(October,03) Since the silver screen stimulated our thinking of micro-invasion of the body with Fantastic Voyage, the saga of medical technology has begun to unfold with ever more amazing devices which provide physicians with better tools to improve health care. One of these new devices is a battery powered diagnostic capsule which, after being swallowed, maps the human small intestine with a video camera. The views are transmitted to a belt mounted receiver carried by the patient. A second battery pack powers the data recorder worn by the patient as a belt pack. While ultra miniature semiconductors are heralded as the backbone of this unique investigational device, batteries in both the capsule and belt data recorder provide the power which makes the product possible.
The M2A Endoscopy capsule produced by Given Imaging Ltd. is shown being held in the fingers to illustrate its small size. It is swallowed to obtain detailed photos and streaming video of the small intestine. Equipped with illuminating light source, camera, processing electronics and data radio transmitter, the capsule is powered by two silver oxide primary batteries during its eight hour journey through the digestive system to provide pictures for medical diagnostics. (Photo: copyright © Given Imaging 2002-2003.) +
One function of the M2A does not require batteries; that is the motive power. Just as food is transported through the esophagus and intestines, alternate circular muscular contractions and dilations called peristalsis move the capsule on its journey through the digestive system.. This ‘free ride’ allows all the battery energy to be focused on obtaining pictures, and storing them in the external belt pack recorder.
To provide the needed miniature capsule size, pictures are transmitted by radio rather than stored in the capsule. Again because of size and battery energy limitations, the capsule transmitter power is small, requiring a series of eight body mounted wire patches to receive the signals for the belt data recorder.
Although the capsule is active from the time it is ingested to its exit from the body, the principal objective is to scan the small intestine which is relatively inaccessible to other non-invasive imaging. In traversing the system, the capsule produces color images of the entire small intestine to allow physicians to identify abnormalities which could lead to a diagnosis of such things as Crohn’s disease (intestinal obstruction in the last 12-14 inches of the small intestine due to scar tissue formed following a chronic inflammation,) ulcers, tumors and bleeding. This picture shows a bowel stricture in a patient with Crohn’s disease. Because of the small size and smooth shape of the capsule, it passes easily in cases of such stricture.
Capsule image of Crohn’s disease
Mapping the small intestine with transit video is a pivotal contribution to identification of disorders and diseases of the small intestine which could previously only be obtained via surgery. While some outcomes may require corrective surgery, other conditions, having been properly observed with the M2A capsule, may only require medication or dietary controls. In situations where no disorder or disease is found, the small intestine can be eliminated from the analysis for which a diagnosis is being sought. (Photo: copyright © Given Imaging 2002-2003.) +
When the digestive system has been mapped, the pill is excreted for disposal while the data recorder is connected to a proprietary workstation which converts the data into graphical information for the physician. The results will show the presence of some disorder or disease, or possibly no abnormality, in which case the physician can search elsewhere, often removing the need for unnecessary surgery.
Given Imaging reports estimations that in the USA alone, there are 24 million people suffering from disorders and diseases of the small intestine. These include cancer, Crohn’s disease, bleeding, iron deficiency, anemia, poor digestion, irritable bowel and intestinal injury. The Given® endoscopy system is the first to be able to provide non-invasive imaging of this entire small intestine. The data prepared for physician review includes positional information within the body to correlate the image with its location.
Because the capsule takes video images, the intestine, at the time of the procedure, should be unobstructed. The patient has a liquid lunch the day before the procedure and nothing to eat for 12 hours before seallowing the capsule. Some physicians are adding bowl cleaning liquids to the regimen, but the preparation discomfort to the patient is minimal. Then because the capsule functions with normal digestive motion, there is no need for anesthetics, or complicated equipment. The overall procedure is pain free, requiring simple setup and initiation. There are no side effects; the patient is ambulatory during the investigation. Post procedural data preparation is automated and stored for repeated review and archiving.
This cutaway view of the capsule shows a complete system for obtaining and sending images. It is 26 mm long and 11 mm in diameter. Microminiaturization has been facilitated by replacing the ordinarily power hungry charge coupled vision sensing semiconductors with lower power complementary metal oxide materials. In addition to size constraints needed to allow passage in the intestine, the energy demands dictated continual radio transmission rather than on board data storage.
The camera has a 1400 field of view and can detect objects as small as 0.1 mm whereas alternate small bowel follow-through resolution is only 0.5 mm. During an eight hour procedure the camera obtains approximately 57,000 images at a rate of two frames per second.
The tubular shape and diameter are critical for mapping the small intestine. This combination of shape and size allows the capsule to have its axis aligned with the traveling central axis of the small intestine allowing it to look either forward or backward. Either orientation is easily accommodated for analysis.
The capsule is made of a biocompatible material which is impervious to digestive liquids for the time of transit. Since data was transmitted as obtained, there is no need for the capsule after completing its path, so it is not recovered for reuse. The disposable nature of the design allows for use of Silver-oxide button primary batteries (zinc/alkaline electrolyte/silver oxide) which are among the highest energy densities at 135 mWh/g and 575 Wh/l. (Photo: copyright © Given Imaging 2002-2003.) +
During the capsule’s journey the patient can be ambulatory with monitoring only by the by medical personnel. When the capsule is eliminated from the body, the belt pack, which contains all the video information accumulated during the procedure, is removed from the patient and connected to the workstation for final data reduction and presentation.
Today, batteries play an increasing role in medical electronics as semiconductor devices shrink in size, allowing more performance. A large part of this product success lies in methods to perform operations with smaller amounts of power, resulting in performance which could only otherwise be accomplished with greater battery energy density. Much as the casual observer prods battery technology to ‘keep up with’ semiconductor shrinking, there are practical electrochemical limits which keep batteries from shrinking or increasing the energy density. The clever designer, not barricaded by such thinking, instead looks to ever lower power electronics, smaller sensors, optimal communications methods and creative system designs, all of which are apparent in the Given Imaging endoscope.
The disposable capsule in the lower part of the photo sends digitized information via radio link to the eight body mounted antenna pickups connected to the belt mounted Data Recorder. After the capsule has traversed the colon, the Data Recorder is removed from the patient and connected to its workstation computer for download in as little as 30-60 minutes with no operator intervention. The data is processed into a visual format of still photos and streaming video presented with time and location information. Although the capsule is not reused, the Data Recorder is reused, necessitating power from rechargeable batteries. Designers selected Nickel-metal hydride batteries which develop 7500 mAh at 6 Volts, in a 920 gram package. The ordinary short application time in clinical use would not be impaired by the moderate self discharge characteristics of Nickel-metal hydride (Photo: copyright © Given Imaging 2002-2003.) +
As the experiential base begins to build, the efficacy of the product begins to unfold. Tens of thousands of people have ingested the capsule with less than 1% having complications of sticking. In cases where it did lodge in the system, the causewas related to stricture or other obstruction which the physician was able to use in formulating a diagnosis.
When compared to other diagnostics such as gastroscopy, colonoscopy, small bowel follow through, push enteroscopy, CT scan, abdominal x-ray, angiography and intraoperative enteroscopy, the results were in favor of the capsule endoscopy which had a diagnostic yield of 71%. The other modalities had a total diagnostic yield of only 41%.
There are few contraindications to the capsule’s use. They include gastrointestinal obstructions and swallowing disorders. People with pacemakers have not yet been cleared; pregnant women and all pediatrics still need clearance. There does not appear to be a problem; it just requires time to properly allow monitoring for these conditions. The M2A procedure is not a replacement for colonoscopy.
The weekly closing price of Given Imaging Ltd. stock has not yet developed a growth pattern. During its formative years, the major effort has been to establish the efficacy of the procedure and obtain the necessary approvals. With FDA plus CE, UL and FCC approval and increasing reimbursement coverage now in place in the US, Europe and Australia, the company should be positioned to develop a growth profile. Whether they will build it or sell it to a large medical devices company is an interesting question. +
Since the capsule traverses the system from the mouth to the large intestine, application is envisioned to be expanded to the esophagus, the stomach and the colon. Beyond these visible applications, the future for using the capsule for restorative surgery, or pharmacological intervention, might expand the work of the little traveler.
The company, Given Imaging Ltd., located in Yoqneam, Israel provides the product worldwide. Reimbursement is now available to over 100 million people. The system is FDA approved in the USA where 84 million people are covered by private insurance (including Blue Cross & Blue Shield and Oxford Health) or Medicare. Austria and Portugal provide reimbursement at public hospitals. Denmark and Sweden also accept the procedure and Australia recently approved reimbursement. The M2A system is CE marked in Europe. For additional information visit the website, www.GivenImaging.com.
The company does not indicate future applications for such a small investigative device; BD could speculate that the future might find some form of such a device used for joint motion, stomach function, esophageal and abdominal investigations. Turning it on and off remotely for long term studies may be of help to both research and clinical medicine in determining patterns of healing. With guidance, propulsion, laser and pharmacological dispensers capsules may be the remote surgeons of tomorrow.
The endoscopy capsule is a pioneering concept for medical technology of the twenty-first century. With the tools of genetic engineering founded on ever increasing DNA knowledge, devices and procedures facilitated by MEMS and nanotechnology will be added to provide contributions to the holistic approach of medical care so aggressively pursued by medical giants such as the Mayo Clinic. Just as medicine seeks to use interdisciplinary treatments, these new technologies will ally with the best of biology, materials, electronics, chemistry and physics to provide health quality of life improvements which should overshadow the stellar developments of the twentieth century.
The Future of Medical Devices is Now Unfolding
As micro devices such as the M2A become clinical realities, the stage is being set for dramatic extensions throughout medicine. Medical device advancements currently being developed include:
An implantable pulse generator delivers electrical pulses to the smooth muscle of the stomach. The goal is to reduce body weight through controlled eating patterns. It is indicated for patients with body mass index in excess of 35. (www.transneuronix.com)
An implantable biosensor -drug delivery system utilizes genetically engineered bioreagents with micromachined hardware to eventually provide integrated, self-regulating therapeutic devices. The heart of the system is a matchstick-sized drug dispensing pill which has rings of hydrogel and polymer. Each ring contracts when stimulated by an electrical current (battery produced) and expanded when the current is reversed. The programmed motion causes selective dispensing of the enclosed drug to specific sites. A working version is undergoing basic feasibility tests. Interest in the smart pill has been expressed by Bayer, Pharmacia & Upjohn and Procter & Gamble(www.chiprx.com)
An alternative drug dispenser is being created at the Massachusetts Institute of Technology and is to be commercialized by MicroCHIPS Inc.. This approach uses 100 to 1000 separate drug doses in individual gold membrane pockets. A dose is delivered by electrical current burning away the cover of the pocket. Implanting of the chip would be done at the delivery site needed, allowing strong doses without peripheral damage. Integration will allow on board programming. Animal testing has already produced successful results.
Verimetra, Inc. is employing MEMS (Microelectromechanical systems) for blood velocity sensors small enough to be embedded in surgical devices. The resulting smart catheters will be targeted for application in embolization of tumors, insulin islet transplantation and prenatal cardiac interventions. Animal trials are planned for late 2003. ( www.verimetra.com)
MEMS continue to provide a platform for other medical tools. Akustica, Inc. builds microphone and speaker chips for sensors and actuators which may facilitate better hearing or provide tools for applications not yet envisoned. (www.akustica.com)
In the field of electrochemistry, the addition of bacteria as a source of electropotential has been discovered by researchers at the University of Massachusetts. According to a study reported in Nature Biotechnology, The bacterium Rhodoferax ferrireducens, which thrives in the presence of metals, metabolizes sugars in the absence of oxygen to generate electrons which were transferred to graphite electrodes, producing current flow. Imagine a device which would receive a continuous flow of blood sugars to feed battery bugs which power implanted micro factories which would control insulin production, dispense cancer fighters and even scour harmful cholesterols from circulatory systems.
Futurists look to other alternatives such as inhalable drugs, light activated medications for skin cancer treatment and nanotech bloodstream robots. Already, Kazushi Ishiyama at Tohuku University, Japan has developed pinhead sized spinning screws to propel the yet undefined devices.
These emerging possibilities offer visions one of the holy grails of medicine - to correct or eliminate prebirth defects allowing all people to enter life with a fair biological start.