Diagnosis of Intestinal Motility by Image Analysis Using Capsule Endoscopy

Conventional intestinal manometry is the current gold standard for the evaluation of
intestinal motility1,2,3,11, and identifies patterns of intestinal dysmotility4,8,9. However
intestinal manometry involves intestinal intubation with consequent discomfort for the
patients. Furthermore, it requires considerable technical expertise and knowledge for
interpretation of the data. Hence, to date this method has limited indications and is
restricted to very few referral centers around the world6,7,10,13.

Vall d'Hebron Hospital, in collaboration with CVC (Barcelona, Spain) have recently developed
a minimally invasive method for evaluation of intestinal motility based on endoluminal image
analysis using the endoscopic PillCam capsule. In contrast to manometry, this technique is
minimally invasive, the technical aspects are simple, and the analysis is performed fully
automated by a computer program. Both the technical procedure of the test and the
endoluminal image analysis program has been developed by a multidisciplinary
medical-engineering team in the Autonomous University of Barcelona over the past 5 years.
The technique has been validated in a group of patients with intestinal dysmotility and
healthy subjects, and has demonstrated over 90% sensitivity and specificity.

In brief, the technique works as follows. In each study a series of features are analyzed:
contractile patterns (contractions evaluated as a diaphragmatic occlusion of the lumen and
by the presence of a radial wrinkle pattern), non contractile patterns (wall and tunnel
patterns), luminal content (turbid pattern), endoluminal motion, and capsule displacement.

The program is based on an automated learning method (machine learning technique). Data from
patients and healthy subjects are used as a training set. Based on these data, the program
develops the function that best discriminates both groups. The performance of the system has
been validated using the leave-one-out method that uses all but one as training set and
evaluates the left-out example.

This technique needs now to be validated in a large multinational population. Using this
expanded pool of studies as a learning set, a robust discrimination algorithm will be
developed, that can be made available for widespread diagnostic application. Furthermore,
whereas manometry only recognizes neuropathic, myopathic5,12 and obstructive motor patterns,
endoluminal image analysis may identify different categories of patients depending on the
clinical presentation and the etiologic factors involved.

This study is designed to provide evidence that the algorithm, using images created by
PillCam SB2 capsules, is at least as good as small bowel manometry in diagnosing severe
dysmotility.

Inclusion criteria - Patients

- Patient's age is 16-80 years, inclusive.

- One of the following SB manometry procedures:

- Underwent SB manometry within five years if results were abnormal

- Underwent SB manometry within 1 year if results were normal

- Scheduled for SB manometry within six months of enrollment date

- Patient was indicated for small bowel manometry based on one or both of the following
symptoms:

- Pseudo obstruction of the small bowel: symptoms resembling mechanical small
bowel obstruction without evidence of luminal compromise of the gut. Mechanical
occlusion is ruled-out by endoscopic and / or radiological studies following the
criteria of the attending physician.

Patients may have any of the following:

- recurrent acute episodes (at least two) with air fluid levels (as evidenced at least
once by abdominal X-ray), or

- chronic symptoms with small bowel dilation resembling a partial mechanical
obstruction.

Patients will be tested during period of (non-acute) remission. - Chronic severe GI
symptoms with inability to maintain normal body weight: abdominal symptoms (such as
nausea, abdominal distension, discomfort or pain) produce inability to maintain a normal
body weight as defined by unintentional weight loss of at least 10% of original body
weight before onset of symptoms or a BMI < 18.5, while on a normal diet (without oral
dietary supplements, enteral or parenteral feeding).

These should be chronic symptoms lasting at least 6 months.

- Patient or legal guardian agrees to sign consent form

Exclusion criteria - Patients

- Acute exacerbation of chronic obstructive symptoms.

- Mechanical obstruction of any kind such as definite long stricture seen on
radiological exam.

- Suspected GI stricture, followed by Agile® study that could not prove patency of the
GI tract.

- Known history of small bowel organic disease such as Crohn's Disease or Celiac.

- Patient suffers from any condition, such as swallowing problems or having an
implanted cardiac pacemaker or defibrillator which precludes compliance with study
and/or device instructions.

- Non-steroidal anti-inflammatory drugs including aspirin, (twice weekly or more)
during the 4 weeks preceding the CE exam.

- Patient has undergone gastrectomy (segmental small bowel resection over 30%).

- During the period between small bowel manometry and Capsule endoscopy, the patient
has undergone any abdominal surgical procedures other than appendectomy,
cholecystectomy, abdominal wall hernia repair or catheter placing for enteral
feeding.

- Manometry was performed before any other allowed GI procedure.

- Patient is pregnant.

- Known abuse of alcohol or illicit substances.

- Patient presently presenting with an acute life threatening condition.

- Participating in another clinical study within 30 days.

Inclusion criteria - Healthy Volunteers

- Volunteer's age is 16-80 years, inclusive.

- Volunteer or legal guardian agrees to sign consent form. 6.5.2 Exclusion criteria -
Healthy Volunteers

- Known diabetes mellitus

- Recurrent Gastrointestinal symptoms

- Volunteer suffers from any condition, such as swallowing problems, which precludes
compliance with study and/or device instructions

- Non-steroidal anti-inflammatory drugs including aspirin, (twice weekly or more)
during the 4 weeks preceding enrollment

- More than one answer above 'mild' on the healthy volunteer symptoms questionnaire
(Appendix C).

- Female volunteer is pregnant

- Known abuse of alcohol or illicit substances.

- Participating in another clinical study within 30 days