical model that can describe the soft viscoelasticity of human body, the nonlinear propagation of focused ultrasound, and the nonlinear oscillations of multiple bubbles is theoretically derived and numerically solved. The Zener viscoelastic model and Keller-Miksis bubble equation, which have been used for analyses of single or few bubbles in viscoelastic liquid, are used to model the liquid containing multiple bubbles. From the theoretical analysis based on the perturbation expansion with the multiple-scales method, the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation, which has been used as a mathematical model of weakly nonlinear propagation in single phase liquid, is extended to viscoelastic liquid containing multiple bubbles. The results show that liquid elasticity decreases the magnitudes of the nonlinearity, dissipation, and dispersion of ultrasound and increases the phase velocity of the ultrasound and linear natural frequency of the bubble oscillation. From the numerical calculation of resultant KZK equation, the spatial distribution of the liquid pressure fluctuation for the focused ultrasound is obtained for cases in which the liquid is water or liver tissue. In addition, frequency analysis is carried out using the fast Fourier transform, and the generation of higher harmonic components is compared for water and liver tissue. The elasticity suppresses the generation of higher harmonic components and promotes the remnant of the fundamental frequency components. This indicates that the elasticity of liquid suppresses shock wave formation in practical applications.

Focused ultrasound is a novel technique for the treatment of aggressive brain tumors that uses both mechanical and thermal mechanisms. This non-invasive technique can allow for both the thermal ablation of inoperable tumors and the delivery of chemotherapy and immunotherapy while minimizing the risk of infection and shortening the time to recovery. With recent advances, focused ultrasound has been increasingly effective for larger tumors without the need for a craniotomy and can be used with minimal surrounding soft tissue damage. Treatment efficacy is dependent on multiple variables, including blood-brain barrier permeability, patient anatomical features, and tumor-specific features. Currently, many clinical trials are currently underway for the treatment of non-neoplastic cranial pathologies and other non-cranial malignancies. In this article, we review the current state of surgical management of brain tumors using focused ultrasound.