Medical device manufacturers are generally well-versed in the capabilities of real-time fluoroscopic X-ray technology in diagnostic imaging, but some remain unaware of its uses in the inspection of complex medical devices. For Gil Zweig, president of Glenbrook Technologies, this needs to be rectified to ensure the quality and safety of these hard-to-image devices.
The US Food and Drug Administration agrees, stating in its recommendations for intravascular stents: "We recommend that you provide a qualitative or quantitative indication of the visibility of the stent in real-time X-ray." But Zweig feels that this is buried too deep in guidelines; it is not yet an actual regulation.
Part of the reason manufacturers are not using this technique is that much of the traditional real-time X-ray inspection technology available is unsuitable for medical devices.
Caesium iodide image intensifiers, linear-array detectors and flat-panel detectors - the three main options available commercially - do not have a high enough resolution for medical device inspection.
X-ray image resolution is defined in terms of line pairs per millimetre (lp/mm). The intrinsic resolution of most existing technologies is 3lp/mm, 4lp/mm at the most. These technologies do not image well at the lower voltages necessary to inspect materials with low radiographic density such as polyether ether ketone (PEEK), a plastic commonly used in the medical industry.
The most advanced patented fluoroscopic real-time X-ray inspection technology, however, has a resolution of 15-20lp/mm. The system also responds to low X-ray voltages in the range of 15-30kV - a suitable range for imaging low-density materials.
This combination means that technology now exists that is suitable for detecting faults in devices that were previously transparent to X-ray.
"Still, there is not a total awareness that there are X-ray systems being built to look at small components at very high magnifications," Zweig explains. "Manufacturers are concerned about whether the technology has the sensitivity to see materials such as PEEK, which is designed as a bone implant and as such has low X-ray absorption. In other words, the manufacturer doesn't want it to be seen in vivo. But there are concerns that air pockets or voids could form while the material is being moulded that could compromise its strength. X-ray inspection technology that can image at low energy levels is needed to reveal these defects."
Tighter device tests
The most advanced systems can do this. The X-ray image can be magnified without moving the specimen towards the X-ray source; a desktop X-ray inspection system produces static and dynamic fluoroscopic images with variable magnification up to 40 times at power levels of less than 5W.
"It can be used in two settings: in the research lab in the development of the device, and in the manufacturing clean room to audit production," says Zweig, who adds that Baxter Healthcare, St Jude Medical and Medtronic are among the manufacturers already making use of real-time X-ray inspection in their production facilities. Manufacturers of femoral artery closure devices can use real-time X-ray to ensure the positioning of the closure device on the anvil, while stent manufacturers are now able to observe the deployment of a stent from a catheter, and look for breaks in a stent after it has been fatigue-tested thousands of times.
Likewise, the quality of the mechanisms in the 'arms' of robotic surgical systems for prostate surgery can be examined, as well as the motion and mechanisms within drug-delivery devices. The list goes on.
"One exciting development is the inspection of vascular stents for fragile plaque," says Zweig, who is a past member of the ANSI IT2-31 sub-committee that established national standards for medical X-ray screen-film systems. "The stent is not so much deployed from the catheter, as it is brought into position; the sheath is then removed from the stent, permitting it to open, so it does not disrupt fragile plaque. This can now be imaged in the form of a movie."
Blood clots are often generated after surgery and can circulate and cause a stroke or heart attack. But a vena cava filter - a relatively large stent-like device - deployed in the vena cava can prevent this.
The filter spreads across the lumen area within the blood vessel to strain particles from the bloodstream, particularly blood clots, preventing them from causing major problems. These devices are often removable, and after the critical period they can be withdrawn.
To evaluate the effectiveness of vascular filters, a considerable amount of laboratory testing must be carried out, and different materials and geometries compared, before clinical trials are conducted on animal or human subjects. This testing involves pumping a flow of blood, carrying real or stimulated blood clots, through a section of a blood vessel with the trial vascular filter in place. However, blood vessels are opaque, so to properly compare and evaluate test results the process of catching blood clots in the vascular filter must be observed and documented with a real-time fluoroscopic X-ray system.
This requires an X-ray beam to be directed through the test device onto a scintillator, which converts the X-rays into energy in the visible spectrum. The machine developed for this purpose also has a rotating mechanical actuator, which enables non-invasive, 180-degree examination of the filter, something Zweig is confident will prove to have other important applications in the future.
The road to acceptance
"What I'm most excited about at the moment is that the small animal research community is discovering the potential of real-time X-ray technology," Zweig says. "A researcher can now perform a surgical procedure on a small animal and view it in magnified fluoroscopic real-time. The technology is slowly being accepted into the small animal preclinical community."
The US Centers for Disease Control and Prevention and the Hospital for Special Surgery in New York have used X-ray inspection in research projects, and Zweig also notes that the technology has been used in a major orthopaedic hospital in New York to study the mechanism of adhesion of tendons to bone in the knee. But there are some areas of the medical device industry that will probably never benefit from the use of real-time X-ray inspection, such as nanotechnology.
"If it's small and it's carbon, it has such a low atomic weight that it's very difficult to see with X-ray," he admits. Yet, the applications of this manufacturing technology are definitely expanding. For Zweig, it's a case of educating the medical device community: "It's about doing the missionary work to teach manufacturers why they should use an X-ray in the first place."
As the technology becomes more widespread, it will become increasingly useful for medical device manufacturers to 'design for inspection'. For example, if drug-delivery devices have field failures and the US Food and Drug Administration needs to determine what failed in a particular component, they would be able to use real-time X-ray technology to carry out an assessment. Right now, however, critical components are often obscured. To combat this, manufacturers of devices that use injection-moulded plastics, for example, need to think about X-ray opacifying them using barium-based or bismuth-based materials, to make them appear darker on an X-ray.
"Every week, we're reading about a new, life-saving device," Zweig says. "I'm just hoping that manufacturers will discover that X-ray inspection can ensure the quality of the products that they are making."