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1 Department of Diagnostic Radiology, University Hospital Essen, Hufelandstr.
55, D-45122 Essen, Germany.
2 Department of Neurology, University Hospital Essen, D-45122 Essen,
Germany.
3 Department of Gastroenterology and Hepatology, University Hospital Essen,
D-45122 Essen, Germany.
Received February 8, 2002;
accepted after revision October 1, 2002.
Address correspondence to T. C. Lauenstein.
Abstract
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SUBJECTS AND METHODS. Six healthy volunteers and six patients with symptoms of functional dyspepsia ingested 10 mL of gadopentetate dimeglumine mixed into 500 mL of a liquid nutrient. On two separate days, gastric emptying was determined using 3D volume measurements that were obtained every 5 min for as long as 25 min on 3D T1-weighted gradient-echo MR imaging with and without the use of IV erythromycin. Gastric volumes and filling of the small bowel were quantified on the 3D data sets using semiautomatic software.
RESULTS. Delineation of the bright gastric lumen proved easy. After 25 min, a significant decrease in gastric volumes could be seen in examinations performed with and without erythromycin. In healthy volunteers, gastric volumes decreased significantly more after the administration of erythromycin. In three patients with functional dyspepsia, MR imaging revealed reduced rates of gastric emptying. The administration of erythromycin resulted in a significantly faster rate of gastric emptying in two of those three patients.
CONCLUSION. Three-dimensional MR imaging is a feasible method of assessing gastric volumes and diagnosing delayed gastric emptying. In patients with reduced rates of gastric emptying, 3D MR imaging may be an appropriate tool with which to monitor therapeutic approaches, such as the use of prokinetic agents like erythromycin.
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Functional dyspepsia is quite prevalent. Yet all the tests currently available to assess gastric motor function have drawbacks—the tests are invasive, inaccurate, or expose the patient to radiation. Gastric barostat studies using an intragastric balloon provide accurate assessment of proximal gastric motor function [6], but the intrinsic invasiveness of this test hampers its acceptance by patients. Scintigraphy can be used as a noninvasive tool with which to quantify gastric emptying, but this modality is associated with considerable exposure to ionizing radiation [7]. Gastric sonography represents an alternative approach [8] that does not expose patients to radiation. However, the clinical impact of gastric sonography has been limited by an inherent operator dependency and quantitative inaccuracies caused by air superimposition. The noninvasive 13C octanoid acid breath test is an indirect test, and its results might be affected by the duration of small-bowel transit.
Recently, MR imaging has been proposed as a means of evaluating gastric emptying [9, 10, 11, 12, 13]. The technique is noninvasive, not dependent on the skill of the operator, and not associated with ionizing radiation. Until recently, MR imaging strategies for assessing gastric motility were based on either echoplanar [9, 10] or two-dimensional [11, 12, 13] techniques, thereby resulting in limited spatial or temporal resolution. Recent hardware and software developments now allow acquisition of three-dimensional (3D) data sets in a single breath-hold [14]. Hence, accurate delineation of gastric volumes is now possible.
The aim of our study was to implement an MR imaging protocol for the accurate assessment of gastric emptying using time-resolved 3D imaging and to evaluate the effect of a prokinetic agent. Erythromycin, a macrolide antibiotic, has been found to be a gastrointestinal prokinetic agent when used in small nonantibiotic doses [15] and has even been proposed as a prokinetic for patients with gastroparesis who do not respond to other conventional prokinetics [16].
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The first part of the study was conducted on six healthy volunteers (age range, 28–37 years; mean age, 32 years) who had no symptoms of dyspepsia nor a history of any other gastrointestinal disorders or surgery and who were not taking any regular medication. The volunteers had indicated in a questionnaire that they did not suffer from illnesses that carry a high probability of leading to gastric motility disorders, such as diabetes or hypothyroidism. MR imaging was performed after an 8-hr fast. Ten mL of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) was added to 500 mL of high-calorie vanilla cream, and the mixture was given to the patients to ingest. We acquired 3D gradient-echo MR imaging data sets before the patients ingested the liquid nutrient as well as at intervals of 5 min for as long as 25 min after the ingestion. After 5–13 days, the MR imaging examination was repeated. In this session, however, 100 mg of erythromycin (Erythromycinlactobionat; Abbott Pharmaceutics, Wiesbaden, Germany) was given IV immediately after the ingestion of the liquid contrast agent.
After successful completion of the MR imaging of the volunteers, we performed MR imaging using the previously described protocol in six patients (age range, 30–57 years; mean age, 39.5 years) who had symptoms of functional dyspepsia. All patients had been referred to the Department of Gastroenterology and Hepatology for evaluation of symptoms such as postprandial fullness, nausea, or early satiety. Morphologic gastric lesions had been excluded by endoscopy.
All patients were examined twice, just as the volunteers had been: once without erythromycin and a second time after IV administration of erythromycin. The two imaging sessions were at least 5 days apart.
All 3D data were reviewed for the presence of artifacts. We adapted our proprietary segmentation software program (based on LINUX) to perform data analysis. We determined the gastric volume with a 3D region-growing algorithm; starting from a user-selected seed point in the hyperintense gadolinium-containing gastric volume, we counted the number of voxels contained in the threshold volume of the stomach. To assure comparability of measurements, we kept the threshold values and blurring factor for edge detection constant for all subjects. All calculations were performed twice to assure reproducibility. The semiautomated segmentation process was supervised by two radiologists. The evaluation time needed to assess the rates of gastric emptying was measured with a stopwatch.
The effect of erythromycin on the rates of gastric emptying was determined with a paired Student's t test. Similarly, the rates of gastric emptying in the patients were compared with the rates in volunteers. Normal gastric emptying was defined as the mean value of the six volunteers ± 3 SDs.
For a standard of reference with which to compare patient data, we had our patients undergo gastric-emptying scintigraphy 12 ± 6 days after the second MR imaging examination. After fasting overnight, all subjects ate a meal consisting of scrambled eggs and bread labeled with
99mTc pertechnetate. Images were obtained with a gamma camera every 10 min for 2 hr. Gastric emptying half-time data were correlated with internal reference values and were rated as delayed, normal, or enhanced, using ± 2 SDs as threshold values.
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The assessment of gastric emptying performed 5–25 min after ingestion of the contrast material showed a constant decrease of gastric volumes in all 24 examinations (Table 1). In the volunteers, the initial gastric volumes calculated immediately after ingestion of oral contrast material ranged from 534 to 601 mL. Without erythromycin, gastric volumes decreased between 95 and 151 mL over the ensuing 25-min period (Figs. 3A, 3B). The mean rate of gastric emptying was 4.64 mL/min with an SD of ± 0.82 mL/min. Administration of the erythromycin resulted in substantial acceleration of gastric emptying. Gastric volumes decreased between 192.3 and 215 mL within 25 min, resulting in a mean rate of gastric emptying of 7.69 ± 0.86 mL/min. The erythromycininduced difference in the rates of gastric emptying was statistically significant (p < 0.01). Figure 4 shows the progression of gastric emptying with and without erythromycin in volunteers at different times during 25-min examination.
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We used the mean values of the volunteer studies as reference standards for the examinations of patients with symptoms of dyspepsia. According to these standards, three of the six patients (Table 2) had rates of gastric emptying without erythromycin that were more than 3 SDs below the mean rates in our volunteers (Figs. 5A, 5B and 6A, 6B). Mean emptying rates for these patients were less than 2 mL/min. The IV administration of erythromycin resulted in a considerable increase of gastric emptying in two patients (patients 1 and 5, Table 2), whereas one patient (patient 3, Table 2) had only a slight increase in the rate of gastric emptying. No significant difference in gastric emptying was found between the remaining three patients and the reference group, either with or without the administration of erythromycin. An additional finding of esophageal reflux was revealed in patient 4 (Fig. 7). Scintigraphy confirmed delayed gastric emptying in three patients (patients 1, 3, and 5) and normal rates of gastric emptying in the other three patients. Compared with an internal reference value for the half-emptying time of 90 ± 30 min, the examinations of patients 1, 3, and 5 showed a prolonged half-emptying time of 166–198 min.
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Because the contrast between the gadolinium-filled gastric lumen and surrounding tissues is so defined, the underlying volumetric analysis is simple enough to be automated. Thus, the prokinetic effect of IV erythromycin was easily quantified. The MR imaging–based method showed altered gastric motility in patients with dyspepsia and correlated with the accepted standard of scintigraphic gastric emptying.
Although MR imaging has been proposed as a method of detecting and staging malignant gastric tumors [14, 17, 18], its clinical impact on the diagnostic workup of patients believed to have gastric tumors has been limited. MR imaging–based analysis of functional gastric disorders was first proposed in 1992 by Schwizer et al. [19]. In that study, long acquisition times combined with two-dimensional imaging strategies resulted in poor image quality, which translated into an imperfect correlation with nuclear scintigraphy [19]. Despite consistent advances in MR imaging technology, examination protocols remained cumbersome. Thus, Kunz et al. [12, 20] proposed the assessment of gastric motor function using an MR sequence with an acquisition time of 60 sec. To avoid breathing-induced motion artifacts, the researchers divided the collection of data into four parts, during which the volunteers were instructed to hold their breath. Differences in inspiratory depths limited the volumetric accuracy.
Marciani et al. [10] proposed using single-shot echoplanar imaging to calculate gastric emptying half-times by collecting transverse volume data sets every 15 min until a gadolinium-labeled meal had completely passed through the patient's stomach. Although those authors were able to show a reliable differentiation between the rates of gastric emptying in healthy volunteers and those in patients, some questions concerning the technique's practicality remained. For example, the mean gastric emptying half-times exceeded 60 min, far too long to be implemented in clinical practice. Postprocessing procedures also exceeded 60 min. Furthermore, the presence of imaging artifacts and limited spatial resolution inherent to echoplanar data collection techniques were additional disadvantages [21].
The proposed concept of time-resolved 3D MR imaging overcomes all these limitations. Gastric emptying rates can be accurately determined within 45 min, including an in-room time of 30 min for the examination itself. It is likely that the examination time could be considerably shortened. Measurements made six times over a period of 25 min indicated that the rates of gastric emptying were linear. Future studies—preferably with larger numbers of patients with nonulcerative dyspepsia—are needed to determine whether a simplified protocol based on measurements obtained at the time the examination is begun and at only one or two other closely spaced times during the examination renders similarly linear results. Further automation of the 3D region-growing algorithm software is likely to reduce the 15 min required for data postprocessing. In the future, a functional gastric MR imaging examination might require only 10–15 min.
The collection of 3D data sets guarantees accurate measurements of gastric volumes. Collection of 3D data sets is the basis for well-established techniques such as MR angiography [22] and MR colonography [23], and 3D data sets have been shown to provide excellent image quality. In a study by Schmithorst et al. [24], image artifacts such as ghosts or geometric distortions that are inherent to echoplanar techniques were not found. Use of an MR scanner equipped with high-performance gradients allowed the acquisition of a 3D gastric data set during a comfortable breath-hold.
Because data acquisition did not have to be divided, exact mapping of gastric morphology was assured. The prokinetic effect of erythromycin was well validated in our volunteers; the rate of gastric emptying significantly accelerated after the IV administration of erythromycin. This finding could be exploited for optimized small-bowel MR imaging: small-bowel filling and distention that are crucial for small-bowel MR imaging can be accelerated [25].
Our results show that functional gastric MR imaging can be used to identify patients with gastric dyspepsia. Three of the six patients had much slower rates of gastric emptying than the mean rates determined in healthy volunteers. All results were confirmed by gastric-emptying scintigraphy. Three-dimensional gastric MR imaging was also sufficiently sensitive to serve as a monitor of therapeutic effects: we observed that the abnormally slow rates of gastric emptying in two patients dramatically increased after the administration of a small dose of erythromycin. A third patient with abnormally slow gastric emptying failed to show a prokinetic effect after the administration of erythromycin. Of course, the proposed MR imaging–based 3D technique can also be used to assess other kinds of prokinetic agents or other therapeutic strategies.
The pathophysiology of gastric motor function is complex. However, impaired fundal relaxation and antral hypomotility are two of the main disturbances in patients with impaired gastric motor function [26, 27]. Because different therapies are used to treat the two disturbances, differentiation between patients with these two abnormalities is desirable and has remained elusive using conventional diagnostic means. The described MR imaging–based 3D protocol has the potential to permit such a differentiation; the data resolution is sufficiently high to reconstruct the gastric anatomy and differentiate the various gastric regions.
In summary, 3D MR imaging is a promising accurate and noninvasive technique for the assessment of gastric motor function. It compares favorably with traditional methodologies because it does not expose patients to radiation and allows regional motor disturbances (e.g., fundic relaxation) to be depicted. Further studies in larger patient populations are warranted to determine motor abnormalities using this new technique.
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  M. E. Spieth, B. S. Gauger, and T. C. Lauenstein Time-Resolved 3D MRI of Gastric Emptying Am. J. Roentgenol., January 1, 2004; 182(1): 259 - 259. [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) and without (
) IV
administration of erythromycin. Range is indicated by [UNK].
