Gastric emptying scintigraphy





Introduction


Gastric motility is important for the proper processing and gastric emptying (GE) of an ingested meal . The gastric motility responses to an ingested meal involve actions of several different regions of the stomach. These include initial proximal gastric fundic relaxation and accommodation of the meal followed by subsequent tonic fundic contractions. This is followed by the onset of distal antral phasic contractions which grind and triturate solids down to small particle size needed to permit coordinated pyloric opening and closing which allows for emptying of the small, solid particles into the small intestine. The small intestine can influence GE through neurohormonal and contractile activity .


Symptoms and clinical disorders referable to the upper digestive tract may be associated with various abnormalities in gastric motility and function including: the rate of GE, impaired accommodation, alterations in gastric myoelectrical motor function, impaired antral contractility, heightened gastric sensation, pyloric sphincter dysfunction, and abnormal duodenal contractility ( Table 11.1 ). Patients with such symptoms undergo various tests of gastric motility to determine if alterations in gastric motility may explain their symptoms. Proper management of gastric motility disorders requires an understanding of pathophysiology, proper use and interpretation of a potential variety of diagnostic tests, and selection of appropriate treatment . These tests include various methods for measuring total and regional GE, contractility, compliance, electrical activity, and tests of sensation ( Table 11.2 ). This chapter will first review normal gastric motility and then review the latest advances for obtaining multiple measures of gastric function that go beyond simple, traditional total GE using more advanced gastric emptying scintigraphy (GES).



Table 11.1

Clinical disorders associated with abnormalities in gastric physiology/function.















Delayed gastric emptying



  • Gastroparesis



  • Functional dyspepsia

Rapid gastric emptying



  • Dumping syndrome



  • Cyclic vomiting syndrome



  • Post fundoplication



  • Functional dyspepsia

Sensory abnormalities



  • Functional dyspepsia



Table 11.2

Tests of gastric motility and function.























Gastric emptying



  • Solid and liquid meal scintigraphy



  • Wireless motility capsule



  • Breath tests ( 13 C)



  • Magnetic resonance imaging (MRI)



  • Ultrasonography



  • Epigastric impedance



  • Radiopaque Markers



  • Barium radiographic study

Antral motor contractility



  • Antroduodenal manometry (ADM)



  • Dynamic antral contraction scintigraphy (DACS) – augmenting routine GE test

Gastric myoelectric activity



  • Electrogastrography (EGG)



  • Biomagnetic field recording – SQUID



  • Applied potential tomography/Epigastric impedance

Accommodation



  • Gastric barostat



  • Gastric mucosal labeling and SPECT Imaging



  • Intragastric meal distribution during routine GE solid meal test

Satiety



  • Water Loading



  • Nutrient Satiety Test



Normal gastric motility


Normal gastric motility is best described in terms of its responses to food intake (fed patterns) and fasting patterns .


Fasting gastric motility


Fasting gastric contractile patterns are characterized by a cyclic motor phenomenon called the migrating motor complex (MMC) . In healthy people, it occurs approximately once every 90 minutes in the fasting state, most prominently at night. The fasting state generally starts approximately four hours after meal ingestion when the stomach has completely emptied a digestible meal. The fasting contractile patterns comprise a period of quiescence (phase I), a period of intermittent pressure activity (phase II), and an activity front during which the stomach and small intestine contract at their highest frequency (phase III). During the phase III MMC, contraction frequencies reach three per minute in the stomach and 11–12 per minute in the proximal small intestine. This interdigestive phase III contractile wave starts in the stomach and migrates down the stomach and small intestine. Phase III of the MMC serves to help empty the stomach of indigestible solids and transport them down the small intestine into the colon (“the intestinal housekeeper”). These antral and small intestinal contractions are generally recorded with antroduodenal manometry which assesses their frequency, amplitude, and coordination.


GES cannot be utilized to study the fasting state of the stomach since it requires the administration of a radiolabeled nutrient meal for imaging.


Gastric responses to meal ingestion


Initial gastric accommodation


Gastric accommodation is a postprandial reflex resulting in reduced proximal gastric tone that occurs with eating a meal . With gastric accommodation, the fundus acts to provide a reservoir function for ingested foods without significantly increasing intragastric pressure. The accommodation reflex has two principal components. Receptive relaxation occurs within seconds of eating and is triggered by both oropharyngeal and gastric stimulation. This response involves relaxation of both the lower esophageal sphincter and proximal stomach. Adaptive relaxation is a slower process triggered by gastric or duodenal distension and likely also modified by specific nutrients . The accommodation reflex is vagally mediated and represents the balance between cholinergic excitatory drive and non-adrenergic, non-cholinergic (NANC) inhibitory input. The afferent signal is generated by activation of stretch-sensitive mechanoreceptors in the stomach wall and by activation of osmolar and chemoreceptors in the stomach and duodenum . The efferent NANC signal involves nitric oxide (NO) as the principal neurotransmitter . A role for vasoactive intestinal polypeptide (VIP) has also been suggested . Gastric tone is also modulated by sympathetic inputs acting directly through post-junctional α1-adrenoceptors, and indirectly on cholinergic nerve terminals mediated by pre-junctional α2-adrenoceptors .


With normal fundic accommodation, the food initially localizes in the proximal portion of the stomach ( Fig. 11.1 ). Impaired gastric accommodation (GA) to a meal may cause postprandial symptoms . With impaired GA, there is increased pressure in the upper stomach compromising the ability of the upper stomach to act as a reservoir for ingested food. This can result in rapid transit into the distal stomach. Impaired accommodation has been shown to be associated with early satiety and weight loss in both functional dyspepsia and idiopathic gastroparesis .




Figure 11.1


Schematic of stomach with regional gastric anatomy, physiology and function. Gastric emptying reflects the coordinated functions of the fundus, body, antrum, pylorus, and duodenum. Important events for gastric emptying include fundic relaxation and accommodation, antral contractions for trituration, pyloric opening and closing, and coordinated antral-pyloric-duodenal motility.


The accommodation reflex can be recorded using an intragastric barostatically controlled balloon which directly records intragastric volume and pressure. This methodology is however invasive, not widely available, and not well tolerated by patients. As a result, alternate and less invasive imaging methods have been sought to measure gastric accommodation.


Single photon emission computed tomography (SPECT) utilizes 3-dimensional nuclear medicine imaging following an injection of technetium-99m pertechnetate which outlines the outer volume of the gastric wall by imaging gastric mucosal uptake similar to its use for visualizing Meckel diverticula ( Fig. 11.2 ). SPECT measurements have been well correlated with the intragastric balloon and have demonstrated that improvement in functional dyspepsia symptoms with low dose antidepressants are associated with increased SPECT measured accommodation .




Figure 11.2


SPECT 3D volume study. These images are 3 dimensional volume reconstructions of the gastric mucosa following intravenous injection of technetium 99 m pertechnetate. Images can be obtained both before meal ingestion (left image) and then after meal ingestion. Immediately post meal ingestion (right image) there is a total increase in gastric volume with a more pronounced fundal volume increase demonstrating normal fundal accommodation to the meal (arrows).


As the intragastric balloon and SPECT technologies are only available at a limited number of specialized clinical laboratories, there have been recent studies showing that one can obtain an index of gastric accommodation as a part of the more widely available, conventional 2-dimensional imaging of solid-meal GES. This is done by evaluating intragastric meal distribution (IMD) from the images of the solid meal distribution immediately post meal ingestion . ( Fig. 11.3A and B ). GES, as most commonly performed, measures total gastric retention and subsequent emptying of the ingested meal over time. A distinct advantage of scintigraphy for measurement of regional GE is its ability to divide the stomach for quantification into functional physiologic and anatomic segments. GES images can be segmented to measure intragastric meal distribution (IMD) and how this changes as the meal progresses from the proximal to distal stomach over time. This provides information regarding fundic accommodation and antral function. Thus, the commonly available GES study can be used to measure both total and regional GE. Both visual inspection and quantification of separate fundic and antral GE are helpful for defining abnormal physiology and to correlate with dyspeptic symptoms especially when total GE values may be normal .




Figure 11.3


Normal gastric emptying study. Different vendor software packages are currently available in most radiology picture archiving (PACS) systems. Here are two commercial vendor examples of how a normal gastric emptying study may be displayed. Both the anterior and posterior images are acquired and displayed to calculate depth corrected and geometric mean meal total counts. Both examples show initial normal fundic accommodation (arrows). (A) Normal study. At 0 min, all activity is in the stomach with preferential solid food activity seen in the fundus consistent with normal fundic accomodation (arrows). The images show normal distal movement into the antrum with normal emptying. The regions of interest drawn (solid contour) to include the entire stomach are shown and are used to obtain the total gastric counts in the stomach at each time point. By 120 min, normally >40% of the radiolabeled meal has exited the stomach. Here there is borderline retention with 44% retained (56% emptied) and by 240 min (<10%) of the original meal is remaining in the stomach (94% emptied). The raw gastric counts as well as a power exponential curve fit to the data are both shown superimposed. Curve fitting permits calculation of the t1/2 empting time (time to 50% retention). (B) Normal study. Another example of how a normal gastric emptying study’s results may appear in a radiology PACS system. Similar to (A) there is normal fundic accommodation (arrows) in image 1/5 (t=0 min) immediately post meal ingestion. Subsequent anterior and posterior images are shown (2=30 min, 3=60 min, 4=120 min, 5=180 min). The raw count curves for the anterior and posterior images as well as the geometric mean corrected counts are show. When the anterior and posterior data are combined to create the geometric mean curve, the lag phase (double arrow line) becomes apparent. The study was terminated at 180 min as only 5.3% was retained and there was no need to continue to image out to 4 hours (normal <10% retained).




Recent studies suggest that 2-dimensional measures of IMD immediately post-meal ingestion may not correlate with gastric accomodation measurement by SPECT . This is however not unexpected as one measures the total volume expansion (solid and liquid) of the stomach (SPECT) while the other only measures the volume distribution of the radiolabeled solids.


Use of 2-dimensional GES to assess proximal gastric accommodation was originally suggested in observational studies by Troncon, et al . Piessevaux et al using scintigraphy in patients with functional dyspepsia quantitated the ratio of the proximal gastric counts to the distal gastric counts . Forty five percent of patients had distal redistribution of the solid phase of the meal consistent with impaired fundic accommodation.


Another recent study has shown that fundic accommodation can be assessed visually during routine 2-dimensional GES with high consistency among trained nuclear medicine physicians or radiologists . A simple, visual assessment of normal IMD was defined as visualization of the majority of gastric activity (e.g. >50%) being present in the upper portion of the stomach in the first set of post meal ingestion (t=0 minutes) images ( Fig. 11.3 ). In this study, semi-automated software quantified IMD with an optimum cutoff of IMD <0.57 was used to define abnormal IMD . Abnormal IMD was associated with early satiety, loss of weight, and low body mass index (BMI); and predominantly seen in nondiabetic patients. Assessment of IMD during GES correlates with patient symptoms and may lead to therapy directed at improving fundic accommodation. Studies using the IMD measurement of gastric accommodation to assess symptom response to treatment are currently underway.


Technical improvements have been made to improve regional assessment of proximal gastric emptying and measurement of IMD using standard GES. To quantitate the retention dynamics of the proximal stomach, Friedman et al rotate the anterior gastric images so that the axis of the body of the stomach is vertically oriented and determine the maximum body axis length (BAL). With this method, a proximal gastric region of interest (ROI) is defined as a rectangle of fixed height, BAL/2, positioned at the most superior aspect of the stomach on the immediate (t=0 min) postprandial image ( Fig. 11.4A ). Time-activity curves were derived from the proximal ROIs ( Fig. 11.4B ) to evaluate proximal retention in healthy volunteers with normal gastric emptying; upper and lower limits of normal proximal retention were established at each acquisition time point.




Figure 11.4


(A) Rotated (15° CCW) anterior stomach images at consecutive 15 minute intervals for 120 minutes and at 3 and 4 hours, beginning immediately following meal ingestion. Total stomach, proximal and zero-time antral ROIs (contours) are shown. (B) Proximal curve from a patient demonstrating rapid proximal emptying in first 15 minutes and emptying within normal limits thereafter. Dotted curves are upper (ULN) and lower (LLN) limits of normal proximal retention.


Gastric emptying of a meal


Normal gastric emptying reflects a coordinated effort between the fundus, antrum, pyloric sphincter, and duodenum . Coordination of these motor events are carefully regulated and governed by gastrointestinal electrical activity through the interstitial cells of Cajal (ICCs) and neural connectivity through enteric nerves and vagal efferent nerves from the central nervous system. Feedback from nutrients and volume in the stomach and small bowel impact on the process of gastric emptying and is conveyed though local enteric sensory nerves, vagal afferent nerves, and hormones.


Fundic and antral smooth muscle contractions are primarily cholinergically mediated. Rhythmic antral contractions, typically at approximately 3 cycles per minute, triturate large food particles into smaller 2–3 mm particles which are then permitted to pass through the pylorus when they are an appropriate size for intestinal digestion. The rate of these contractions is governed by the electrical pacemaker of the stomach involving the interstitial cells of Cajal.


Pyloric sphincter relaxation synchronized with antral contractions, allows the smaller food particles and chyme to pass out of the stomach into the duodenum . Pyloric relaxation is mediated through release of inhibitory nerves, especially nitric oxide and possibly vasoactive intestinal polypeptide (VIP) .


Solid and liquid foods empty from the stomach at different rates . Liquids empty from the stomach at a monoexponential rate as their emptying depends primarily on the gastric–duodenal pressure gradient with less reliance on coordinated antral contractions and pyloric opening ( Fig. 11.5 ). As discussed above, solids are initially retained selectively within the stomach until particles have been triturated to a size smaller than 2–3 mm. The time from meal ingestion to onset of solid emptying from the stomach is often referred to as the “lag phase” ( Fig. 11.3B ). This lag phase includes the time for fundal accommodation and initial trituration. The solid emptying curve is therefore more complex than that for liquids. Once the small solid particles are created and suspended with the gastric liquid content, the solids and liquids empty at the same monoexponential rate .




Figure 11.5


Normal gastric emptying of liquids. As opposed to normal solid gastric emptying( Fig. 11.3A,B ), liquids distribute rapidly throughout the stomach with no preferential fundic accommodation. The shape of the anterior, posterior, and geometric mean emptying curves demonstrate no initial lag prior to the onset of emptying and the shape of the emptying curves are monoexponential as liquids do not undergo preferential fundic accomodation nor require any trituration prior to emptying.


The current conventional gastric emptying scintigraphy test


The technical details for performing GES have recently been standardized and are well summarized in a Society of Nuclear Medicine and Molecular Imaging guideline . The following on patient preparation and glycemic control are important areas for referring physicians to understand to help ensure optimum quality results.


Patient preparation


Patients should discontinue medications that may affect GE for an adequate period before the testing based on drug half-life. Generally, this is for three days prior to the test. The drugs to be primarily concerned about include narcotic opioid analgesics and anticholingergic agents that delay GE and prokinetic agents that accelerate gastric emptying. Other agents may also have an impact on gastric emptying including those used to treat diabetes, including pramlintide (an amylin-like compound), and exenatide (a GPL1 receptor agonist). Serotonin receptor antagonists such as ondansetron, which have little effect on gastric emptying, may be given for severe symptoms of nausea and vomiting before performing GES. As marijuana use has become more common and can slow GE, patients must be questioned and instructed to avoid this recreational drug before undergoing GES .


Hyperglycemia (glucose level >270 mg/dL) delays GE in diabetic patients ; therefore, it is recommended to defer GE testing until euglycemia can be achieved if pretest hyperglycemia is present. The Society of Nuclear Medicine and Molecular Imaging Guideline on GE recommends that the pre study fasting BGL should be less than or equal to 200 mg/dL . An American Gastroenterological Association (AGA) practice guideline states “markedly uncontrolled glucose levels (>200 mg/dL) may delay GE and aggravate symptoms of gastroparesis (strong recommendation, high level of evidence)” and recommends deferring GE testing until relative euglycemia is achieved to obtain accurate GE results. The AGA guideline further states “Patients with diabetes should have blood glucose measured before starting the GE test and hyperglycemia treated, with test started after blood glucose is <275 mg/dL” (strong recommendation, moderate-high level of evidence) . A recent review on how best to achieve euglycemic control in diabetics prior to GES has been published .


Because of the hormonal changes that occur during the menstrual cycle, premenopausal women should be studied during the first 10 days of the onset of their menstrual cycle. As premenopausal women have slower GE than men , some advocate using separate reference values for premenopausal women .


Methodology


For many years, GE studies were performed using various local protocols and different radiolabeled meals. A consensus has been published that now provides guidance and standardization on how to perform a radiolabeled solid-meal GE study. This consensus statement from the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine recommends a standardized method for measuring GE by GES . A low-fat egg white meal (Eggbeaters™ (ConAgra Foods, Inc.; Downers, IL) or use of equivalent generic egg white) with imaging at 0, 1, 2, 4, hours after meal ingestion, as described in a published multicenter study , provides information about normal, delayed, and rapid GE and is the currently recommended method for performing a solid-meal GE test. This test meal has a low fat content and thus will produce different results than other higher fat or caloric meals .


There has also been an evolution on the total time that is needed for adequately imaging GE. For years, many imaging centers measured GE only out to 90 or 120 minutes. Imaging periods of ≤2 hours have been shown to have significant day-to-day variability (up to 20%) in rates of GE which increases as the study time period decreases . Extending scintigraphy to 4 hours is now included in the Society of Nuclear Medicine and Molecular Imaging Guideline to improve detection of delayed GE. Adoption of this standardized protocol has helped to resolve the prior lack of uniformity in GES testing and added improved reliability and clinical utility to the results of the GES test .


Interpretation of gastric emptying scintigraphy


The simplest approach for interpreting a solid meal GE study is to report the retention percent at defined times after meal ingestion (usually 2 and 4 hours). Using the currently accepted liquid egg-white consensus meal, abnormally delayed GE is defined at 2 hour retention >60% and/or 4 hour retention >10%. Fig. 11.6 shows a typical report summary for a patient with delayed GE with 81% retained at 2 hours and 50% at 4 hours. Rapid GE may also be encountered in patients with symptoms of delayed GE. With impaired fundic accommodation GE can be accelerated ( Fig. 11.7 ).


Feb 4, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on Gastric emptying scintigraphy
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