Measurement of Gastrointestinal and Colonic Motor Functions in Humans and Animals

The ability to assess the complex motor functions of the gastrointestinal tract accurately has been of tremendous value to understanding and treating digestive diseases. Unlike other smooth or cardiac muscle organ systems with relatively more rhythmic and patterned motor behavior, the complexity of the diverse motor behaviors of the alimentary canal have made the development and use of clinical and preclinical tests of gastrointestinal motor function a great challenge. It is perhaps this complexity, as well as the importance of gastrointestinal function to overall health and well-being, that have fascinated early physiologists and continue to push modern physiologists and clinical diagnosticians to develop new and more accurate measurements of motility. It is also because of this complexity that the standardization of these measures presents hurdles to broad adoption and that the measurements of the more complex motility functions remain restricted mainly to tertiary referral centers. The ability to assess the complex motor functions of the gastrointestinal tract accurately has been of tremendous value to understanding and treating digestive diseases. Unlike other smooth or cardiac muscle organ systems with relatively more rhythmic and patterned motor behavior, the complexity of the diverse motor behaviors of the alimentary canal have made the development and use of clinical and preclinical tests of gastrointestinal motor function a great challenge. It is perhaps this complexity, as well as the importance of gastrointestinal function to overall health and well-being, that have fascinated early physiologists and continue to push modern physiologists and clinical diagnosticians to develop new and more accurate measurements of motility. It is also because of this complexity that the standardization of these measures presents hurdles to broad adoption and that the measurements of the more complex motility functions remain restricted mainly to tertiary referral centers. SummaryAccurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis, and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both human beings and animals. Further opportunity remains to enhance such tests, especially when such tests are able to provide value in both the preclinical and the clinical settings. Accurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis, and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both human beings and animals. Further opportunity remains to enhance such tests, especially when such tests are able to provide value in both the preclinical and the clinical settings. Assessing motility in human beings has 3 obvious values. First, standardized clinical tests have diagnostic value in stratifying patients who present with a relatively limited repertoire of symptoms in the complex multifactorial digestive diseases into more manageable subsets and in the identification of underlying pathophysiology. Second, these clinical tests provide measures that can be used to objectively determine the efficacy of therapies for digestive diseases in the clinic and during drug and device development in clinical trials. Third, motility measurements in human beings have value in broadening our understanding of the physiology and pathophysiology of the gastrointestinal tract to generate new hypotheses and new drug targets to understand and treat digestive diseases. Motility tests in nonhuman animals also have value that parallels the value of tests for human beings. First, animals serving as companions, or in labor, sports, and food production industries, benefit from the diagnostic value of accurate motility tests in veterinary medicine. Second, motility tests provide the basis for objective measures to assess the efficacy and dosing guidelines of new therapies in preclinical drug and device development. Third, animal models provide the basis for understanding the physiology and pathophysiology of the gastrointestinal tract. This latter value historically has been greater in nonhuman animals because of the ability to conduct terminal or ex vivo experiments followed by anatomic or biochemical assessments that are not possible in human beings. The purpose of this review is to critically assess the current state of motility tests (listed in Table 1, and examples given in Figure 1), based on these values in both human beings and non–human beings. It is organized by region of the alimentary canal in an oral to anal direction, followed by measures of whole-gut transit. The hope is that such juxtaposition of human and nonhuman tests will enlighten both the benefit and deficiencies in each to aid in the de novo or cross-development of new motility tests.Table 1Tests Currently Available for Measuring Gastrointestinal and Colonic MotilityFunctionTests availableGastric capacity or accommodationBarostat balloon measurementsNutrient drink testSPECTUltrasonographyMRIHigh-resolution intragastric manometryGastric emptyingScintigraphyWireless pH and motility capsuleStable isotope breath testsGastric transit in preclinical studiesAnalysis of gastric contentsStable isotope breath testsScintigraphySmall-bowel transitBreath hydrogen testsStable isotope breath testsScintigraphyWireless pH and motility capsuleWhole-gut transit in preclinical studiesNonabsorbable marker such as carmine redScintigraphy using steel beads and barium in miceColonic transitRadiopaque markersScintigraphyWireless pH and motility capsuleGastrointestinal, colonic, and anorectal contractilityAntropyloroduodenal manometryWireless pH and motility capsuleColonic phasic contractility (including high-resolution manometry) and toneAnorectal manometryColonic motility and transit in preclinical studiesBead expulsionColonic manometry (including high-resolution manometry)ScintigraphyNew MRI applicationsAll the earlier-described functions as well as anorectal and pelvic floor motion and anatomic integrityNOTE. Tests with the strongest validation or most widely available and used are indicated in italics. Open table in a new tab NOTE. Tests with the strongest validation or most widely available and used are indicated in italics. In the interest of brevity, we will not describe tests of esophageal motility here. High-resolution manometry has become the diagnostic tool of choice, about which many recent reviews have been published.1Savarino E. Zentilin P. Savarino V. et al.Functional testing: pharyngeal pH monitoring and high-resolution manometry.Ann N Y Acad Sci. 2013; 1300: 226-235Crossref PubMed Scopus (0) Google Scholar, 2Carlson D.A. Pandolfino J.E. High-resolution manometry and esophageal pressure topography: filling the gaps of convention manometry.Gastroenterol Clin North Am. 2013; 42: 1-15Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 3Zerbib F. Roman S. Current therapeutic options for esophageal motor disorders as defined by the Chicago Classification.J Clin Gastroenterol. 2015; 49: 451-460PubMed Google Scholar One of the principal functions of the proximal stomach is the storage of ingested food. The gastric fundus and body are able to accommodate large volume changes, while maintaining a relatively low intragastric pressure. Altered gastric tone and distensibility may occur in several disease states, including tumor infiltration, vagal dysfunction, and post–gastric surgery status, and in up to 40% of patients with functional dyspepsia.4Hunt R.H. Camilleri M. Crowe S.E. et al.The stomach in health and disease.Gut. 2015; 64: 1650-1668Crossref PubMed Scopus (0) Google Scholar The gold standard for the measurement of tone in hollow organs was the barostat,5Azpiroz F. Malagelada J.R. Physiological variations in canine gastric tone measured by an electronic barostat.Am J Physiol Gastrointest Liver Physiol. 1985; 248: G229-G237PubMed Google Scholar which estimates changes in tone by the change of volume of air in an infinitely (typically polyethylene) compliant balloon maintained at a constant pressure to maintain the balloon in apposition with the stomach lining. The barostat maintains the constant pressure by infusion or aspiration of air in response to relaxation or contraction of stomach tone. This method is not used extensively in clinical practice because it requires intubation and results in stress and discomfort during the tests, which may last 3 hours or longer.6Tutuian R. Vos R. Karamanolis G. et al.An audit of technical pitfalls of gastric barostat testing in dyspepsia.Neurogastroenterol Motil. 2008; 20: 113-118PubMed Google Scholar Development and validation studies of the barostat to measure compliance, tone, and postprandial accommodation in the dog were performed by Azpiroz and Malagelada.5Azpiroz F. Malagelada J.R. Physiological variations in canine gastric tone measured by an electronic barostat.Am J Physiol Gastrointest Liver Physiol. 1985; 248: G229-G237PubMed Google Scholar Since then, the barostat has been used extensively in animals including cats,7Coulie B. Tack J. Sifrim D. et al.Role of nitric oxide in fasting gastric fundus tone and in 5-HT1 receptor-mediated relaxation of gastric fundus.Am J Physiol. 1999; 276: G373-G377PubMed Google Scholar rabbits,8Zhao J. Liao D. Gregersen H. Tension and stress in the rat and rabbit stomach are location- and direction-dependent.Neurogastroenterol Motil. 2005; 17: 388-398Crossref PubMed Scopus (0) Google Scholar pigs,9Tournadre J.P. Allaouchiche B. Malbert C.H. et al.Metabolic acidosis and respiratory acidosis impair gastro-pyloric motility in anesthetized pigs.Anesth Analg. 2000; 90: 74-79Crossref PubMed Google Scholar horses,10Lorenzo-Figueras M. Jones G. Merritt A.M. Effects of various diets on gastric tone in the proximal portion of the stomach of horses.Am J Vet Res. 2002; 63: 1275-1278Crossref PubMed Google Scholar rats,8Zhao J. Liao D. Gregersen H. Tension and stress in the rat and rabbit stomach are location- and direction-dependent.Neurogastroenterol Motil. 2005; 17: 388-398Crossref PubMed Scopus (0) Google Scholar, 11Rouzade M.L. Fioramonti J. Bueno L. Decrease in gastric sensitivity to distension by 5-HT1A receptor agonists in rats.Dig Dis Sci. 1998; 43: 2048-2054Crossref PubMed Scopus (0) Google Scholar and mice.12Monroe M.J. Hornby P.J. Partosoedarso E.R. Central vagal stimulation evokes gastric volume changes in mice: a novel technique using a miniaturized barostat.Neurogastroenterol Motil. 2004; 16: 5-11Crossref PubMed Scopus (0) Google Scholar The nutrient drink test has been proposed as a surrogate method for estimating gastric volumes. In this test, a standardized liquid nutrient drink, such as Ensure (1 kcal/mL; Ross Products, Division of Abbott Laboratories, Columbus, OH), is ingested at a standard rate of 30 mL/min, and the volume to normal fullness and the maximum tolerated volume are recorded as measures of satiation. Postprandial symptoms of nausea, fullness, bloating, and pain are measured 30 minutes after the meal.13Chial H.J. Camilleri C. Delgado-Aros S. et al.A nutrient drink test to assess maximum tolerated volume and postprandial symptoms: effects of gender, body mass index and age in health.Neurogastroenterol Motil. 2002; 14: 249-253Crossref PubMed Scopus (68) Google Scholar Tack et al14Tack J. Caenepeel P. Piessevaux H. et al.Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia.Gut. 2003; 52: 1271-1277Crossref PubMed Scopus (0) Google Scholar suggested that a high-caloric, slowly administered drinking test compared favorably with the barostat in predicting impaired gastric accommodation, especially in patients with a maximum tolerated volume less than 750 kcal. Because of the obvious limitations of feedback regarding sensory experiences, there are no reports of the use of nutrient drink tests in nonhuman animals. Single-photon emission computed tomography (SPECT) imaging has been validated extensively in vitro and in vivo for the measurement of gastric volumes during fasting and postprandially in human beings, including comparison with the barostat.15Bouras E.P. Delgado-Aros S. Camilleri M. et al.SPECT imaging of the stomach: comparison with barostat and effects of sex, age, body mass index, and fundoplication.Gut. 2002; 51: 781-786Crossref PubMed Scopus (0) Google Scholar, 16De Schepper H.U. Cremonini F. Chitkara D. et al.Assessment of gastric accommodation: overview and evaluation of current methods.Neurogastroenterol Motil. 2004; 16: 275-285Crossref PubMed Scopus (0) Google Scholar, 17Delgado-Aros S. Vella A. Camilleri M. et al.Comparison of gastric volumes in response to isocaloric liquid and mixed meals in humans.Neurogastroenterol Motil. 2004; 16: 567-573Crossref PubMed Scopus (0) Google Scholar After intravenous administration of 10 mCi technetium-99m (99mTc)-pertechnetate, a substrate for the sodium/iodide symporter that is accumulated and secreted into the lumen by parietal and mucin-secreting cells of the gastric mucosa, tomographic images of the stomach are acquired using a large field-of-view, dual-headed gamma camera, with the patient in a supine position. From the transaxial images of the stomach, 3-dimensional images are reconstructed using a commercially available software analysis program that is used for other 3-dimensional volume rendering with transaxial imaging (eg, computed tomography [CT], magnetic resonance imaging [MRI]) and total gastric volume is measured during fasting and during the first 10 minutes after a standard liquid nutrient meal (300 mL Ensure). This allows reconstruction of the stomach based on the location of the mucosal layer, and the estimated volume serves as a surrogate for the internal volume of the stomach. SPECT shows the effects of disease on post-meal gastric accommodation and effects of medications such as nitrates, erythromycin, glucagon-like peptide-1, and octreotide18Delgado-Aros S. Kim D.Y. Burton D.D. et al.Effect of GLP-1 on gastric volume, emptying, maximum volume ingested and postprandial symptoms in humans.Am J Physiol Gastrointest Liver Physiol. 2002; 282: G424-G431PubMed Google Scholar, 19Liau S.S. Camilleri M. Kim D.Y. et al.Pharmacological modulation of human gastric volumes demonstrated noninvasively using SPECT imaging.Neurogastroenterol Motil. 2001; 13: 533-542Crossref PubMed Scopus (0) Google Scholar in health and diseases such as diabetes, fundoplication, and functional dyspepsia.20Delgado-Aros S. Vella A. Camilleri M. et al.Effects of glucagon-like peptide-1 and feeding on gastric volumes in diabetes mellitus with cardio-vagal dysfunction.Neurogastroenterol Motil. 2003; 15: 435-444Crossref PubMed Scopus (0) Google Scholar, 21Bredenoord A.J. Chial H.J. Camilleri M. et al.Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms.Clin Gastroenterol Hepatol. 2003; 1: 264-272Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Intraindividual and interindividual coefficients of variance in postprandial and accommodation volumes by SPECT were not significantly different and ranged from 16% to 22%.22Breen M. Camilleri M. Burton D. et al.Performance characteristics of the measurement of gastric volume using single photon emission computed tomography.Neurogastroenterol Motil. 2011; 23: 308-315Crossref PubMed Scopus (0) Google Scholar The effects of liquid and solid equicaloric meals on gastric volumes have been described, and measurements of gastric volume with the same caloric liquid meal an average of 9 months apart showed a coefficient of variation of 10%.23De Schepper H. Camilleri M. Cremonini F. et al.Comparison of gastric volumes in response to isocaloric liquid and mixed meals in humans.Neurogastroenterol Motil. 2004; 16: 567-573Crossref PubMed Scopus (0) Google Scholar It also is possible to measure gastric emptying and volume simultaneously.24Simonian H.P. Maurer A.H. Knight L.C. et al.Simultaneous assessment of gastric accommodation and emptying: studies with liquid and solid meals.J Nucl Med. 2004; 45: 1155-1160PubMed Google Scholar, 25Burton D.D. Kim H.J. Camilleri M. et al.Relationship of gastric emptying and volume changes after a solid meal in humans.Am J Physiol Gastrointest Liver Physiol. 2005; 289: G261-G266Crossref PubMed Scopus (0) Google Scholar The noninvasive nature of the method is attractive and is used extensively at the Mayo Clinic in research and practice, especially in suspected disorders of gastric accommodation such as dyspepsia. However, the test involves radiation exposure, and SPECT equipment and the 3-dimensional reconstruction and volume rendering are not widely available. Another potential pitfall is that the resolution of the imaging does not equal that of CT or MRI. Although NanoSPECT-CT (Mediso Medical Imaging Systems, Budapest, Hungary) of gavaged technetium-labeled activated charcoal diethylene triaminepentaacetic acid has been used to assess gastrointestinal transit in mice,26Padmanabhan P. Grosse J. Asad A.B. et al.Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT.EJNMMI Res. 2013; 3: 60Crossref PubMed Scopus (0) Google Scholar to our knowledge SPECT imaging has not been used to assess gastric accommodation specifically in nonhuman animals. Given the rapidly advancing use of 99mTc-pertechnetate and other sodium/iodide symporter substrates in numerous animal models27Dadachova E. Carrasco N. The Na/I symporter (NIS): imaging and therapeutic applications.Semin Nucl Med. 2004; 34: 23-31Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 28Portulano C. Paroder-Belenitsky M. Carrasco N. The Na+/I- symporter (NIS): mechanism and medical impact.Endocr Rev. 2014; 35: 106-149Crossref PubMed Scopus (0) Google Scholar as well as descriptions of methods to circumvent the high stomach signal that confounds such studies,29Suksanpaisan L. Pham L. McIvor S. et al.Oral contrast enhances the resolution of in-life NIS reporter gene imaging.Cancer Gene Ther. 2013; 20: 638-641Crossref PubMed Scopus (0) Google Scholar it is reasonable to assume that this well-validated approach to assess gastric accommodation in human beings can be reverse-translated easily for use in preclinical studies. Imaging-based methods to measure gastric volume include 3-dimensional reconstruction of images acquired by ordinary ultrasonography assisted by magnetic scan-head tracking.30Gilja O.H. Hausken T. Odegaard S. et al.Monitoring postprandial size of the proximal stomach by ultrasonography.J Ultrasound Med. 1995; 14: 81-89Crossref PubMed Google Scholar, 31Liao D. Gregersen H. Hausken T. et al.Analysis of surface geometry of the human stomach using real-time 3D ultrasonography in vivo.Neurogastroenterol Motil. 2004; 16: 315-324Crossref PubMed Scopus (0) Google Scholar Thus, an outline of the total stomach volume visualized after ingestion of a liquid meal (that serves as a contrast medium)32Gilja O.H. Hausken T. Odegaard S. et al.Ultrasonography and three-dimensional methods of the upper gastrointestinal tract.Eur J Gastroenterol Hepatol. 2005; 17: 277-282Crossref PubMed Scopus (0) Google Scholar has been applied in adolescents and compared with simultaneously measured gastric volumes by SPECT.33Manini M.L. Burton D.D. Meixner D.D. et al.Feasibility and application of 3-dimensional ultrasound for measurement of gastric volumes in healthy adults and adolescents.J Pediatr Gastroenterol Nutr. 2009; 48: 1-7Crossref PubMed Scopus (0) Google Scholar The first application of MRI using a spin-echo T1-weighted imaging sequence addressed the volume of the stomach during fasting, but not in the postprandial period.34de Zwart I.M. Mearadji B. Lamb H.J. et al.Gastric motility: comparison of assessment with real-time MR imaging or barostat measurement initial experience.Radiology. 2002; 224: 592-597Crossref PubMed Scopus (64) Google Scholar Volumes measured with MRI and barostat differ significantly because the barostat measures only the proximal stomach, whereas MRI records the entire stomach volume; however, there was a statistically significant correlation between the 2 methods, and MRI also was able to show volume effects induced by glucagon (increase) and erythromycin (decrease). MRI, using 3-dimensional gradient-echo and 2-dimensional half-Fourier acquisition single-shot turbo spin echo sequences,35Fidler J. Bharucha A.E. Camilleri M. et al.Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans.Neurogastroenterol Motil. 2009; 21: 42-51Crossref PubMed Scopus (0) Google Scholar has been used to measure postprandial gastric volume change, which exceeded the ingested meal volume by 106 ± 12 mL (SEM). The advantage of MRI over SPECT is the ability to distinguish air from fluid under fasting and postprandial conditions, respectively. MRI also has shown that the postprandial volume excess mainly comprised air (61 ± 5 mL), which was not significantly different when the volume ingested was ingested in 30- or 150-mL aliquots. Fasting and postprandial gastric volumes measured by MRI generally were reproducible within subjects. Gastric volumes measured by SPECT were higher than MRI, reflecting the fact that SPECT reconstruction includes the volume occupied by the imaged gastric wall. Although MRI has many advantages, including a lack of radiation exposure, it is not widely used to measure gastric accommodation in clinical practice or research. By using a high-resolution manometry catheter, which typically is used for esophageal motility measurements, Janssen et al36Janssen P. Verschueren S. Ly H.G. et al.Intragastric pressure during food intake: a physiological and minimally invasive method to assess gastric accommodation.Neurogastroenterol Motil. 2011; 23: 316-322Crossref PubMed Scopus (0) Google Scholar showed that, during nutrient drink ingestion, there is a reduction in intraluminal pressure that provides a less-invasive alternative to the barostat for the assessment of gastric accommodation. The method also has been used to show pharmacologic effects, such as with peppermint oil37Papathanasopoulos A. Rotondo A. Janssen P. et al.Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health.Neurogastroenterol Motil. 2013; 25: e263-e271Crossref PubMed Scopus (0) Google Scholar and liraglutide.38Rotondo A. Janssen P. Mulè F. et al.Effect of the GLP-1 analog liraglutide on satiation and gastric sensorimotor function during nutrient-drink ingestion.Int J Obes (Lond). 2013; 37: 693-698Crossref PubMed Scopus (0) Google Scholar Gamma camera scintigraphy is the most widely used test for the assessment of gastric motility; it provides a direct, noninvasive quantification of gastric emptying.39Camilleri M. Hasler W. Parkman H.P. et al.Measurement of gastrointestinal motility in the GI laboratory.Gastroenterology. 1998; 115: 747-762Abstract Full Text Full Text PDF PubMed Google Scholar A simplified protocol with imaging at 1, 2, and 4 hours with a standard meal was first proposed at the Mayo Clinic,40Camilleri M. Zinsmeister A.R. Greydanus M.P. et al.Towards a less costly but accurate test of gastric emptying and small bowel transit.Dig Dis Sci. 1991; 36: 609-615Crossref PubMed Scopus (0) Google Scholar and a variation subsequently was validated in a large multinational study in 123 subjects41Tougas G. Eaker E.Y. Abell T.L. et al.Assessment of gastric emptying using a low-fat meal: establishment of international control values.Am J Gastroenterol. 2000; 95: 1456-1462Crossref PubMed Google Scholar and was adopted by the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine.42Abell T.L. Camilleri M. Donohoe K. et al.Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine.Am J Gastroenterol. 2008; 103: 753-763Crossref PubMed Scopus (0) Google Scholar A standard, 2% fat meal consisted of 4 ounces of Eggbeaters (Conagra Foods, Omaha, NE) or equivalent egg white substitute, 2 slices of bread, strawberry jam (30 g), and 120 mL water (total 240 kcal) and was radiolabeled with 0.5–1 mCi 99mTc-sulfur colloid. This is a relatively small meal, which may not reliably induce symptoms in patients with functional dyspepsia, although it is useful for diagnosing gastroparesis. The Mayo Clinic method uses 2 natural eggs and contains 30% of the calories as fat (total, 320 kcal). The test meal determines the rate of emptying,43Camilleri M. Shin A. Editorial: novel and validated approaches for gastric emptying scintigraphy in patients with suspected gastroparesis.Dig Dis Sci. 2013; 58: 1813-1815Crossref PubMed Google Scholar and normal values are essential for interpretation of the test when performed clinically; thus, Mayo Clinic published data from 319 healthy controls.44Camilleri M. Iturrino J. Bharucha A.E. et al.Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants.Neurogastroenterol Motil. 2012; 24 (1076–e562)Crossref Scopus (0) Google Scholar There is significant intraindividual variation in gastric emptying rates of 12%–15%, even in healthy individuals.44Camilleri M. Iturrino J. Bharucha A.E. et al.Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants.Neurogastroenterol Motil. 2012; 24 (1076–e562)Crossref Scopus (0) Google Scholar, 45Choi M.G. Camilleri M. Burton D.D. et al.[13C]octanoic acid breath test for gastric emptying of solids: accuracy, reproducibility, and comparison with scintigraphy.Gastroenterology. 1997; 112: 1155-1162Abstract Full Text PDF PubMed Scopus (0) Google Scholar The performance characteristics of the 30% fat, 320-kcal meal have been documented.44Camilleri M. Iturrino J. Bharucha A.E. et al.Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants.Neurogastroenterol Motil. 2012; 24 (1076–e562)Crossref Scopus (0) Google Scholar The main indications for use of this test are the investigation of unexplained nausea, vomiting, and dyspeptic symptoms; screening for impaired gastric emptying in diabetic patients being considered for incretin treatment to enhance glycemic control (eg, pramlintide and GLP-1 agonists); and assessment of patients with suspected diffuse gastrointestinal motility disorder in combination with small-bowel and colonic transit. In human research, the gastric emptying test is used to understand the pathophysiology of symptoms or in the development of pharmacologic agents. There is a vast amount of literature on the use of radioscintigraphy to measure gastric emptying in large animals. The first application documented the effects of vagotomy and carbachol on gastric emptying in dogs.46Tinker J. Kocak N. Jones T. et al.Supersensitivity and gastric emptying after vagotomy.Gut. 1970; 11: 502-505Crossref PubMed Google Scholar These nondigestible wireless capsules can measure pH, pressure, and temperature throughout the gastrointestinal tract. The abrupt change in pH from the gastric acidic milieu to the almost alkaline duodenum usually is associated with antral phasic contractions of the migrating motor complex (MMC), and it signals that the capsule has left the stomach.47Kuo B. Viazis N. Bahadur S. Noninvasive simultaneous measurement of intra-liminal pH and pressure: assessment of gastric emptying and upper GI manometry in healthy subjects.Neurogastroenterol Motil. 2004; 16: 666Google Scholar When taken with a meal, the capsule generally empties from the stomach after liquids and triturable solids have emptied, usually with phase III of the MMC or, in approximately one third of cases, with high-amplitude antral contractions.48Cassilly D. Kantor S. Knight L.C. et al.Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy.Neurogastroenterol Motil. 2008; 20: 311-319Crossref PubMed Scopus (0) Google Scholar Patients ingest the capsule with a standard meal and, from 6 hours after capsule ingestion, patients can engage in normal daily activity, including ad libitum feeding. The wireless capsule acquires data continuously for up to 5 days, and this permits calculation of gastric, small-bowel, colon, and whole-gut transit. These wireless capsules also measure intraluminal pressure. In validation studies conducted with simultaneous gastric emptying by scintigraphy in healthy subjects and patients with gastroparesis,49Kuo B. McCallum R.W. Koch K.L. et al.Comparison of gastric emptying of a non-digestible capsule to a radio-labeled meal in healthy and gastroparetic subjects.Aliment Pharmacol Ther. 2008; 27: 186-196Crossref PubMed Scopus (0) Google Scholar the gastric emptying time for the capsule and the scintigraphic gastric emptying time at 4 hours were correlated significantly (r = 0.73), and the capsule discriminated between normal or delayed gastric emptying with a sensitivity of 0.87 at a specificity of 0.92.49Kuo B. McCallum R.W. Koch K.L. et al.Comparison of gastric emptying of a non-digestible capsule to a radio-labeled meal in healthy and gastroparetic subjects.Aliment Pharmacol Ther. 2008; 27: 186-196Crossref PubMed Scopus (0) Google Scholar The advantages of the motility capsule are that the study can be conducted anywhere, there is a lack of radioactivity, and it has an ability to determine small-bowel, colon, and whole-gut transit times, as well as contractility.50Kloetzer L. Chey W.D. McCallum R.W. et al.Motil