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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.

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a rapidly increasing cause of mortality whose dismal prognosis is mainly due to overwhelming chemoresistance. New therapeutic approaches include physical agents such as ultrasonic cavitation, but clinical applications require further insights in the mechanisms of cytotoxicity. 3-D in vitro culture models such as spheroids exploit realistic spatial, biochemical and cellular heterogeneity that may bridge some of the experimental gap between conventional in vitro and in vivo experiments.PurposeTo assess the feasibility and efficiency of inertial cavitation associated or not with chemotherapy, in a spheroid model of PDAC.MethodsWe used DT66066 cells, derived from a genetically-engineered murine PDAC, isolated from KPC-transgenic mice (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1- Cre). Spheroids were obtained by either a standard centrifugation-based method, or by using a magnetic nano-shuttle method allowing the formation of spheroids within 24 hours and facilitating their handling. The spheroids were exposed to ultrasonic inertial cavitation in a specially designed setup. Eight or nine spheroids were analyzed for each of 4 conditions: control, gemcitabine alone, US cavitation alone, US cavitation + gemcitabine. Five US inertial cavitation indexes, corresponding to increased US intensities, were evaluated. The effectiveness of treatment was assessed after 24 hours with the following criteria: spheroid size (growth), ratio of phase S-entered cells (proliferation), proportion of cells in apoptosis or necrosis (mortality). These parameters were assessed by quantitative immunofluorescence techniques.ResultsThe 3D culture model presented excellent reproducibility. Cavitation induced a significant decrease in the size of spheroids, an effect significantly correlated to an increasing cavitation index (p < 0.0001). The treatment induced cell death whose predominant mechanism was necrosis (p < 0.0001). There was a tendency to a synergistic effect of US cavitation and gemcitabine at 5μM concentration, however significant in only one of the cavitation indexes used (p = 0. 013).ConclusionUltrasonic inertial cavitation induced a significant reduction of tumor growth in a spheroid model of PDAC., with necrosis rather than apoptosis as a Cell dominant mechanism of cell death. More investigations are needed to understand the potential role of inertial cavitation in overcoming chemoresistance.

Background: Long lasting elevation is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water jet injection of saline solution or by viscous macromolecular solutions. In a previous animal study, we assessed the Nestis Enki II system to combine jet injection and viscous solutions. In the present work, we used this combination in humans in different sites of the digestive tract. Methods: We retrospectively report all of the consecutive ESD procedures performed with jet injection of viscous solutions in four centers. Information was collected about the lesion, the procedure, the histological result, and the outcomes for the patient. Results: In total, 45 resections were completed by six operators: five experts and one beginner with only one previous experience in human ESD. Lesions were located in the esophagus (10), the stomach (11), the duodenum (1), the colon (1) and the rectum (22). Average maximal lesion diameter was 4.8 cm (SD 2.4, range 2 – 11 cm), average lesion surface area was 19.8 cm2 (SD 17.7, range 2.2 – 72 cm2), and average duration of procedure was 79.9 min (SD 50.3 min, range 19 – 225 min). ESD could be conducted while the endoscope was retroflexed at its maximum in 26 cases. Four adverse events were observed: two diminutive perforations and two delayed bleeding occurrences treated conservatively. The R0 resection rate was 91.1 %. The catheter was obstructed in six occurrences of bleeding. Conclusion: Endoscopic submucosal dissection using high pressure injection of viscous macromolecular solutions is safe and effective in different parts of the digestive tract. It does not impede working with the endoscope in the maximal retroflexed position.

Sonoporation using low-frequency high-pressure ultrasound (US) is a non-viral approach for in vitro and in vivo gene delivery. In this study, we developed a new sonoporation device designed for spatial and temporal control of ultrasound cavitation. The regulation system incorporated in the device allowed a real-time control of the cavitation level during sonoporation. This device was evaluated for the in vitro transfection efficiency of a plasmid coding for Green Fluorescent Protein (pEGFP-C1) in adherent and non-adherent cell lines. The transfection efficiency of the device was compared to those observed with lipofection and nucleofection methods. In both adherent and non-adherent cell lines, the sonoporation device allowed high rate of transfection of pEGFP-C1 (40-80%), as determined by flow cytometry analysis of GFP expression, along with a low rate of mortality assessed by propidium iodide staining. The transfection efficiency and toxicity of sonoporation on the non-adherent cell lines Jurkat and K562 were similar to those of nucleofection, while these two cell lines were resistant to transfection by lipofection. Moreover, sonoporation was used to produce three stably transfected human lymphoma and leukemia lines. Significant transfection efficiency was also observed in two fresh samples of human acute myeloid leukemia cells. In conclusion, we developed a user-friendly and cost-effective ultrasound device, well adapted for routine in vitro high-yield transfection experiments and which does not require the use of any transfection reagent or gas micro-bubbles.

The work aims to develop a new image-processing method to improve the guidance of transesophageal high intensity focused ultrasound (HIFU) atrial fibrillation therapy. Our proposal is a novel registration approach that aligns intraoperative 2D ultrasound with preoperative 3D-CT information. This approach takes advantage of the anatomical constraints imposed at the transesophageal HIFU probe to simplify the registration process. Our proposed method has been evaluated on a physical phantom and on real clinical data. [ABSTRACT FROM AUTHOR]

Heart rhythm disorders, such as atrial fibrillation or ventricular tachycardia can be treated by catheter-based thermal ablation. However, clinically available systems based on radio-frequency or cryothermal ablation suffer from limited energy penetration and the lack of lesion’s extent monitoring. An ultrasound-guided transesophageal device has recently successfully been used to perform High-Intensity Focused Ultrasound (HIFU) ablation in targeted regions of the heart in vivo. In this study we investigate the feasibility of a dual therapy and imaging approach on the same transesophageal device. We demonstrate in vivo that quantitative cardiac shear-wave elastography (SWE) can be performed with the device and we show on ex vivo samples that transesophageal SWE can map the extent of the HIFU lesions.First, SWE was validated with the transesophageal endoscope in one sheep in vivo. The stiffness of normal atrial and ventricular tissues has been assessed during the cardiac cycle () and mapped (). Second, HIFU ablation has been performed with the therapy-imaging transesophageal device in ex vivo chicken breast samples (n  =  3), then atrial (left, ) and ventricular (left , right ) porcine heart tissues. SWE provided stiffness maps of the tissues before and after ablation. Areas of the lesions were obtained by tissue color change with gross pathology and compared to SWE.During the cardiac cycle stiffness varied from 0.5   ±   0.1 kPa to 6.0   ±   0.3 kPa in the atrium and from 1.3   ±   0.3 kPa to 13.5   ±   9.1 kPa in the ventricles. The thermal lesions were visible on all SWE maps performed after ablation. Shear modulus of the ablated zones increased to 16.3   ±   5.5 kPa (versus 4.4   ±   1.6 kPa before ablation) in the chicken breast, to 30.3   ±   10.3 kPa (versus 12.2   ±   4.3 kPa) in the atria and to 73.8   ±   13.9 kPa (versus 21.2   ±   3.3 kPa) in the ventricles. On gross pathology, the size of the lesions ranged from 0.1 to 1.5 cm2 in the imaging plane area. Elasticity-estimated depths and widths of the lesions differed respectively with a median of 0.2 mm (first quartile Q1:  −0.8 mm; third quartile Q3: 2.6 mm) for a mean squared error (MSE) of 5.1 mm2 and a median of 0.2 mm (Q1:  −2.7 mm; Q3: 2.7 mm) for a MSE of 11.1 mm2 from gross pathology.We have demonstrated the feasibility of the HIFU thermal ablation monitoring using a dual therapy and imaging transesophageal device. The combination of HIFU, ultrasound imaging and SWE on the same transesophageal system could lead to a new clinical device for a safer and controlled treatment of a wide variety of cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Ultrasound speckle is a granular texture pattern appearing in ultrasound imaging. It can be used to distinguish tissues and identify pathologies. Lorentz force electrical impedance tomography is an ultrasound-based medical imaging technique of the tissue electrical conductivity. It is based on the application of an ultrasound wave in a medium placed in a magnetic field and on the measurement of the induced electric current due to Lorentz force. Similarly to ultrasound imaging, we hypothesized that a speckle could be observed with Lorentz force electrical impedance tomography imaging. In this study, we first assessed the theoretical similarity between the measured signals in Lorentz force electrical impedance tomography and in ultrasound imaging modalities. We then compared experimentally the signal measured in both methods using an acoustic and electrical impedance interface. Finally, a bovine muscle sample was imaged using the two methods. Similar speckle patterns were observed. This indicates the existence of an ‘acousto-electrical speckle’ in the Lorentz force electrical impedance tomography with spatial characteristics driven by the acoustic parameters but due to electrical impedance inhomogeneities instead of acoustic ones as is the case of ultrasound imaging. [ABSTRACT FROM AUTHOR]