Search Results (68)

Background: Echocardiography is crucial to understanding cardiac function in the Intensive Care Unit (ICU), often by measuring the left ventricular ejection fraction (LVEF). Traditionally, measures of LVEF are completed as part of a comprehensive examination by an expert sonographer or cardiologist, but front-line practitioners increasingly perform focused point-of-care estimates of LVEF while managing life-threatening illness. The two main echocardiographic windows used to grossly estimate LVEF are parasternal and apical windows. Artificial intelligence (AI) algorithms have recently been developed to assist non-experts in obtaining and interpreting point-of-care ultrasound (POCUS) echo images. We tested the feasibility, accuracy and reliability of novice users estimating LVEF using POCUS-AI echo. Methods: A total of 30 novice users (most never holding an ultrasound probe before) received 2 h of instruction, then scanned ICU patients (10 patients, 80 scans) using the Exo Iris POCUS probe with AI guidance tool. They were permitted up to 5 min to attempt parasternal long axis (PLAX) and apical 4 chamber (A4C) views. AI-reported LVEF results from these scans were compared to gold-standard LVEF obtained by an expert echo sonographer. To further assess accuracy, this sonographer also scanned another 65 patients using Exo Iris POCUS-AI vs. conventional protocol. Results: Novices obtained images sufficient to estimate LVEF in 96% of patients in <5 min. Novices obtained PLAX views significantly faster than A4C (1.5 min vs. 2.3 min). Inter-rater reliability of LVEF estimation was very high (ICC 0.88–0.94) whether images were obtained by novices or experts. In n = 65 patients, POCUS-AI LVEF was highly specific for a decreased LVEF ≤ 40% (SP = 90% for PLAX) but only moderately sensitive (SN = 56–70%). Conclusions: Estimating cardiac LVEF from AI-enhanced POCUS is highly feasible even for novices in ICU settings, particularly using the PLAX view. POCUS-AI LVEF results were highly consistent whether performed by novice or expert. When AI detected a decreased LVEF, it was highly accurate, although a normal LVEF reported by POCUS-AI was not necessarily reassuring. This POCUS-AI tool could be clinically useful to rapidly confirm a suspected low LVEF in an ICU patient. Further improvements to sensitivity for low LVEF are needed. Full article

Liver disease is a major global health concern. Given the critical role of medical image categorization in fibrosis staging (low, moderate, severe, cirrhotic) and the challenges posed by limited medical image datasets, this paper aims to leverage ultrasound imaging to assess liver margin characteristics at the level of Glisson’s capsule—here referred to as Glisson’s line—to develop a simple, automated model for accurately distinguishing fibrosis stages. The proposed approach combines traditional image processing techniques in a pre-processing stage with machine learning algorithms for classification. The pre-processing phase introduces an attention-focusing mechanism that stretches the gray levels of Glisson’s line while shrinking the intensity levels associated with the liver parenchyma and surrounding tissues. This results in the so-called region of contrast interest (ROCI), where potential classification distractors are minimized. For classification, a convolutional neural network (CNN)-based model is used to process original, rotated, and transformed ultrasound images. To address dataset imbalance and overfitting, a 10-fold cross-validation strategy was implemented. The results demonstrate that, by effectively enhancing the information content of Glisson’s line, different liver fibrosis stages can be accurately distinguished without the need for explicit edge detection, achieving accuracy levels comparable to those reported in the literature. The novelty of this work lies in analyzing the morphology of Glisson’s capsule—obtained through this method—rather than focusing on the liver parenchyma and texture, as is traditionally carried out. Full article

Background: The blood–brain barrier (BBB) plays an important role in regulating homeostasis of the central nervous system (CNS), and it is an obstacle for molecules with a molecular weight higher than 500 Da seeking to reach it, making many drugs ineffective simply because they cannot be delivered to where they are needed. As a result, crossing the BBB remains the rate-limiting factor in brain drug delivery during the treatment of brain diseases, specifically tumors such as diffuse intrinsic pontine glioma (DIPG), a highly aggressive pediatric tumor with onset in the pons Varolii, the middle portion of the three contiguous parts of the brainstem, located above the medulla and below the midbrain. Methods: Currently, radiotherapy (RT) relieves DIPG symptoms but chemotherapy drugs do not lead to significant results as they do not easily cross the BBB. Focused ultrasound (FUS) and microbubbles (MBs) can temporarily open the BBB, facilitating radiotherapy and the entry of drugs into the CNS. A patient-derived xenograft DIPG model exposed to high-intensity focalized ultrasound (HIFU) or low-intensity focalized ultrasound (LIFU) combined with MBs was treated with doxorubicin, panobinostat, olaparib, ONC201 (Dordaviprone^®) and anti-PD1. Panobinostat has also been used in children with diffuse midline glioma, a broad class of brain tumors to which DIPG belongs. Results: Preliminary studies were performed using FUS to temporarily open the BBB and allow a milder use of radiotherapy and facilitate the passage of drugs through the BBB. The data collected show that after opening the BBB with FUS and MBs, drug delivery to the CNS significantly improved. Conclusions: FUS associated with MBs appears safe and feasible and represents a new strategy to increase the uptake of drugs in the CNS and therefore enhance their effectiveness. This review reports pre-clinical and clinical studies performed to demonstrate the usefulness of FUS in patients with DIPG treated with some chemotherapy. The papers reviewed were published in PubMed until the end of 2024 and were found using a combination of the following keywords: diffuse intrinsic pontine glioma (DIPG), DIPG H3K27-altered, blood–brain barrier and BBB, focused ultrasound (FUS) and radiotherapy (RT). Full article

For the more efficient application of ultrasound in future therapies, fundamental research is needed on the mode of action of ultrasound on biological systems using therapeutic frequencies. To address this need, a new versatile high-throughput platform for focused ultrasound in vitro application was designed, developed, and characterized. The applicator was aligned with the dimensions of a 96-well plate and frequencies commonly used in the therapeutic ultrasound range (0.5–2.0 MHz). Two different platform configurations were developed: (a) a low-intensity version with 96 individual transducers allowing dry coupling of the well plate; and (b) a high-intensity version with water cooling, supporting parallel sonication of 32 out of 96 wells. The platforms were characterized by performing an analysis of the homogeneity of the sound pressure and intensity, the impact of filled volume per well, the cross-coupling effect between the wells, and the influence of the well plate. The low-intensity design delivers pressure levels up to 605 kPa inside the well with maximum I_SPPA values between 0.78 and 12.38 W/cm². In contrast, the high-intensity system achieves pressures up to 1460 kPa and a maximum I_SPPA of 72 W/cm² inside the wells. The successfully developed high-throughput platform supports parallelized sonication in standard, well-plate formats and is suitable for focused ultrasound applications in vitro. Full article

Background/Objective: The blood–brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood. This study aimed to characterize the time-dependent changes in BBB permeability, transporter function, and inflammatory responses in both sonicated and non-sonicated brain tissues following LiFUS treatment. Methods: We employed in situ brain perfusion to assess alterations in BBB integrity and transporter function, as well as multiplex cytokine analysis to quantify the inflammatory response. Results: Our findings show that LiFUS significantly increased vascular volume and glucose uptake, with reduced P-gp function in brain tissues six hours post treatment, indicating biphasic BBB disruption. Additionally, elevated levels of pro-inflammatory cytokines, including TNF-α and IL-6, were observed in both sonicated and non-sonicated regions. A comparative analysis between wild-type and immunodeficient mice revealed distinct patterns of cytokine release, with immunodeficient mice showing lower serum concentrations of IFN-γ and TNF-α, highlighting the potential impact of immune status on the inflammatory response to LiFUS. Conclusions: This study provides new insights into the biphasic nature of LiFUS-induced BBB disruption, emphasizing the importance of understanding the timing and extent of secondary physiological changes. Full article

MEMS acoustic sensors are a type of physical quantity sensor based on MEMS manufacturing technology for detecting sound waves. They utilize various sensitive structures such as thin films, cantilever beams, or cilia to collect acoustic energy, and use certain transduction principles to read out the generated strain, thereby obtaining the targeted acoustic signal’s information, such as its intensity, direction, and distribution. Due to their advantages in miniaturization, low power consumption, high precision, high consistency, high repeatability, high reliability, and ease of integration, MEMS acoustic sensors are widely applied in many areas, such as consumer electronics, industrial perception, military equipment, and health monitoring. Through different sensing mechanisms, they can be used to detect sound energy density, acoustic pressure distribution, and sound wave direction. This article focuses on piezoelectric, piezoresistive, capacitive, and optical MEMS acoustic sensors, showcasing their development in recent years, as well as innovations in their structure, process, and design methods. Then, this review compares the performance of devices with similar working principles. MEMS acoustic sensors have been increasingly widely applied in various fields, including traditional advantage areas such as microphones, stethoscopes, hydrophones, and ultrasound imaging, and cutting-edge fields such as biomedical wearable and implantable devices. Full article

Background and Objectives: Cartilage repair remains a critical challenge in orthopaedic medicine due to the tissue’s limited self-healing ability, contributing to degenerative joint conditions such as osteoarthritis (OA). In response, regenerative medicine has developed advanced therapeutic strategies, including cell-based therapies, gene editing, and bioengineered scaffolds, to promote cartilage regeneration and restore joint function. This narrative review aims to explore the latest developments in cartilage repair techniques, focusing on mesenchymal stem cell (MSC) therapy, gene-based interventions, and biomaterial innovations. It also discusses the impact of patient-specific factors, such as age, defect size, and cost efficiency, on treatment selection and outcomes. Materials and Methods: This review synthesises findings from recent clinical and preclinical studies published within the last five years, retrieved from the PubMed, Scopus, and Web of Science databases. The search targeted key terms such as “cartilage repair”, “stem cell therapy”, “gene editing”, “biomaterials”, and “tissue engineering”. Results: Advances in MSC-based therapies, including autologous chondrocyte implantation (ACI) and platelet-rich plasma (PRP), have demonstrated promising regenerative potential. Gene-editing tools like CRISPR/Cas9 have facilitated targeted cellular modifications, while novel biomaterials such as hydrogels, biodegradable scaffolds, and 3D-printed constructs have improved mechanical support and tissue integration. Additionally, biophysical stimuli like low-intensity pulsed ultrasound (LIPUS) and electromagnetic fields (EMFs) have enhanced chondrogenic differentiation and matrix production. Treatment decisions are influenced by patient age, cartilage defect size, and financial considerations, highlighting the need for personalised and multimodal approaches. Conclusions: Combining regenerative techniques, including cell-based therapies, gene modifications, and advanced scaffolding, offers a promising pathway towards durable cartilage repair and joint preservation. Future research should focus on refining integrated therapeutic protocols, conducting long-term clinical evaluations, and embracing personalised treatment models driven by artificial intelligence and predictive algorithms. Full article

The growing interest in minimal and non-invasive therapies, especially in the field of cancer treatment, highlights a significant shift toward safer and more effective options. Ablative therapies are well-established tools in cancer treatment, with known effects including locoregional control, while their role as modulators of the systemic immune response against cancer is emerging. The HIFU developed with magnetic resonance imaging (MRI) guidance enables treatment precision, improves real-time procedural control, and ensures accurate outcome assessment. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) induces deep coagulation necrosis within an elliptical focal area, effectively encompassing the entire tumor site and allowing for highly targeted radical ablation. The applications of MRgFUS in oncology are rapidly expanding, offering pain relief and curative treatment options for bone metastatic lesions. Additionally, the MRgFUS plays an effective role in targeted optional therapies for early prostate and breast cancers. Emerging research also focuses on the potential uses in treating abdominal cancers and harnessing capabilities to stimulate immune responses against tumors or to facilitate the delivery of anticancer drugs. This evolving landscape presents exciting opportunities for improving patient outcomes and advancing cancer treatment methodologies. In neuro-oncology, MRgFUS utilizes low-intensity focused ultrasound (LIFU) along with intravenous microbubbles to open the blood-brain barrier (BBB) and enhance the intra-tumoral delivery of chemotherapy drugs. Full article

Gliomas are a wide group of common brain tumors, with the most aggressive type being glioblastoma multiforme (GBM), with a 5-year survival rate of less than 5% and a median survival time of approximately 12–14 months. The standard treatment of GBM includes surgical excision, radiotherapy, and chemotherapy with temozolomide (TMZ). However, tumor recurrence and progression are common. Therefore, more effective treatment for GBM should be found. One of the main obstacles to the treatment of GBM and other gliomas is the blood–brain barrier (BBB), which impedes the penetration of antitumor chemotherapeutic agents into glioblastoma cells. Nowadays, one of the most promising novel methods for glioma treatment is Magnetic Resonance-guided Focused Ultrasound (MRgFUS). Low-intensity FUS causes the BBB to open transiently, which allows better drug delivery to the brain tissue. Under magnetic resonance guidance, ultrasound waves can be precisely directed to the tumor area to prevent side effects in healthy tissues. Through the open BBB, we can deliver targeted chemotherapeutics, anti-tumor agents, immunotherapy, and gene therapy directly to gliomas. Other strategies for MRgFUS include radiosensitization, sonodynamic therapy, histotripsy, and thermal ablation. FUS can also be used to monitor the treatment and progression of gliomas using blood-based liquid biopsy. All these methods are still under preclinical or clinical trials and are described in this review to summarize current knowledge and ongoing trials. Full article

This study explores the feasibility of using low-intensity focused ultrasound (LIFU) to induce rotational sensations in the human semicircular canal (SCC) through the acoustic streaming effect. Existing vestibular stimulation methods, such as galvanic vestibular stimulation (GVS), caloric vestibular stimulation (CVS), and magnetic vestibular stimulation (MVS), face limitations in spatial and temporal resolution, with unclear mechanisms. This study investigates whether LIFU can overcome these limitations by modulating endolymph motion within SCC. A 3D finite element model was constructed to simulate the effects of LIFU-induced acoustic streaming on SCC (particularly the endolymph), with thermal effects evaluated to ensure safety. Fluid–structure interaction (FSI) was used to analyze the relationship between endolymph flow and cupula deformation. By adjusting the focal point of the ultrasound transducer, we were able to alter fluid flow pattern, which resulted in variations in cupula displacement. The results demonstrated that LIFU successfully induces fluid motion in SCC without exceeding thermal safety limits (<1 °C), suggesting its potential for controlling rotational sensations, with cupula displacement exceeding 1 μm. This novel approach enhances the understanding of LIFU’s thermal and neuromodulatory effects on the vestibular system, and thereby offers promising implications for future therapeutic applications. Full article

Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely and non-invasively stimulate deep brain structures with millimetric precision, offering distinct advantages in terms of accessibility to non-cortical regions over other NIBS methods. However, to date, several tFUS aspects still need to be characterized; furthermore, there are only a handful of studies that have utilized tFUS in psychiatric populations. This narrative review provides an up-to-date overview of key aspects of this NIBS technique, including the main components of a tFUS system, the neuronavigational tools used to precisely target deep brain regions, the simulations utilized to optimize the stimulation parameters and delivery of tFUS, and the experimental protocols employed to evaluate the efficacy of tFUS in psychiatric disorders. The main findings from studies in psychiatric populations are presented and discussed, and future directions are highlighted. Full article

Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system’s ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy. Full article

Background: Salvage robot-assisted radical prostatectomy (sRARP) after PSA failure in patients who underwent initial radiotherapy or focal therapy has rarely been reported in Japan. We aimed to report the oncologic and functional outcomes of the first 10 cases of sRARP. Methods: Ten patients underwent sRARP after failing to respond to initial radiotherapy or focal therapy. Initial definitive treatment included volumetric modulated arc therapy, intensity-modulated radio therapy, stereotactic body radiotherapy, heavy-ion radiotherapy, low-dose-rate brachytherapy, and high-intensity focused ultrasound. We retrospectively investigated 10 cases on oncologic and functional outcomes of sRARP. Results: The median PSA level at sRARP, amount of blood loss, and console time were 2.17 ng/mL, 100 mL, and 136 min, respectively. Positive surgical margins were found in half of the cases. Median follow-up was 1.1 years. There were no 30-day major complications. No patients had erections after sRARP. Urinary continence and biochemical recurrence (BCR) rate were 40% and 30% at 1 year after sRARP, respectively. Conclusions: Salvage RARP may be a feasible option after PSA failure in patients who underwent radiotherapy or focal therapy as initial treatment, showing acceptable BCR rate. Full article

Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median overall survival of less than 2 years and a nearly 100% mortality rate under standard therapy that consists of surgery followed by combined radiochemotherapy. Therefore, new therapeutic strategies are urgently needed. The success of chimeric antigen receptor (CAR) T cells in hematological cancers has prompted preclinical and clinical investigations into CAR-T-cell treatment for GBM. However, recent trials have not demonstrated any major success. Here, we delineate existing challenges impeding the effectiveness of CAR-T-cell therapy for GBM, encompassing the cold (immunosuppressive) microenvironment, tumor heterogeneity, T-cell exhaustion, local and systemic immunosuppression, and the immune privilege inherent to the central nervous system (CNS) parenchyma. Additionally, we deliberate on the progress made in developing next-generation CAR-T cells and novel innovative approaches, such as low-intensity pulsed focused ultrasound, aimed at surmounting current roadblocks in GBM CAR-T-cell therapy. Full article

This paper presents baseline results from the NutriEcoMuscle study, a multicenter observational study conducted in Spain which focused on changes in nutritional status, body composition, and functionality in post-intensive care unit (ICU) COVID-19 patients following a nutritional intervention. Assessments at hospital discharge included Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria, the Barthel index, handgrip strength (HGS) and the Timed Up-and-Go test, bioelectrical impedance analysis (BIA), and nutritional ultrasound (US). The study involved 96 patients (71.9% male, mean age 58.8 years, mean BMI 28.8 kg/m², 36.5% obese). All patients were malnourished at discharge according to GLIM and SGA. Functional status declined from admission up to hospital discharge. A total of 33.3% of patients had a low fat-free mass index (FFMI) and 29.5% had a low phase angle (PhA). Myosteatosis was observed in 83.7% of the population. There was a positive correlation between rectus femoris cross-sectional area, PhA, FFMI, and HGS. In conclusion, post-critically ill COVID-19 patients commonly suffer from malnutrition and reduced muscle mass, causing a loss of independence at hospital discharge. BIA and US could be valuable tools for assessing body composition in these patients. The NutriEcoMuscle study highlights the need for a thorough nutritional and morphofunctional status assessment of post-ICU patients. Full article