Development of Biomedical Microrobot for Intravascular Therapy

International Journal of Advanced Robotic Systems, Vol. 7, No. 1 (2010) ISSN 1729-8806, pp. 091-098

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Development of Biomedical Microrobot for Intravascular Therapy Sukho Park1, Kyoungrae Cha2, and Jongoh Park3,* 1 School of Mechanical Systems Engineering, Chonnam National University, Korea 2 School of Mechanical Systems Engineering, Chonnam National University, Korea 3,* Corresponding Author : School of Mechanical Systems Engineering, Chonnam National University, Korea Email: [email protected], Phone : +82-62-530-1686 Abstract: Recently, coronary artery disease such as angina pectoris and myocardial infarction has become the major causes of death. As a method of medical treatment for the disease, the pharmacological approaches and the surgical operations are executed. Especially, percutaneous coronary intervention (PCI) using catheters are the mostly preferred treatment for coronary artery diseases. The PCI technologies are advanced and the various useful devices are developed and utilized. However, some clinical operations such as the treatment of chronic total occlusion (CTO) remain a limitation of PCI and a major challenge. As robot-assisted coronary interventions, this paper proposes the microrobot for the therapy of CTO. The microrobot consists of the functions of position recognition, locomotion and treatment in the blood vessels. The functions of the microrobot can be validated through in-vitro & in-vivo experiments. The innovative technologies and surgical concept using the microrobot are currently being developed. Keywords: Intravascular microrobot; Chronic total occulusion (CTO ); Percutaneous coronary intervention (PCI); Biomedical microrobot; Coronary artery; Locomotion; Position recognition; Drilling tool

1. Introduction

Owing to the carnivorous dietary life and the lack of exercise, cardiovascular disorders show an increasing tendency. Among cardiovascular disorders, coronary artery diseases such as angina pectoris and myocardial infarction become the major causes of death (Mieres, J. H., 2006; Heart Association & American Stroke Association., 2007). The circulation of the coronary artery could supply blood to and from the heart muscle itself. These healthy coronary arteries are able to regulate the coronary blood flow for the heart muscle and the heart beating. However, the relatively narrow vessels of the coronary arteries are commonly affected by atherosclerosis and can become blocked, causing angina or a heart attack. For the treatment of the coronary artery diseases, pharmacological approaches and surgical operations are executed. As the pharmacological approaches, a dissolving agent for a thrombus, an anti-coagulator, and vasodilator are usually in use. However, for the patients who show no response to the drugs, the surgical operations such as coronary artery bypass draft (CABG) and percutaneous coronary intervention (PCI) can be applied. Firstly, CABG which makes a detour vessel method instead of blocked artery is effective so long as the distal target vessel is anatomically suitable for insertion of a bypass graft. However, the limitations of CABG are well known and include risk of surgical mortality, significant expense, and long term recovery

time. Compared with the CABG, the catheter based PCI method is a simpler surgical operation, and thus widely used in hospitals. The catheter based PCI is a method of making a hold in a clogged blood vessel or of enlarging the hole of narrow blood vessel. Generally, PCI is minimally invasive and less costly procedure compared with coronary intervention. Recently, the catheter based PCI technologies show a remarkable advance and the various useful devices such as balloon, drug-eluting stent, excision knife, and diamond drill ball are developed and utilized. However, the treatment of chronic total occlusion (CTO) remains a limitation of PCI and a major challenge. CTO of a coronary artery is defined as occlusion longer than 6 weeks after a clinical event or sometimes of an unknown duration. Chronically occluded coronary arteries account for approximately 20-30% of the coronary disease (Sachdeva, R. et al., 2006; Prasad, A. et al., 2007). For PCI, a guide wire is generally used and should be inserted into the blocked region in the blood vessel. However, in case of CTO, the insertion of the guide wire is very difficult because of the fibro-calcific plaque of CTO region or PCI. Therefore, for the treatment of CTO, a new device and a new therapy are strongly required (Saito, S. et al., 2003). FlowCardia Inc., suggested a catheter-based systems for the recanalization of coronary and peripheral CTO. The device is named as CROSSERTM and a monorail catheter delivered over standard

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guidewire to the site of CTO. It utilizes mechanical vibration with high frequency, and is designed to quickly cross CTO (CROSSERTM Website). However, CROSSERTM showed long operation time and low efficiency. Cath Lab proposed FrontrunnerTM CTO catheter for the treatment of it. Using the concept of controlled blunt micro-dissection, the Frontrunner enables users to separate and fracture atherosclerotic plaque in various tissue planes throughout the entire length of a total occlusion (FrontrunnerTM Website). The micro-dissection of the device has the possibility of the rupture of blood vessel. ASAHI suggested the special torus catheter with its threaded stainless steel construction, enables the exchange and support required for treating CTO (ASAHI Website). This catheter is difficult to clearly remove CTO and is hard to apply the curved blood vessel. The mentioned devices are restrictively used and have some limitations. This paper, as robot-assisted coronary interventions, proposes a microrobot for the therapy of CTO. Fig. 1 shows the concept images of the microrbot for intravascular treatment. The microrobot could be introduced into the body through the vascular system. The microrobot could locomote in the blood vessel and could reach to a target lesion and perform the medical treatment of it in the focus. Therefore, the microrobot system should have locomotion performance, position recognition function, treatment ability and overall control part. First of all, for the microrobot to reach the target position of CTO in the blood vessel, the locomotion function of the microrobot is essential. For the locomotion of the microrobot, the relative position value between the microrobot and the blood vessel and the absolute position value are necessary. And the microrobot should have treatment tools for the therapy of CTO. Finally, for the control of overall system, the control part of the microrobot system should be included. In the following chapter, we will describe the detail functions of our proposed microrobot system.

2. Main Functions of Microrobot

For the intravascular treatment, the proposed microrobot should have the following main functions, as shown in Fig. 2. The overall size of the microrobot is designed to be about 1mm in diameter and about 5~10mm in length. First of all, the microrobot could have locomotion and steering function to move inside of vascular system with many branches. In addition, for the locomotion of the microrobot, its position coordinate value and the relative position and posture should be modeled and realized. Secondly, therefore, the position recognition function is necessary and we planned the position recognition method using intraoperational bi-plane X-ray angiography images and pre-operational images of CT

Fig. 1. Concept Images of Microrobot for Intravascular Treatment

Fig. 2. Main Functions of Microrobot

(Computerized Tomography) or MRI (Magnetic Resonance Imaging). Thirdly, for the treatment of the coronary artery disease, especially CTO, the medical treatment tools of the microrobot should be developed. As candidates of the medical tools, micro-drill and injection devices were adopted and the fabrication method of the micro-drill and the micro injection are going to be developed. Fourthly, in the treatment process of the coronary artery disease, thromboses and particles could be generated and become dangerous factors in the vascular system. Finally, for the actuation of the components in the microrobot, the actuation power is necessary. However, the size of the microrobot is too small to contain battery. Therefore, wireless power supplying function should be integrated in the microrobot.

2.1. Locomotion Function of Microrobot For a long time, many researchers have focused on the locomotion of microrobot in the blood vessel. However, the blood vessels have too small diameter and is filled with the blood liquid. In addition, the blood shows the pulsatile blood pressure and flow. In order to move in the blood vessel, the microrobot should overcome the blood flow and therefore the actuation force of the microrobot should be high enough. In the previous researches, there

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are two wireless approaches such as electromagnet based microrobot (Yesin, K. B. et al., 2006) and MRI (Magnetic Resonance Imaging) system based actuation (Martel, S. et al., 2007). The two methods could be feasible solutions of the locomotion of the microrobot in the vascular system. Yesin, K. B. et al. (2006) proposed the electromagnetic actuation (EMA) by using two coil pair system, Helmholtz coil and Maxwell coil. The Helmholtz coil pair can generate uniform magnetic flux density and the Maxwell coil pair can make uniform gradient magnetic flux. In the electromagnetic actuation, the uniform magnetic flux of the Helmholtz coil is related to the torsion of the microrobot and creates its rotation. And the uniform gradient magnetic flux of the Maxwell coil generates the linear force and makes a linear motion of the microrobot. If the rotational and linear motion of the microrobot could be controlled, the microrobot could locomote in 2D plane. However, the microrobot actuated by electro-magnet coil system shows 2D motions in a plane and thus has some limitations for the applications. A new EMA system for the microrobot is to be proposed,

(a) (b)

Fig. 3. (a) EMA system for the locomotion in 3D space and (b) 3D locomotion of the microrobot in 3D blood vessel phantom (Jeong, S. M. et al. , 2009)

(a) (b)

(c) (d)

Fig. 4 (a) X-ray angiography for monitoring the micro robot (b) The rabbit in EMA system for In-vivo test (b) Delivered micro robot into ascending aorta (d) Micro robot traveling by blood pressure from ascending aorta to descending aorta

which is able to move in 3D space. Fig. 3 (a) and Fig. 3(b) show our proposed 3D EMA structures. As shown in Fig. 3 (a), the EMA system consists of stationary Helmholtz & Maxwell coil pairs and rotational Helmholtz & Maxwell coil pairs. In 2D plane, Helmholtz coil pair can rotate the microrobot to the desired direction and two Maxwell coils can propulse the microrobot to the aligned direction(Choi, H.C., 2009). If the rotational Helmholtz & Maxwell coil pairs was turned, 3D locomotion of the microrobot can be achieved (Jeong S. M. et al. , 2009). As shown in Fig. 3 (b), using the proposed 3D EMA system, the microrobot can locomote in 3D blood vessel phantom, where the microrobot is a cylindrical (diameter 1mm, height 1mm) neodymium magnet. For the feasibility test of the EMA system, the In-vivo test was peformed to evluate the motion of the micro robot in the actual blood vessel of a living organism under the similar condition as the coronary intervention. The X-ray angiography was used for monitoring the postion of micro robot in the blood vessel as shown in Fig. 4(a), and Fig. 4(b) shows the rabbit was put in the EMA system for manipulating the robot. When the magnetic field activated, the micro robot was delivered through the distal opening of the catheter into the descending aorta using a guide wire. Fig. 4(c) shows that the micro robot was inserted into the rabbit’s aorta via the internal carotid artery using a 4 French guiding catheter. The robot was migrated to the descending aorta due to the blood flow as shown in the Fig. 4(d). There are a lot of factor influencing the motion of micro robot such as blood pressure, blood viscousity, and vescular shape, etc. The pulsatile blood pressure is the dominant obstacle to the travel and makes the micro robot fluctuated or swept out in some case. In this paper, the micro robot has sufficient driving force to go upstream bucking against blood pressure, which is verified by experimental results as shown in Fig. 5. The micro robot started from the region of kidney branch and traveled to the aortic branch. Martel, S. et. al (2007) demonstrated magnetic propulsion of magnetic core in a carotid artery of a living swine using MRI system. The gradient coil in the conventional MRI gradient coil was used and the coil system generates a gradient magnetic flux and thus linear force. MRI gradient coils were suitable for the locomotion of the magnetic core. We consider MRI based actuation as a candidate method for the locomotion of the microrobot and focus on the actuation mechanism. Conventional MRI system and the gradient coils are shown in Fig. 6 and MRI based locomotion of the microrobot is to be tested. For the locomotion test using MRI, MRI compatible phantom system which resembles the vascular system will be fabricated and the movement of the microrobot will be tested.


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Fig. 5. The micro robot migration going upstrem againt the blood pressure in the rabbit aorta. The yellow dotted line marks the micro robot.

Fig. 6. MRI System and Gradient Coil for MRI-based Locomotion

Compared with the wireless moving microrobot, the locomotion of the wired microrobot could be thought. For the actuation of the microrobot, very small sized actuator which can be installed inside the microrobot is necessary. However, there is no appropriate actuator with such small size and high power.

2.2. Position Recognition Function of Microrobot For the position recognition of the microrobot in the blood vessel, from the pre-operation images, such as CT and MRI images, the vascular system should be extracted. That is, using 2D images of the CT and MRI image, 3D image can be reconstructed. And from the reconstructed 3D image, the segmentation of the concern part such as the blood vessel can be executed. Finally, we can get the 3D image of the vascular system. Fig. 7 shows 3D reconstructed rendering image of the heart and the segmentation of the coronary artery. From the segmentation data of the coronary artery, the condition of the vessel can be indirectly analyzed and estimated. For the position recognition of the microrobot, we will use bi-plane X-ray angiography images. Previously, as a

pre-operational procedure, we could get the 3D rendering and segmentation date of the coronary artery, and plan the locomotion path of the microrobot. During the operational procedure, the microrobot and the blood vessel can be imaged by using bi-plane X-ray angiography. Using the two plane image, 3D blood vessel image and the microrobot can be reconstructed. In additon, the intra-operational images of the blood vessel and the microrobot can be registered to the pre-operational 3D segmentation data of the coronary artery. The aforementioned intra-operation imaging and the registration on the pre-operation image are described in Fig. 8. Therefore, the position recognition of the microrobot can be realized by the image processing and the registration of the pre-operational CT or MRI images and the intra-operational X-ray angiography images.

2.3. Treatment Function of Microrobot For the treatment of the coronary artery disease, the medical tools of the microrobot is to be developed. Our target disease is CTO and the insertion of the guide wire is very difficult because of the fibro-calcific plaque of CTO region. Therefore, we decided to use the drill and

Fig. 7. 3D rendering of the heart and segmentation of the coronary artery

Fig. 8. Bi plane X-ray angiography image and 3D Image Model Registration


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Fig. 9. Micro-drill Fabrication using Molding Method

drug injection for the treatment of the CTO. Drilling is appropriate to penetrate the fibro-calcific plaque of CTO and drug injection can be used for the removal of the remaining plaque. For the drilling of the CTO in coronary artery, the development of the micro-drill tool is necessary. The fabrication process is based on the micro-molding method, as shown in Fig. 9. First of all, the desired shape of the micro-drill tool tip can be made by micro-RP (Rapid Prototyping). And the master for the micro-drill is molded from the original RP micro-drill. Finally, the micro-drill tool is fabricated by molding technique using the master. For the assembly of the micro-drill into the microrobot, the micro-drill tool should be designed smaller than the diameter of the microrobot. After the drilling by the micro-drill tool, for the removal of the remaining plaque, drug injection function can be introduced. A micro pump for the drug injection should be installed and the development of the drug which targets on CTO and dissolves CTO is necessary. Fig. 10 shows the structure of the dissolving drug. The target consists of nano drug delivery with CTO dissolving enzyme and CTO targeting ligand. Nano drug delivery with CTO dissolving enzyme provides the nano-sized body of the drug which contains the CTO dissolving enzyme. CTO targeting ligand makes the drug targeting to CTO lesion. In the treatment of CTO using the microrobot, the centering mechanism of the microrobot in blood vessel is essential. If the micro-drill of the microrobot were slant, the drill tool can be an injury to the vessel. Therefore, during the drilling of the microrobot, the centering mechanism is to be kept. Fig. 11 proposes the centering mechanism of microrobot using hydrogel actuator. The hydrogel can increase its volume by electric voltage or pH change. The proper arrangement of the hydrogel actuator around the microrobot can embody the centering mechanism.

Fig. 10. CTO Targeting and Dissolving Nano Drug

Fig. 11. Centering Mechanism of the Microrobot in Blood Vessel

Fig. 12. Thrombus collection function (Cho, S. M., 2008)

2.4. Thrombus Collection Function of Microrobot During the treatment process of the coronary artery disease, thrombi and particles can be generated and become dangerous factors in the vascular system. The thrombus and particle can cause some critical disease, such as a stroke and the angiostenosis of other vessels. Therefore, the thrombus and the particles should be captured and removed. Therefore, the thrombus collection mechanism as shown Fig. 12 should be developed and installed in the microrobot (Cho, S. M.,


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2008). For the collection mechanism, the electroactive polymer actuator, such as IPMC (Ionic Polymer Metal Composite) and PVDF (Polyvinylidene Fluoride).

2.5. Power Transfer Function of Microrobot For the actuation of the components in the microrobot, the actuating power is necessary. Generally, the power can be delivered by electrical lines or a battery. In the initial status, the wired electrical power supplier will be adopted. However, for the wireless microrobot, the electrical lines should be removed. And the size of the microrobot is too small to contain battery. Finally, therefore, wireless power supplying function should be integrated in the microrobot. Recently, MIT team demonstrates wireless power transfer (ScienceDaily Website). They show wireless power transfer over two-meter distance, from the coil on the left to the coil on the right, when it powers a 60W light bulb. Generally, the electrical power can be delivered by the resonance of the high frequency electrical wave. However, the efficiency of the wireless power transfer module is too low to use the application. Therefore, the integration of the power transfer function is postponed until the wireless power transfer technology is developed.

3. Overall Microrobot System

The microrobot could be introduced into the body through the vascular system. The microrobot could move in the blood vessel and could reach to a target lesion and perform the medical treatment on it. In the previous section, the functions of the microrobot were described. However, the microrobot cannot operate by itself. For the operation of the microrobot, the overall microrobot system as shown in Fig. 13 is necessary. In this section, we will introduce overall microrobot system. Fig. 13 shows an example of the overall system which consists of the microrobot, the microrobot controller, the monitoring station, the system controller and the electromagnetic controller. The microrobot controller is for the control of the function of the microrobot. Surgeon could monitor the operational situation and the information from the sensors and the controllers through the monitoring station. The system controller and the electromagnet controller could actuate and control the position of the microrobot.

3.1. Hardware Platform Fig. 14 describes the hardware platform for the microrobot system. For the operation, the overall microrobot system uses pre-operational images, such as CT and MRI. The CT images are transferred through PACS (Picture Archiving and Communication Systems), where PACS is defined as computers or networks dedicated to the storage, retrieval, distribution and presentation of images.

Fig. 13. Overall Structure of Microrobot System

Fig. 14. Hardware Platform of Microrobot System

Fig. 15. Software Platform of Microrobot System

Fig. 16. Interaction between S/W Platform and H/W Platform of Microrobot System


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3.2. Software Platform As shown in Fig. 15, software platform is originated from the pre-operation images (CT or MRI) and the images are fused with bi-plane X-ray angiography images for the position recognition of the microrobot. The fused images can be used in the diagnosis and therapy in vascular system. Generally, the medical images are stored in an independent format. The most common format for image storage is DICOM (Digital Imaging and Communications in Medicine). Finally, Fig. 16 shows the diagram of the functional interaction between S/W platform and H/W platform. Basically, S/W platform gives the information of the microrobot’s position and trajectory and the geometry of the intravascular blood vessel. In addition, H/W platform generates the images of the microrobot inside human body, the locomotive force of the microrobot and the actuation of the treatment tools.

4. Conclusion

This paper, as robot-assisted coronary interventions, introduced the frontier program of the microrobot for intravascular therapy. For the treatment of the coronary artery, the microrobot should have the various functions as follows: the locomotion, the position recognition, the treatment tool, the thrombus collection and the wireless power supply. The microrobot could be controlled by using the proposed hardware and software platform. Through this program of the microrobot, we expect that a new and innovative medical treatment method for the intravascular therapy will be developed. In our plan, firstly, we will develop the prototype of the microrobot for femoral arteries until 2012. Secondly, the proto-microrobot for coronary arteries will be developed until 2014. Finally, our dream where the microrobot freely moves inside the blood vessel will be realized and the microrobot will be applied to the real operation for the coronary artery disease, such as CTO.

5. Acknowledgement

This research has been supported by the Strategy Technology Development Programs (No. 10030039) from the Korea Ministry of Knowledge Economy.

6. References

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Prasad, A.; Rihal, C. S.; Lennon, R. J.; Wiste, H. J.; Singh, M. & Holmes, D. R. (2007). Trends in Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusions: A 25-Year Experience From the Mayo Clinic, Journal of the American College of Cardiology 49(15), pp. 1611-1618.

Saito, S.; Tanaka, S.; Hiroe, Y.; Miyashita, Y.; Takahashi, S.; Satake, S, & Tanaka, K. (2003). Angioplasty for Chronic Total Occlusion by Using Tapered-Tip Guidewires, Catheterization and Cardiovascular Interventions, 59:305-311.

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Yesin, K. B.; Vollmers, K.; & Nelson, B. J. (2004). Guidance of Magnetic Intraocular Microrobots by Active Defocused Tracking, Proc. 2004 IEEE/RSJ International Conference on Intelligent Robotics and Systems.

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Jeong, S. M.; Choi, H. C.; Choi. J. H.; Yu, C. S.; Park, J. O. & Park, S. H (2009). Novel Electromagnetic Actuation (EMA) Method for 3 Dimensional Locomotion of Intravascular Microrobot, Sensors & Actuators: A (submitted)

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Development of Biomedical Microrobot for Intravascular Therapy

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