MRI-compatible ultrasonic probe for minimally invasive therapy

The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ultrasound (US) probes. Particularly, a more realistic analysis with application-specific imaging targets can be extremely valuable to assess the expected performance of US probes in their potential clinical field of application. The experimental protocol presented in this work was purposely designed to provide an application-specific assessment procedure for newly-developed US probe prototypes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology in relation to brain imaging. The protocol combines the use of a bovine brain fixed in formalin as the imaging target, which ensures both realism and repeatability of the described procedures, and of neuronavigation techniques borrowed from neurosurgery. The US probe is in fact connected to a motion tracking system which acquires position data and enables the superposition of US images to reference Magnetic Resonance (MR) images of the brain. This provides a means for human experts to perform a visual qualitative assessment of the US probe imaging performance and to compare acquisitions made with different probes. Moreover, the protocol relies on the use of a complete and open research and development system for US image acquisition, i.e. the Ultrasound Advanced Open Platform (ULA-OP) scanner. The manuscript describes in detail the instruments and procedures involved in the protocol, in particular forthe calibration, image acquisition and registration of US and MR images. The obtained results prove the effectiveness of the overall protocol presented, which is entirely open (within the limits of the instrumentation involved), repeatable, and covers the entire set of acquisition and processing activities for US images.

Ultrasound (US) image guidance systems used in radiotherapy are typically calibrated for soft tissue applications, thus introducing errors in depth-from-transducer representation when used in media with a different speed of sound propagation (e.g. fat). This error is commonly referred to as the speed artifact. In this study we utilized a standard US phantom to demonstrate the existence of the speed artifact when using a commercial US image guidance system to image through layers of simulated body fat, and we compared the results with calculated/predicted values. A general purpose US phantom (speed of sound (SOS) = 1540 m s−1) was imaged on a multi-slice CT scanner at a 0.625 mm slice thickness and 0.5 mm × 0.5 mm axial pixel size. Target-simulating wires inside the phantom were contoured and later transferred to the US guidance system. Layers of various thickness (1–8 cm) of commercially manufactured fat-simulating material (SOS = 1435 m s−1) were placed on top of the phantom to study the depth-related alignment error. In order to demonstrate that the speed artifact is not caused by adding additional layers on top of the phantom, we repeated these measurements in an identical setup using commercially manufactured tissue-simulating material (SOS = 1540 m s−1) for the top layers. For the fat-simulating material used in this study, we observed the magnitude of the depth-related alignment errors resulting from the speed artifact to be 0.7 mm cm−1 of fat imaged through. The measured alignment errors caused by the speed artifact agreed with the calculated values within one standard deviation for all of the different thicknesses of fat-simulating material studied here. We demonstrated the depth-related alignment error due to the speed artifact when using US image guidance for radiation treatment alignment and note that the presence of fat causes the target to be aliased to a depth greater than it actually is. For typical US guidance systems in use today, this will lead to delivery of the high dose region at a position slightly posterior to the intended region for a supine patient. When possible, care should be taken to avoid imaging through a thick layer of fat for larger patients in US alignments or, if unavoidable, the spatial inaccuracies introduced by the artifact should be considered by the physician during the formulation of the treatment plan.

Acquiring good image quality is one of the main challenges for fully-automatic robot-assisted ultrasound systems (RUSS). The presented method aims at overcoming this challenge for orthopaedic applications by optimizing the orientation of the robotic ultrasound (US) probe, i.e. aligning the central axis of the US probe to the tissue's surface normal at the point of contact in order to improve sound propagation within the tissue. We first optimize the in-plane orientation of the probe by analyzing the confidence map of the US image. We then carry out a fan motion and analyze the resulting forces estimated from joint torques to align the central axis of the probe to the normal within the plane orthogonal to the initial image plane. This results in the final 3D alignment of the probe's main axis with the normal to the anatomical surface at the point of contact without using external sensors for surface reconstruction or localizing the point of contact in an anatomical atlas. The algorithm is evaluated both on a phantom and on human tissues (forearm, upper arm and lower back). The mean absolute angular difference (±STD) between true and estimated normal on stationary phantom, forearm, upper arm and lower back was 3.1 ± 1.0°, 3.7 ± 1.7°, 5.3 ± 1.3° and 6.9 ± 3.5°, respectively. In comparison, six human operators obtained errors of 3.2 ± 1.7° on the phantom. Hence the method is able to automatically position the probe normal to the scanned tissue at the point of contact and thus improve the quality of automatically acquired ultrasound images.

We propose a system for thoracic aortic stent-graft deployment that employs a magnetic tracking system (MTS) and intraoperative ultrasound (US). A preoperative plan is first performed using a general public utilities-accelerated cardiac modeling method to determine the target position of the stent-graft. During the surgery, an MTS is employed to track sensors embedded in the catheter, cannula, and the US probe, while a fiducial landmark based registration is used to map the patient's coordinate to the image coordinate. The surgical target is tracked in real time via a calibrated intraoperative US image. Under the guidance of the MTS integrated with the real-time US images, the stent-graft can be deployed to the target position without the use of ionizing radiation. This navigation approach was validated using both phantom and animal studies. In the phantom study, we demonstrate a US calibration accuracy of 1.5 ± 0.47 mm, and a deployment error of 1.4 ± 0.16 mm. In the animal study, we performed experiments on five porcine subjects and recorded fiducial, target, and deployment errors of 2.5 ± 0.32, 4.2 ± 0.78, and 2.43 ± 0.69 mm, respectively. These results demonstrate that delivery and deployment of thoracic stent-graft under MTS-guided navigation using US imaging is feasible and appropriate for clinical application.

The tumor microenvironment presents a physical barrier for successful drug delivery. Low-intensity pulsed ultrasound (US) in combination with a microbubble (MB) contrast agent has been shown to safely and reversibly increase microvascular permeability. This procedure temporarily allows anticancer drugs to more effectively extravasate to the targeted tumor tissue. Previously, focused US therapies were performed throughout a single two-dimensional plane using either a single or a multiple focused US configuration. This research demonstrated that a multi-focus, multi-repetition approach was superior to a single focus US therapy. The goal of this research was to build upon those findings and introduce a new three-dimensional (3-D) focused US therapeutic system that incorporates US imaging guidance and functionality for user-defined planning in volume space. To evaluate drug delivery, a small molecule infrared (IR) dye was used for in vivo detection in live animals and represents a surrogate anticancer drug. 3-D US therapy was compared to a 2-D approach using breast cancer-bearing mice. Prior to US therapy, each mouse received a bolus injection of MBs (Lantheus Medical Imaging) and IR dye. Both 2-D and 3-D US therapy was performed using a custom US image-guided system (HIFUPlex-06, Verasonics Inc). In vivo optical imaging (Pearl Trilogy, LI-COR Biosciences) was performed at 0, 24, and 48 h. Tumors were then excised for ex vivo optical imaging and analysis. Preliminary results revealed up to a 3-fold increase in dye uptake ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$p &lt; 0.03$</tex> ) at both 24 and 48 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$h$</tex> for tumors treated with the 3-D US therapy. These findings were consistent with ex vivo optical imaging results.

There is no real need to discuss the potential advantages – mainly the excellent soft tissue contrast, nonionizing radiation, flow, and molecular information – of magnetic resonance imaging (MRI) as an intraoperative diagnosis and therapy system particularly for neurological applications and oncological therapies. Difficult patient access in conventional horizontal-field superconductive magnets, very high investment and operational expenses, and the need for special nonferromagnetic therapy tools have however prevented the widespread use of MRI as imaging and guidance tool for therapy purposes. The interventional use of MRI systems follows for the last 20+ years the strategy to use standard diagnostic systems and add more or less complicated and expensive components (eg, MRI-compatible robotic systems, specially shielded in-room monitors, dedicated tools and devices made from low-susceptibility materials, etc) to overcome the difficulties in the therapy process. We are proposing to rethink that approach using an in-room portable ultrasound (US) system that can be safely operated till 1 m away from the opening of a 3T imaging system. The live US images can be tracked using an optical inside–out approach adding a camera to the US probe in combination with optical reference markers to allow direct fusion with the MRI images inside the MRI suite. This leads to a comfortable US-guided intervention and excellent patient access directly on the MRI patient bed. This was combined with an entirely mechanical MRI-compatible 7 degrees of freedom holding arm concept, which shows that this test environment is a different way to create a cost-efficient and effective setup that combines the advantages of MRI and US by largely avoiding the drawbacks of current interventional MRI concepts.

Image-guided biopsy is the most common technique for breast cancer diagnosis. Although magnetic resonance imaging (MRI) has the highest sensitivity in breast lesion detection, ultrasound (US) biopsy guidance is generally preferred due to its non-invasiveness and real-time image feedback during the insertion. In this work, we propose an autonomous robotic system for US-guided biopsy of breast lesions identified on pre-operative MRI. After initial MRI to breast registration, the US probe attached to the robotic manipulator compresses the breast tissues until a pre-determined force level is reached. This technique, known as preloading, will allow to minimize lesion displacement during the needle insertion. Our workflow integrates a deformation compensation strategy based on patient-specific biomechanical model to update the US probe orientation keeping the target lesion on the US image plane during compression. By relying on a deformation model, the proposed system does not require lesion visibility on US. Experimental evaluation is performed to assess the performance of the system on a realistic breast phantom with 15 internal lesions, considering different preloading forces. The deformation compensation strategy allows to improve localization accuracy, and as a consequence final probe positioning, for all considered lesions. Median lesion localization error is 3.3 mm, which is lower than the median lesion radius, when applying a preloading of 2 N, which guarantees both minimal needle insertion error and tissue stress.

Noninvasive ultrasound (US) brain therapies, including US brain stimulation, US drug delivery by BBB opening, or US thrombolysis, have great potential in clinical applications. But target positioning is a challenge. Dual-mode US system provides a promising solution, which can carry out US therapy function under the guidance of US imaging. However, the brain skull usually deteriorates the brain image seriously, because of the great amplitude of US echoes reflected from the skull. In order to improve the guidance function of US image, we investigated the relationship of skull structures and US image in rodents. Computerized tomography (CT) images of the heads of four rats were scanned by a micro-CT system. US skull imaging was carried out by a custom-built US imaging and stimulation system with a dual-mode 2D matrix array with 1 MHz center frequency and 256 elements. The features of the CT images and the US images of rat skulls were carefully recognized, which were used to identify the coordinates of the rat brain from US images. After the US imaging and brain position was determined, multi-target BBB opening was carried out based on the identified coordinate. The result indicated that the deviation of the coordinate was less than 1 mm. US skull imaging will be a useful method for image-guided noninvasive therapy applications.

Daily monitoring of internal tissues with shape-conformable and breathable ultrasound (US) imaging probes is promising for early detection of diseases. In recent years, textile substrates are widely used for wearable devices since they satisfy both conformability and breathability. However, it is not currently possible to use textile substrates for US probes due to the reflection or attenuation of US waves at the air gaps in the textiles. In this paper, we fabricated a shape-conformable and breathable US imaging probe by sandwiching the US elements between two woven polyester textiles on which copper electrodes were formed through electroless plating. The air gaps between the fibers at the electrode parts were filled with copper, allowing for high penetration of US waves. On the other hand, the non-electrode parts retain air gaps, leading to high breathability. The fabricated textile-based probe showed low flexural rigidity (0.066 × 10−4 N m2 m−1) and high air permeability (11.7 cm3 cm−2 s−1). Human neck imaging demonstrated the ability of the probe to monitor the pulsation of the common carotid artery and change in the internal jugular vein diameter, which led to the early detection of health issues such as arteriosclerosis and dehydration, and the capability of stable 24-hour monitoring.

Single-plane ultrasound (US) probes are commonly used to initiate ultrasound-guided peripheral intravenous (USGPIV) access for patients with difficult intravenous access (DIVA) in the emergency department (ED), although their use is not yet standardized across all EDs. This pilot project introduced the use of a biplane US probe for USGPIV access at a Level 1 Trauma Center ED. Following the training of 10 registered nurses (RNs) in the application of biplane US probes, the project aimed to decrease reliance on ED providers (e.g., NPs, PAs, and physicians) for USGPIV insertions in DIVA patients, allowing providers to focus on other critical tasks and improving patient care efficiency. Primary outcomes measured included the average number of attempts required, progression to critical care access devices, ED patient flow times, and RN utilization rates of the biplane US probe post-training. Results showed that the biplane method improved outcomes compared to the single-plane method, with a 23.8% decrease in the average number of attempts required to obtain access, an 80% decrease in subsequent critical care vascular access placement, and an increase in the rate of both single-plane and biplane US probe use after training compared to baseline. While ED flow rate did not improve, this pilot project demonstrated that biplane US probes for USGPIV access in the ED setting improve patient outcomes.

Sixteen pregnant patients with pelvic masses detected with ultrasound (US) were studied with magnetic resonance (MR) imaging at 0.35 T. Two patients were in their first trimester, eight in the second, and six in the last. On MR images, 34 masses were seen, including 19 uterine leiomyomas. With US, 20 masses were detected. All masses not seen with US were leiomyomas. Only 20 masses (in 11 patients) were removed for histologic study. In nine cases, MR imaging and US provided similar information on the origin, extent, and type of mass. In seven patients, MR imaging contributed additional information. MR imaging depicted more leiomyomas than US in three patients. In another case, MR images showed that a mass depicted with US was actually a loop of bowel. MR images allowed differentiation between a solid soft-tissue mass and a hemorrhagic fluid-containing mass, correctly depicted the presence of an abdominal pregnancy, and allowed evaluation of the parametrium for spread of cervical carcinoma.

Current interstitial techniques of tumor ablation face challenges that ultrasound (US) technologies could meet. The ablation radius and directionality of the US beam could improve the efficiency and precision. Here, a nine-gauge magnetic resonance (MR)-compatible dual-mode US catheter prototype was experimentally evaluated for ultrasound image-guided high-intensity focused ultrasound (USgHIFU) conformal ablations. The prototype consisted of 64 piezocomposite linear-array elements and was driven by an open research programmable dual-mode US platform. After verifying the US image guidance capabilities of the prototype, the high-intensity focused US (HIFU) output performances (dynamic focusing and HIFU intensities) were quantitatively characterized, together with the associated 3-D HIFU-induced thermal heating in tissue phantoms [using MR thermometry (MRT)]. Finally, the ability to produce robustly HIFU-induced thermal ablations in in vitro liver was studied experimentally and compared to numerical modeling. Investigations of several HIFU dynamic focusing allowed overcoming the challenges of miniaturizing the device: monofocal focusing maximized deep energy deposition, while multifocal strategies eliminated grating lobes. The linear-array design of the prototype made it possible to produce interstitial US images of tissue and tumor mimics in situ. Multifocal pressure fields were generated without grating lobes and transducer surface intensities reached up to . Seventeen elementary thermal ablations were performed in vitro. Rotation of the catheter proved the directionality of ablation, sparing nontargeted tissue. This experimental proof of concept demonstrates the feasibility of treating volumes comparable to those of primary solid tumors with a miniaturized USgHIFU catheter whose dimensions are close to those of tools traditionally used in interventional radiology while offering new functionalities.

In this study, we developed a focused ultrasound (FUS) thermal therapy system with ultrasound image guidance and thermocouple temperature measurement feedback. Hydraulic position devices and computer-controlled servo motors were used to move the FUS transducer to the desired location with the measurement of actual movement by linear scale. The entire system integrated automatic position devices, FUS transducer, power amplifier, ultrasound image system, and thermocouple temperature measurement into a graphical user interface. For the treatment procedure, a thermocouple was implanted into a targeted treatment region in a tissue-mimicking phantom under ultrasound image guidance, and then the acoustic interference pattern formed by image ultrasound beam and low-power FUS beam was employed as image guidance to move the FUS transducer to have its focal zone coincident with the thermocouple tip. The thermocouple temperature rise was used to determine the sonication duration for a suitable thermal lesion as a high power was turned on and ultrasound image was used to capture the thermal lesion formation. For a multiple lesion formation, the FUS transducer was moved under the acoustic interference guidance to a new location and then it sonicated with the same power level and duration. This system was evaluated and the results showed that it could perform two-dimensional motion control to do a two-dimensional thermal therapy with a small localization error 0.5 mm. Through the user interface, the FUS transducer could be moved to heat the target region with the guidance of ultrasound image and acoustic interference pattern. The preliminary phantom experimental results demonstrated that the system could achieve the desired treatment plan satisfactorily.

Robotic ultrasonography potentially acts as an essential aid to medical diagnosis. To overcome the limitations in robotic ultrasonography, in this paper, we proposed a novel self-adaptive parallel manipulator (SAPM) that can automatically adjust the ultrasound (US) probe pose to adapt to various contours of scanned areas, provide approximate constant operating forces/torques, achieve mechanical measurement, and cushion undesired produced forces. A novel parallel adjustment mechanism is proposed to attain automatic pose adjustment with 3 degrees of freedom (DOFs). This mechanism enables the US probe to adapt to different scanned areas and to perform the scanning with approximate constant forces and torques. Besides, we present a mechanical measurement and safety protection method that can be integrated into the SAPM and used as operation status monitoring and early warning during scanning procedures by capturing operating forces and torques. Experiments were carried out to calibrate the measurement and buffer units and evaluate the performance of the SAPM. Experimental results show the ability of the SAPM to provide 3-DoFs motion and operating force/torque measurement and automatically adjust the US probe pose to capture US images of equally good quality compared to a manual sonographer scan. Moreover, it has characteristics similar to soft robots that could significantly improve operation safety, and could be extended to some other engineering or medical applications.

BackgroundStress echocardiography (SE) has recently regained momentum as an important diagnostic tool for the assessment of both ischemic and non-ischemic heart disease. Performing SE during physical exercise is challenging due to a suboptimal patient position and vigorous movements of the patient’s chest. This hampers a stable ultrasound position and reduces the diagnostic performance of SE. A stable ultrasound probe position would facilitate producing high quality images during continuous measurements. With Probefix (Usono, Eindhoven, The Netherlands), a newly developed tool to fixate the ultrasound probe to the patient’s chest, stabilization of the probe during physical exercise is possible.Implementation and resultsThe technique of SE with the Probefix and its’ feasibility are evaluated in a small pilot study. Probefix fixates the ultrasound probe to the patient’s chest, using two chest straps and a fixation device. The ultrasound probe position and angle may be altered with a relative high degree of freedom. We tested the Probefix for continuous echocardiographic imaging in 12 study subjects during supine and upright ergometer stress tests. One patient was unable to perform exercise and in two study subjects good quality images were not achieved. In the other patients (82%) a stable probe position was obtained, with subsequent good quality echocardiographic images during SE.ConclusionWe have demonstrated the feasibility of the Probefix support during ergometer tests in supine and upright positions and conclude that this external fixator may facilitate continuous monitoring of cardiac function in a group of patients.