Note: Descriptions are shown in the official language in which they were submitted.
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METHOD AND SYSTEM FOR MONITORING
GASTROINTESTINAL FUNCTION AND
PHYSIOLOGICAL CHARACTERISTICS
FIELD OF THE INVENTION
The present invention relates generally to methods for non-invasive assessment
of
gastrointestinal function and physiological characteristics.
BACKGROUND OF THE INVENTION
Advances in the pharmaceutical industry in the past decades have been
essential in
extending the length and quality of the human life. In addition to new
compounds,
advances in oral medication formulation and delivery methods have helped
improve
efficacy while minimizing dosage and reducing side effects. However, the human
body's
digestive tract is heterogeneous, and differences in digestive enzymes,
absorption rates,
micro flora, and other factors make certain sites in the gastro-intestinal
tract more or less
ideal for the delivery of specific medications.
Drug companies have focused considerable efforts in targeted drug delivery,
i.e. location
and rate of drug delivery within the gastrointestinal ("GI") tract. These
efforts have
resulted in variations in the forms of basic delivery designs, e.g., gel
capsule vs. hard
tablet, coating formulations, etc., and more recently, advanced control over
micro- and
nana-particle size. While these advances have proven beneficial, the human
element
remains: the GI system is intensely variable, both inter-and intra-subject. A
key variable,
gastrointestinal motility and, hence, gastrointestinal (or digestive) transit
time, complicates
determining the ideal targeted drug delivery.
Gastrointestinal motility also can, and in many instances will, have a
significant impact on
the clinical evaluation of the efficacy of a pharmaceutical formulation.
Indeed, as is well
known in the art, if an orally delivered pharmaceutical formulation, e.g., gel
capsule
containing a pharmaceutical formulation, exits the gastrointestinal tract
prior to optimum
dissolution and, hence, absorption, the efficacy of the formulation will be
greatly
diminished. Moreover, it has been found that in some instances, the capsule
can remain in
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the upper gastrointestinal tract (i.e. upper fundus) for extended periods of
time (e.g.,
> 5 hrs).
It is also well known that there is a direct relationship by and between
gastrointestinal
motility and gastrointestinal function. Indeed, in many instances,
gastrointestinal motility
can reflect normal and/or abnormal gastrointestinal function, e.g.,
gastrointestinal
obstruction.
Various methods and systems have been employed to assess gastrointestinal
motility and
transit time. A commonly employed method comprises gamma scintigraphy. There
are,
however, several significant drawbacks associated with gamma scintigraphy.
A drawback associated with gamma scintigraphy is that the method is presently
limited to
a small number of facilities and experts due to the issues (and controls)
associated with
handling radiological substances and the equipment expense. A further drawback
is that
large scale clinical drug trials are impractical.
Further methods and systems for assessing gastrointestinal motility include
the acquisition
and evaluation of gastrointestinal sounds. For example, in U.S. Pat. No.
5,301,679, a
method and system are disclosed for providing diagnostic information for
various
diseases, including diseases of the gastrointestinal tract, by capturing body
sounds with a
microphone placed on the body surface or inserted orally or rectally into the
gastrointestinal tract.
Other systems also employ microphones sensitive to gastrointestinal sounds
within
specific frequency ranges and are exemplified by Dalle, et al., "Computer
Analysis In
Bowel Sounds", Computers in Biology and Medicine, Vol. 4 (3-4), pp. 247-254
(Feb.
1975); Sugrue et al., "Computerized Phonoenterography: The Clinical
Investigation of the
New System", Journal of Clinical Gastroenterology, Vol. 18, No. 2, pp. 139-144
(1994);
Poynard, et al., "Qu'attendre des systemes experts pour le diagnostic des
troubles
fonctionnes intestinaux", Gastroenterology Clinical Biology, pp. 45c-48c
(1990).
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A significant drawback associated with the conventional acoustic methods and
systems is
that the scope of information that can be derived from the recorded sounds is
limited.
Indeed, there is little, if any, disclosure directed to the relationship
between
gastrointestinal sounds and gastrointestinal transit times.
It would therefore be desirable to provide a method and system for evaluating
gastrointestinal motility and determining gastrointestinal transit time by
abdominal
auscultation.
SUMMARY OF THE INVENTION
Embodiments of the present invention provide systems and methods for
monitoring
gastrointestinal function and, optionally, other physiological parameters,
such as pulse and
respiration rates. The systems and methods of the invention can thus provide a
variety of
information, including gastrointestinal transit time and other physiological
parameters.
In accordance with one aspect of the invention, there is provided a system and
method for
monitoring gastrointestinal function that can be effectively employed to
acquire one or
more signals associated with acoustic energy (i.e. sound) emanating from an
abdominal
region of a body and determine at least one gastrointestinal parameter based
on the
acoustic energy signal(s).
In accordance with one embodiment of the invention, there is thus provided a
system for
monitoring gastrointestinal function of a subject, comprising: (a) at least
one sensor
mountable on or in a body region of the subject, the sensor being adapted to
sense acoustic
energy and generate at least one acoustic energy signal representing the
acoustic energy,
and (b) a processing unit adapted to receive the acoustic energy signal, the
processing unit
being further adapted to process the acoustic energy signal and determine the
occurrence
of at least one gastrointestinal parameter or event.
In one embodiment, the gastrointestinal parameter comprises an event selected
from the
group consisting of gastrointestinal mixing, emptying, contraction and
propulsion, and
gastrointestinal transit time.
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In one embodiment, the gastrointestinal parameter comprises an event
associated with a
gastrointestinal system disorder that is selected from the group consisting of
reflux
disease, irritable bowel disease, ulcerative colitis, constipation, diarrhea,
and a mitigating
motor complex disorder.
In accordance with another embodiment of the invention, there is provided a
system for
monitoring gastrointestinal function and physiological characteristics,
comprising: (a) at
least one acoustic energy sensor mountable on or in a body region of a
subject, the
acoustic energy sensor being adapted to sense acoustic energy representing a
gastrointestinal sound generated by the subject and generate an acoustic
energy signal
representing the acoustic energy, (b) at least one physiological sensor
mountable on or in a
body region of the subject, the physiological sensor being adapted to sense a
physiological
characteristic associated with the subject and generate a physiological
characteristic signal
representing the physiological characteristic, and (c) a processing unit
adapted to receive
the acoustic energy and physiological characteristic signals, the processing
unit being
further adapted to process the acoustic energy and physiological
characteristic signals and
determine the occurrence of at least one gastrointestinal parameter or event
as a function
of the acoustic signal.
In accordance with another embodiment of the invention, there is provided a
system for
monitoring gastrointestinal function of a subject, comprising: (a) at least
one acoustic
energy sensor mountable proximate a body region of the subject, the acoustic
energy
sensor being adapted to sense acoustic energy generated by the subject and
generate at
least one acoustic energy signal representing the acoustic energy, (b) at
least one spatial
parameter sensor mountable proximate a body region of the subject, the spatial
parameter
sensor being adapted to monitor at least one spatial parameter associated with
the subject's
body and generate at least one spatial parameter signal representing the
spatial parameter,
and (c) a processing unit adapted to receive the acoustic energy and spatial
parameter
signals, the processing unit being further adapted to determine the occurrence
of at least
one gastrointestinal parameter as a function of the acoustic energy and
spatial parameter
signals.
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In one embodiment, the spatial parameter sensor comprises a motion sensor that
is adapted
to monitor motion of the subject's body and the spatial parameter comprises
the motion of
the subject's body.
In one embodiment, the spatial parameter sensor comprises an orientation
sensor that is
adapted to monitor orientation of the subject's body and the spatial parameter
comprises
the orientation of the subject's body.
In accordance with another embodiment of the invention, there is provided a
system for
monitoring gastrointestinal function and physiological characteristics,
comprising: (a) at
least one acoustic energy sensor mountable proximate a body region of a
subject, the
acoustic energy sensor being adapted to sense acoustic energy generated by the
subject
and generate at least one acoustic energy signal representing the acoustic
energy, (b) at
least one spatial parameter sensor mountable proximate a body region of the
subject, the
spatial parameter sensor being adapted to monitor at least one spatial
parameter associated
with the subject's body and generate at least one spatial parameter signal
representing the
spatial parameter, (c) at least one physiological sensor mountable proximate a
body region
of the subject, the physiological sensor being adapted to sense a
physiological
characteristic associated with the subject and generate at least one
physiological
characteristic signal representing the physiological characteristic, and (d) a
processing unit
adapted to receive the acoustic energy, spatial parameter and physiological
characteristic
signals, the processing unit being further adapted to determine the occurrence
of at least
one gastrointestinal parameter as a function of the acoustic energy and
spatial parameter
signals.
In one embodiment, the spatial parameter sensor comprises a motion sensor that
is adapted
to monitor motion of the subject's body and the spatial parameter comprises
the motion of
the subject's body.
In one embodiment, the spatial parameter sensor comprises an orientation
sensor that is
adapted to monitor orientation of the subject's body and the spatial parameter
comprises
the orientation of the subject's body.
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In accordance with another embodiment of the invention, there is provided a
method of
determining a gastrointestinal parameter associated with a subject, comprising
the steps of:
(a) sensing acoustic energy generated by the subject's gastrointestinal system
and
generating an acoustic energy signal representing the acoustic energy, (b)
sensing at least
one spatial parameter associated with the subject and generating a spatial
parameter signal
representing the spatial parameter, and (c) determining at least one
gastrointestinal
parameter as a function of the acoustic energy and spatial parameter signals.
In accordance with another embodiment of the invention, there is provided a
method of
determining a gastrointestinal parameter associated with a subject, comprising
the steps of:
(a) sensing acoustic energy generated by the subject's gastrointestinal system
and
generating an acoustic energy signal representing the acoustic energy, (b)
sensing at least
one spatial parameter associated with the subject and generating a spatial
parameter signal
representing the spatial parameter, (c) sensing a physiological characteristic
associated
with the subject and generate at least one physiological characteristic signal
representing
the physiological characteristic and (d) determining at least one
gastrointestinal parameter
as a function of the acoustic energy and spatial parameter signals
In accordance with yet another embodiment of the invention, there is provided
a method of
monitoring gastrointestinal function and physiological characteristics of
multiple subjects,
comprising the steps of. (a) sensing first acoustic energy generated by a
first subject's
gastrointestinal system and generating a first acoustic energy signal
representing said first
acoustic energy, (b) sensing a first physiological characteristic associated
with the first
subject, (c) sensing a second physiological characteristic associated with a
second subject,
and (d) determining at least one gastrointestinal parameter associated with
the first subject
as a function of the first acoustic energy signal.
In one embodiment, the second subject comprises a fetus of the first subject.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGURE IA is an illustration of a portion of a human torso showing a typical
gastrointestinal tract;
FIGURE 1 B is an illustration of a human stomach;
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FIGURE 2A is a schematic illustration of one embodiment of a gastrointestinal
analysis
system, according to the invention;
FIGURE 2B is a schematic illustration of another embodiment of the
gastrointestinal
analysis system shown in FIGURE 2A, according to the invention;
FIGURE 3 is a further illustration of the partial human torso shown in
FIGURE 1, showing the placement of gastrointestinal sound (or acoustic)
sensors,
according to one embodiment of the invention;
FIGURE 4 is a schematic illustration of an analyzer, showing the sub-systems
or modules
thereof, according to one embodiment of the invention;
FIGURE 5 is a graphical illustration of a cumulative motion parameter (AccM)
as a
function of time, according to the invention;
FIGURE 6 is a further illustration of a portion of a human torso having a
system vest
disposed thereon, according to one embodiment of the invention;
FIGURE 7 is a schematic illustration of a gastrointestinal motility analysis
system having
additional physiological sensors, according to another embodiment of the
invention;
FIGURE 8 is a summary of gama scintigraphy results acquired during a
gastrointestinal
motility study; and
FIGURES 9-15 are graphical illustrations of gastrointestinal sound signals,
reflecting
gastrointestinal sounds acquired during the gastrointestinal motility study
summarized in
Figure 8.
DETAILED DESCRIPTION OF THE INVENTION
Before describing the present invention in detail, it is to be understood that
this invention
is not limited to particularly exemplified structures, apparatus, systems,
materials or
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methods as such may, of course, vary. Thus, although a number of apparatus,
systems and
methods similar or equivalent to those described herein can be used in the
practice of the
present invention, embodiments of the apparatus, systems and methods according
to the
present invention are described herein.
It is also to be understood that like referenced characters generally refer to
the same parts
or elements throughout the views shown in the figures.
Unless defined otherwise, all technical and scientific terms used herein have
the same
meaning as commonly understood by one having ordinary skill in the art to
which the
invention pertains. Further, all publications, patents and patent applications
cited herein,
whether supra or infra, are hereby incorporated by reference in their
entirety.
Finally, as used in this specification and the appended claims, the singular
forms "a", "an",
"the" and "one" include plural referents unless the content clearly dictates
otherwise.
Thus, for example, reference to "a sensor" includes two or more such sensors;
reference to
"a gastrointestinal event" includes two or more such events and the like.
Definitions
The term "pharmaceutical composition", as used herein, is meant to mean and
include any
compound or composition of matter or combination of constituents, which, when
administered to an organism (human or animal) induces a desired pharmacologic
and/or
physiologic effect. The term therefore encompasses substances traditionally
regarded as
actives, drugs, prodrugs, and bioactive agents, as well as biopharmaceuticals
(e.g.,
peptides, hormones, nucleic acids, gene constructs, etc.).
The term "pharmaceutical", as used herein, is meant to mean and include a
pharmaceutical
composition that precipitates acoustic energy or a gastrointestinal sound (or
sounds) from
the gastrointestinal tract when orally administered to a human or animal, such
as, without
limitation, pharmaceutical compositions in the form of hard tablets, gel
capsules (hard and
soft), caplets and other solid dosage forms.
The term "ingestible", as used herein, is meant to mean and include any
substance or item
that precipitates acoustic energy or a gastrointestinal sound (or sounds) from
the
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gastrointestinal tract when orally administered to a human or animal. An
"ingestible" can
thus comprise a pharmaceutical, as well as a non-pharmaceutical composition,
such as,
without limitation, a placebo.
The term "gastrointestinal function", as used herein, means and includes,
without
limitation, the operation of all of the organs and structures associated with
the
gastrointestinal system.
The terms "gastrointestinal system disorder" and "adverse gastrointestinal
system event",
as used herein, mean and include, without limitation, any dysfunction of the
gastrointestinal system, including, without limitation, a dysfunction that
impedes the
digestive process, such as gastrointestinal blockage.
The term "gastrointestinal event", as used herein means and includes an
activity or
function associated with the gastrointestinal system, including, without
limitation,
gastrointestinal mixing, emptying, contraction and propulsion. A
"gastrointestinal event"
can also comprise an event associated with a "gastrointestinal system
disorder" or
"adverse gastrointestinal system event", such as, without limitation, reflux
disease,
irritable bowl disease, ulcerative colitis, constipation, diarrhea, and a
mitigating motor
complex (MMC) phase disorder.
The term "gastrointestinal parameter", as used herein, means and includes a
characteristic
associated with gastrointestinal function, including, without limitation, a
gastrointestinal
event and gastrointestinal transit time.
The term "gastrointestinal sound", as used herein, means and includes acoustic
energy
(and all signals embodied therein) generated by a gastrointestinal event.
The term "gastrointestinal transit time", as used herein, is meant to mean the
motile time
through one or more sections of the gastrointestinal tract that can be
impacted by the
composition of the materials being passed, state of the gastrointestinal
tract, psychological
stress, gender, and other factors. "Gastrointestinal transit time" is a
generic term that can
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be used to describe the overall gastrointestinal transit time, the fundus-
rectal transit time,
and various other motile times through one or more sections of the
gastrointestinal tract.
The term "overall gastrointestinal transit time", as used herein, means the
motility time of
a pharmaceutical or ingestible from the point it is administered via its
intended route (e.g.,
oral, rectal) through the various sections of the gastrointestinal tract and
its exit from the
body.
The term "fundus-rectal gastrointestinal transit time", as used herein, means
the motility
time of a pharmaceutical or ingestible from entry into the fundus of the
stomach through
ejection from the rectum (see Figs. IA and 1B).
The term "signal voltage envelope", as used herein, means an envelope that is
derived
from a plurality of acoustic energy signal voltages. The "signal voltage
envelope" has
upper and lower boundaries defined by the acoustic energy signal voltages.
The term "signal amplitude envelope", as used herein, means an envelope that
is derived
from a plurality of acoustic energy signal amplitudes. The "signal amplitude
envelope"
has upper and lower boundaries defined by the acoustic energy signal
amplitudes.
The term "Vthreshold", as used herein, means the minimum voltage at which
values may be
considered significant. According to the invention, if the signal voltage
envelope is
below V reshold, there is no response (i.e. the signal is below the detector's
sensitivity). If
the signal voltage envelope is larger than Vthreshold for longer than a pre-
determined amount
of time, the value is deemed significant.
The terms "physiological characteristic" and "physiological parameter", as
used herein,
mean and include any characteristic associated with organism (human or animal)
and/or
body organ function other than a gastrointestinal parameter, including,
without limitation,
ECG, pulse rate, blood pressure, blood gas saturation (e.g., oxygen
saturation), respiration
rate skin temperature, and core temperature. The noted terms also include
pharmacokinetic (PK) parameters.
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The term "spatial parameter", as used herein, means and includes any
characteristic
associated with a subject's body orientation (e.g., whether a subject is
supine, prone,
sitting, standing, etc.) and/or body motion (e.g., whether a subject is
stationary, changing
body position, walking, etc.).
The terms "spatial parameter value" and "spatial parameter factor", as used
herein, mean
and include a numeric value representing a spatial parameter and/or the affect
of a "spatial
parameter" on a gastrointestinal parameter or event.
The term "subject", as used herein, means and includes a human or an animal.
The term
also includes an unborn human, i.e. fetus, or animal.
The present invention provides systems and methods for monitoring
gastrointestinal
function and, optionally, other physiological characteristics associated with
a patient or
subject. As set forth in detail herein, in some embodiments, the methods and
systems of
the invention can be effectively employed to acquire one or more signals
associated with
acoustic energy (i.e. sound) emanating from an abdominal region of a subject's
body and
determine (i) at least one gastrointestinal parameter based on the acoustic
energy signal(s)
and/or the onset thereof, and/or (ii) an event associated with a
gastrointestinal system
disorder (and/or a gastrointestinal system disorder) and/or the onset thereof.
As discussed in detail herein, some embodiments of the systems and methods of
the
invention are also adapted to effectively account for spatial parameters
associated with the
subject, such as the subject's body orientation and/or motion.
The methods and systems of the invention can also be effectively employed to
acquire one
or more signals associated with a physiological parameter or characteristic,
such as pulse
rate, respiration rate and blood pressure.
Implementation of the methods and systems of embodiments of the present
invention, as
described herein, can involve performing or completing selected tasks or steps
manually,
automatically, or a combination thereof. In some embodiments of the present
invention,
several selected steps could be implemented by hardware or by software on any
operating
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system or any firmware or a combination thereof. For example, as hardware,
selected
steps of embodiments of the invention could be implemented as a chip or a
circuit. As
software, selected steps of embodiments of the invention could be implemented
as a
plurality of software instructions being executed by a computer using any
suitable
operating system. In any case, selected steps of the method and system of the
invention
could be described as being performed by a data processor, such as a computing
platform
for executing a plurality of instructions.
Referring first to Fig. IA, there is shown an illustration of a typical
gastrointestinal tract
(designated generally "10"). As illustrated in Fig. 1, the gastrointestinal
tract 10 generally
includes the oesophagus or esophagus 12, stomach 13, small intestines 15 and
large
intestines 16. The large intestines include the cecum 17, colon 18 and rectum
19.
Referring to Fig. 1B, the stomach 13 includes the fundus region (or fundus)
14a and
pyloric antrum (or antrum) 14b.
As is well known in the art, gastrointestinal motility (in a normal
male/female subject) is
typically characterized by the repeated appearance of three distinctive
phases, called the
migrating motor complex (MMC). Phase 1 comprises a period or phase of no
contractions. Phase 2, which follows phase 1, comprises a phase of
intermittent, variable-
amplitude contractions. Phase 3, which follows phase 2, comprises a phase of
repetitive
propagating contractions. The migrating motor complex has an average cycle of
80 to
150 min.
It is also well established and known in the art that distinctive sounds
emanate from the
gastrointestinal tract during each of the noted phases. See, e.g., T.
Tomomasa, et al.,
"Gastrointestinal Sounds and Migrating Motor Complex In Fasted Humans", The
American Journal of Gastroenterology, Vol. 94, No. 2, pp. 374-381 (1999); J.
Farrar,
et al., "Gastrointestinal Motility as Revealed by Study of Abdominal Sounds",
Gastroenterology, Vol. 29, No. 5, pp. 789-800 (1955); W.B. Cannon,
"Auscultation of the
Rhythmic Sounds Produced by the Stomach and Intestines", Laboratory of
Physiology,
VI, pp. 339-353 (1905).
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As indicated above, although there have been various studies relating to
gastrointestinal
sounds and publications resulting therefrom, there is scant information
relating to the
relationships between gastrointestinal sounds and the migrating motor complex.
There is
also very little information relating to the relationship between
gastrointestinal sounds and
gastrointestinal transit time.
Referring now to Fig. 2A, there is shown a schematic illustration of one
embodiment of a
gastrointestinal analysis system 20 of the invention. As illustrated in Fig.
2A, the system
20 includes a plurality of acoustic energy sensors 22a, 22b, 22c and at least
one analyzer
24. In the embodiment shown in Fig. 2A, the system 20 also includes display
means 26.
According to the invention, the acoustic energy sensors 22a, 22b, 22c can
independently
comprise contact or non-contact transducers that detect vibrations and/or
sounds at or near
the skin surface of a subject and convert these vibrations and/or sounds into
electrical
signals. Other sensors can include internal sensors, such as intra-esophageal
and intra-
gastric sensors, that are introduced into the subject (or patient) using a
nasal-gastric tube or
the like.
By way of example only, the acoustic energy sensors 22a, 22b, 22c can be
electronic
stethoscopes, contact microphones, non-contact vibration sensors, such as
capacitive or
optical sensors, or any other suitable type of sensors. The acoustic energy
sensors 22a,
22b, 22c are preferably, but not necessarily, selected to have acoustic
impedance that
matches the impedance of the skin surface to provide optimal acoustic coupling
to the skin
surface. Still further, due to background noise and the relatively low
amplitude of the
vibrations or sounds which are generated at or near the skin surface by
gastric sounds, the
acoustic energy sensors 22a, 22b, 22c are also preferably, but not
necessarily, selected to
provide a high signal-to-noise ratio, high sensitivity and/or good ambient
noise shrouding
capability.
According to the invention, the acoustic energy sensors 22a, 22b, 22c and
spatial
parameter sensors 22d, 22e send low level (i.e. low power) electrical signals
via wires 23,
or any other suitable media, such as wireless radio frequency, infrared, etc.,
to the analyzer
24.
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A suitable acoustic energy sensor that can be employed within the scope of the
invention
is disclosed in U.S. Pat. No. 6,512,830.
While three acoustic energy sensors are shown in Fig. 2A, additional or fewer
sensors can
be used to detect gastric sounds at multiple locations on the subject's
abdomen 11, or any
other locations on the subject's body that are of interest and which may be
useful in
evaluating gastrointestinal function, and/or gastrointestinal motility (and/or
transit time).
For example, a single acoustic energy sensor may be strategically located on
the subject's
body and/or may be moved sequentially to different key locations on the
subject's body to
detect gastrointestinal sounds.
Referring now to Fig. 2B, there is shown another embodiment of the
gastrointestinal
analysis system 20. As illustrated in Fig. 2B, the system 20 similarly
includes acoustic
energy sensors 22a, 22b, 22c, analyzer 24 and display 26. However, in this
embodiment,
the system 20 further includes at least one, preferably, two spatial parameter
sensors 22d,
22e.
In one embodiment of the invention, spatial parameter sensor 22d comprises a
motion
sensor that is adapted to monitor spatial parameters associated with the
subject's body
motion, e.g., whether the subject is stationary, changing body position,
walking, etc., and
transmit at least one motion signal representing same to the analyzer 24.
In one embodiment of the invention, spatial parameter sensor 22e comprises an
orientation
sensor that is adapted to monitor spatial parameters associated with the
subject's body
orientation, e.g., whether the subject is supine, prone, sitting, standing,
etc., and transmit at
least one orientation signal representing same to the analyzer 24.
As will readily be appreciated by one having ordinary skill in the art, body
motion and
orientation can be determined by a number of conventional methods and means,
including,
without limitation, optical encoders, proximity and Hall effect switches,
laser
interferometry and accelerometers.
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As will also be appreciated by one having ordinary skill in the art, the
motion and
orientation sensors 22d, 22e can comprise integral, multi-function devices.
Thus, in some
embodiments of the invention, sensors 22d, 22e comprise multi-function 3-axis
accelerometers (referred to hereinafter as "motion/orientation sensors"). By
virtue of the
multi-function capability of 3-axis accelerometers, in some of the noted
embodiments,
only one motion/orientation sensor, e.g., 2d, is employed to monitor body
motion and
orientation.
As discussed in detail below, the analyzer 24 can include amplifiers, filters,
transient
protection and other circuitry that amplifies signals sent by the acoustic
energy sensors
22a, 22b, 22c, (and, optionally, motion/orientation sensors 22d, 22e) that
attenuates noise
signals, and/or that reduces the effects of aliasing. In particular, the
analyzer 24 can
include a low-pass filter having a cutoff frequency in the range of
approximately 1100 -
1400 Hz. In one embodiment of the invention, the low-pass filter has a cutoff
frequency
in the range of approximately 1200 - 1300 Hz.
Alternatively or additionally, a high-pass filter can be incorporated within
the analyzer 24.
This high-pass filter may, for example, have a cutoff frequency in the range
of
approximately 70-90 Hz so that undesirable noise and sounds, such as muscle
noise,
breathing sounds, cardiac sounds, non-gastric gastrointestinal sounds or any
other
undesirable sounds or noise are substantially attenuated or eliminated before
the signals
sent by the acoustic energy sensors 22a, 22b, 22c are processed further.
The spectral energy of the most potentially corrupting non-gastrointestinal
sounds is often
in a frequency band of approximately 20 - 250 Hz. However, the amplitude of
these
corrupting sounds can be reduced, in some cases significantly reduced, for
adult subjects
by considered positioning of the acoustic energy sensors 22a, 22b, 22c.
Referring now to Fig. 3, there is shown a preferred placement of acoustic
energy sensors
22a, 22b, 22c, motion/orientation sensors 22d, 22e, according to one
embodiment of the
invention. As illustrated in Fig. 3, acoustic energy sensor 22a is preferably
placed in the
upper left quadrant proximate the gastric fundus, acoustic energy sensor 22b
is preferably
placed in the lower right quadrant proximate the cecum, and acoustic energy
sensor 22c is
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preferably placed in the lower left quadrant proximate the small intestine,
more preferably,
proximate the descending colon.
According to embodiments of the invention, the acoustic energy sensors 22a,
22b, 22c can
be disposed in locations other than those specifically depicted in Fig. 3
without departing
from the scope and the spirit of the invention. For example, acoustic energy
sensor 22a
can be located on a traverse line approximately two-thirds of the distance
between the
umbilicus and xyphoid to the right of the midline, acoustic energy sensor 22b
can be
located over the left coastal margin and acoustic energy sensor 22c can be
located at the
midline at approximately one-half of the distance between the umbilicus and
symphosis
pubis.
In the embodiment illustrated in Fig. 3, the motion/orientation sensors 22d,
22e are
preferably disposed proximate the anterior surface of the abdomen, preferably,
proximate
the center of the chest region.
According to the invention, the motion/orientation sensors 22d, 22e can
similarly be
disposed in locations other than those specifically depicted in Fig. 3 without
departing
from the scope of the invention. Further, as indicated above, only one
motion/orientation
sensor, such as sensor 2d, can be employed.
Referring to Fig. 4, according to one embodiment of the invention, the
analyzer 24 is
adapted to perform the following functions: (i) receive recorded acoustic
energy (or
gastrointestinal sound) signals from the sensors (e.g., acoustic energy
sensors 22a, 22b,
22c) 30, (ii) store the acoustic energy signals in a memory medium 32, and
(iii) process
the acoustic energy signals (using signal processing module 33) to, according
to
embodiments of the invention, derive at least one gastrointestinal parameter
and/or
gastrointestinal event (and/or occurrence thereof) relating thereto. In some
embodiments
of the invention, the analyzer 24 is further adapted to compare the
gastrointestinal
parameter or event to at least one physiological characteristic or parameter,
such as a
pharmacokinetic (PK) parameter, that is induced in a subject by the
administration of a
pharmaceutical composition.
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In some embodiments of the invention, the analyzer 24 is further adapted to
determine an
event associated with a gastrointestinal system disorder (and/or a
gastrointestinal system
disorder), such as gastrointestinal system blockage.
In another embodiment of the invention, the analyzer 24 is further adapted to
(i) receive
recorded motion and orientation signals from the motion/orientation sensors
22d, 22e via
line 30, (ii) store the motion and/or orientation signals in the memory medium
32, and (iii)
determine at least one gastrointestinal parameter and/or gastrointestinal
event (and/or
occurrence thereof) relating thereto and/or gastrointestinal system disorder
(and/or a
gastrointestinal system disorder) as a function of the recorded acoustic
energy, motion
and/or orientation signals. In this embodiment, the analyzer 24 thus includes
algorithms
and/or derived spatial parameter factors (discussed in detail below) that
effectively
account for the spatial parameters reflected in the motion and orientation
signals in the
derived gastrointestinal parameter(s), event(s) and disorder(s). For example,
a spatial
signal may be used to adjust an acoustic signal.
As illustrated in Fig. 4, the analyzer 24 is also adapted to provide at least
one output signal
39 representing recorded acoustic energy and/or the subject's body motion
and/or
orientation and/or, according to further envisioned embodiments of the
invention
(discussed below), a physiological characteristic.
According to embodiments of the invention, the signal processing module 33 is
adapted to
also perform the following: (i) filter extraneous artifacts from the signals
34, (ii) determine
a signal amplitude envelope based on the signals 36, and (iii) determine the
dominant
frequency of the signals 38.
According to the invention, the filtering step 34 can be performed with
software, e.g.,
computer program, or hardware. Thus, in some embodiments of the invention, the
analyzer 24 is programmed to filter the acoustic energy signals and extract
the frequency
band of interest from the signals.
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In one embodiment, the frequency of interest is in the range of approximately
70-1400 Hz.
In another embodiment, the frequency of interest is in the range of
approximately 90-1200
Hz.
According to the invention, various conventional programs can be employed
within the
scope of the invention to perform the noted filtering step 34.
In other embodiments of the invention, the filtering step 34 is performed via
hardware. In
one embodiment, the analyzer circuit includes high and low pass filters that
are adapted to
filter the extraneous artifacts from the signals 34. According to the
invention, various high
and low pass filters can be employed within the scope of the invention. In one
embodiment, the high pass filter comprises a Blackman windowed, balanced 401-
tap FIR
with a cutoff set at 80 Hz and the low pass filter comprises a Blackman
windowed,
balanced 400-tap FIR with a cutoff set at 1250 Hz.
In one embodiment, the signal amplitude envelope is determined using a sliding
Hilbert
transform with a 5 gsec window. As is well known in the art, Hilbert
transforms are
commonly used to determine a signal envelope. See, e.g., Tomomasa, et al.,
"Gastrointestinal Sounds and Migrating Motor Complex In Fasted Humans", The
American Journal of Gastroenterology, Vol. 94, No. 2, pp. 374-381 (1999);
Farrar, et al.,
"Gastrointestinal Motility as Revealed by Study of Abdominal Sounds",
Gastroenterology, Vol. 29, No. 5, pp. 789-800 (1955); which are incorporated
by
reference herein.
Applicants have found that the Hilbert transform smoothed out the short
"pops", i.e.
intermittent acoustic energy spikes, and transformed the bipolar acoustic
energy signals
into a signal that can be readily analyzed using a simple Vnreshold, as
defined above.
According to embodiments of the invention, the dominant frequency of the
acoustic
energy signals can similarly be determined by various conventional means. In
one
embodiment, the dominant frequency was determined by isolating peaks >
Vthreshold for
time > 5gsec.
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As indicated above, a key feature and advantage of the embodiments of the
present
invention is the ability of the gastrointestinal analysis systems and methods
to effectively
account for spatial parameters, i.e. body motion and orientation, in
determinations of
gastrointestinal parameters, events and disorders.
Referring to Fig. 5, there is shown a graphical illustration of a cumulative
composite
motion measure (AccM) as a function of time. The AccM is a summation of both
the X
and Y body axis. As demonstrated in Fig. 5, the acoustic signal of the
acoustic sensor
(Channel 1) captures the tablet leaving the stomach (denoted "a") while the
motion/orientation signal of the motion/orientation sensor (i.e. 3-axis
accelerometer)
captures the subject rising to an upright position to eat a meal(denoted
"(3"). Fig. 5 further
demonstrates a shift (i.e. increase) in the recorded signal resulting from the
subject's
motion.
Accordingly, in some embodiments of the invention, the analyzer 24 includes
algorithms
and/or derived spatial parameter factors that effectively account for the
spatial parameters
reflected in the motion and orientation signals in the derived
gastrointestinal parameter(s),
event(s) and disorder(s).
As stated above, spatial parameters, i.e. body motion and orientation, can be
determined
by a number of conventional means, such as optical encoders, proximity and
Hall effect
switches, laser interferometers and multi-axis accelerometers. According to
some
embodiments of the invention, the output of these predominantly digital
devices, i.e.
motion and/or orientation signals, is translated into a spatial parameter
value or factor.
A subject matrix is then generated and stored in the memory medium 32; the
matrix
including a plurality of body positions and motions, and corresponding spatial
parameter
factors.
Referring to Table I, there is shown an exemplar subject matrix. As shown in
Table I,
when the subject is standing and still the maximum value or spatial parameter
is "0 1 1",
as reflected in the X, Y and Z axis outputs.
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Table I
Body position X axis output (v) Y axis output (v) Z axis output (v)
Supine left 0 0 0
Supine right 1 0 0
Standing still 0 1 1
Sitting still 0 0.5 0
Walking 0-1 1 0- 1
The spatial parameter factor can then be employed to adjust the recorded
acoustic signal.
For example, one could adjust the Vthreshold for each of the acoustic energy
sensors (e.g.,
22a, 22b, 22c) based on predicted GI activity at that location.
To take a particular spatial example, if the spatial factor is one (0 1-1,
i.e. standing), one
could place a greater emphasis on the acoustic signals of acoustic energy
sensors 22b and
22c (see Fig. 6) in determining GI movement, as these sensors would be more
proximate
to the internal source of the acoustic signal.
A further example would be in determining orientation during sleeping, which
is taught
to relate to gastric emptying. If, during sleep, the spatial parameter factor
was (1 0 0),
one would expect enhanced gastric emptying due to the stomach contents pooling
of the
pylorus. In this example, one could place a greater emphasis on the acoustic
signals of
acoustic energy sensors 22a and 22c (see Fig. 6).
Referring back to Figs. 2A and 2B, according to the invention, the display
means 26 can
comprise any suitable medium that is capable of providing at least one visual
display
representing recorded acoustic energy signals (pre-and post-processed) and/or
body
motion and/or body orientation and/or recorded physiological characteristics.
In one
embodiment, the display means 26 comprises a computer monitor.
According to other embodiments of the invention, the display means 26 can also
comprise an audible display. The audible display can be adapted to provide a
sound or
tone representing, for example, body motion, a gastrointestinal event or a MMC
phase.
The audible display can be further adapted to provide different sounds or
tones
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representing body motion or a selective gastrointestinal event or a
gastrointestinal system
disorder or MMC phases or characteristic relating thereto, e.g., initiation of
a phase.
The display means 26 can also provide at least one visual display representing
recorded
acoustic energy signals (pre-and post-processed) and/or body motion and/or
body
orientation and/or recorded physiological characteristics, and at least one
audible sound or
tone representing body motion or at least one gastrointestinal event or
physiological
characteristic.
As will be appreciated by one having ordinary skill in the art, the display
means 26 can
also be an integral component or feature of the analyzer 24.
As will be appreciated by one having ordinary skill in the art, the acoustic
energy sensors
22a, 22b, 22c, motion sensor 22d, and orientation sensor 22e (or multi-
function
motion/orientation sensors 22d, 22e) of the invention can be positioned on a
subject's
body in various conventional means. By way of example, the sensors 22a, 22b,
22c, 22d,
22e can include an adhesive ring or surface on the housing that is adapted to
temporarily
engage the skin of the subject. The sensors 22a, 22b, 22c, 22d, 22e can also
be attached to
the subject's skin via a strip of medical tape or elastic bandage.
Referring now to Fig. 6, in one embodiment of the invention, the acoustic
energy sensors
22a, 22b, 22c, and a motion/orientation sensor 22d are positioned and
maintained in a
substantially static position against the subject's body via a vest 40.
According to the
invention, the vest 40 can comprise various sizes and materials.
In one embodiment, the vest 40 is adjustable and comprises a light weight,
mesh
material, e.g., nylon or Lycra . In one embodiment of the invention, the vest
40 includes
at least one pocket that is configured to receive and seat at least one
sensor. Preferably,
the vest 40 includes a plurality of pockets that are configured to receive and
position a
plurality of sensors; the pockets being positioned to correspond to selective
positions on a
subject's body when worn by the subject.
In another envisioned embodiment, the vest 40 and sensor(s) include a simple
male-
female snap system. In one embodiment, the vest 40 can include a plurality of
positioned
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female portions of the snap system and the sensors can include a male portion
that can
engage and, hence, be secured on the vest 40 by the receiving vest female
portions. In
other embodiments, the vest 40 can include a plurality of positioned male
portions of the
snap system and the sensors can include a female portion that can engage and,
hence, be
secured on the vest 40 by the receiving vest male portions.
In some embodiments of the invention, the vest 40 includes at least one pocket
that is
adapted to receive and seat an acoustic energy sensor, e.g., sensor 22a. The
vest 40 also
preferably includes an analyzer pocket that is adapted to receive and seat the
analyzer 24.
In the embodiment shown in Fig. 6, the vest 40 includes at least four (4)
pockets 42
adapted to receive and seat acoustic energy sensors 22a, 22b, 22c, and the
motion/orientation sensor 22d. The vest 40 also includes an analyzer pocket 44
that is
adapted to receive the analyzer 24.
As will be readily apparent to one having ordinary skill in the art, the vest
40 provides
the system 20 with mobility.
In further envisioned embodiments of the invention, the gastrointestinal
motility analysis
system 20 includes at least one, preferably, a plurality of additional
sensors, i.e.
physiological sensors, which are adapted to record one or more physiological
characteristics. Such physiological characteristics include, without
limitation, ECG, pulse
rate, SO2, skin temperature, core temperature and respiration rate.
According to embodiments of the invention, the additional physiological
sensors can be
strategically positioned on a subject to monitor and/or evaluate one or more
physiological
characteristics. By way of example, a first physiological sensor (i.e. pulse
rate sensor) can
be disposed proximate the subject's heart to monitor pulse rate and a second
physiological
sensor (i.e. respiration rate sensor) can be disposed proximate a diaphragm to
monitor the
subject's respiration rate.
Referring now to Fig. 7, there is shown a schematic illustration of one
embodiment of a
gastrointestinal motility analysis system 50, according to the present
invention. As
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illustrated in Fig. 7, the system 50 includes multiple function sensors 22a-
22e and 51-58
for monitoring gastrointestinal function (or motility), body motion and
orientation, and
physiological characteristics of a subject.
In one embodiment of the invention, physiological sensor 51 comprises an ECG
sensor
adapted to monitor cardiac performance and/or function, physiological sensor
52
comprises a pulse rate sensor adapted to monitor the subject's pulse rate,
physiological
sensor 53 comprises an SO2 sensor adapted to monitor the subject's blood
oxygen level,
physiological sensor 54 comprises a first temperature sensor adapted to
monitor the
subject's skin temperature, physiological sensor 55 comprises a second
temperature sensor
adapted to monitor the subject's core temperature, and physiological sensor 56
comprises
a respiration sensor that is adapted to monitor the subject's respiration rate
and tidal
volume.
As illustrated in Fig. 7, the system 50 also includes one additional sensor
57. In one
embodiment, sensor 57 comprises an acoustic sensor that is adapted to monitor
non-
gastrointestinal related acoustic energy, such as a cough. According to the
invention, the
signals from the acoustic sensor 57 can be used to identify and extract non-
gastrointestinal
related signals or artifacts that may have been recorded by the acoustic
energy sensors 22a,
22b, 22c.
According to the invention, the additional sensors 51-57 can similarly be
attached directly
to the skin of the subject. The sensors 51-57 can also be incorporated into
vest 40, as
described above.
As indicated above, while the system 50 is shown with three acoustic energy
sensors 22a,
22b, 22c, the system 50 can include less than three acoustic energy sensors,
e.g., sensor
22a, or more such sensors.
It is also to be understood that while the system 50 is shown with twelve (12)
sensors, i.e.
sensors 22a-22e and 51-57, the system 50 can include any number of the
sensors, e.g. one
sensor, three sensor, six sensors, etc., and/or any combination of at least
one of the
acoustic energy sensors 22a-22c and zero or more of the sensors 51-57. For
example, the
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system 50 can include acoustic energy sensors 22a, 22b, motion/orientation
sensor 22d,
and physiological sensors 52 and 57 or acoustic energy sensor 22a and
physiological
sensors 52 and 56.
Gastrointestinal systems, according to embodiments of the invention, including
system
50, can also be effectively employed to monitor gastrointestinal function and
physiological
characteristics of multiple subjects. By way of example, in the case of a
pregnant subject,
three or more sensors can be strategically positioned on the pregnant
subject's body to
monitor gastrointestinal function and at least one physiological
characteristic of the
pregnant subject and at least one physiological characteristic of the unborn
child, e.g., a
gastrointestinal sensor (e.g. acoustic energy sensor 22a) disposed proximate
the pregnant
subject's abdominal region to monitor gastrointestinal motility, a first pulse
rate sensor
(e.g., physiological sensor 52) disposed proximate the pregnant subject's
heart to monitor
the pregnant subject's pulse rate, and a second pulse rate sensor disposed
proximate the
pregnant subject's abdominal region (and, hence, unborn child) to monitor the
unborn
child's pulse rate.
Method and system embodiments of the present invention can thus be effectively
employed in numerous applications. The applications include, without
limitation, the
following:
= To monitor gastrointestinal motility during research of a pharmaceutical
composition, and clinical trials related thereto, to better assess research
and clinical
data.
= To monitor gastrointestinal function and/or motility and determine
abnormalities,
i.e. gastrointestinal system disorders, associated therewith.
= To monitor gastrointestinal function and/or motility during pregnancy;
particularly,
high risk pregnancies where gastrointestinal obstruction is often encountered.
= To monitor gastrointestinal function and/or motility of a pregnant subject
and
physiological characteristics of the pregnant subject and unborn child, e.g.,
pulse
rate, during pregnancy.
The methods and systems of the present invention can also be readily employed
to
facilitate the diagnosis and treatment of various eating disorders. Indeed, as
is well known
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in the art, various gastrointestinal events and, hence, the acoustic energy
(or sound)
associated therewith, reflect digestive activity (or the lack thereof). By way
of example,
an extended period of time (e.g., 12 hours) without one or more phases of a
migrating
motor complex (MMC) could be indicative of a bulimic or anorexic subject.
Conversely,
an extended period of repeated MMC phases could be indicative of excessive
overeating.
EXAMPLES
The following examples are provided to enable those skilled in the art to more
clearly
understand and practice the present invention. They should not be considered
as limiting
the scope of the invention, but merely as being illustrated as representative
thereof.
Example 1
Six male subjects were initially provided with a health assessment. All
subjects passed
the initial health assessment. The subjects then spent the night at the test
center and fasted
(i.e. water only) for at least 11 hours before the study began.
Three acoustic energy sensors were positioned on each subject. Sensor #1 was
placed 4-6
inches below the patient's right nipple, i.e. proximate the gastric fundus.
Sensor #2 was
placed 11-11.5 inches below the right nipple, i.e. proximate the cecum. Sensor
#3 was
placed in the Lower Left Quadrant, approximately 11 inches below the left
nipple, i.e.
proximate the loudest part of the small intestine/descending colon. The
sensors were held
firmly against each subject's body by a lightweight, close fitting nylon mesh
vest, such as
vest 40.
The sensors were custom modified Welch-Allen Master Elite Plus Stethoscopes.
Unlike
traditional stethoscopes, these pressure-based microphones employ a technology
that is
less sensitive to indirect vibration and hence ambient noise. Further, the
sensors also
contain signal processing circuitry that improves signal-to-noise ratio and
deliver either
traditional audio, or mono line-out signals.
Without disturbing the microphone head or signal processing electronics, the
housing was
removed and the microphones were repackaged passing the power and line-out
signals to
custom front-end analog electronics with long wiring that allows for patient
mobility.
Additionally, the volume was set at maximum and the onboard filtering was set
to "all-
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pass", which encompasses a frequency band in the range of 100 -
1200 Hz.
All microphone channels were amplified and low-pass filtered via an analog
2-pole 1200 Hz low-pass Bessel filter, and then sampled onto a National
Instruments
DAQPad-6015 at 8000 Hz. Data was recorded in 10-minute segments and post
processed
via software written in National Instruments LabVIEW 7.1.
Gamma scintigraphy was also performed simultaneously to assess
gastrointestinal
motility. A dissolvable hard gelatin capsule and a non-disintegrating tablet
with
radioactive markers (11'InC13 and 99mTc-DTPA, respectively) were administered
to each
subject. The tablet and the capsule were taken simultaneously with a glass of
water, since
it is known that capsules taken without water can stick to the esophagus for
up to two
hours.
As is well known in the art, the radionucleotide markers emit gamma rays of
different
characteristic energies. Thus, the tablet and capsule's contents could be
separately
tracked.
Removable stickers containing small point sources of i i "InC13 encased in
plastic were
placed on the chest and hip of each subject as a reference to ensure
consistent placement
of the subject under the gamma camera in between pictures. Pictures were taken
every 20
seconds and integrated images stored every 1 minute by the gamma scintigraphy
system.
Tablet and capsule position in the gastrointestinal tract were determined and
recorded for
subsequent analysis.
Gastrointestinal sounds were also recorded during the ingestion of the
dissolvable hard
gelatin capsule and a non-disintegrating tablet. The recorded sounds i.e.
sound files were
stored in an analyzer according to embodiments of the invention. The sound
files were
processed as discussed above.
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During the first of the study, the subjects were asked to remain quiet in a
supine position
under the gamma scintigraphy camera. Several parameters were subsequently
analyzed.
Individual sound dominant frequency, duration, and intensity were also all
calculated.
The Sound Index (or SI) was also calculated. SI, as used herein, means the sum
of the
absolute amplitudes for all detected sound over a one (1) minute time period,
expressed as
mV/min.
As discussed above, it is known that in a fasted state, upper tract digestion
occurs in a 4-
stage cyclic pattern with the largest contractions of the stomach (i.e., Phase
3) usually
initiated with a migrating motor complex (MMC) that proceeds from the stomach
towards
the ileum of the small intestine. The period between MMC's has been well
established
and is typically around 2 hours (although times ranging from 1 to 3 hours are
not
uncommon).
During the studies, clearly identifiable MMC's were observed in most subjects
(- 66.7%)
as identified by large SI's in all three sensors; with Sensors #1 and #2 being
the loudest.
Referring now to Fig. 8, there is shown a summary of the gamma scintigraphy
assessment.
As reflected in Fig. 8, in all studies, but one, i.e. an "outlier", gamma
scintigraphy
determined that the tablets were ejected from the stomach between 11-29
minutes (mean
18.88 min). Thus, it can be inferred that the test tablets were passed with
the liquid from
the stomach.
Interestingly, the "outlier" displayed an MMC without tablet movement. Tablet
movement within the stomach only came later corresponding to a large sound and
SI in
channel 1 around 1 hour, 40 minutes. Complete tablet ejection did not occur
during the
entire duration of the study, i.e. 5 hours and 51 minutes. The cause of this
is uncertain, but
highlights the need for gastrointestinal transit monitoring.
Referring now to Figs. 9-15, there are shown graphs reflecting the sounds
recorded by the
sensors, i.e. minute sound indices versus time. As reflected in Figs. 9-15, in
all 6 studies,
where gastric emptying of the tablet did occur during monitoring, significant
bowel sounds
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and SI's were recorded at the time of emptying. In 5 subjects, channel #1 (or
Sensor #1),
which monitored gastric sounds, produced the highest SI recorded to that
point.
Tablets that landed in the antrum, where muscular activity occurs, moved
corresponding to
first large sound in channel #1. Tablets that landed in the antrum generally
took two or
three large SI's to move, with the first or second SI corresponding to
movement into the
fundus.
For the "outlier", bowel sounds generally matched the scintigraphy data. There
appeared
to be an MMC around 1 hour, 40 minutes (i.e. strong signal in all three
channels), which
did not affect the tablet's movement. However, afterwards, the next
considerable SI was
incident with movement of the tablet from the initial location of upper fundus
to the
antrum of the stomach. Afterwards, there were intermittent sounds recorded in
channel 1,
but no tablet movement. Notable though, are the very low levels of sound in
the other two
sensors, implying overall gastrointestinal quiescence.
The results of this study reflect that in subjects that are quiet in a supine
position,
discernable bowel sounds recorded by a sensor of the invention correspond to
tablet
ejection, as shown by gamma scintigraphy. Indeed, movements of tablet position
(antrum
or fundus) in the stomach were also marked by large sounds. Overall quiet
sounds were
detected in the patient who never experienced gastric tablet ejection. MMC's
were also
clearly identifiable in several subjects.
As will be readily apparent to one skilled in the art, embodiments of the
present invention
can provide one or more advantages, such as:
= The provision of a method and system for monitoring gastrointestinal
motility that
can be effectively employed during research of a pharmaceutical composition,
and
clinical trials related thereto, to better assess research and clinical data.
= The provision of a method and system for monitoring gastrointestinal
motility that
has the potential to reduce the time and resources associated with research of
a
pharmaceutical composition and clinical trials related thereto.
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= The provision of a method and system for monitoring gastrointestinal
function that
can be readily employed by a medical practitioner as a diagnostic aid during
assessments of gastrointestinal behavior.
Without departing from the spirit and scope of this invention, one of ordinary
skill can
make various changes and modifications to the invention to adapt it to various
usages and
conditions. As such, these changes and modifications are properly, equitably,
and intended
to be, within the full range of equivalence of the following claims.
29
