Gastric Emptying Scintigraphy

GES was first described in 1966 by Griffith et al. [1] and is currently considered the gold standard for the diagnosis of gastroparesis. In this test, and after an overnight fast, the patient ingests a standardized, radiotracer-bound, low-fat meal (255 kcal) resembling a physiologic meal within 10 minutes. A longer time of ingestion can alter results. Most institutions use 99mTc sulfur colloid-labeled egg sandwich [2] or Egg Beaters egg whites (120 g) with 1–2 slices of bread, strawberry jam (30 g), and water (120 mL). For accurate quantification of gastric emptying, the radiotracer should be tightly bound to the solid phase to prevent it separating from the solid meal and emptying with the liquid phase, generating false-negative results [3, 4]. While earlier studies labeled both solids and liquid phases of a meal, current standardized tests only label the solid phase of a meal, because liquid emptying becomes abnormal only at very advanced stages of gastroparesis. Testing liquid emptying is of value however when evaluating for postsurgical anatomic problems or ruling out dumping syndrome in postsurgical patients [4]. After ingestion, standard imaging of the gastric area is performed with the patient standing after meal consumption (baseline) and then at 1, 2, and 4 hours postprandially with the percentage of radioactivity remaining in the stomach recorded at the different stages using a computerized software and normalized to the baseline value (t = 0). Gastric emptying is considered delayed if there is >60% retention at 2 hours and/or >10% retention at 4 hours [5–7] (Fig. 3.1). The emptying half-time can also be calculated by extrapolation using the power exponential curve; however, results would only be accurate if the patient does actually empty at least 50% of the ingested meal at the time of imaging [8].

While a 2-hour GES was previously performed to determine gastric emptying, recent studies have proposed a longer duration of 4 hours for a more reliable assessment [9–11]. A study comparing a 2–4-hour GES found a 29% increase in the number of abnormal studies at 4 hours compared to 2-hour tests [11]. In preparation for the test, patients are asked to discontinue all medications that could alter gastrointestinal motility for 2–7 days prior to the procedure, including prokinetics, narcotics, anticholinergics, and alcohol. On the day of the test, fasting blood glucose should be <275 mg/dL to prevent the slowing of gastric emptying secondary to hyperglycemia [4].

Stable Isotope Breath Test

The stable isotope breath test comprises the use of the stable isotope ¹³carbon (¹³C) in a substrate, like octanoic acid, a medium-chain fatty acid. The ¹³C-labeled substrate is then bound to a digestible meal such as a muffin, or spirulina platensis, a blue green algae composed of 50–60% protein, 30% starch, and 10% lipids [14]. After an overnight fast, testing starts by collecting pre-meal breath samples, followed by meal ingestion. Upon meal ingestion and following gastric emptying, ¹³C-octanoate is absorbed in the duodenum and liquefied to chyme. It is then transported through the portal circulation to the liver where it is metabolized to ¹³carbon dioxide (¹³CO2) and exhaled during expiration. Since stomach emptying is the rate limiting step of the testing process described, the amount of ¹³CO2 in an exhaled breath test is representative of gastric emptying [15–17]. Post-meal breath samples are collected every 30 minutes and analyzed by isotope-ratio mass spectrometry. Samples are collected every 30 minutes for a total of 4–6 hours. Some studies recommended at least 6 hours of breath sampling because of possible overestimation of T_1/2 by 4-hour breath testing [15, 18, 19]. Similarly to GES, agents altering gastric emptying need to be discontinued 2–7 days prior to testing, smoking and alcohol need to be discontinued on the day of testing, done after an overnight fast [19].

Wireless Motility Capsule

The wireless motility capsule (WMC) (SmartPill Corporation, Buffalo, NY) has been approved by the US Food and Drug Administration (FDA) for the evaluation of gastric emptying and colonic transit time in patients with suspected slow transit constipation [23]. The capsule measures 26.8 mm in length and 11.7 mm in diameter and comprises three sensors for temperature, pH, and pressure [24]. Once ingested, the WMC records measurements of the three variables continuously as it travels through the gastrointestinal tract, and data is transmitted wirelessly and in real time, to a receiver the patient wears on their waste for the study period. Gastric emptying time is considered delayed if it is 5 hours or greater and is defined as the duration it takes for the capsule to reach to duodenum, determined by an increase in pH by >3 units. Small bowel transit time normally takes 2.5–6 hours and is determined from the time the pH increases by >3 units to the time it drops by >1 unit and is sustained for at least 30 minutes. This drop marks the passage of the capsule to the cecum. Colon transit time (normal if 59 hours or less) is determined from the time the WMC enters cecum until it is expelled from the body, marked by sudden drop in temperature or loss of signal [24]. Testing begins in the morning after an overnight fast. Patients are instructed to refrain from taking medications that would alter gastric emptying 2–3 days prior to the test day. Similarly, acid suppressant medications are held to prevent interfering with the pH measurements of the WMC. Proton pump inhibitors are held 7 days prior and histamine receptor blockers 3 days prior to the procedure. On the day of testing, patients ingest a standardized meal consisting of a nutrient bar: Smartbar® followed by 50 cc of water. Patients fast for the 6 hours following meal consumption. They are asked to push the EVENT button and make entry in diary for certain events for the duration of the study after which the receiver is collected and data is downloaded for analysis [24].

Antroduodenal Manometry

Antroduodenal manometry provides information about gastric and duodenal contractions and consists of inserting a manometry catheter or transducer with pressure sensors into the pyloric channel endoscopically or under radiographic fluoroscopy [7, 32, 33]. Pressure measurements of the antral, pyloric, and duodenal contraction waves are obtained in fasting and postprandial states. The test can be performed over 5–8 hours in a stationary setting or in a 24-hour ambulatory setting with the latter used to characterize duodenal motor function. In gastroparesis, antroduodenal manometry demonstrates a reduced antral motility index [7, 33].

Other Imaging Modalities

Transabdominal ultrasonography and magnetic resonance imaging (MRI) have been proposed as noninvasive diagnostic tools for gastroparesis, but their use remains limited to research purposes for reasons discussed below.

Two-dimensional ultrasonography can provide data about gastric emptying by measuring changes in the antral area, and complete gastric emptying is determined once the antral area returns to its preprandial baseline. Three-dimensional ultrasound can add data on meal distribution and volume inside the stomach [36]. Duplex sonography has also been proposed to look at transpyloric flow and liquid contents [4]. While ultrasound seems to be an appealing noninvasive technique, its use remains limited [3] in the clinical setting because of the significant expertise it requires and given poor performance in obese patients [4].

MRI is another appealing tool that can measure gastric accommodation and emptying every 15 minutes using transaxial abdominal images [3]. It can also differentiate gastric meal from air and hence give information about gastric emptying and gastric secretions [37]. It is expensive however, requires specialized equipment, and is not standardized across centers limiting its use to research only, except for some European centers [4, 7].