Technical note
Penetration of an artificial arterial thromboembolism in a live animal using an intravascular therapeutic microrobot system

https://doi.org/10.1016/j.medengphy.2016.01.001Get rights and content

Highlights

  • We proposed the intravascular therapeutic microrobot system, which employs an EMA system and bi-plane X-ray devices.

  • We demonstrated a stable locomotion of the microrobot and executed a penetration test of an artificial arterial thromboembolism in the aorta of a live animal.

  • The average length of the artificial thrombus occlusion was about 18 mm and the microrobot could penetrate the occlusion for 40.2 s.

Abstract

The biomedical applications of wireless robots are an active area of study. In addition to moving to a target lesion, wireless locomotive robots can deliver a therapeutic drug for a specific disease. Thus, they hold great potential as therapeutic devices in blood vessel diseases, such as thrombi and occlusions, and in other diseases, such as cancer and inflammation. During a percutaneous coronary intervention (PCI), surgeons wear a heavy shielding cloth. However, they cannot escape severe radiation exposure owing to unstable shielding. They may also suffer from joint pains because of the weight of the shielding cloth. In addition, the catheters in PCIs are controlled by the surgeon's hand. Thus, they lack steering ability. A new intravascular therapeutic system is needed to address these problems in conventional PCIs. We developed an intravascular therapeutic microrobot system (ITMS) using an electromagnetic actuation (EMA) system with bi-plane X-ray devices that can remotely control a robot in blood vessels. Using this proposed ITMS, we demonstrated the locomotion of the robot in abdominal and iliac arteries of a live pig by the master-slave method. After producing an arterial thromboembolism in a live pig in a partial iliac artery, the robot moved to the target lesion and penetrated by specific motions (twisting and hammering) of the robot using the proposed ITMS. The results reveal that the proposed ITMS can realize stable locomotion (alignment and propulsion) of a robot in abdominal and iliac arteries of a live pig. This can be considered the first preclinical trial of the treatment of an artificial arterial thromboembolism by penetration of a blood clot.

Introduction

A number of recent studies have investigated the biomedical applications of various wireless microrobots [1], [2]. In addition to moving to a target lesion, wireless locomotive microrobots can deliver therapeutic drugs for specific diseases. Thus, they hold great potential as therapeutic devices for blood vessel diseases, such as thrombi and occlusions, and for other diseases, such as cancer and inflammation [3]. A significant force is needed to enable stable locomotion of a microrobot in a pulsating blood flow.

Various actuation methods for wireless microrobots have been studied. Among these, the use of an external magnetic field has shown strong promise in intravascular treatment [1], [2]. A magnetic resonance imaging (MRI) system has been used as an actuator for the locomotion of a microrobot [4], [5], [6], [7]. Kósa et al. proposed a swimming microrobot with three polymer-based tails containing wound coils [4]. They used a Helmholtz coil of an MRI system to generate a uniform magnetic field and a gradient coil of an MRI system to generate an alternating magnetic field. An electromotive force in the coil of the tail was generated, the tails were oscillated by Lorentz force, and the wireless microrobot was propelled forward. However, an additional circuit was needed to steer the microrobot. Martel et al. executed locomotion tests of ferromagnetic bead (diameter: 1.5 mm) in the carotid artery using an MRI system [5]. The MRI system can move the ferromagnetic bead and recognize its position at the same time in a live pig. However, this experiment was executed in the vessel which has no blood flow using a balloon catheter. And, because the system consists of a Helmholtz coil pair and three gradient coil pairs, the microrobot is aligned only to the direction of Helmholtz coil and propelled to x-, y-, and z-direction. Therefore, this system is appropriate to the actuation of a spherical type microrobot. Also, through the MRI system, drug-loaded microbeads were delivered with magnetic nanoparticles (MNPs) to a localized disease site [6], [7]. Nelson et al. proposed an OctoMag system, which enabled 5-DOF locomotion of an intraocular therapeutic microrobot [8]. Their system was aimed at human eyeball surgery, and the configuration of its electromagnetic coils is not suitable to control a microrobot placed in the coronary artery or aorta. Park et al. proposed a spiral microrobot using an electromagnetic actuation (EMA) system to penetrate a thrombus occlusion [9]. Their microrobot had a screw thread shape, and it drilled through the occlusive thrombus using a rotational motion. However, the rotational torque of the microrobot for the drilling should be increased, and the damage of the inner wall of blood vessels should be minimized for in vivo test. Kuo et al. proposed a hydrogel-based micro-gripper containing MNPs for thrombus removal in blood vessels [10]. The micro-gripper with the MNPs moved through an electromagnetic field, and it was activated using the increased MNP temperature by an alternating magnetic field. However, the actuation response of the micro-gripper was relatively slow, and its complicated shape made it difficult to realize stable motion in a pulsating blood flow.

In this paper, we describe an intravascular therapeutic robot system (ITMS), which employs an EMA system and bi-plane X-ray devices. We demonstrate stable locomotion test of the robot and execute a penetration test of an artificial arterial thromboembolism in the aorta of a live animal. Through various animal tests with the proposed ITMS, we verify stable locomotion of the robot in a blood vessel with pulsating flow and penetration of a thrombus occlusion in a blood vessel.

Section snippets

Intravascular therapeutic robot system

The concept design of the proposed ITMS is shown in Fig. 1(a). The proposed ITMS consists of the following five parts: (I) a robot performing locomotion and a therapeutic function in a blood vessel, (II) an EMA system for alignment and propulsion of the robot, (III) bi-plane X-ray devices, combined with the EMA system, that can be used for the position detection of the robot in an animal blood vessel, (IV) a medical image-based controller, and (V) a bed device for stable arrangement of an

Locomotion of the robot in the blood vessel

First, the locomotion of the robot using the proposed ITMS was tested in the aorta of a live pig. Fig. 4(a)–(b) shows the computerized tomography angiography (CTA) images (AP view, lateral view). Using these images, the operator can confirm the shape of the blood vessel of the animal (pig). Fig. 4(c) presents an overlapped AP image of the X-ray device, where the robot moved from the abdominal aorta to the right/left external/internal iliac artery. The detailed results of the locomotion test are

Conclusion and discussion

In this paper, we described the use of an ITMS, which employed an EMA system and bi-plane X-ray devices, to remotely control a robot in blood vessels. Using the proposed ITMS, we demonstrated stable locomotion of the robot in abdominal and iliac arteries of a live pig. In addition, after creating an artificial thrombus occlusion in a partial iliac artery, we demonstrated the penetration of this occlusion by specific motions (twisting and hammering) of the robot. Therefore, the present study

Conflict of interest

The authors have declared that no competing interest exists.

Ethical approval

This animal study adhered to the Guide for the Care and Use of Laboratory Animals, published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996) and was approved by the Institutional Animal Care and Use Committee (IACUC) of Chonnam National University Medical School and Chonnam National University Hospital (approval number: CNU IACUC-H-2008-11).

After the experiment, the pigs were euthanized with an intracoronary injection of potassium chloride (15%, 20 mL) in

Acknowledgment

This work was supported by Samsung Research Funding Center of Samsung Electronics under Project Number SRFC-IT1401-06.

References (18)

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