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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 ISPPA values between 0.78 and 12.38 W/cm2. In contrast, the high-intensity system achieves pressures up to 1460 kPa and a maximum ISPPA 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. [ABSTRACT FROM AUTHOR]

High intensity focused ultrasound is used as a surgical tool to treat completely non-invasively several diseases. Examples of clinical applications are uterine fibroids, prostate cancer, thyroid nodules, and varicose veins. Precise targeting is key for improving the treatment outcome. A method for an automated, robot-assisted tracking system was developed and evaluated. A wireless ultrasound scanner was used to acquire images of the target, in this case, a blood vessel. The active contour approach by Chan and Vese was used to segment and track while moving the scanner along the target structure with a collaborative robotic arm. The performance was assessed using a custom made Agar phantom. The mean tracking error, which is defined as the remaining distance of the lesion to the images’ centre line, was 0.27 mm ± 0.18 mm.

Magnetic resonance image (MRI)-guidance for minimally invasive interventions instead of CT-guidance is a promising technique to reduce radiation exposure for both patients and clinicians. Technical challenges have to be managed in order to meet safety regulations while enabling inroom system control and communication. Using nonproprietary software and hardware, several gradations for a setup for interventional MRI were elaborated. Eventually, a quickly and easily installable setup was established for technical support during MRI-guided interventions in the PET/MRI suite at the Department of Nuclear Medicine at University Hospital Leipzig. It is adaptable for most MRI suites.

Introduction: Image-guided invasive procedures on the liver require a steep learning curve to acquire the necessary skills. The best and safest way to achieve these skills is through hands-on courses that include simulations and phantoms of different complications, without any risks for patients. There are many liver phantoms on the market made of various materials; however, there are few multimodal liver phantoms, and only two are cast in a 3D-printed mold. Methods: We created a virtual liver and 3D-printed mold by segmenting a CT scan. The InVesalius and Autodesk Fusion 360 software packages were used for segmentation and 3D modeling. Using this modular mold, we cast and tested silicone- and gelatin-based liver phantoms with tumor and vascular formations inside. We tested the gelatin liver phantoms for several procedures, including ultrasound diagnosis, elastography, fibroscan, ultrasound-guided biopsy, ultrasound-guided drainage, ultrasound-guided radio-frequency ablation, CT scan diagnosis, CT–ultrasound fusion, CT-guided biopsy, and MRI diagnosis. The phantoms were also used in hands-on ultrasound courses at four international congresses. Results: We evaluated the feedback of 33 doctors regarding their experiences in using and learning on liver phantoms to validate our model for training in ultrasound procedures. Conclusions: We validated our liver phantom solution, demonstrating its positive impact on the education of young doctors who can safely learn new procedures thus improving the outcomes of patients with different liver pathologies. [ABSTRACT FROM AUTHOR]

Background: Patients with liver pathology benefit from image-guided interventions. Training for interventional procedures is recommended to be performed on liver phantoms until a basic proficiency is reached. In the last 40 years, several attempts have been made to develop materials to mimic the imaging characteristics of the human liver in order to create liver phantoms. There is still a lack of accessible, reproducible and cost-effective soft liver phantoms for image-guided procedure training. Methods: Starting from a CT-scan DICOM file, we created a 3D-printed liver mold using InVesalius (Centro de Tecnologia da informação Renato Archer CTI, InVesalius 3 open-source software, Campinas, Brazil) for segmentation, Autodesk Fusion 360 with Netfabb (Autodesk software company, Fusion 360 2.0.19426 with Autodesk Netfabb Premium 2023.0 64-Bit Edition, San Francisco, CA, USA) for 3D modeling and Stratasys Fortus 380 mc 3D printer (Stratasys 3D printing company, Fortus 380 mc 3D printer, Minneapolis, MN, USA). Using the 3D-printed mold, we created 14 gelatin-based liver phantoms with 14 different recipes, using water, cast sugar and dehydrated gelatin, 32% fat bovine milk cream with intravenous lipid solution and technical alcohol in different amounts. We tested all these phantoms as well as ex vivo pig liver and human normal, fatty and cirrhotic liver by measuring the elasticity, shear wave speed, ultrasound attenuation, CT-scan density, MRI signal intensity and fracture force. We assessed the results of the testing performed, as well as the optical appearance on ultrasound, CT and MRI, in order to find the best recipe for gelatin-based phantoms for image-guided procedure training. Results: After the assessment of all phantom recipes, we selected as the best recipe for transparent phantoms one with 14 g of gelatin/100 mL water and for opaque phantom, the recipes with 25% cream. Conclusions: These liver gelatin-based phantom recipes are an inexpensive, reproducible and accessible alternative for training in image-guided and diagnostic procedures and will meet most requirements for valuable training. [ABSTRACT FROM AUTHOR]

The integration of surgical robotics into the operating room requires reliable and flexible communication with other medical devices. The IEEE 11073 SDC standard can provide the necessary requirements to deploy robotics for the application of focused ultrasound in radiation therapy. The aim of this work was to implement and evaluate an SDC compliant connection between two collaborative robots. For this purpose, the KUKA LBR iiwa 7 R800 was adapted and the connectivity modelled and then tested successfully with 42 transmittable properties. Latency measurements were conducted to evaluate the network stability, resulting in a median round trip time of 10.13 ms.

Robotic assistance in clinical interventions provides high precision and performance. However, the acceptance of such systems is still very low. The idea of collaborative robotics promises practical solutions for this problem. To further promote these ideas in the medical domain, novel concepts for user interactions are needed. This work presents a preliminary study on the recognition accuracy of touch gesture interaction with a KUKA LBR iiwa robotic arm. A recognition application utilising a set of 4 different touch gestures was implemented and evaluated by eight participants. The overall recognition accuracy of the system is 89.8%.

Organ motion is a major problem for Focused Ultrasound Surgery (FUS) of liver tumors. We present a liver phantom mimicking human respiratory motion (20 mm range, 3 − 7 s/cycle) and the evaluation of an ultrasound-tracked steered FUS system on that phantom. Temperature curves are recorded while sonicating in moving and static phantom. The temperature curves correlate well and show the ability of the system to compensate breathing like motion.

Background: Focused ultrasound (FUS) has become an important non-invasive therapy for prostate tumor ablation via thermal effects in the clinic. The cavitation effect induced by FUS is applied for histotripsy, support drug delivery, and the induction of blood vessel destruction for cancer therapy. Numerous studies report that cavitation-induced sonoporation could provoke multiple anti-proliferative effects on cancer cells. Therefore, cavitation alone or in combination with thermal treatment is of great interest but research in this field is inadequate. Methods: Human prostate cancer cells (LNCap and PC-3) were exposed to 40 s cavitation using a FUS system, followed by water bath hyperthermia (HT). The clonogenic assay, WST-1 assay, and Transwell® invasion assay, respectively, were used to assess cancer cell clonogenic survival, metabolic activity, and invasion potential. Fluorescence microscopy using propidium iodide (PI) as a probe of cell membrane integrity was used to identify sonoporation. The H2A.X assay and Nicoletti test were conducted in the mechanism investigation to detect DNA double-strand breaks (DSBs) and cell cycle arrest. Immunofluorescence microscopy and flow cytometry were performed to determine the distribution and expression of 5α-reductase (SRD5A). Results: Short FUS shots with cavitation (FUS-Cav) in combination with HT resulted in, respectively, a 2.2, 2.3, and 2.8-fold decrease (LNCap) and a 2.0, 1.5, and 1.6-fold decrease (PC-3) in the clonogenic survival, cell invasiveness and metabolic activity of prostate cancer cells when compared to HT alone. FUS-Cav immediately induced sonoporation in 61.7% of LNCap cells, and the combination treatment led to a 1.4 (LNCap) and 1.6-fold (PC-3) increase in the number of DSBs compared to HT alone. Meanwhile, the combination therapy resulted in 26.68% of LNCap and 31.70% of PC-3 with cell cycle arrest in the Sub-G1 phase and 35.37% of PC-3 with cell cycle arrest in the G2/M phase. Additionally, the treatment of FUSCav combined with HT block the androgen receptor (AR) signal pathway by reducing the relative Type I 5α-reductase (SRD5A1) level to 38.28 ± 3.76% in LNCap cells, and decreasing the relative Type III 5α-reductase 3 (SRD5A3) level to 22.87 ± 4.88% in PC-3 cells, in contrast, the relative SRD5A level in untreated groups was set to 100%. Conclusion: FUS-induced cavitation increases the effects of HT by interrupting cancer cell membranes, inducing the DSBs and cell cycle arrest, and blocking the AR signal pathway of the prostate cancer cells, with the potential to be a promising adjuvant therapy in prostate cancer treatment. [ABSTRACT FROM AUTHOR]