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.

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.

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.

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.

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.

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.

Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study.

OBJECTIVES: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. RESULTS: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). CONCLUSIONS: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.

Long-term safety and efficacy of focused ultrasound capsulotomy for obsessive-compulsive disorder and major depressive disorder.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluate the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). METHODS: This phase I single center open label study recruited treatment-resistant OCD and MDD. Outcomes were measured 6mo, 12mo, and 18-24months (long-term) after MRgFUS capsulotomy. Neuropsychological testing and neuroimaging were conducted at baseline and 12mo postoperatively. The primary outcome was safety. The secondary outcome was clinical response, defined for OCD as ≥35% improvement in Yale-Brown obsessive-compulsive scale (YBOCS) scores, and for MDD as a ≥50% reduction in the Hamilton Depression Rating Scale (HAMD-17) scores, compared to baseline. RESULTS: No serious adverse effects were registered. In patients with OCD (n=15), baseline YBOCS scores (31.9±1.2) were significantly reduced by 23% (p=0.01) at 6mo and 35% (p<0.0001) at 12mo. In patients with MDD (n=12), a 26% and 25% non-significant reduction in HAMD-17 scores (baseline 24.3±1.2) was observed at 6mo and 12mo, respectively. Neuropsychological testing revealed no negative effects of capsulotomy. In the OCD and MDD cohorts we found a correlation between clinical outcome and lesion laterality, with more medial left (OCD, p=0.08) and more lateral right (MDD, p<0.05) placed lesions being respectively associated with a stronger response. In the MDD cohort, more ventral tracts appeared to be associated with a poorer response. CONCLUSIONS: MRgFUS capsulotomy is safe in patients with OCD and MDD and particularly effective in the former population.

Integrating High-intensity Focused Ultrasound with Chemotherapy for the Treatment of Invasive Hydatidiform Mole in Reproductive-age Women.

Invasive hydatidiform mole, a form of gestational trophoblastic neoplasm in reproductive-age women, poses a significant threat to life due to its associated signs and symptoms. This case report details the management of a 24-year-old Chinese woman with no prior pregnancy history, who presented at our hospital 23 days postcurettage, experiencing persistent vaginal bleeding for 3 days. While two rounds of chemotherapy effectively reduced human chorionic gonadotropin levels, a subsequent magnetic resonance imaging (MRI) revealed suspicious growth lesions in the uterus. High-intensity focused ultrasound (HIFU) treatment was administered under ultrasound guidance, resulting in notable grayscale changes to optimize the efficacy of chemotherapy and restrict lesion progression. Subsequent ultrasound and MRI assessments during follow-up demonstrated a transparent texture in the muscle layer at the lesion site. This case suggests that the combination of chemotherapy and HIFU, guided by ultrasound, may represent a promising therapeutic approach for managing invasive hydatidiform mole.

Focused ultrasound-induced cell apoptosis for the treatment of tumours.

Cancer is a serious public health problem worldwide. Traditional treatments, such as surgery, radiotherapy, chemotherapy, and immunotherapy, do not always yield satisfactory results; therefore, an efficient treatment for tumours is urgently needed. As a convenient and minimally invasive modality, focused ultrasound (FUS) has been used not only as a diagnostic tool but also as a therapeutic tool in an increasing number of studies. FUS can help treat malignant tumours by inducing apoptosis. This review describes the three apoptotic pathways, apoptotic cell clearance, and how FUS affects these three apoptotic pathways. This review also discusses the role of thermal and cavitation effects on apoptosis, including caspase activity, mitochondrial dysfunction, and Ca2+ elease. Finally, this article reviews various aspects of FUS combination therapy, including sensitization by radiotherapy and chemotherapy, gene expression upregulation, and the introduction of therapeutic gases, to provide new ideas for clinical tumour therapy.

A Systematic Review and Single-Arm Meta-Analysis on the Efficacy of High-Intensity, Focused Ultrasound for Benign Prostatic Hyperplasia Treatment: A Forgotten Option?

Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of prostate tissue, commonly affecting older men. This condition leads to lower urinary tract symptoms (LUTS), which significantly affect the quality of life. Over time, extensive research has been conducted regarding BPH treatment, exploring various treatment options. High-intensity focused ultrasound (HIFU) is a non-invasive treatment modality that has shown promise in initial studies. However, evidence regarding its long-term efficacy and safety remains inconclusive. This study evaluates HIFU's safety and efficacy for BPH treatment, identifying gaps for future research. The study conducted comprehensive searches across the PubMed, Google Scholar, Cochrane Central, and ClinicalTrials.gov databases, covering English-language articles from 1994 to 2023. Inclusion criteria focused on peer-reviewed studies, with more than 10 patients utilizing ultrasound image-guided HIFU for BPH while excluding other HIFU modalities lacking ultrasound image guidance. Data extraction targeted primary outcomes (peak flow rate, International Prostate Symptom Score (IPSS), postvoid residual volume) and secondary outcomes (treatment time, follow-up duration). Statistical analysis utilized a random effects model with heterogeneity assessed by I² statistics and the Q test, alongside subgroup analysis based on study design. The risk of bias assessment employed the Cochrane Collaboration tool for randomized controlled trials and the methodological index for nonrandomized studies. Among 560 identified articles, 12 studies with 522 patients met the inclusion criteria. Primary outcomes showed improvements in Qmax (1 month: 2.50 ml/s, 12 months: 6.22 ml/s) and IPSS (1 month: -9.37 points, 12 months: -11.60 points). Reported complications included transient hematuria, hematospermia, and urinary retention. HIFU presents significant clinical improvements in treating BPH, albeit with slow progression attributed to specific techniques and the ablative approach. Manageable complication profiles are observed, yet study design flaws hinder a comprehensive evaluation of HIFU efficacy. The authors suggest areas for clinical optimization, emphasizing the necessity of further research.

A Systematic Investigation of Process Parameters for Small-Volume Aqueous Suspension Production by the Use of Focused Ultrasonication.

Aqueous suspensions containing crystalline drug in the sub-micron range is a favorable platform for long-acting injectables where particle size can be used to obtain a desired plasma-concentration profile. Stabilizers are added to the suspensions and screened extensively to define the optimal formulation composition. In the initial formulation screening the amount of drug compound can be limited, necessitating milling methods for small-volume screening predictable for scale-up. Hence, adaptive focused ultrasound was investigated as a potential milling method for rapid small-volume suspensions by identifying the critical process parameters during preparation. Suspensions containing drug compounds with different mechanical properties and thereby grindability, i.e., cinnarizine, haloperidol, and indomethacin with brittle, elastic, and plastic properties, respectively, were investigated to gain an understanding of the manufacturing with adaptive focused acoustics as well as comparison to already established milling techniques. Using a DoE-design, peak incident power was identified as the most crucial process parameter impacting the milling process for all three compounds. It was possible to decrease the sizes of drug particles to micron range after one minute of focused ultrasound exposure which was superior compared to other milling techniques (e.g., non-focused ultrasound exposure). The addition of milling beads decreased the drug particle sizes even further, thus to a lower degree than other already established milling techniques such as milling by dual centrifugation. This study thereby demonstrated that adaptive focused ultrasonication was a promising method for rapid homogenization and particle size reduction to micron range for different compounds varying in grindability without altering the crystalline structure.

Patient satisfaction following treatment with micro-focused ultrasound with visualization: A retrospective cross-sectional study.

BACKGROUND: There has been increased public interest in noninvasive skin tightening procedures that produce the best possible cosmetic outcomes. Micro-focused ultrasound with visualization (MFU-V) is a secure, efficient method of treating skin laxity approved by the FDA. Few studies have assessed patient satisfaction following MFU-V. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted between January 2022 and 2023. After obtaining the author's permission, a previously examined and published questionnaire was used to contact all participants (n = 98) who had received MFU-V therapy in a private clinic in Riyadh, Saudi Arabia, between 2016 and 2020 via phone interview. RESULTS: All 98 patients undergoing MFU-V were female. About two-thirds indicated they were satisfied or very satisfied with the results. Those receiving treatment around the eye and submentum reported lower satisfaction levels than those receiving therapy in other regions. The number of treatment locations and satisfaction were positively correlated. Patients treated by consultants rather than laser experts reported much higher satisfaction levels. Satisfaction and the amount of time for improvement to occur following treatment were correlated statistically. Pain and tingling were the most frequent adverse effects the respondents reported, followed by skin redness and swelling; however, adverse effects were not connected with satisfaction. Cost (78.6%) was cited as the main deterrent to seeking treatment again. CONCLUSION: MFU-V, an FDA-approved procedure, has proven effective and safe for treating facial and neck skin laxity. When patients are carefully selected and physicians properly trained, higher satisfaction is achieved.

Comparing the effect of FUAS and myomectomy on the elasticity of myometrium around targeted uterine fibroid.

BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

Transcranial blood-brain barrier opening in Alzheimer's disease patients using a portable focused ultrasound system with real-time 2-D cavitation mapping.

Background : Focused ultrasound (FUS) in combination with microbubbles has recently shown great promise in facilitating blood-brain barrier (BBB) opening for drug delivery and immunotherapy in Alzheimer's disease (AD). However, it is currently limited to systems integrated within the MRI suites or requiring post-surgical implants, thus restricting its widespread clinical adoption. In this pilot study, we investigate the clinical safety and feasibility of a portable, non-invasive neuronavigation-guided FUS (NgFUS) system with integrated real-time 2-D microbubble cavitation mapping. Methods : A phase 1 clinical study with mild to moderate AD patients (N = 6) underwent a single session of microbubble-mediated NgFUS to induce transient BBB opening (BBBO). Microbubble activity under FUS was monitored with real-time 2-D cavitation maps and dosing to ensure the efficacy and safety of the NgFUS treatment. Post-operative MRI was used for BBB opening and closure confirmation as well as safety assessment. Changes in AD biomarker levels in both blood serum and extracellular vesicles (EVs) were evaluated, while changes in amyloid-beta (Aß) load in the brain were assessed through 18F-florbetapir PET. Results : BBBO was achieved in 5 out of 6 subjects with an average volume of 983 ± 626 mm3 following FUS at the right frontal lobe both in white and gray matter regions. The outpatient treatment was completed within 34.8 ± 10.7 min. Cavitation dose significantly correlated with the BBBO volume (R 2 > 0.9, N = 4), demonstrating the portable NgFUS system's capability of predicting opening volumes. The cavitation maps co-localized closely with the BBBO location, representing the first report of real-time transcranial 2-D cavitation mapping in the human brain. Larger opening volumes correlated with increased levels of AD biomarkers, including Aß42 (R 2 = 0.74), Tau (R 2 = 0.95), and P-Tau181 (R 2 = 0.86), assayed in serum-derived EVs sampled 3 days after FUS (N = 5). From PET scans, subjects showed a lower Aß load increase in the treated frontal lobe region compared to the contralateral region. Reduction in asymmetry standardized uptake value ratios (SUVR) correlated with the cavitation dose (R 2 > 0.9, N = 3). Clinical changes in the mini-mental state examination over 6 months were within the expected range of cognitive decline with no additional changes observed as a result of FUS. Conclusion : We showed the safety and feasibility of this cost-effective and time-efficient portable NgFUS treatment for BBBO in AD patients with the first demonstration of real-time 2-D cavitation mapping. The cavitation dose correlated with BBBO volume, a slowed increase in pathology, and serum detection of AD proteins. Our study highlights the potential for accessible FUS treatment in AD, with or without drug delivery.

Effect of Magnetic Resonance Imaging on the Motion Accuracy of Magnetic Resonance Imaging-compatible Focused Ultrasound Robotic System.

Purpose: The current study provides insights into the challenges of safely operating a magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) robotic system in a high-field MRI scanner in terms of robotic motion accuracy. Materials and Methods: Grid sonications were carried out in phantoms and excised porcine tissue in a 3T MRI scanner using an existing MRgFUS robotic system. Fast low-angle shot-based magnetic resonance thermometry was employed for the intraprocedural monitoring of thermal distribution. Results: Strong shifting of the heated spots from the intended points was observed owing to electromagnetic interference (EMI)-induced malfunctions in system's operation. Increasing the slice thickness of the thermometry sequence to at least 8 mm was proven an efficient method for preserving the robotic motion accuracy. Conclusions: These findings raise awareness about EMI effects on the motion accuracy of MRgFUS robotic devices and how they can be mitigated by employing suitable thermometry parameters.

Therapeutic ultrasound transducer technology and monitoring techniques: a review with clinical examples.

The exponential growth of therapeutic ultrasound applications demonstrates the power of the technology to leverage the combinations of transducer technology and treatment monitoring techniques to effectively control the preferred bioeffect to elicit the desired clinical effect.Objective: This review provides an overview of the most commonly used bioeffects in therapeutic ultrasound and describes existing transducer technologies and monitoring techniques to ensure treatment safety and efficacy.Methods and materials: Literature reviews were conducted to identify key choices that essential in terms of transducer design, treatment parameters and procedure monitoring for therapeutic ultrasound applications. Effective combinations of these options are illustrated through descriptions of several clinical indications, including uterine fibroids, prostate disease, liver cancer, and brain cancer, that have been successful in leveraging therapeutic ultrasound to provide effective patient treatments.Results: Despite technological constraints, there are multiple ways to achieve a desired bioeffect with therapeutic ultrasound in a target tissue. Visualizations of the interplay of monitoring modality, bioeffect, and applied acoustic parameters are presented that demonstrate the interconnectedness of the field of therapeutic ultrasound. While the clinical indications explored in this review are at different points in the clinical evaluation path, based on the ever expanding research being conducted in preclinical realms, it is clear that additional clinical applications of therapeutic ultrasound that utilize a myriad of bioeffects will continue to grow and improve in the coming years.Conclusions: Therapeutic ultrasound will continue to improve in the next decades as the combination of transducer technology and treatment monitoring techniques will continue to evolve and be translated in clinical settings, leading to more personalized and efficient therapeutic ultrasound mediated therapies.

Histological characterization of HIFU lesions.

Background: High intensity focused ultrasound (HIFU) can destroy tissue by thermal ablation which may be accompanied by acoustic cavitation and/or tissue water boiling, but the biological and histological effects of these treatments have not been fully documented. Here, detailed histological analysis over time using well characterized HIFU exposures in in vivo rat livers is described.Methods: Exposures used invoked either (i) thermal, with acoustic cavitation and/or tissue water boiling or (ii) predominantly thermal damage. Cavitation activity was detected using both active and passive methods. Histological assessment involved hematoxylin and eosin (H&E), picrosirius red and immunohistochemical staining.Results: Distinct concentric damage regions were identified after HIFU exposures. The outermost ring showed a red H&E-stained rim that was characterized by hemorrhage. The adjacent inner band appeared white due to increased extracellular spaces. The morphology of the next zone depended on the exposure. Where there was no tissue acoustic cavitation/water boiling, this was the lesion center, in which heat-fixed cells were seen. Where acoustic cavitation/boiling occurred, a centermost zone with irregular holes up to several hundred microns across was seen. Cleaved caspase-3 and Hsp70 staining in the periphery of both types of HIFU exposures was seen within the outermost ring of hemorrhage, where an inflammatory response was also observed. By day 7, a distinct acellular region in the center of the HIFU lesions had been created.Conclusions: These results identify the morphological effects and elucidate the similarities and differences of HIFU-induced thermal lesions in the presence or absence of acoustic cavitation/tissue water boiling.