Catheterization Using X-ray Video (Fluoroscopy)

Professor Hasebe is a specialist in diagnostic imaging studies using x-rays and also a medical specialist in the use of catheters in intravascular treatment, known as catheterization (Interventional Radiology: IVR). Intravascular treatment is a method in which a tube called a catheter is inserted in a blood vessel along a thin tubular wire of less than one millimeter diameter called a guidewire, and catheters for medical treatment and treatment devices are inserted through that catheter. In the case of a blood vessel that is clogged and narrowed by cholesterol in arteriosclerosis, a treatment device with a balloon called a balloon catheter is inserted and the blood vessel is expanded by inflating the balloon. Alternatively, the blood vessel is widened by the placement of a metal wire mesh device (a stent) in the blood vessel. Conventionally, the mainstream method has been to treat the problem by medication or surgery to bypass the coronary arteries. As the use of conventional surgery causes damage to the body, it could not be used for the elderly or physically weak patients. Accordingly, the use of intravascular treatment (minimally invasive treatment) as a surgical method that, as far as possible, does not damage the body has expanded and spread.

In recent surgery in particular, the trend has been towards minimally invasive treatment methods that, as far as possible, do not cause damage to the body, which has reduced the burden on patients. At the Tokai University Hachioji Hospital, through the use of interventional radiology (IVR) in treatment such as intravascular treatment (surgery under local anesthetic), the time required for surgery is shortened, reducing the burden on the patient and also reducing the number of days they spend in hospital.

When intravascular treatment is carried out, it is performed while looking at an x-ray fluoroscopy monitor screen to check the position of the catheter. Small precious metal instruments are attached to the front and rear of the catheter and balloon, and these serve as markers as x-rays penetrate the human body but do not pass through the precious metal parts. The role of the precious metal as markers is extremely important, as a deviation of millimeters could cause fatal adverse reactions or complications. As precious metal markers are currently used in all catheters and treatment devices that have sophisticated functions, their role is enormous. While looking at these markers, narrowed blood vessels are expanded by checking the position of a balloon, placing a stent and adjusting its position in millimeters.

Doctor of Medicine and Doctor of Engineering

One of Professor Hasebe’s strengths is that not only is he a doctor of medicine but he also has a doctorate in materials engineering. From personally carrying out operations as a doctor, he is able to grasp materials issues that he would not otherwise have understood. After obtaining qualifications as a doctor (medical: doctorate) in the School of Medicine at his alma mater, Keio University, he also obtained an engineering degree (doctorate) from the Faculty of Science and Technology at Keio University. Currently, he has a concurrent position as a visiting professor in the Keio University Faculty of Science and Technology. In addition, he has studied abroad at Harvard Medical School (Brigham and Women’s Hospital), and has been an engineering researcher and conducted medical-engineering collaboration at the Massachusetts Institute of Technology (MIT). At that time, he felt that the latest medicine needed to utilize engineering (technology) for future advancement. For that reason, on returning to Japan, he made every effort to pursue medical-engineering collaboration. Subsequently, together with Professor Tetsuya Suzuki (currently, Director of the Keio Leading-edge Laboratory of Science and Technology (KLL)), he managed a medical-engineering collaboration team for more than 15 years, in which he left many achievements in the field of medical-engineering collaboration using engineering. Graduates from that medical-engineering collaboration team have also expanded their sphere of activity into overseas research laboratories and universities in Japan, as well as the Japan Aerospace Exploration Agency (JAXA), JR Central Japan Railway, JR East Japan Railway, and other leading companies, and have recently engaged as president and researchers in successful examples of promotion of medical venture companies established in Japan.

As he accurately grasps the needs of doctors and medical settings, Professor Hasebe is able to make appropriate requests in the materials development process for the development of medical devices that can actually be used for patients. However, the majority of advanced medical devices that are placed in the body are manufactured overseas, and their specifications cannot readily be changed, even if they are not optimal for Japanese people. To launch devices that meet clinical needs as early as possible, it is necessary to develop devices through domestic technology. Moreover, as there is an unfavorable trade balance of 600 billion yen in the export-import of medical devices, Professor Hasebe wanted to make domestic technology a basis for balancing that imbalance. Also, he expects there to be a growing market for medical devices globally in the future. He is passionate about domestic technology but he believes that, to contribute to many people’s lives, technology should be widely expanded globally, regardless of whether it is from domestic or overseas companies.

As it has the fine processing technologies, not just for materials procurement, but also for the making of medical devices, TANAKA has become involved in industry-academic collaboration in research and development.

From Precious Metal Particles to Markers

In the intravascular treatment (IVR: Interventional Radiology) managed by Professor Hasebe, blood vessels are widened or, conversely, blocked off while looking at x-ray images. Myocardial infarction or angina may occur from coronary blood vessels that are clogged due to arteriosclerosis, and blockage of blood vessels in the leg may cause inability to walk, pain, and decaying of tissues in the leg. In such cases, intravascular treatment is carried out to widen the blood vessels. Conversely to arteriosclerosis, in cases where there is swelling of a blood vessel (aneurysm), as it is highly likely to lead to death if the aneurysm bursts, it is treated by filling and blocking off the aneurysm and the blood vessels flowing into it. An example of application of the treatment method for inhibiting blood vessels is the treatment of cancers such as liver cancer, in which catheterization is also carried out. As liver cancers are nourished by arterial blood, they are treated by starving the cancer by blocking the feeding vessels. Filling is transported via catheters in the blood vessels near the cancer, and anticancer drugs are infused at the same time. This has become a common treatment for such cancers. Also, in emergency medical care, when blood flow cannot be stopped from a vascular injury or internal organ damage arising from a pelvic fracture due to a traffic accident or other such cause, bleeding is halted by inserting filling through catheters from inside the blood vessels.

Other than metals, polymers have been put forward as candidates for materials to be used in indwelling devices. As common polymers are hydrolized, there are issues of durability in the body. It has become common for polymers which dissolve in living organisms to be used intentionally as medical materials. However, in cases where the aim is for the material to be placed in the body for a long time, the use of metals is, in the end, the best choice for reasons including their good compatibility with the body, avoidance of excessive reactions (excellent bio-compatibility), the ability to carry out fine processing of the metals, and their superior durability. Among those metals, precious metals such as platinum provide extremely high performance with respect to stability in living organisms, biocompatibility, fine workability, and visibility under radioscopy.

Active Collaboration between Medicine and Engineering

In the future, advanced technology will continue to be used in the development of medical devices that meet medical needs. As technology improves, even more outstanding products will be created, and the use of these by patients will extend their quality of life and longevity. Active medical-engineering and industry-government-academia collaboration has developed, and it is likely that this trend will continue to be promoted as a national policy in the future. In addition, medical venture companies are engaged in a development race in Silicon Valley, Europe and elsewhere. To date, development has been led by the major medical device makers, but in recent years the trend towards acceleration of development has gained momentum through partnerships between medical venture companies with specific advanced technologies and medical settings. In addition, many medical venture companies that have produced results have received investment from major medical device makers, or have been acquired by them. Promising medical venture companies have also appeared in Japan. It is likely that the trend towards partnerships between engineering and medical needs will become even more vigorous going forward.

Competitive Ability, Even as a Newcomer, through Quality

TANAKA is a relative newcomer to working with platinum as materials for indwelling medical devices. Even so, we are confident of making inroads into the medical treatment field. Chihiro Nakanishi of the Company’s New Business Company Technology Development Control Department is confident that “Even though the Company is a newcomer, we can break into the market because we have the fundamental materials quality and basic advanced fine processing technology to do so.”

To begin with, a strong point of TANAKA’s technology is its ability to produce platinum with the “four nines” purity level of 99.99%. After acquiring the platinum raw materials, more highly refined ingots are produced in the Company’s plant, and purity is checked. As the Company’s products are processed from these high purity ingots, the ingots are rolled and made into fine wire. Finally, the product is completed by winding the 30 µm or 20 µm diameter fine wire. At this point, if there are any impurities, the fine wire will break during the process. Being able to process the fine wire is a reflection of its purity.

At the medical device makers to which the product is delivered, it is processed into small coils of less than one millimeter diameter, providing an easy-to-use shape and performance for doctors. Medical device makers manufacture these coils into the latest form used in medical devices and deliver the devices to medical settings.

Platinum alloys are essential materials for doctors who carry out catheterization using x-rays. As it is difficult for x-rays to pass through platinum, if the platinum is arranged in several places within the catheter, there will be high visibility under radioscopy, and the position of the catheter can be clearly understood in millimeters. To doctors, this is a unique means for carrying out advanced medical treatment safely and with peace of mind, as the tip of the catheter and treatment device can be delivered to the affected part without fail. In addition, platinum has the characteristics of stability, low toxicity, and very good compatibility with the body, even when placed in the body for a long time.

However, even if fine wire made out of pure materials satisfies the mechanical characteristics requirements, this does not mean that it meets the qualities required for medical devices. To do so, a medical device must be of a level that can satisfy doctors, meaning that the doctors using it sense in their hands that they can work with it. TANAKA has confidence in the state of its fine wire, which has a clean as a mirror surface. It says that if a purity percentage number is inserted on the surface of an ingot, that number is still apparent from the surface of the product when it is made into fine wire, even though numbers are not shown on the Company’s products.

When Professor Terumitsu Hasebe of Tokai University was motivated by the desire to make medical devices that are easier to use but which did not exist at the time, by chance TANAKA was considering whether it could make use of its fine processing of precious metals technology in the medical field. At that time, Professor Hasebe and an officer of TANAKA also had a connection as high school and university classmates and their ideas as to what they could do together had begun to overlap. In addition, they were joined by Professor Yoshinori Hiramatsu (Representative Director of Dream Medical Partners, and visiting lecturer in the School of Medicine at Tokai University) who has had experience at a major medical device maker and is familiar with applications for the approval of devices, and pharmaceutical affairs. In that way, an industry-academia collaboration between a materials maker and a university school of medicine with a clinical setting was born.

The United States and Europe are leaders in the development of catheterization devices. Minimally invasive treatment using catheters is currently one of the cutting edge treatments. To TANAKA, which “Contributes to society through precious metals” (Chihiro Nakanishi), advancing into the medical field is a business appropriate to the times.