The current study proposes simple methods for assessing the performance of robotic devices intended for Magnetic Resonance Imaging (MRI)-guided needle biopsy. In-house made agar-based breast phantoms containing biopsy targets served as the main tool in the evaluation process of an MRI compatible positioning device comprising a needle navigator. The motion accuracy of mechanical stages was assessed by calliper measurements. Laboratory evaluation of needle targeting included a repeatability phantom test and a laser-based method. The accuracy and repeatability of needle targeting was also assessed by MRI. The maximum error of linear motion for steps up to 10mm was 0.1mm. Needle navigation relative to the phantom and alignment with the various biopsy targets were performed successfully in both the laboratory and MRI settings. The proposed biopsy phantoms offered tissue-like signal in MRI and good haptic feedback during needle insertion. The proposed methods could be valuable in the process of validating the accuracy of MRI-guided biopsy robotic devices in both laboratory and real environments.

The mechanical properties of therapeutic ultrasound (US) have attracted scientific interest for thrombolysis enhancement in combination with thrombolytic agents and microbubbles (MBs). The aim of the study was to develop an in vitro model to observe how the effects of sonothrombolysis change in the case where a tissue-mimicking material (TMM) is placed in the path of the US beam before the clot. Fully retracted blood clots were prepared and pulse sonicated for 1 h under various conditions. The system was in a state of real circulating flow with a branch of an open bypass and an occluded tube containing a blood clot, thus mimicking the case of ischemic stroke. The effectiveness of thrombolysis was quantified in milligrams of clots removed. An agar-based TMM was developed around the occluded tube. The clot breakdown in a TMM was found to be more pronounced than in water, presumably due to the retention of the acoustic field. A higher level of acoustic power was required to initiate clot lysis (>76 W acoustic power) using only focused US (FUS). The greatest thrombolysis enhancement was observed with the largest chosen pulse duration (PD) and the use of MBs (150 mg clot mass lysis). The synergistic effect of FUS in combination with MBs on the enzymatic fibrinolysis enhanced thrombolysis efficacy by 260% compared to thrombolysis induced using only FUS. A reduction in the degree of clot lysis was detected due to the attenuation factor of the intervening material (30 mg at 1 and 4 ms PD). In vitro thrombolytic models including a TMM can provide a more realistic evaluation of new thrombolytic protocols. However, higher acoustic power should be considered to compensate for the attenuation factor. The rate of clot lysis is slow and the clinical use of this method will be challenging.

A robotic device featuring three motion axes was manufactured for preclinical research on focussed ultrasound (FUS). The device comprises a 2.75MHz single element ultrasonic transducer and is guided by Magnetic Resonance Imaging (MRI). The compatibility of the device with the MRI was evaluated by estimating the influence on the signal-to-noise ratio (SNR). The efficacy of the transducer in generating ablative temperatures was evaluated in phantoms and excised porcine tissue. System's activation in the MRI scanner reduced the SNR to an acceptable level without compromising the image quality. The transducer demonstrated efficient heating ability as proved by MR thermometry. Discrete and overlapping thermal lesions were inflicted in excised tissue. The FUS system was proven effective for FUS thermal applications in the MRI setting. It can thus be used for multiple preclinical applications of the emerging MRI-guided FUS technology. The device can be scaled-up for human use with minor modifications.

Focussed Ultrasound (FUS) combined with microbubbles (MBs) was proven a promising modality for non-invasive blood brain barrier disruption (BBBD). Herein, two devices for FUS-mediated BBBD in rodents are presented. A two-axes robotic device was manufactured for navigating a single element FUS transducer of 1MHz relative to the brain of rodents. A second more compact device featuring a single motorized vertical axis was also developed. Their performance was assessed in terms of motion accuracy, MRI compatibility and trans-skull BBBD in wild type mice using MBs in synergy with pulsed FUS. Successful BBBD was evidenced by the Evans Blue dye method, as well as by Fibronectin and Fibrinogen immunostaining. BBB permeability was enhanced when the applied acoustic intensity was increased. The proposed devices constitute a cost-effective and ergonomic solution for FUS-mediated BBBD in small animal models. Further experimentation is needed to examine the repeatability of results and optimise the therapeutic protocol.

The article is devoted to a review of the literature about the thin endometrium and its correction today. The problem of thin endometrium is very significant in cases of unsuccessful embryo implantation. There is no generally accepted approach to the definition of “thin endometrium” and ways of its correction in the literature. Phosphodiesterase type 5 (PDE5) inhibitors are considered to play a role in increasing endometrial thickness and improving pregnancy outcomes. Their action consists of various mechanisms, in particular, such as the induction of vasodilating effect through the effect on signaling to vascular smooth muscle, through the regulation of cell proliferation and induction of angiogenesis by increasing the expression of tumor suppressor factor (p53) and vascular endothelial growth factor A, the inhibition of inflammation by reducing the regulation of proinflammatory cytokines. Although PDE5 inhibitors increase the endometrial thickness through the various mechanisms, especially in women with thin endometrium, it does not necessarily mean that they have a positive effect in all clinical situations. Meanwhile, the successful outcome may be affected by the time of use of the drug, the type of infertility treatment, the main diseases such as pelvic disorders and inflammation. Therefore, there are ambiguous issues that need further research in this problem. Oral PDE5 inhibitors are also used as first-line therapy for the treatment of erectile dysfunction (ED), they have proven effectiveness, tolerability, action and couple satisfaction. Avanafil is the only selective inhibitor of the PDE5 isoenzyme with a low frequency of side effects compared to other drugs in this group. The high tolerability of these drugs has made them an attractive tool for the study of further physiological functions outside the ED with benefits for many non-sexual consequences.

A robotic system for Magnetic Resonance guided Focussed Ultrasound (MRgFUS) therapy of tumours in the breast, bone, thyroid, and abdomen was developed. A special C-shaped structure was designed to be attached to the table of conventional magnetic resonance imaging (MRI) systems carrying 4 computer-controlled motion stages dedicated to positioning a 2.75MHz spherically focussed transducer relative to a patient placed in the supine position. The developed system was evaluated for its MRI compatibility and heating abilities in agar-based phantoms and freshly excised tissue. Compatibility of the system with a clinical high-field MRI scanner was demonstrated. FUS heating in the phantom was successfully monitored by magnetic resonance thermometry without any evidence of magnetically induced phenomena. Cigar-shaped discrete lesions and well-defined areas of overlapping lesions were inflicted in excised tissue by robotic movement along grid patterns. The developed MRgFUS robotic system was proven safe and efficient by ex-vivo feasibility studies.

BackgroundConventional motion algorithms utilized during High Intensity Focused Ultrasound (HIFU) procedures usually sonicate successive tissue cells, thereby inducing excess deposition of thermal dose in the pre-focal region. Long delays (~60 s) are used to reduce the heating around the focal region. In the present study the experimental evaluation of six motion algorithms so as to examine the required delay and algorithm for which the pre-focal (near-field) and post-focal (far-field) heating can be reduced using thermal dose estimations is presented. Materials and MethodsA single element spherically focused transducer operating at 1.1 MHz and focusing beam at 9 cm, was utilized for sonication on a 400 mm2 area of an agar-based phantom. Movement of the transducer was performed with each algorithm, using 0–60 s (10 s step) delays between sonications. Temperatures were recorded at both near and far-field regions and thermal dose calculations were implemented. ResultsWith the algorithms used in the present study, a delay of 50–60 s was required to reduce heating in the near-field region. A 30 s delay induced a safe thermal dose in the far-field region using all algorithms except sequential which still required 60 s delay. ConclusionsThe study verified the conservative need for 60 s delay for the sequential plan treatment. Nevertheless, present findings suggest that prolonged treatment times can be significantly reduced in homogeneous tissues by selection of the optimized nonlinear algorithm and delay.

A prototype robotic system that uses magnetic resonance guided focused ultrasound (MRgFUS) technology is presented. It features three degrees of freedom (DOF) and is intended for thermal ablation of abdominal cancer. The device is equipped with three identical transducers being offset between them, thus focussing at different depths in tissue. The efficacy and safety of the system in ablating rabbit liver and kidney was assessed, both in laboratory and magnetic resonance imaging (MRI) conditions. Despite these organs' challenging location, in situ coagulative necrosis of a tissue area was achieved. Heating of abdominal organs in rabbit was successfully monitored with MR thermometry. The MRgFUS system was proven successful in creating lesions in the abdominal area of rabbits. The outcomes of the study are promising for future translation of the technology to the clinic.

BackgroundRobotic‐assisted diagnostic and therapeutic modalities require a highly accurate performance to be certified for clinical application. In this paper, three simple methods for assessing the accuracy of motion of magnetic resonance‐guided focused ultrasound (MRgFUS) robotic systems are presented.MethodsThe accuracy of motion of a 4 degrees of freedom robotic system intended for preclinical use of MRgFUS was evaluated by calliper‐based and magnetic resonance imaging (MRI) methods, as well as visually by performing multiple ablations on a plastic film.ResultsThe benchtop results confirmed a highly accurate motion in all axes of operation. The spatial positioning errors estimated by MRI evaluation were defined by the size of the imaging pixels. Lesions arrangement in discrete and overlapping patterns confirmed satisfactory alignment of motion trajectories.ConclusionsWe believe the methods presented here should serve as a standard for evaluating the accuracy of motion of MRgFUS robotic systems.

BackgroundA magnetic resonance image (MRI) guided robotic device for focussed ultrasound therapy of prostate cancer (PC) was developed. The device offers movement in 5 degrees of freedom (DOF) and uses a single‐element transducer that operates at 3.2 MHz, has a diameter of 25 mm and focuses at 45 mm.MethodsThe MRI compatibility of the system was evaluated in a 1.5 T scanner. The ability of the transducer to create lesions was evaluated in laboratory and MRI settings, on ex vivo pork tissue and in vivo rabbit thigh tissue.ResultsCavitational and thermal lesions were created on the excised pork tissue. In vivo experiments proved the efficacy of the system in ablating muscle tissue without damaging intervening areas.ConclusionsThe MRI compatible robotic system can be placed on the table of any commercial MRI scanner up to 7 T. The device has the ability of future use for transrectal focal therapy of PC with the patient in supine position.