Standardization and Quantification of Radionuclide Solid Gastric-Emptying Studies

MATERIALS AND METHODS

Twenty healthy subjects (9 male, 11 female) volunteered to undergo a radionuclide solid gastric-emptying study. The healthy volunteers had no known serious health problems and had been questioned particularly about gastrointestinal or hepatobiliary problems. Their ages ranged from 21 to 35 y (mean ± SD, 28.7 ± 6.3 y). Patient weight ranged from 52 to 100 kg (mean, 74 ± 14 kg). These subjects also participated in prior investigations quantifying the lag phase (6) and comparing the LAO view with the GM (10). The gastric-emptying study was acquired using a triple-head γ-camera (TRIAD; Trionix).

The subjects took nothing by mouth after midnight the night before the study, which was the first study performed the next morning. Each subject ingested a ^99mTc (37 MBq)-sulfur colloid–labeled egg-white sandwich (3 fried egg whites, 2 pieces of toast, butter, salt, and pepper [260 kcal, 40 g of carbohydrate, 5 g of fat, and 93 g of protein]) along with 200 mL of water over a period of 5–10 min while seated. Imaging commenced immediately after the subjects had ingested the meal and had lain supine on the table of the triple-head γ-camera.

With the triple-head system, 2 sets of 3 simultaneous projections could be acquired. Each was acquired for 30 s: first, the anterior, right posterior oblique (RPO), and left posterior oblique (LPO) projections; then, after a suitable rotation of the gantry, the posterior, LAO, and right anterior oblique (RAO) projections. This sequence was repeated continuously for 90 min. The data were decay corrected to the start of acquisition. Images were reviewed in cinematic display to assist in placement of the manually drawn regions of interest about the stomach. Time–activity curves were derived for the anterior, posterior, LAO, RAO, LPO, RPO, and for the anterior/posterior, LAO/RPO, and RAO/LPO conjugate views (GM).

Various quantitative parameters were determined using the derived time–activity curves. These included the percentage gastric emptying (%GE) at 90 min (maximum counts − minimum/maximum counts) × 100, the half-time (t_1/2, in minutes) derived from an exponential fit, and the %/min emptying rate from the slope of a linear fit. An anterior/posterior GM inflection point lag phase, defined as the time that the second phase of emptying began, was determined by visual inspection of the gastric time–activity curve. The results were statistically analyzed and compared to determine the similarities and differences of the quantitative methodologies and the advantages of each.

RESULTS

Table 1 shows the results for all 20 subjects. One subject appeared to be an outlier (patient 20), and statistical analysis was calculated with and without this subject. The results were basically the same whether or not this subject was included, although a slightly greater mean %GE and smaller SDs were calculated when this subject was excluded. The statistical results discussed below are for the remaining 19 subjects except when stated otherwise.

A trend was noted when comparing the %GE of the anterior/posterior GM with the anterior and LAO views. The range of reference values was determined on the basis of the 95% confidence interval of the t distribution for 19 subjects (18° of freedom). The reference values (±2 SDs from the mean) were highest for the anterior/posterior GM (≥33%), followed by the LAO GM (≥31%) and then the anterior GM (≥30%). Correlation coefficients between the methods were high: GM/anterior, r = 0.874; GM/LAO, r = 0.918; anterior/LAO, r = 0.924. There was no statistical difference among them.

The 3 maximum/minimum (%GE) GM results had a high statistical correlation: anterior/posterior versus LAO/RPO, r = 0.905; anterior/posterior versus RAO/LPO, r = 0.909; LAO/RPO versus RAO/LPO, r = 0.897. There was no statistical difference among them.

The 3 exponential-fit GM results were compared: anterior/posterior versus LAO/RPO, r = 0.905; anterior/posterior versus RAO/LPO, r = 0.909; LAO/RPO versus RAO/LPO, r = 0.897. There was no significant difference among them.

The 3 linear-fit GM methods were compared: anterior/posterior versus LAO/RPO, r = 0.918; anterior/posterior versus RAO/LPO, r = 0.863; LAO/RPO versus RAO/LPO, r = 0.919. There was no statistically significant difference among them. Two subjects were excluded from the results because the time–activity curves were noisy and difficult to fit.

The LAO method and the LAO/RPO GM mean methods were compared: The respective mean %GE values (52% and 51%), SD values (10.7% and 10.3%), and lower limit of reference values (31% and 31%) were nearly identical. The correlation coefficient was high (r = 0.900), and there was no statistically significant difference between the 2 methods.

The 3 methods of GM quantification (maximum/minimum, linear, and exponential) were compared: exponential versus linear (anterior/posterior), r = 0.944; maximum/minimum versus linear (LAO/RPO), r = 0.809; maximum/minimum versus exponential (RAO/LPO), r = 0.925. There was no significant difference among them.

Correlation was poor between the lag phase, as defined by the inflection point (10), and the overall %GE (r = 0.26), the anterior/posterior linear rate of emptying (r = 0.23), and the anterior/posterior exponential rate of emptying (r = 0.12).

DISCUSSION

Many different methodologies for performing solid gastric-emptying studies have been described over the years (2). Reference values have been established with some of these methods; however, the reference range is method specific, depending on the type of meal, the acquisition and processing methodology, the imaging equipment, and the quantitative technique (11–15). Thus, in a clinical setting, a laboratory needs either to establish its own reference values based on the methodology it uses or, alternatively, to closely follow a method described in the literature and use its established reference values.

Much of the earlier literature is not helpful for establishing a standardized procedure in the modern nuclear medicine clinic. Many past studies included such difficulties as the use of single-head cameras, noncontinuous and infrequent image acquisition, alternation of anterior and posterior acquisitions, and complicated quantification. One would like a methodology that allows for easy set-up and acquisition, patient comfort, attenuation compensation, a rapid framing rate, and straightforward and easy-to-understand quantification. The purpose of this study was to compare and analyze various methods of acquisition and quantification in healthy subjects and to establish a simple methodology and reference values that can be used with the dual-head γ-cameras available today in most nuclear medicine laboratories.

Published investigations have proven the importance of attenuation correction in obtaining accurate solid gastric-emptying studies (12,14,16). It is necessary to correct for the variable attenuation of the radiolabeled meal as it moves in the stomach from the relatively posterior fundus to the more anterior antrum. Although this effect is likely to be more important in obese patients, it is not uncommon in normal-weight subjects and cannot be predicted beforehand. In the past, many investigations used intermittent imaging, with images acquired every 15–30 min. A relatively rapid framing rate of 60 s produces a statistically reliable time–activity curve and more accurate quantification (10,13).

The antrum of the stomach is responsible for solid gastric emptying. Two phases of solid emptying have repeatedly been demonstrated (17,18): an initial delay before emptying begins, the lag phase, and continuous emptying, typically linear. The lag phase is presumably due to the time required for the antrum to grind food into particles small enough to pass through the pylorus. Some have recommended quantification of the lag phase and the rate of emptying, although individual studies have found that the lag phase may be delayed in certain diseases (19,20) and may be shortened by drug therapy, improving emptying (21,22). Other investigators have found that delayed emptying is usually due to a delay in both phases and similarly improves after therapy (23–25). However, the data are contradictory, and other investigators have not confirmed these findings. A likely explanation for this discrepancy may be the very different methodologies used. This is an area needing further investigation using standardized methodology. In this study, we found no correlation between the length of the lag phase and the overall %GE. We do not recommend quantification of the lag phase for routine clinical purposes. The protocol we have described would also be useful for answering such questions in research investigations.

Many publications have used a t_1/2 of emptying or a fitted exponential curve to calculate a t_1/2 rate of solid gastric emptying. This makes little physiologic sense, since gastric emptying is usually linear. Many technical problems are involved in using a t_1/2, such as determining whether time zero is at the start or end of the lag phase. If a rapid framing rate is not used, the length of the lag phase and, thus, time zero may be erroneously determined, resulting in inaccurate results. Although a linear emptying rate makes more sense, few have used this method (17). A modified power exponential has been put forth and used as a reproducible standardized method for establishing the lag phase and a rate of emptying (18). However, we have shown that the lag phase calculated by the modified power exponential does not correspond to other published methods of lag phase calculation (10).

The LAO method for attenuation compensation is not a mathematic correction. Because the stomach contents move roughly parallel to the head of the γ-camera in this projection, the variation in soft-tissue attenuation is minimized. This method was initially described by us in 1989 (5) and has been subsequently validated in other studies (6–9). The present study again validates this method, showing no significant difference between the LAO and LAO/RPO or anterior/posterior GM methods.

The present investigation attempted to establish a simple, straightforward methodology that can be used in any clinic that has a dual-head γ-camera. Our investigation showed a high correlation in reference values among all the methods described. The anterior/posterior GM mean method has been the accepted gold standard for attenuation correction. Attenuation correction using the GM method has been validated on a phantom model (12). Others have shown that the GM method compensates for variable attenuation as the meal moves through the stomach by eliminating the artifactual rise in the time–activity curve, with expected improvement in emptying results (3,4,11). Our data show that the anterior/posterior GM method has a smaller SD and higher reference values than do the anterior and LAO methods, other GM conjugate views (LAO/RPO and RAO/LPO), or exponential or linear emptying methods. Although the other GM conjugate view methods would be expected to provide similar results, we found more variability and a considerably larger reference range using these methods than using the anterior/posterior GM method. The reason is uncertain but may be methodologic because of the variability in selection of the appropriate fitted curve due to the multiexponential shape of many posterior, RPO, and LPO time–activity curves.

Two publications have suggested that quantification at 4 h may improve the sensitivity for detecting delayed emptying (26,27). Only 4 (26) and 6 (27) imaging time points were acquired in these 2 studies. One study found delayed emptying in symptomatic patients more frequent at 4 h compared with 2 h and thus concluded that the 4-h study was superior (26). A second multiinstitutional study established reference values using a large number of healthy subjects and proposed their 4-h study as a screening test (27). They did not attempt to demonstrate that the 4-h study was superior to shorter imaging studies, only that the 4-h study is a simple methodology, with reference values based on a large number of subjects. They noted that their method cannot be used to evaluate gastric physiology—for example, the lag phase or the rate of emptying—because of the limited number of imaging time points. Our proposed standardized protocol is also simple to perform, has established reference values, and can also be used to study gastric physiology and be completed in 90 min.

CONCLUSION

We have described and validated a standardized method for solid gastric emptying that can be used with a dual-head γ-camera. We recommend the use of the anterior/posterior GM method and the calculation of an overall %GE at 90 min, which combines the lag phase and the rate of emptying into a single value. Our protocol is described in the Appendix. Abnormal solid gastric emptying was determined to be less than 33%.

APPENDIX