Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B7/00—Instruments for auscultation
  • A61B7/008—Detecting noise of gastric tract, e.g. caused by voiding
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
  • A61B5/11—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb
  • A61B5/1123—Discriminating type of movement, e.g. walking or running
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
  • A61B5/4222—Evaluating particular parts, e.g. particular organs
  • A61B5/4255—Intestines, colon or appendix
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
  • A61B5/0205—Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
  • A61B5/024—Detecting, measuring or recording pulse rate or heart rate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
  • A61B5/0816—Measuring devices for examining respiratory frequency
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
  • A61B5/316—Modalities, i.e. specific diagnostic methods
  • A61B5/318—Heart-related electrical modalities, e.g. electrocardiography [ECG]

Definitions

• the present invention relates generally to methods for non-invasive assessment of gastrointestinal function and physiological characteristics.
• GI gastrointestinal
• 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 the upper gastrointestinal tract (i.e. upper fundus) for extended periods of time (e.g., > 5 hrs).
• gastrointestinal motility can reflect normal and/or abnormal gastrointestinal function, e.g., gastrointestinal obstruction.
• 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.
• 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.
• 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).
• acoustic energy i.e. sound
• 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.
• the gastrointestinal parameter comprises an event selected from the group consisting of gastrointestinal mixing, emptying, contraction and propulsion, and gastrointestinal transit time.
• 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.
• 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.
• 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.
• 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
• 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.
• 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
• 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.
• 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.
• 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.
• 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
• 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.
• the second subject comprises a fetus of the first subject.
• FIGURE IA is an illustration of a portion of a human torso showing a typical gastrointestinal tract
• FIGURE IB is an illustration of a human stomach
• 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.
• FIGURES 9-15 are graphical illustrations of gastrointestinal sound signals, reflecting gastrointestinal sounds acquired during the gastrointestinal motility study summarized in Figure 8.
• pharmaceutical composition 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.).
• pharmaceutical 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.
• ingestible is meant to mean and include any substance or item that precipitates acoustic energy or a gastrointestinal sound (or sounds) from the 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.
• gastrointestinal function means and includes, without limitation, the operation of all of the organs and structures associated with the gastrointestinal system.
• 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.
• gastrointestinal event 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.
• MMC mitigating motor complex
• gastrointestinal parameter means and includes a characteristic associated with gastrointestinal function, including, without limitation, a gastrointestinal event and gastrointestinal transit time.
• gastrointestinal sound means and includes acoustic energy (and all signals embodied therein) generated by a gastrointestinal event.
• gastrointestinal transit time 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 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.
• all gastrointestinal transit time 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.
• fundus-rectal gastrointestinal transit time 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 IB).
• signal voltage envelope 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.
• signal amplitude envelope 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.
• Vthreshoid means the minimum voltage at which values may be considered significant. According to the invention, if the signal voltage envelope is below Vthreshoid, there is no response (i.e. the signal is below the detector's sensitivity). If the signal voltage envelope is larger than Vthreshoid for longer than a pre-determined amount of time, the value is deemed significant.
• 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.
• PK pharmacokinetic
• spatial parameter 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.).
• 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.
• subject 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.
• 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.
• acoustic energy i.e. sound
• 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 can involve performing or completing selected tasks or steps manually, automatically, or a combination thereof.
• several selected steps could be implemented by hardware or by software on any operating system or any firmware or a combination thereof.
• selected steps of embodiments of the invention could be implemented as a chip or a circuit.
• 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.
• 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.
• Fig. IA there is shown an illustration of a typical gastrointestinal tract (designated generally "10").
• 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.
• the stomach 13 includes the fundus region (or fundus) 14a and pyloric antrum (or antrum) 14b.
• gastrointestinal motility in a normal male/female subject
• MMC migrating motor complex
• 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.
• Fig. 2A there is shown a schematic illustration of one embodiment of a gastrointestinal analysis system 20 of the invention.
• the system 20 includes a plurality of acoustic energy sensors 22a, 22b, 22c and at least one analyzer 24.
• the system 20 also includes display means 26.
• 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 intragastric sensors, that are introduced into the subject (or patient) using a nasal-gastric tube or the like.
• 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.
• 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.
• 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.
• low level i.e. low power
• any other suitable media such as wireless radio frequency, infrared, etc.
• 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.
• acoustic energy sensors 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).
• 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.
• the system 20 similarly includes acoustic energy sensors 22a, 22b, 22c, analyzer 24 and display 26.
• the system 20 further includes at least one, preferably, two spatial parameter sensors 22d,
• 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.
• 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.
• 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.
• the motion and orientation sensors 22d, 22e can comprise integral, multi-function devices.
• sensors 22d, 22e comprise multi-function 3 -axis accelerometers (referred to hereinafter as "motion/orientation sensors").
• 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.
• 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.
• 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.
• 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.
• 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.
• 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
• acoustic energy sensor 22c is preferably placed in the lower left quadrant proximate the small intestine, more preferably, proximate the descending colon.
• 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.
• 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
• acoustic energy sensor 22c can be located at the midline at approximately one-half of the distance between the umbilicus and symphosis pubis.
• the motion/orientation sensors 22d, 22e are preferably disposed proximate the anterior surface of the abdomen, preferably, proximate the center of the chest region.
• 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.
• 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.
• the sensors e.g., acoustic energy sensors 22a, 22b, 22c
• process the acoustic energy signals using signal processing module 33
• 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.
• PK pharmacokinetic
• 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.
• 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.
• 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).
• a spatial signal may be used to adjust an acoustic signal.
• 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.
• 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.
• the filtering step 34 can be performed with software, e.g., computer program, or hardware.
• the analyzer 24 is programmed to filter the acoustic energy signals and extract the frequency band of interest from the signals.
• 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.
• the filtering step 34 is performed via hardware.
• the analyzer circuit includes high and low pass filters that are adapted to filter the extraneous artifacts from the signals 34.
• various high and low pass filters can be employed within the scope of the invention.
• 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.
• the signal amplitude envelope is determined using a sliding Hubert transform with a 5 ⁇ sec window.
• Hubert 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.
• the Hubert 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 Vthreshoid, as defined above.
• the dominant frequency of the acoustic energy signals can similarly be determined by various conventional means.
• the dominant frequency was determined by isolating peaks > Vthreshoid for time > 5 ⁇ sec.
• 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.
• 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.
• the acoustic signal of the acoustic sensor (Channel 1) captures the tablet leaving the stomach (denoted " ⁇ ") 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 " ⁇ ").
• Fig. 5 further demonstrates a shift (i.e. increase) in the recorded signal resulting from the subject's motion.
• 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).
• spatial parameters i.e. body motion and orientation
• conventional means such as optical encoders, proximity and Hall effect switches, laser interferometers and multi-axis accelerometers.
• 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.
• 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. Table I
• the spatial parameter factor can then be employed to adjust the recorded acoustic signal. For example, one could adjust the V t hreshoid for each of the acoustic energy sensors (e.g., 22a, 22b, 22c) based on predicted GI activity at that location.
• the acoustic energy sensors e.g., 22a, 22b, 22c
• the spatial factor is one (0 1-1, i.e. standing)
• 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).
• 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.
• the display means 26 comprises a computer monitor.
• 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 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.
• the display means 26 can also be an integral component or feature of the analyzer 24.
• 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.
• 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.
• 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.
• the vest 40 can comprise various sizes and materials.
• the vest 40 is adjustable and comprises a light weight, mesh material, e.g., nylon or Lycra®.
• the vest 40 includes at least one pocket that is configured to receive and seat at least one sensor.
• 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.
• the vest 40 and sensor(s) include a simple male- female snap system.
• the vest 40 can include a plurality of positioned 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.
• 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.
• 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.
• 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.
• the vest 40 provides the system 20 with mobility.
• 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.
• physiological characteristics include, without limitation, ECG, pulse rate, SO 2 , skin temperature, core temperature and respiration rate.
• the additional physiological sensors can be strategically positioned on a subject to monitor and/or evaluate one or more physiological characteristics.
• a first physiological sensor i.e. pulse rate sensor
• a second physiological sensor i.e. respiration rate sensor
• a schematic illustration of one embodiment of a gastrointestinal motility analysis 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.
• 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 SO 2 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
• physiological sensor 56 comprises a respiration sensor that is adapted to monitor the subject's respiration rate and tidal volume.
• the system 50 also includes one additional sensor 57.
• sensor 57 comprises an acoustic sensor that is adapted to monitor non- gastrointestinal related acoustic energy, such as a cough.
• 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.
• 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.
• the system 50 can include less than three acoustic energy sensors, e.g., sensor 22a, or more such sensors.
• 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.
• the 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 can also be effectively employed to monitor gastrointestinal function and physiological characteristics of multiple subjects.
• 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.
• a first pulse rate sensor e.g., physiological sensor 52
• second pulse rate sensor disposed proximate the pregnant subject's abdominal region (and, hence, unborn child) to monitor the unborn child's pulse rate.
• 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 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.
• MMC migrating motor complex
• 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.
• 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- 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 Lab VIEW 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 ( 111 InCl 3 and 99m Tc-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.
• the radionucleotide markers emit gamma rays of different characteristic energies.
• the tablet and capsule's contents could be separately tracked.
• Removable stickers containing small point sources of 111 InCl 3 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.
• 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.
• SI Sound Index
• MMC migrating motor complex
• gamma scintigraphy 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.
• 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 and SFs 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.
• 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. MMCs were also clearly identifiable in several subjects.
• embodiments of the present invention can provide one or more advantages, such as:

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• 2008
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