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 Table of Contents  
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 32-43

Magnetic resonance image-guided focused ultrasound robotic system with four computer-controlled axes with endorectal access designed for prostate cancer focal therapy

1 Electrical Engineering Department, Cyprus University of Technology; Research & Development, MedSonic Ltd, Limassol, Cyprus
2 Electrical Engineering Department, Cyprus University of Technology, Limassol, Cyprus
3 Radiology Department, German Oncology Centre, Limassol, Cyprus

Date of Submission20-Jan-2020
Date of Decision24-Apr-2020
Date of Acceptance08-Jul-2020
Date of Web Publication26-Aug-2020

Correspondence Address:
Christakis Damianou
Electrical Engineering Department, Cyprus University of Technology, Limassol
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/digm.digm_1_20

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Background: A magnetic resonance image (MRI)-guided robotic system dedicated for prostate cancer (PC) was produced that carries a small spherically focused, single-element, ultrasonic transducer which can be potentially utilized endorectally. Materials and Methods: The developed robotic device utilizes four computer-controlled axes. An agar-based phantom was developed, which included a cavity that mimics the rectum geometry. Experiments with the system were performed in a 1.5T MRI system using the gel phantom. The transducer has a diameter of 18 mm, operates with 3 MHz, and focuses energy at 40 mm. Results: The functionality of the robot was assessed by means of magnetic resonance thermometry, demonstrating sufficient heating in both axes of operation (linear and angular). Conclusions: A functional MRI-guided robotic system was produced, which can create significant and controlled thermal exposures. The intention is to use the proposed device endorectally in the future for the focal treatment of PC.

Keywords: Magnetic resonance image, prostate, ultrasound

How to cite this article:
Giannakou M, Menikou G, Ioannides K, Damianou C. Magnetic resonance image-guided focused ultrasound robotic system with four computer-controlled axes with endorectal access designed for prostate cancer focal therapy. Digit Med 2020;6:32-43

How to cite this URL:
Giannakou M, Menikou G, Ioannides K, Damianou C. Magnetic resonance image-guided focused ultrasound robotic system with four computer-controlled axes with endorectal access designed for prostate cancer focal therapy. Digit Med [serial online] 2020 [cited 2023 Mar 24];6:32-43. Available from: http://www.digitmedicine.com/text.asp?2020/6/1/32/293501

  Introduction Top

Prostate cancer (PC) is the second most frequently diagnosed type of cancer in the male population worldwide.[1] According to the GLOBOCAN 2018 estimates published by the International Agency for Research on Cancer, 1,276,106 new cases of PC were reported worldwide and 358,989 deaths (3.8% of all deaths caused by cancer in men) in 2018.[2] Conventional prognostic tests such as prostate-specific antigen (PSA), Gleason scoring, and clinical staging are no more considered adequate since they do not take into consideration the genomic aberrations of the disease that affect the associate risk, treatment outcome, and drug response.[3] Nowadays, oncogenetic testing and biomarker profiling is considered the optimized approach for designing customized therapeutic interventions.[4],[5]

Patients diagnosed with localized or locally advanced PC, depending on the severity of the disease, are usually offered the following treatment options: active surveillance, radical prostatectomy (RP), external beam radiation therapy, interstitial prostate brachytherapy, and hormonal therapy.[6] The European Association of Urology guidelines recommend RP for intermediate and a combination of RP and extended pelvic lymph node dissection for high-risk PC cancer populations.[7]

In a recently published update of the PC Intervention Versus Observation Trial study, it was demonstrated that on a 20-year follow-up of men diagnosed with localized PC, the use of RP showed insignificantly reduced mortality compared to observation approach.[8] RP is correlated with several postoperative complications with the most frequent being urinary incontinence, urethral stricture, obstructive infertility, and sexual dysfunction which often result in lengthy hospitalization.[9],[10]

There is growing scientific evidence and clinical experience that patients with low-risk disease may benefit more from a minimally invasive focal therapy. In addition, complications associated with prostatectomy and other “whole gland” interventions can be avoided. It is becoming clear that a number of patients with local and small PC could be provided focal treatment in which only the focus of the target is attacked: between the two extremes of active surveillance and radical treatment; there must be an intermediate approach. Analogous to lumpectomy for breast cancer, the goal of PC focal therapy is to effectively treat the area of the prostate that contains the cancer. This approach could potentially minimize the previously indicated side effects in the surrounding tissue. There is still ongoing debate on the treatment's efficacy and in setting the correct criteria for identifying appropriate candidates for focal therapy.

Different modalities are proposed to achieve whole gland, subtotal, or focal ablation with the guidance of imaging modalities, such as ultrasound (US) or magnetic resonance image (MRI). Brachytherapy and radiation external beam therapy are the most commonly used as minimally invasive techniques, not only for the therapy of localized PC, but also for the palliation of high-grade tumors.[11],[12] Other minimally invasive techniques such as cryoablation, irreversible electroporation, vascular-targeted photodynamic therapy, radiofrequency, and laser ablation, have also been utilized for focal therapy with promising results.[13]

In the 1990s, focused US surgery (FUS) was utilized for the treatment of PC.[14],[15] FUS is a noninvasive therapy that is used for localized PC and sometimes for salvage therapy. It is a minimally invasive technique that uses focused US to thermally ablate above the threshold of necrosis portion of tissue. Each sonication heats only a small focal target, so always multiple sonications must be used to ablate an entire target area. Due to the propagation mechanism of US, this technique is performed with caution near nerves, bone, and rectum.

Magnetic resonance-guided FUS (MRgFUS), which was introduced in the last decade as an integrated therapeutic modality, possessed very attractive features since it combined clinical imaging necessary for treatment planning along with real-time monitoring of the efficacy and safety of the procedure.[16] Currently, this technique is approved by the Federal and Drugs Administration (FDA) for fibroid ablation and shows great potential in bone metastasis pain palliation. Promising results for managing malignancies of the pancreas, prostate, liver, kidney, breast, and bone have been obtained.[17]

Two FDA-approved US-guided FUS devices are currently available for PC: Ablatherm (EDAP TMS SA, Vaulx-en-Velin, France) and Sonablate (Focus Surgery Inc., Indianapolis, IN, USA, now called SONACARE).[18] The Ablatherm has both the imaging (7.5 MHz) and therapeutic (3 MHz) transducers included in a unique endorectal probe focused at 40 mm. The Sonablate uses a single transducer (4 MHz) for both imaging and treatment. Several probes are available with many focal lengths ranging from 25 to 45 mm. The prostate is visualized using real-time US generated by the probe using low acoustic intensity. Once the target area is identified, the prostate tissue is ablated with high intensities (1000–3000 W/cm 2) focused in a small (1–3 mm wide) focal plane. Each pulse heats the tissue to 60°C–80°C for close to 5 s duration. The US frequency used in the existing systems is optimum for therapy, but is not very effective for imaging (bad spatial resolution). The most important difference between the two devices is patient positioning. Both devices are approved for commercial distribution in the European Union, USA, Canada, South Korea, Japan, and Russia. In a recent clinical study, 918 patients with localized PC were treated with the Sonablate device. The authors reported that the cancer-specific survival rate was 97.4% and the 10-year overall survival was 89.6%.[19] Similar survival rates have been reported for patients treated with the Ablatherm device.[20]

Best results after FUS in terms of negative biopsies and low PSA levels were achieved in patients with low-grade PC.[21] In a review publication by Chaussy and Thüroff,[22] FUS is the best short-term cancer control option in terms of percentage of negative biopsies and decrease of PSA serum levels. FUS treatment could be complicated by adverse events involving the bladder function (2%–58%).[21] Other complications included rectal burn (0%–15%) and rectourethral fistula (0%–3%). The studies performed using an Ablatherm device reported higher complication rates with respect to the Sonablate studies. However, until long-term results are provided, cautious optimism is recommended.

Multiparametric MRI utilizing T2-weighted, diffusion-weighted (DWI) MRI, and dynamic contrast-enhanced MRI (DCE-MRI) represent the state-of-the-art for detection, localization, and staging of PC.[23],[24] T2-weighted imaging provides evaluation of morphology. DWI and DCE-MRI provide functional information about the prostate, which helps improve PC detection as well as characterization of tumor aggressiveness. This advantage makes MRI the most suitable technique for targeting focal cancer lesions in the prostate.

The first attempt of using MRgFUS in prostate applications was tested in a preclinical animal study by McDannold et al.,[25] where canines were treated using a transrectal probe. The temperature was monitored using a single-slice SPoiled Gradient-Recalled (SPGR) sequence. In another animal study by Kinsey et al.,[26] a transurethral probe was used to treat the prostate of 3 canines and temperature was monitored using proton resonance frequency shift (PRFS) methods.

One of the first experiences in human prostate MRgFUS was presented by Napoli et al.,[27] where patients with localized PC underwent treatment with the ExAblate system before RP. The system combines a 2.3 MHz, 1000 element/channel phased array transducer, and a robotic transducer positioning system. Recently, in a phase 1 trial by Ghai et al.,[28] eight patients with low/intermediate-risk PC were treated with MRgFUS to evaluate the feasibility and safety of focal therapy. The study concluded that MRgFUS is a feasible and safe method of noninvasively ablating low/intermediate-risk PC with acceptable short-term oncologic outcomes.

An alternative approach for MRgFUS is to access the prostate using a transurethral probe. With this approach, a wider variety of applicators can be used (planar, curvilinear, and tubular). A planar applicator can be used with faster penetration and large volume of treatment.[29],[30] The advantage of curvilinear applicators is greater control over selective heating. The tubular applicator [31],[32] allows electronic control of an angular heating pattern. Both the planar and curvilinear applicator needed about 10–30 min to ablate larger lesions in the prostate because of a narrow acoustic beam width (4 mm).[20] The tubular applicator does not need mechanical rotation, unlike the others, so it may reduce potential motion artifacts.[31],[32]

The proposed system was guided by MRI. MRI provides near real-time temperature mapping which provides essential information about the location of the focal spot. It also offers temperature mapping of the ultrasonic exposure. In this work, a dedicated mechanical device was designed to move with 4° of freedom a transrectal MRgFUS transducer during a thermal procedure. Compared to the US-guided FUS system, the proposed system is superior due to the MRI guidance. Compared to the Exblate system, it is considered superior because single-element transducer was used with the same success which makes the system less complex and affordable.

The proposed robotic system is a substantial extension of the robotic system developed previously by our group.[33] The previous system that included one linear and one angular axis had many disadvantages, since the absence of the two extra stages makes it impossible to be used efficiently by physicians. In addition, the previous system had accuracy problems and it was not ergonomic. With the proposed system, all the existing technical problems were overcome.

The proposed system includes two linear stages and two angular stages. The system has been inspired by existing FUS systems with ultrasonic imaging.[21],[34] The proposed system uses safe materials to be able to perform MRI imaging for guidance and monitoring. One PC-controlled axis was needed for linear motion along the axis of the rectum (Y) to position the transducer over the tumor in the prostate gland, and another PC-controlled linear axis was needed to lift the robot in the up-down direction (Z), adjusting the system to the variable height of the rectum relative to the MRI table. One angular axis (θ) was needed to rotate the transducer around the XY-plane, so that different positions in the prostate can be treated. Another PC-controlled axis was needed to move the endorectal probe angularly, so that it is aligned with the inclined rectum.

  Materials and Methods Top

Robotic system

Mechanical design of the positioning device

The developed robotic device possesses 4° of freedoms: (1) a linear axis for motion along the rectum (Z-axis in MRI), (2) an angular axis for rotation within the rectum (theta axis, XY plane for MRI), (3) a linear axis to lift the robot up and down since the height of the rectum varies from patient to patient (Y-axis in MRI), and (4) Angular axis to set the entry angle to the rectum (Phi axis).

[Figure 1]a shows the Computer-Aided Design (CAD) drawing of the linear axis (Z axis) for motion along the rectum. The Z-plate was coupled to a long plastic screw, which was attached to the motor shaft. The Z-axis was moved within the guide slot produced within the so-called base. An encoder strip was placed in the Z-axis plate and moves inside the encoder module (US Digital Corporation, Vancouver, WA 98684, USA), which is not visible in this drawing. [Figure 1]b shows the corresponding linear axis to lift the robot up and down (Y axis). Again, here, a screw was attached to a motor shaft. The Y-axis plate carries a structure, which holds the base and which was rotated by the Φ axis. The encoder principle was the same as the Z-stage. [Figure 1]c shows the CAD drawing of the angular axis to set the entry angle to the rectum (Φ axis). This was achieved by attaching the base to the Φ structure. A planetary gear attached to the Φ structure creates rotational motion. A circular encoder plastic strip was attached to the gear and rotates within an angular encoder (same principle was applied for the Θ axis). [Figure 1]d shows the corresponding angular axis for rotation within the rectum (Θ axis). The motor in the front of the Z-plate establishes angular motion (Θ stage). The angular gear was attached to the bottom of the Z-plate. An angular encoder was placed on the shaft of the motor and ensures accurate angular movement of the shaft.
Figure 1: (a) CAD drawing of the linear axis (Z axis), (b) Linear axis to lift the robot up and down (Y-axis), (c) CAD drawing of the angular axis (Φ axis), and (d) Angular axis (Θ axis)

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The plastic enclosure that houses the transducer was made out of acrylonitrile butadiene styrene (ABS) plastic. The concept of the transducer enclosure is shown in [Figure 2]. The water enclosure which was attached into the base included two thin water inlets for filling the enclosure with degassed water. In addition, by circulating cold water, cooling of the transducer can be achieved. The transducer was attached to the shaft of the Θ stage. At the far end of the water enclosure, the width of the water container was reduced, because at this point, the sphincter of the patient surrounds the water container, and thus pressure to the sphincter had to be reduced. The water enclosure will be inserted in the rectum in future clinical trials. Since the transducer shaft that connects to the Θ shaft is immersed in water, a structure to seal the water was produced.
Figure 2: The concept of the transducer enclosure

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The transducer material was made out of P762-type piezoceramic (Ferroperm, Kvistgaard, Denmark). A backing material (epoxy) was used behind the transducer element. The transducer's impedance was matched to 50 Ω. A cooling system was used that circulates cold water (15°) on the transducer's face using a peristaltic pump (Cole Parmer, 7518-40, Vernon Hills, IL, USA) to avoid overheating of the piezoelectric material. To reduce the influence on the MRI image, a custom-made low-pass filter with 10 MHz cutoff frequency was used.

The entire robotic system was developed using the software Microstation (V8, Bentley Systems, Inc., Exton, Pennsylvania, United States). After completion of the design, drawings of the individual parts were sent to a 3D printer (FDM400, Stratasys, 7665 Commerce Way, Eden Prairie, Minnesota, 55344, USA) for production. This 3D printer produces parts made out ABS.

The four axes were driven by piezoelectric ultrasonic motors (USR60-S3N, Shinsei Kogyo Corp., Tokyo, Japan). The positioning robotic system was designed, so that it can be placed on the table of any high-field MRI scanner. It has a maximum height of 19 cm, a length of 62 cm, and a width of 28 cm. The motion range of the robot was set to Z: 8 cm, Θ: ±90°, Φ: 0–90°, and Y: 6 cm, which is sufficient to treat any prostate size. The robotic system weights around 2.3 kg. [Figure 3]a shows the CAD drawing of the complete robotic system. [Figure 3]b shows the photo of the positioning device with the four computer-controlled stages without cables to improve visualization. [Figure 4] shows the concept of using this robotic system in the MRI scanner. It was assumed that the patient is lying in supine position on the table with slightly elevated legs to provide an optimal access to the rectum for the US transducer. Then, the water enclosure is inserted in the rectum of the patient after proper positioning of the Y-axis and the Φ axis.
Figure 3: (a) CAD drawing of the complete robotic system without cables in order to improve visualization. (b) Photo of the positioning device with the four computer-controlled stages

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Figure 4: Concept of using this robotic system in the magnetic resonance image scanner

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Feedback control

Four optical encoders were used (US Digital Corporation). The EM1 optical encoders work in conjunction with a polymer plastic strip materials and it uses light-emitting diode source and a monolithic detector. For the two linear axes, the EM1-0-500-I (US Digital Corporation) encoder was used, whereas for the angular motion, the EM1-2-2500-I (US Digital Corporation) encoder was used. The encoder output is connected to the counter input of a data acquisition (DAQ) board USB 6251 (National instruments, Austin, Texas, USA).


A user-friendly program written in C# (Visual Studio 2010 Express, Microsoft Corporation, USA) has been developed to control the robotic system. The software has the following functionalities: (a) communication with MRI, (b) movement of the 4 axes either in user-defined steps or in grid sequences (for Z and Θ axes) by specifying the pattern, the step, and the number of steps, (c) history (functions activated), (d) patient information, (e) transducer coordinates, (f) MR thermometry, and (g) temperature measurement using thermocouples.

Electronic system

The enclosure hosting the motor drivers was placed outside the MRI room since magnetic materials are involved. A DC supply (24 V, 2 A) drives the Shinsei drives of the motors. Wires from the Shinsei drivers are connected to a USB 6251 DAQ interface card (National Instruments, Austin, Texas, United States) via a connecting block. The USB 6251 interface card includes timing and digital I/O modules. The motors were driven when the ground and clockwise terminals of the Shinsei drivers were connected (clockwise rotation) or when the ground and anticlockwise terminals of the Shinsei drivers were connected (anticlockwise rotation). This was achieved by initiating a command from the software which places 2 digital output terminals of the DAQ interface (for example, ground and clockwise) in the same potential. Movement of a certain axis can be achieved also manually by means of an ON-OFF-ON switch.

High-intensity focused ultrasound system

The high-intensity focused ultrasound (HIFU) system consists of a signal generator (HP 33120A, Agilent technologies, Englewood, CO, USA), an RF amplifier (250 W, AR, Souderton, PA, USA), and a spherical transducer made from piezoelectric ceramic (Ferroperm). The transducer operates at 3 MHz and has focal length of 40 mm and diameter of 18 mm.

Agar-based phantom

To evaluate the functionality of the transducer, an agar-based phantom was developed. This phantom was used also to evaluate the effectiveness of the thermal exposure using MR thermometry. An agar/silica/evaporated milk phantom was developed which can be produced in the laboratory setting at a very low cost. One of the ingredients of the phantom was agar powder of bacteriological-grade type (Himedia Laboratories, Mumbai, Maharashtra, India). To control the acoustic properties of the phantom, crystalline silica dioxide powder (Merck Millipore, Darmstadt, Germany) was added, which is insoluble in water and possesses a high melting temperature (1750°C). Evaporated milk was added in the gel. Being a low scatterer and rich in proteins and fats, evaporated milk controlled the attenuation of the gel primarily through the process of acoustic absorption. The recipe of the agar-based phantom consisted of 2% w/v agar, 2% w/v silica dioxide, and 40% v/v evaporated milk.

[Figure 5]a shows the CAD drawing of the enclosure of the agar phantom. A structure having the size and shape of the transducer enclosure was placed on the agar phantom. When the agar phantom was prepared, the structure was removed, thus creating the shape and size of the rectum. [Figure 5]b shows the creation of cavity that mimics the rectum. The FUS probe was covered with a condom, lubricated, and inserted into the phantom. The condom was filled with 200–250 mL of degassed water to ensure effective coupling of the probe to the agar material (mimicking the rectal wall). The placement of the transducer probe inside the phantom was confirmed using an ultrasonic system (Philips HD7 series US Systems, Philips and Neusoft Medical Systems Co. Ltd, Shenyang, China) and by high-resolution MRI.
Figure 5: (a) CAD drawing of the enclosure of the agar-based phantom, and (b) the creation of cavity that mimics the rectum

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Magnetic resonance imaging

The 4-d robotic HIFU system was tested in a 1.5 T MR system (Signa, General Electric, Fairfield, CT, USA) using a lumbar coil (USA instruments, Cleveland, OH, USA) to acquire the MRI signal.

High-resolution MR imaging was performed to visualize the insertion of the transducer in the prostate phantom. Thus, a T2-weighted fast-spin echo (FSE) sequence was used with the following parameters: repetition time (TR) = 2500 ms, echo time (TE) = 60 ms, slice thickness = 3 mm (gap 0.3 mm), matrix = 256 × 256, field of view (FOV) = 16 cm, number of excitations (NEX) = 3, and echo train length (ETL) = 8.

For fast imaging that is used for MRI thermometry, T1-weighted spoiled gradient (SPGR) was used with the following parameters: TR = 50 ms, TE = 2.7 ms, FOV = 16 cm, matrix = 256 × 256, flip angle = 30°, and NEX = 1.

Magnetic resonance thermometry

The temperature during FUS exposure was estimated using the PRFS method.[28] This method relates the associated phase shift derived from the frequency shift of the MR signal due to the local temperature elevation (ΔT). This relationship is described by:

Where φ (T) and φ (T0) are the absolute phases of the MR signal at a starting and final temperature T and T0, respectively, γ is the gyromagnetic ratio, α is the PRF change coefficient, B0 is the magnetic field strength, and TE is the echo time.

The SPGR pulse sequence was used to extract the MRI thermometry maps. Phase maps were reconstructed by calculating the phase on a pixel-by-pixel basis after combining pixel data from real and imaginary channels. Although the scanner was capable of producing directly phase image reconstructions, the applied intrascan gradient nonlinearity corrections induce phase interpolation problems. Transient phase shifts developed during the acquisition of nontreated (mask) and treated images were compensated by subtracting internal references in regions away from the treated site. Temperature elevation was returned by the software as the maximum value in a prescribed region of interest (ROI) that was manually positioned. Color coded temperature elevation maps were reconstructed with a typical heat map scale, where cold to hot corresponds to blue to red. The limits of the heat map scale in every map was adjusted using the maximum and minimum temperature elevations recorded in the ROI. The maximum temperature and cumulative thermal dose were calculated at each time interval for each plane and provide adequate online guidance for temperature-targeting multiple slices over the entire target.

  Results Top

[Figure 6]a shows the placement of the transrectal transducer in the cavity (mimics rectum) of the agar-based phantom. [Figure 6]b shows the ultrasonic imaging of the transrectal transducer. High backscatter signal due to reflection was seen in the face of the spherically focused transducer and also in the two agar–water interfaces. In previous studies of our group,[33] the MR compatibility of the same encoders and ultrasonic motors was demonstrated, and therefore there was no need to repeat it for this study.
Figure 6: (a) Placement of the transrectal transducer in the cavity (mimics rectum) of the agar-based phantom. (b) Ultrasonic imaging of the transrectal transducer

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Having developed the prostate phantom, the next step was to evaluate the ability of the transducer to produced high temperatures that can potentially ablate tissue. [Figure 7] shows the temperature versus time measurement for the proposed transducer with acoustical power of 28 W for 120 s. The temperature was measured at the focus of the transducer which was placed 40 mm deep into the prostate phantom. The baseline temperature was at the room temperature of 20°C.
Figure 7: Temperature versus time measurement for the proposed transducer with acoustical power of 28 W for 120 s at a 40 mm focal depth

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The next series of figures were performed in the MRI setting. [Figure 8]a shows the robotic system and prostate phantom as placed on the table of the GE MRI scanner, and [Figure 8]b shows the robotic system as placed inside the MRI (rear view). No MRI compatibility tests are presented since the same motors and encoders were used as in previous studies of our group.[33],[35] [Figure 9]a shows the T2-W FSE MRI of the prostate phantom in the axial plane. [Figure 9]b shows the corresponding image at the sagittal plane, and finally [Figure 9]c shows the corresponding image in the coronal plane. Note the excellent contrast between water, agar-based phantom, and transducer. The images did not reveal any air spaces between the water enclosure that hosted the transducer and the agar-based phantom.
Figure 8: (a) Robotic system and prostate phantom as placed on the table of the GE magnetic resonance image scanner, and (b) Robotic system as placed inside the magnetic resonance image (rear view)

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Figure 9: (a) T2-W fast spin echo magnetic resonance image of the prostate phantom in an axial plane. (b) The corresponding image at a sagittal plane, and finally (c) the corresponding image in a coronal plane

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Having established excellent coupling, the next step was to evaluate the functionality of the transducer and robot using MR thermometry. [Figure 10]a shows MR thermometry map in a coronal plane at different time intervals (every 12 s) using acoustical power of 15 W for 60 s. [Figure 10]b shows the corresponding MR thermometry map in an axial plane with the same time intervals. This figure demonstrates the growth of the thermal beam (highlighted with an arrow) of the proposed transducer. [Figure 11]a shows MR thermometry map in a coronal plane at 10 mm spatial steps of the Z-axis. The power used was 15 W for 60 s. Note that significant heat was created. [Figure 11]b shows the corresponding MR thermometry map in an axial plane at 10° angular steps of the theta stage.
Figure 10: (a) Magnetic resonance thermometry map in a coronal plane at different time intervals (every 12 s) using acoustical power of 15 W for 60 s. (b) the corresponding magnetic resonance thermometry map in an axial plane with the same time intervals

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Figure 11: (a) Magnetic resonance thermometry map in a coronal plane at 10 mm linear steps of the Z-axis. The power used was 15 W for 60 s. (b) Magnetic resonance thermometry map in an axial plane at 10° angular steps of the theta stage. The power used was 15 W for 60 s

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  Discussion Top

Currently, there are four main technologies that use focused US for the treatment of PC:

  1. The Ablatherm (EDAP TMS SA, Vaulx-en-Velin, France) which uses ultrasonic imaging for guidance and monitoring of the procedure [20]
  2. Sonablate (Focus Surgery Inc., Indianapolis, IN, USA, now called SONACARE). The Sonablate uses a single transducer (4 MHz) for both imaging and treatment [19]
  3. The third technology uses MR-guided US using a transurethral approach.[29] In the transurethral system, the transducer which is unfocused delivers heat that propagates from the transducer to the area of interest. Inevitable, prostate tissue that is within the transducer and the target is unnecessarily heated. Because of the insertion through the urethra, the transducer has to be unfocused due to the limited space. The transurethral approach is less complex than the US-guided systems. The device has CE approval and clinical trials are underway
  4. The fourth technology comes from the Israeli company Insightec and uses endorectal approach also, under MRI guidance. The difference of that approach is that the transducer which is unfocused is divided in 1000 elements and steering of the beam is achieved electronically.[25],[27] The device has received CE marking and clinical trials are underway.

In this study, we propose a technology with endorectal coupling (same as the two US-guided FUS technology, and the endorectal MRgFUS). We also use MRI guidance (same as the transrectal MRgFUS and transurethral MRgFUS). The proposed approach is similar to the endorectal MRgFUS of Insightec, with one major difference: we use single-element transducer. Our difference compared to the US-guided FUS system is that there is no need in our transducer to allow space for ultrasonic imaging. Regarding the functionality of the proposed technology, linear and angular rotation is achieved similarly to what US-guided technologies are using.[21] We had shown that with this simple robotic system, it is possible to create thermal heating above the threshold of necrosis.

Extensive evaluation is required in the future in animal experiments (the most popular animal model reported is the dog model). The success of focused US in ablating at levels above the threshold of necrosis has been already confirmed.[21] This would demonstrate the added benefit of MRI, which provides almost in real-time MR thermometry of the heated region. These features make MRI-guided procedures much better than US-guided procedures.

Our group has extensive experience with agar-based phantoms. The suitability of agar phantoms as tissue-mimicking replicas for MR-guided HIFU applications has been investigated by characterizing relevant acoustic and thermal properties by Menikou and Damianou.[36] The first phantom that we developed was a head phantom made out of ABS.[37] The brain in this phantom was mimicked with agar-based phantom. The scattering coefficient was controlled using silica and the absorption with evaporation milk. This agar-based recipe (agar, silica, and milk) was also used in a bone phantom,[38] which was used to evaluate ultrasonic exposures in bone. Recently, this recipe was utilized for a different application which includes ribs.[39] The absorption of this agar-based phantom can be easily controlled using evaporation milk and therefore it is suitable to represent soft tissue. In this current application, we utilize it for prostate. The advantage of the agar-based phantom is that it is easy to produce, it is inexpensive, and has proven very effective in producing relevant MR thermometry maps due to its proper ultrasonic absorption. The shape of the thermal beam produced in this phantom, followed the beam reported by other studies.[25]

To our knowledge, this is the first agar-based prostate that was produced and evaluated. The proposed robotic system is the evolution of other MRI-guided focused US systems developed by our group for other applications. The study by Damianou et al.[40] and Mylonas and Damianou [35] reported the development of robotic systems for brain interventions using three linear stages. Later, in a different study in 2014 by Yiallouras et al.,[33] a device that included a linear and an angular axis was developed for endorectal intervention using focused US for PC. An upgraded version of the aforementioned prostate robot that employed three PC-controlled axes of motion was later introduced.[41] In addition, our group developed a similar robotic system for endovaginal interventions for gynecological tumors (Epaminonda et al. 2015[42]). The experience learned from the earlier designs is that with these piezoelectric motors, the effect on the MRI is minimal, because during imaging, the motors and encoders are de-energised. In addition, because of the use of MR compatible encoders, the positional error of the linear stage is in the order of 0.05 mm, and the corresponding error for the angular stage is 0.2°. These errors are by far better than the requirements needed for oncological interventions. Therefore, we are now in a position to develop easily new applications for MR compatible positioning devices for FUS.

The proposed device has been proven very functional, and therefore the ultimate goal is to utilize it in the clinical environment, provided that experience is gained during preclinical trials in animals (as already stated in a dog model).


This work was supported by the Project PROFUS E! 6620. PROFUS is implemented within the framework of the EUROSTARS Program and is cofunded by the European Community and the Research Promotion Foundation, under the EUROSTARS Cyprus Action of the EUREKA Cyprus Program (Project Code: EUREKA/EUSTAR/0311/01).

The project has been funded by the Research Promotion foundation of Cyprus under the project PROSTASONIC (ENTERPRISES/0918/0012).

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]

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1 Magnetic resonance image–guided focused ultrasound robotic system for transrectal prostate cancer therapy
Marinos Giannakou,Theocharis Drakos,Georgios Menikou,Nikolas Evripidou,Antria Filippou,Kyriakos Spanoudes,Leonidas Ioannou,Christakis Damianou
The International Journal of Medical Robotics and Computer Assisted Surgery. 2021;
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