A novel scoring system based on magnetic resonance imaging for the prediction of the difficulty of ultrasound-guided high-intensity focused ultrasound ablation for uterine fibroids.

OBJECTIVE: To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. MATERIALS AND METHODS: A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model. RESULTS: Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index -0.2) +1×(abdominal wall thickness -5). CONCLUSIONS: This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.

Closed-Loop Control of Macrophage Engineering Enabled by Focused-Ultrasound Responsive Mechanoluminescence Nanoplatform for Precise Cancer Immunotherapy.

Macrophage engineering has emerged as a promising approach for modulating the anti-tumor immune response in cancer therapy. However, the spatiotemporal control and real-time feedback of macrophage regulatory process is still challenging, leading to off-targeting effect and delayed efficacy monitoring therefore raising risk of immune overactivation and serious side effects. Herein, a focused ultrasound responsive immunomodulator-loaded optical nanoplatform (FUSION) is designed to achieve spatiotemporal control and status reporting of macrophage engineering in vivo. Under the stimulation of focused ultrasound (FUS), the immune agonist encapsulated in FUSION can be released to induce selective macrophage M1 phenotype differentiation at tumor site and the near-infrared mechanoluminescence of FUSION is generated simultaneously to indicate the initiation of immune activation. Meanwhile, the persistent luminescence of FUSION is enhanced due to hydroxyl radical generation in the pro-inflammatory M1 macrophages, which can report the effectiveness of macrophage regulation. Then, macrophages labeled with FUSION as a living immunotherapeutic agent (FUSION-M) are utilized for tumor targeting and focused ultrasound activated, immune cell-based cancer therapy. By combining the on-demand activation and feedback to form a closed loop, the nanoplatform in this work holds promise in advancing the controllability of macrophage engineering and cancer immunotherapy for precision medicine.

Weighted ultrasound entropy imaging for HIFU ablation monitoring with improved sensitivity and contrast.

BACKGROUND: Although B-mode imaging has been widely used in ultrasound-guided high-intensity focused ultrasound (HIFU) treatment, challenges remain in improving its quality and sensitivity for monitoring the thermal dose. Recently, quantitative ultrasound (QUS) imaging has been recognized with the potential to better sense the changes in the microstructure of ablated tissues. PURPOSE: This study proposed to use a QUS method called weighted ultrasound entropy (WUE) imaging to monitor the HIFU ablation. METHODS: Based on ex-vivo and in-vivo experiments, WUE images reflecting tissue changes during HIFU treatment under different acoustic power levels (174-308 W) were reconstructed with a newly established imaging framework. The performance of the proposed WUE imaging in the monitoring of HIFU treatment was compared with the corresponding B-mode images in terms of their contrast-to-noise ratios (CNRs) between the focal region and the background. RESULTS: It was found that HIFU irradiation with higher power generated larger WUE values in the focal region, and the bright spots grew in size as the acoustic sonication proceeded. Compared with the in-situ B-mode images, the WUE images had higher image quality in indicating lesion formation, with a 39.2%-53.4% improvement in the CNR at different stages. Meanwhile, a correlation (R = 0.84) between the damage area estimated in WUE images and that measured from the dissected ex-vivo tissue samples was found. CONCLUSIONS: WUE imaging is more sensitive and accurate than B-mode imaging in monitoring HIFU therapy. These findings suggest that WUE imaging could be a promising technique for assisting ultrasound-guided HIFU ablation.

Case report: Sequential treatment strategy for advanced basal cell carcinoma in Gorlin-Goltz syndrome: integration of vismodegib, radiotherapy, surgery, and high-intensity focused ultrasound.

Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor's aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes.

Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults.

Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. Methods: We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Transcranial focused ultrasound (TFUS) is an emerging brain stimulation technique with the ability to noninvasively alter the activity of deep brain regions. Studying the potential for TFUS to alter behavioral response and processing, this study employed MRI-guided TFUS targeting the right amygdala in older adults. We found that TFUS targeting the right amygdala increased self-reported arousal in response to negative images, providing preliminary evidence that a single session of TFUS may be capable of affecting emotional reactivity.

Model-based navigation of transcranial focused ultrasound neuromodulation in humans: Application to targeting of the amygdala and thalamus.

BACKGROUND: Transcranial focused ultrasound (tFUS) neuromodulation has shown promise in animals but is challenging to translate to humans because of the thicker skull that heavily scatters ultrasound waves. OBJECTIVE: We develop and disseminate a model-based navigation (MBN) tool for acoustic dose delivery in the presence of skull aberrations that is easy to use by non-specialists. METHODS: We pre-compute acoustic beams for thousands of virtual transducer locations on the scalp of the subject under study. We use the hybrid angular spectrum solver mSOUND, which runs in ∼4 seconds per solve per CPU yielding pre-computation times under one hour for scalp meshes with up to 4,000 faces and a parallelization factor of 5. We combine this pre-computed set of beam solutions with optical tracking, thus allowing real-time display of the tFUS beam as the operator freely navigates the transducer around the subject' scalp. We assess the impact of MBN versus line-of-sight targeting (LOST) positioning in simulations of 13 subjects. RESULTS: Our navigation tool has a display refresh rate of ∼10 Hz. In our simulations, MBN increased the acoustic dose in the thalamus and amygdala by 8-67% compared to LOST and avoided complete target misses that affected 10-20% of LOST cases. MBN yields a lower variability of the deposited dose across subjects than LOST. CONCLUSIONS: MBN may yield greater and more consistent (less variable) ultrasound dose deposition than transducer placement with line-of-sight targeting, and thus may become a helpful tool to improve the efficacy of tFUS neuromodulation.

Initial treatment for surgery-naïve desmoid tumors by high intensity focused ultrasound.

Introduction: Desmoid tumor (DT) is a rare proliferative disease occurring in connective tissues, characterized by high infiltration and recurrence rates. While surgery remains the primary treatment, its recurrence risk is high, and some extra-abdominal desmoid tumors are inoperable due to their locations. Despite attempts with radiotherapy and systemic therapy, the efficacy remains limited. Methods: We used low-power cumulative high-intensity focused ultrasound (HIFU) therapy as an initial treatment for desmoid tumor patients either ineligible or unwilling for surgery. Low-power cumulative HIFU employs slower heat accumulation and diffusion, minimizing damage to surrounding tissues while enhancing efficacy. Results: Fifty-seven non-FAP desmoid tumor patients, previously untreated surgically, underwent low-power cumulative HIFU therapy. Among them, 35 had abdominal wall DT, 20 had extra-abdominal DT, and 2 had intra- abdominal DT, with an 85% median ablation ratio. Abdominal wall DT patients showed significantly better response rates (91.4% vs. 86%) and disease control rates (100% vs. 32%) than that of non-abdominal wall DT patients. Median event- free survival time was not reached after a median follow-up duration of 34 months. Discussion: With its high response rate, durable efficacy, and mild adverse effects, our findings suggest that low-power cumulative HIFU presents a promising novel treatment for desmoid tumors, particularly abdominal wall DT patients.

Functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS and fUS revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We saw a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with the brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV response with peak CBV, activated area, and correlation coefficient increasing with ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalizes and linearly correlates with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths and the evoked hemodynamic responses colocalized and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as an understanding of how FUS displaces brain tissue and affects cerebral hemodynamics.

Differential Analysis of Pregnancy Outcomes After Treatment of HIFU and LEEP in Patients with Cervical High-Grade Squamous Intraepithelial Lesions.

Purpose: To verify whether there is lower incidence of adverse pregnancy outcomes after high-intensity focused ultrasound (HIFU) treatment than loop electrosurgical excision procedure (LEEP) in young women of childbearing age. Patients and Methods: This retrospective cohort study enrolled 46 patients treated with HIFU and 46 patients treated with LEEP. To compare the differences between the two groups, Fisher's exact test or the Kruskal-Wallis (K-W/H) test was used in the univariate analysis, while the logistic regression method was applied for further verification. Results: Basic characteristics showed no differences between the two groups (P > 0.05) except for parity (P < 0.001). Preterm birth rates were 6.52% and 0.00% in patients with cervical high-grade squamous intraepithelial lesions (HSIL) treated with LEEP and HIFU, respectively. The incidence rates of premature rupture of membranes (PROM) were respectively 15.22% and 21.74% in the two groups. There was no significant difference in pregnancy outcomes between the two groups (P > 0.05). Conclusion: This study is the first to compare the pregnancy outcomes of patients with cervical HSIL who treated with LEEP and HIFU procedures. Both HIFU treatment and LEEP are available options for patients of reproductive age with cervical HSIL. Therefore, it is necessary to conduct prospective single-center or multicenter randomized controlled studies.

Prospective close monitoring of the effect of vascular-targeted photodynamic therapy and high intensity focused ultrasound of localized prostate cancer by multiparametric magnetic resonance imaging.

PURPOSE: The aim of this study is to describe the anatomical and functional changes observed in multiparametric magnetic resonance imaging (mpMRI) during follow-up after focal therapy (FT) for localized prostate cancer (PCa). MATERIALS AND METHODS: In this prospective study, we analyzed pre- and postoperatively acquired mpMRI of 10 patients after FT (7 days; 3, 6, 9, 12 months). 7/10 (70%) patients underwent vascular-targeted photodynamic therapy (VTP). 3/10 (30%) patients underwent high-intensity focused ultrasound (HIFU). MpMR image analysis was performed using a semi-automatic software for segmentation of the prostate gland (PG) and tumor zones. Signal intensities (SI) of T2-weighted (T2w), T1-weighted (T1w),diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) images as well as volumes of the prostate gland (PGV) and tumor volumes (TV) were evaluated at each time point. RESULTS: The results showed a significant increase of PGV 7 days after FT (p = 0.042) and a significant reduction of PGV between 7 days and 6, 9 and 12 months after FT (p < 0.001). The TV increased significantly 7 days after FT (p < 0.001) and decreased significantly between 7 days and 12 months after FT (p < 0.001). There was a significant increase in SI of the ADC in the ablation zone after 6, 9 and 12 months after FT (p < 0.001). 1/9 patients (11%) had recurrent tumor on rebiopsy characterized as a a small focal lesion on mpMRI with strong diffusion restriction (low SI on ADC map and high SI on b-value DWI). CONCLUSION: MpMRI is able to represent morphologic changes of the ablated zone after FT and might be helpful to detect recurrent tumor.

Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain.

BACKGROUND: The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. OBJECTIVE/HYPOTHESIS: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). METHODS: N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. RESULTS: Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. CONCLUSIONS: LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.

Boiling histotripsy exhibits anti-fibrotic effects in animal models of liver fibrosis.

Liver fibrosis is a hallmark of chronic liver disease which could lead to liver cirrhosis or liver cancer. However, there is currently lack of a direct treatment for liver fibrosis. Boiling histotripsy (BH) is an emerging non-invasive high-intensity focused ultrasound technique that can be employed to mechanically destruct solid tumour at the focus via acoustic cavitation without significant adverse effect on surrounding tissue. Here, we investigated whether BH can mechanically fractionate liver fibrotic tissue thereby exhibiting an anti-fibrotic effect in an animal model of liver fibrosis. BH-treated penumbra and its identical lobe showed reduced liver fibrosis, accompanied by increased hepatocyte specific marker expression, compared to the BH-untreated lobe. Furthermore, BH treatment improved serological liver function markers without notable adverse effects. The ability of BH to reduce fibrosis and promote liver regeneration in liver fibrotic tissue suggests that BH could potentially be an effective and reliable therapeutic approach against liver fibrosis.

Current state of clinical ultrasound neuromodulation.

Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.

Staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of bilateral essential tremor and Parkinson's disease related tremor: a systematic review and critical appraisal of current knowledge.

Introduction: Essential tremor (ET) and Parkinson's Disease (PD) are debilitating neurodegenerative disorders characterized by tremor as a predominant symptom, significantly impacting patients' quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Thalamotomy is an innovative therapeutic option for the treatment of unilateral medically refractory tremor with fewer adverse effects compared to traditional surgical interventions. A recent CE approval allows appropriate patients to have their second side treated. Objective: The objective of this systematic review was to analyze available current knowledge about the use of MRgFUS for the treatment of bilateral ET and PD related tremor, to identify the effectiveness and the risks associated with bilateral treatment. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from May 2014 to January 2024 and by identifying ongoing studies registered on the clinicaltrials.gov website. Data were summarized by considering the following information topics: the number of patients involved, the selected lesion target, the assessment tool used to evaluate clinical changes, the observed improvement, the reported side effects, and the time interval between the two treatments. The study was registered in PROSPERO (ID: CRD42024513178). Results: Nine studies were eligible for this review, 7 for ET and 2 for PD. The involved population included a variable number of patients, ranging from 1 to 11 subjects for ET and from 10 to 15 subjects for PD. The main lesional targets were the ventral intermediate nucleus of the thalamus, the pallidothalamic tract and the cerebellothalamic tract bilaterally. All studies investigated the tremor relief through the Clinical Rating Scale for Tremor (CRST) in patients with ET, and through the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD. A variable degree of improvement was observed, with all patients expressing overall satisfaction with the bilateral treatment. Adverse events were mild and transient, primarily involving gait disturbances, dysarthria, and ataxia. A standardized protocol for administering the two consecutive treatments was not identifiable; typically, the timing of the second treatment was delayed by at least 6 months. Conclusion: Available evidence supports the effectiveness and safety of staged bilateral MRgFUS treatments for ET and PD-related tremor.

High-Intensity Focused Ultrasound Increases Facial Adipogenesis in a Swine Model via Modulation of Adipose-Derived Stem Cell Cilia.

Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine (n = 2) via modulation of ASC cilia. Expression of CD166, an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor (AURKA), and increased expression of a cilia increasing factor (ARL13B) and PPARG and CEBPA, which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.

Suppressing the HIFU interference in ultrasound guiding images with a diffusion-based deep learning model.

BACKGROUND AND OBJECTIVES: In ultrasound guided high-intensity focused ultrasound (HIFU) surgery, it is necessary to transmit sound waves at different frequencies simultaneously using two transducers: one for the HIFU therapy and another for the ultrasound imaging guidance. In this specific setting, real-time monitoring of non-invasive surgery is challenging due to severe contamination of the ultrasound guiding images by strong acoustic interference from the HIFU sonication. METHODS: This paper proposed the use of a deep learning (DL) solution, specifically a diffusion implicit model, to suppress the HIFU interference. We considered the images contaminated with HIFU interference as low-resolution images, and those free from interference as high-resolution. While suppressing HIFU interference using the diffusion implicit (HIFU-Diff) model, the task was transformed into generating a high-resolution image through a series of forward diffusion steps and reverse sampling. A series of ex-vivo and in-vivo experiments, conducted under various parameters, were designed to validate the performance of the proposed network. RESULTS: Quantitative evaluation and statistical analysis demonstrated that the HIFU-Diff network achieved superior performance in reconstructing interference-free images under a variety of ex-vivo and in-vivo conditions, compared to the most commonly used notch filtering and the recent 1D FUS-Net deep learning network. The HIFU-Diff maintains high performance with 'unseen' datasets from separate experiments, and its superiority is more pronounced under strong HIFU interferences and in complex in-vivo situations. Furthermore, the reconstructed interference-free images can also be used for quantitative attenuation imaging, indicating that the network preserves acoustic characteristics of the ultrasound images. CONCLUSIONS: With the proposed technique, HIFU therapy and the ultrasound imaging can be conducted simultaneously, allowing for real-time monitoring of the treatment process. This capability could significantly enhance the safety and efficacy of the non-invasive treatment across various clinical applications. To the best of our knowledge, this is the first diffusion-based model developed for HIFU interference suppression.

Controlled ultrasonic interventions through the human skull.

Transcranial focused ultrasound enables precise and non-invasive manipulations of deep brain circuits in humans, promising to provide safe and effective treatments of various neurological and mental health conditions. Ultrasound focused to deep brain targets can be used to modulate neural activity directly or localize the release of psychoactive drugs. However, these applications have been impeded by a key barrier-the human skull, which attenuates ultrasound strongly and unpredictably. To address this issue, we have developed an ultrasound-based approach that directly measures and compensates for the ultrasound attenuation by the skull. No additional skull imaging, simulations, assumptions, or free parameters are necessary; the method measures the attenuation directly by emitting a pulse of ultrasound from an array on one side of the head and measuring with an array on the opposite side. Here, we apply this emerging method to two primary future uses-neuromodulation and local drug release. Specifically, we show that the correction enables effective stimulation of peripheral nerves and effective release of propofol from nanoparticle carriers through an ex vivo human skull. Neither application was effective without the correction. Moreover, the effects show the expected dose-response relationship and targeting specificity. This article highlights the need for precise control of ultrasound intensity within the skull and provides a direct and practical approach for addressing this lingering barrier.

Noninvasive Monitoring of Tissue Temperature Changes Induced by Focused Ultrasound Exposure using Sparse Expression of Ultrasonic Radio Frequency Echo Signals.

Background: Noninvasive therapies such as focused ultrasound were developed to be used for cancer therapies, vessel bleeding, and drug delivery. The main purpose of focused ultrasound therapy is to affect regions of interest (ROI) of tissues without any injuries to surrounding tissues. In this regard, an appropriate monitoring method is required to control the treatment. Methods: This study is aimed to develop a noninvasive monitoring technique of focused ultrasound (US) treatment using sparse representation of US radio frequency (RF) echo signals. To this end, reasonable results in temperature change estimation in the tissue under focused US radiation were obtained by utilizing algorithms related to sparse optimization as orthogonal matching pursuit (OMP) and accompanying Shannon's entropy. Consequently, ex vivo tissue experimental tests yielded two datasets, including low-intensity focused US (LIFU) and high-intensity focused US (HIFU) data. The proposed processing method analyzed the ultrasonic RF echo signal and expressed it as a sparse signal and calculated the entropy of each frame. Results: The results indicated that the suggested approach could noninvasively estimate temperature changes between 37°C and 47°C during LIFU therapy. In addition, it represented temperature changes during HIFU ablation at various powers, ranging from 10 to 130 W. The normalized mean square error of the proposed method is 0.28, approximately 2.15 on previous related methods. Conclusion: These results demonstrated that this novel proposed approach, including the combination of sparsity and Shanoon's entropy, is more feasible and effective in temperature change estimation than its predecessors.

Sonodynamic therapy for adult-type diffuse gliomas: past, present, and future.

BACKGROUND: Intra-axial brain tumors persist as significant clinical challenges. Aggressive surgical resection carries risk of morbidity, and the blood-brain barrier (BBB) prevents optimal pharmacological interventions. There is a clear clinical demand for innovative and less invasive therapeutic strategies for patients, especially those that can augment established treatment protocols. Focused ultrasound (FUS) has emerged as a promising approach to manage brain tumors. Sonodynamic therapy (SDT), a subset of FUS, utilizes sonosensitizers activated by ultrasound waves to generate reactive oxygen species (ROS) and induce tumor cell death. OBJECTIVE: This review explores the historical evolution and rationale behind SDT, focusing on its mechanisms of action and potential applications in brain tumor management. METHOD: A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Preclinical studies have demonstrated the efficacy of various sonosensitizers, including 5-aminolevulinic acid (5-ALA), fluorescein, porphyrin derivatives, and nanoparticles, in conjunction with FUS for targeted tumor therapy and BBB disruption. Clinical trials have shown promising results in terms of safety and efficacy, although further research is needed to fully understand the potential adverse effects and optimize treatment protocols. Challenges such as skull thickness affecting FUS penetration, and the kinetics of BBB opening require careful consideration for the successful implementation of SDT in clinical practice. Future directions include comparative studies of different sonosensitizers, optimization of FUS parameters, and exploration of SDT's immunomodulatory effects. CONCLUSION: SDT represents a promising frontier in the treatment of aggressive brain tumors, offering hope for improved patient outcomes.

Effect of High-Intensity Focused Ultrasound on Different Types of Adenomyosis Based on Magnetic Resonance Imaging Classification.

OBJECTIVE: We aimed to analyze the effect of high-intensity focused ultrasound (HIFU) on different types of adenomyosis (AM) based on magnetic resonance imaging (MRI) classification. METHODS: A total of 206 AM patients who underwent HIFU between January 2017 and December 2021 were included in this retrospective study. The size and location of AM were evaluated based on T2-weighted imaging (T2WI) of MRI. Patients were divided into internal (subtype I), external (subtype II), intramural (subtype III), and full-thickness (subtype IV) AM groups. All patients underwent an MRI examination before and one day after HIFU. After ultrasound-guided HIFU ablation, the parameters of ultrasonic energy input during HIFU treatment among different groups were recorded and compared. The adverse reactions and complications among different groups were compared. RESULTS: The lesion volume in the subtype IV group was significantly larger than the subtype II and III groups (P < .05). The HIFU irradiation time, treatment time, and total energy input in the subtype IV group were significantly higher than the subtype I and III groups (P < .05). The number of cases of abdominal pain and vaginal fluid in the treatment area in the subtype IV group was significantly higher than in the subtype II group. CONCLUSION: Although HIFU has different treatment strategies and parameters for different subtypes of AM, it can achieve a satisfactory ablation rate, which is safe and effective.