Imaging and Advanced Technology

Michael B. Wallace, Section Editor

The Future Is Wireless: Advances in Wireless Diagnostic and Therapeutic

Technologies in Gastroenterology
VIRENDER K. SHARMA
Division of Gastroenterology, Department of Medicine, Mayo Clinic in Arizona, Scottsdale, Arizona

rthur C. Clarke in his essay Hazards of Prophecy:

The Failure of Imagination, proposed 3 laws of
prediction. The first law is that, When a distinguished
but elderly scientist states that something is possible, he
is almost certainly right. When he states that something
is impossible, he is very probably wrong. Others are not
so forward thinking when it comes to embracing innovation. The wireless music box has no imaginable commercial value. Who would pay for a message sent to
nobody in particular? were the comments of David
Sarnoffs associates in response to his urgings for investment in the radio in the 1920s. Although the associate
was probably neither elderly nor a scientist, he was almost certainly in good company at the time. Skepticism
about new technologies has existed in all walks of life and
at all stages of history. Yet, every day new technologies
come online and affect every sphere of our lives, including medicine.
Advances in wireless technologies have tremendously
enhanced diagnostic and therapeutic capabilities in gastroenterology and have improved our ability to take care
of our patients. Furthermore, they have allowed patients
the freedom to not be physically tied to their physician or
the testing facility, and have testing performed in the
comfort of their home. As gastroenterologists, advances
in wireless technologies are allowing us to perform gastrointestinal (GI) diagnostic procedures with increased
patient comfort, and to look and treat deeper in the GI
tract, beyond the reach of traditional wired devices and
endoscopes. There are great advances being made in wireless diagnostic and therapeutic technologies in gastroenterology. This article gives an overview of the advances
that will significantly impact the specialty of gastroenterology in the near future.

Wireless Diagnostic Technologies

Bravo pH Testing
Esophageal pH testing have been the gold standard for diagnosing gastroesophageal reflux disease
(GERD); however, the test has been underutilized because of patient discomfort associated with the traditional nasopharyngeal wired pH monitoring system. The
GASTROENTEROLOGY 2009;137:434 465

Bravo pH capsule (GIVEN Imaging, Atlanta, GA) is a

wireless, radio-telemetry based, intra-esophageal pH
monitoring system that eliminates the discomfort of an
indwelling nasopharyngeal catheter. The Bravo pH capsule measures 25 6 5.5 mm and is placed either
transorally or transnasally with or without sedation after
either endoscopic or manometric localization of the
lower esophageal sphincter (LES). The pH capsule consists of a battery, radio transmitter, and an antimony pH
electrode at its distal tip to measure esophageal pH. The
pH electrode samples esophageal pH every 6 seconds and
data are transmitted every 12 seconds for 48 hours to an
external receiver unit worn by the patient.1 A composite
pH score of 14 on any of the two 24-hour recordings
has a high sensitivity, specificity, and positive and negative predictive values, and an accuracy of 95%.2 The bravo
pH capsule is significantly better tolerated by the patients
and allows pH monitoring under more physiologic conditions, improving the accuracy of the test in detecting
GERD. The Bravo pH capsule is primarily used to establish the diagnosis of GERD in patients with atypical
symptom, symptoms not responding to medication, or
conclusively establish the diagnosis before anti-reflux
surgery. The Bravo pH testing should ideally be performed while the patient is off antisecretory medications.

Wireless pH/Impedance Testing

Multichannel intraluminal impedance testing has
gained significant interest and clinical acceptance for the
diagnosis of weakly acidic or non-acid reflux. Current
impedance pH testing systems use nasopharyngeal catheters to measure changes in esophageal impedance (conductivity across 2 closely spaced electrodes) owing to
intraesophageal refluxate or food bolus. The system uses
directionality (anterograde indicating a swallow and retrograde indicating a reflux event) of the impedance
change to diagnose a swallow or a reflux event. Additional pH sensors on the impedance catheter are used to
2009 by the AGA Institute

0016-5085/09/$36.00
doi:10.1053/j.gastro.2009.06.029

Imaging and Advanced Technology continued

assess the pH of the refluxate. Recently, a wireless, impedance-based pH monitoring system has been developed. The battery-less system uses inductive links between 2 coils. An external coil forms a resonance circuit
with a radiofrequency source worn externally by the patient and a small coil with inter-digitated electrodes implanted in the esophagus to detect changes in esophageal
impedance. The impedance changes in the esophagus,
caused by fluid passing, can be detected by either amplitude or frequency modulation. The system in vitro and in
vivo has been shown to measure pH accurately using
impedance changes and may be better tolerated than the
current catheter-based impedance system.3 Impedance
testing is primarily used to establish the etiology of
symptoms not responding to antisecretory medication or
to detect reflux of non-acidic content as a source of
patients symptoms. The impedance/pH testing is ideally
performed on maximal antisecretory therapy.

Wireless Whole Gut Pressure and pH

Monitoring System
This Smart Pill system (SmartPill Corporation,
MotiliGI, Buffalo, NY) consists of a wireless motility
capsule, data receiver, docking station, computer, and
data analysis software. The shape and dimensions of the
Smart Pill capsule (cylindrical, 26.8 mm long 11.7 mm
in diameter) are similar to the video capsule endoscopes.
The capsule houses sensors for pH, temperature, and
pressure and wirelessly transmits this information at 434
MHz using RF-technology. The capsule measures pH
(range, 0.059.0 pH units) with an accuracy of 0.5 pH
units, pressure (range, 0 350 mmHg) with an accuracy of
5 mmHg and temperature (range, 25 49C) with an
accuracy of 1C. The data receiver is powered by rechargeable batteries. After completion of study, the data
are downloaded to a Windows PC-compatible laptop and
data are analyzed. The initial studies reveal promising
results in determining the gastric and whole gut transit
using the Smart Pill. However, the clinical utility of
various physiologic parameters throughout the GI tract
and their alteration in various disease states need to be
further elucidated. SmartPill is approved by the US Food
and Drug Administration (FDA) for the measurement of
gastric emptying in patients with suspected gastroparesis.4 Another novel ingestible event marker system (Proteus, CA) has been recently reported to measure physiologic transit times with high detection accuracy. The
ingestible event marker system offers promise of a new
physiologic monitoring system; however, its clinical utility in gastroenterology remains to be established.5

Wireless GI Imaging
GI endoscopy has been the mainstay of GI diagnostics and therapeutics. A major paradigm shift in GI

endoscopy happened with the advent of wireless GI imaging using capsule endoscopes. The capsule endoscopy
system consists of an ingestible capsule, a data recorder,
and a computer work station to download and analyze
the capsule images. The small bowel capsule endoscope
measures 11 24 26 mm in dimension, weigh around
3.4 g, and obtain 23 images per second. There are 5
capsule endoscopy systems available: PillCam (GIVEN
Imaging), EndoCapsule (Olympus, Center Valley, PA),
MiroCam (Intromedic, Seoul, Korea), OmOm capsule
(Jinshan Science and Technology, Chongqing, China),
and Sayaka (RF System Labs, Nagano, Japan); however,
only the PillCam and EndoCapsule are currently FDA
approved for use in the United States. PillCam uses a
complimentary oxide silicone chip and EndoCapsule uses
a charge couple device chip for imaging. Both these
capsule endoscopes use RF-based communication technology. MiroCam is currently undergoing FDA approval
trials in the United States and uses a complimentary
oxide silicone chip for imaging and the Human Body
Communication technology for transmission of images.
Human Body Communication technology uses 2 external
capsule electrodes to transmit and a single skin electrode
to receive the data using the human body as an electrical
conductor. This methodology uses less energy, allowing
the capsule to obtain images at higher frame rate (3
images per second) and for a longer duration (11 hours)
compared with other capsule endoscopy systems. Preliminary data from OmOm capsule suggests that the
OmOm capsule has comparable test characteristics to the
other 3 capsule endoscopes. In addition, GIVEN imaging
has an FDA-approved esophageal capsule endoscope
PillCam ESO for the evaluation of esophageal disease
such as Barretts esophagus and esophageal varices and a
colon capsule endoscope PillCam Colon that is undergoing FDA trials in the United States for the evaluation of
various colonic diseases. Both the esophageal and colon
capsule endoscopes have cameras at both ends. The
esophageal capsule endoscope acquires images at 79
fps/camera per second and the colon capsule endoscope
acquires images 2 fps/camera per second.6
The future advances in capsule endoscopy system will
improve the efficiency and diagnostic capabilities of these
endoscopes, and offer opportunities for therapy. Externally rechargeable batteries using RF, microwave, ultrasound, or electric induction technology will eliminate
battery life constraints and make prolonged capsule endoscopy, including tethered capsule endoscopy, possible.
Sayaka (RF System Labs) is a new, battery-free capsule
endoscope that uses induction charging to draw power.
The camera is mounted on the side as opposed to the end
of the capsule. The camera rotates along the long access
of the capsule taking 30 en face images per second over
the entire inner surface of the entire GI tract. The cap435

Imaging and Advanced Technology continued

tured images are transmitted to the receiver and then

processed into an extensive series of overlapped mosaicing images. These mosaic images are created to replicate a 6- to 8-meter-long digestive canal. The result is a
pipe shaped tract that can be stored in a long and continuous form and can be dissected to view in long form.
Any area of interest can also be magnified up to 75 times
on the screen for detailed viewing.7 Check cap is developing an imaging capsule aiming to provide a 3-dimensional (3D) reconstruction of the colon without the need
to clean the bowel. This imaging capsule contains a tiny,
sonar-like device that transmits x-rays with minimal radiation (the equivalent of a chest x-ray, or 1/300 of a
computed tomographic colography), to the intestinal
wall, which are reflected back and captured by the imaging capsule. The analysis of distances creates 3D images
of the colons internal surface, enabling the detection of
clinically significant polyps (Figure 1). Because x-rays,
unlike optic alternatives, can see through colon content
and are transmitted a full 360radius around the capsule,
bowel cleansing is unnecessary and colonic folds do not
obstruct the view. The imaging capsule travels painlessly
through the colon, and is excreted naturally. A gastroenterologist analyzes the data thats been transmitted to a
waist- or wrist-worn receiver; a colonoscopy is needed if
polyps are detected.
In addition, improvement in the chip technology and
emergence of hybrid imaging chips will further improve
image resolution and will capture more image information for digital image analysis of normal and pathology.
Blue light imaging including recent integration of the
Fuji Intelligent Chromo Endoscopy (FICE) with PillCam
capsule endoscopy system, optical biopsies, and chemical
or immunologic tagging and imaging of pathology will
further improve disease recognition. The Nano-based

Figure 1. A 3D reconstruction of a porcine colon using the check cap

imaging capsule. The blue circle highlights a 5-mm polyp that was
created in the porcine colon using an isodense submucosal silicone
implants and was detected by the imaging capsule.
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capsule-Endoscopy with Molecular Imaging and Optical

biopsy (NEMO) project is a consortium of industry and
academic institutions that plan to develop a new capsule
endoscopy system that will combine optical and nano
technologies, biosensing, and maneuvering technologies
to create a unique capsule endoscope capable of secretion
analysis and detection of marked and deep tissue diseases. The consortium predicts that the fusion of optical
images with data from molecular analysis may provide a
novel and effective device for mass screening for GI cancer. In addition, advanced wireless imaging with capsule
technology will improve wireless laparoscopy and NOTES
applications.
Future improvements in the battery technology using
carbon nanotubes and Bucky tubes will reduce the size
and improve the efficiency of batteries that occupy the
most space in a capsule endoscope, thus freeing up space
for additional diagnostic and therapeutic component.
Pilot data from centers developing diagnostic and therapeutic capsules have demonstrated the feasibility studies of performing mucosal biopsies using a spring loaded
Crosby capsule type device guided by real-time imaging
capability and RF-controlled remote manipulation. Other
biopsy devices that have been successfully demonstrated
in animal modes include a capsule with a single-crystal
silicon planar microspikes with protruding barbs for microscale biopsy that utilizes Micro-Electro-Mechanical
Systems (MEMS) technology. Other capsules have used a
rotational microbiopsy device consisting of a trigger with
a paraffin block, rotational tissue-cutting razor with a
torsion controller designed to operate sequentially so
that the tissue sampling, sealing, and fixing are achieved
in single operation8 (Figure 2). Prototype coagulation
capsules are being tested. In addition, the feasibility of
manipulating the capsule endoscope or creating a locomotion or propulsion mechanism using external magnets, electrostimulation, hydrojets, shape memory alloy
coils, and MEMS-based modular actuators have already
been demonstrated.9 The Versatile Endoscopic Capsule
for gastrointestinal TumOr Recognition and therapy
(VECTOR) project, funded by European Commission, is
developing a minirobot endowed with actuation modules, mechanisms, sensors, embedded controls, and humanmachine interface with the task to navigate and
intervene in the GI tract for early detection of GI cancer
(Figure 3).
Researchers at the City University and City College
of New York have developed a video capsule endoscope
called Compact Photonic Explorer (CPE), with the
capability to externally manipulate the capsule by remote controlled radio signal and computer software.
The CPE measures 5 mm, and includes a transport
capsule that contains imaging, data transmission, and
collection capabilities. The CPE can detect disease and

Imaging and Advanced Technology continued

bilities, and ultrasound capabilities in their capsule

endoscopes.

Engineering-Based Capsule for

Targeted Drug Delivery
Multiple wireless capsules have been developed
for targeted drug delivery for better understanding the
pharmacokinetics of various new drugs. However, the
same technology can be used to deliver the drug or
therapeutic agent to a specific area of the GI tract,
thereby reducing the dose of the drug administered and
associated side effects. The high-frequency capsule (Battelle-Institute V, Frankfurt am-Maine, Germany) uses an
external RF trigger to melt a thread, thus releasing a
needle that pierces a balloon and delivers a therapeutic
agent at a specific site. The location of the capsule is
monitored using fluoroscopy, which tends to be inaccurate
and may expose the patient to excessive radiation. The
Gastrotarget telemetric capsule (Gastrotarget, Tonawanda,
NY) and Telemetric capsule (INSERM U61, Strasbourg
Cedex, France) use RF signal and complex localization
algorithms to deliver the drug in a specific area of the GI
tract. Recently, IntelliSite Capsule (Innovative Devices,
Raleigh, NC) and Enterion Capsule (Pheaton Research,
Nottingham, UK) have become popular tools for collecting absorption data in GI tract and can also be used for
targeted drug delivery.10 iPill (Philips Research, Eindhoven, The Netherlands) is a prototype capsule that measures 11 26 mm and incorporates a microprocessor,
battery, pH sensor, temperature sensor, RF wireless transceiver, fluid pump, and drug reservoir (Figure 4). The RF
wireless transceiver is used to communicate with a control unit outside the body. Using the information on pH
change measured by the iPill, and data about gut transit
times, the iPills location in the gut can be determined
with fair accuracy. Targeted drug delivery is performed by
the iPills internal pump under the control of the micro-

Figure 2. Prototype Rotational Micro Biopsy Capsule Device. (Courtesy Prof. Doyoung Jeon, Department of Mechanical Engineering,
Sogang University, Seoul, Korea.)

monitor bodily functions by combining imaging, polarization, spectroscopy, fluorescence, and biosensor
technologies. The investigators claim that in the future
CPE will be able to perform therapies like laser tissue
removal and tissue welding at precise locations within
the intestinal tract. Olympus has announced that they
have developed wireless power supply, fluid sampling
capabilities, remote manipulation, drug delivery capa-

Figure 3. Vision of VECTOR Capsule with different diagnostic and

therapeutic capabilities.
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Imaging and Advanced Technology continued

Figure 4. Philips Researchs intelligent pill (iPill) for electronically

controlled drug delivery. The iPill
is an 11- 26-mm capsule that
incorporates a microprocessor,
battery, pH sensor, temperature
sensor, RF wireless transceiver,
fluid pump, and drug reservoir.

processor, allowing accurate control of the drug delivery

profiles such as a burst, progressive release, or a multilocation dosing. The iPill drug delivery system is currently being evaluated in patients with Crohns disease
and colon cancer.11

Implantable Microstimulator
The GI tract is a complex neuromuscular organ
and various devices are being developed for GI neurostimulation to treat a host of GI neuromuscular or motility disorders such as gastroparesis, obesity, and GERD.
Investigators from The Johns Hopkins University School
of Medicine have demonstrated the feasibility of the Bion
(Advanced Bionics Corporation, Valencia, CA) a self-contained, battery-powered, remotely programmable, microstimulator (7 g; 3.3 27 mm; Figure 5) in raising the LES
438

pressure in both porcine and canine models. In the canine

study, the micro-stimulator was endoscopically implanted
into the LES. The micro-stimulator was remotely turned on
resulting in a dose-dependent increase in the LES pressure
in all the dogs. The authors concluded that this minimally
invasive procedure may be a novel approach to treatment of
GERD and other GI motility disorders.12

Conclusion
Multiple advances in wireless technology are on the
horizon and will significantly affect diagnostic and therapeutic gastroenterology and endoscopy. These advances will
allow us to look deeper, see better, and measure more
physiologic parameters in the GI tract. In addition, wireless
technologies will help us to target and treat GI disease with
minimal invasiveness, and improved patient safety and

Imaging and Advanced Technology continued

2.

3.

4.

5.

6.
7.
8.

9.

10.

11.

12.
Figure 5. Bion MicroStimulator (27 mm long 3.3 mm in diameter).

comfort. In the words of Sir Arthur C. Clarke, in his second

law of prediction, the only way of discovering the limits of
the possible is to venture a little way past them into the
impossible; we are headed in that direction, wirelessly. If
Clarkes third law of predictionthat any sufficiently advanced technology is indistinguishable from magicis any
guide, achieving what was previously impossible ought to
make patients and gastroenterologists alike feel excited
about our wireless future.
References
1. Pandolfino JE, Schreiner MA, Lee TJ, et al. Comparison of the Bravo
wireless and Digitrapper catheter-based pH monitoring systems for

measuring esophageal acid exposure. Am J Gastroenterol 2005;

100;1466 1476.
Ayazi S, Lipham JC, Portale G, et al. Bravo catheter-free pH
monitoring: normal values, concordance, optimal diagnostic
thresholds, and accuracy. Clin Gastroenterol Hepatol 2009;7:
60 67.
Hsu L, Tang S, Huang W, et al. An implantable, batteryless and
wireless capsule with integrated impedance and pH sensors for
detecting the reflux of acidic and non-acidic materials. Gastroenterology 2009;136:W1080.
Rao SS, Kuo B, McCallum RW, et al. Investigation of colonic and
whole-gut transit with wireless motility capsule and radiopaque
markers in constipation. Clin Gastroenterol Hepatol 2009;
7:537544.
Epstein M. Ingestible event marker system- a novel physiologicallysized device platform for frequent, repeated use. Gastrointest Endosc 2009;69:AB 106.
Swain P. The future of wireless capsule endoscopy. World J
Gastroenterol 2008;14:4142 4145.
RF System Lab. Sayaka. Available from: http://www.rfamerica.
com/sayaka/index.html.
Kong K, Cha J, Jeon D, et al. A rotational micro biopsy device for the
capsule endoscope. Intelligent Robots and Systems, 2005. (IROS
2005). 2005 IEEE/RSJ International Conference, August 2 6,
2005, pp. 1839 1843. Available from: http://ieeexplore.ieee.org/
stamp/stamp.jsp?arnumber1545441&isnumber32977.
Menciassi A, Stefanini C, Gorini S, et al. Legged locomotion in the
gastrointestinal tract. Proceedings of 2004 IEEE/RSJ International Conference on Intelligent Robots and Systems. 2004. p.
937942.
Wilding I, Hirst P, Connor A. Development of a new engineeringbased capsule for human drug absorption studies. Pharmaceutical Science & Technology Today 2000;11:385392.
Philips Technology. Philips intelligent pill technology. Available from:
http://www.research.philips.com/newscenter/backgrounders/
081111-ipill.html.
Clarke JO, Jagannath SB, Kalloo AN, et al. An endoscopically
implantable device stimulates the lower esophageal sphincter on
demand by remote control: a study using a canine model. Endoscopy 2007;39:7276.

Reprint requests
Address requests for reprints to: Virender K. Sharma, MD, AGAF,
Division of Gastroenterology, Mayo Clinic in Arizona, 13400 East
Shea Boulevard, Scottsdale, Arizona 85259. e-mail: sharma.
virender@mayo.edu.
Conicts of interest
Dr Sharma is a consultant for Intromedic.
Funding
Dr Sharma received grant support from Given Imaging, Olympus Inc.

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