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(Radiology. 1999;212:507-513.)
© RSNA, 1999

Nuclear Medicine

Pediatric Inflammatory Bowel Disease: Assessment with Scintigraphy with 99mTc White Blood Cells1

Martin Charron, MD, FRCPC, Fernando J. del Rosario, MD and Samuel A. Kocoshis, MD

1 From the Departments of Radiology (M.C.) and Gastroenterology (F.J.d.R., S.A.K.), Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine, Pittsburgh, Pa. Received July 15, 1998; revision requested September 24; final revision received January 13, 1999; accepted February 16. Address reprint requests to M.C., 335 S Linden Ave, Pittsburgh, PA 15208 (e-mail: charron@pop.pitt.edu).


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To evaluate the sensitivity and specificity of scintigraphy with technetium 99m white blood cells (WBC) for detection of colonic inflammation in children with and children without inflammatory bowel disease (IBD).

MATERIALS AND METHODS: In 215 patients, uptake of 99mTc WBC in 3,440 bowel segments was graded. In 137 of the 215 patients, the 99mTc WBC scans were interpreted blindly and findings compared with results at colonoscopy and endoscopic biopsy. Planar, single photon emission computed tomographic, and maximum-activity-projection images were reviewed together. In 78 children without recent endoscopic biopsy results, 99mTc WBC scan findings were compared with laboratory values, the gastroenterologist's initial clinical assessment, and findings at long-term clinical follow-up.

RESULTS: In 128 of 137 children with recent biopsies, findings at histologic examination and on 99mTc WBC scans were correlated. There were seven false-negative and two false-positive studies. Sensitivity was 90%, specificity 97%, positive predictive value 97%, negative predictive value 93%, prevalence of disease 53%, and overall accuracy 93%. In 75 of 78 (96%) children without recent biopsies, 99mTc WBC scan findings were consistent with the laboratory values, gastroenterologist's clinical assessment, and long-term clinical follow-up findings.

CONCLUSION: Scintigraphy with 99mTc WBC is a useful noninvasive diagnostic test to determine the extent and distribution of inflammation in children with IBD.

Index terms: Children, gastrointestinal tract, 75.261 • Colitis, ulcerative, 75.261 • Colon, radionuclide studies, 75.1265 • Gastrointestinal tract, radionuclide studies, 75.1265 • Inflammation, radionuclide studies, 74.1265, 75.1265 • Intestines, radionuclide studies, 74.1265, 75.1265 • Leukocytes • Radionuclide imaging, in infants and children, 74.1265, 75.1265


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The treatment of patients with inflammatory bowel disease (IBD) depends on knowledge of the location, extent, and activity of the inflammation. The diagnosis of IBD in children is often complex and difficult. For many years, barium enema examination was the cornerstone of diagnostic testing; recently, colonoscopy is used more liberally.

Promising results have been published about the clinical use of technetium 99m white blood cells (WBC) in the assessment of IBD in adults (1,2) and in a small series of children (3,4). The purpose of this retrospective study was to evaluate the accuracy of 99mTc WBC scintigraphy for detection of acute inflammation in a large population of children with and children without IBD. In a smaller group of children without recent biopsy results, we compared the scintigraphic result with the laboratory values, the gastroenterologist's clinical assessment, and the long-term clinical follow-up findings.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Patients
We retrospectively reviewed the charts of 215 consecutive children (100 boys and 115 girls; average age, 12 years; median age, 13 years) who underwent 99mTc WBC scintigraphy between September 16, 1992, and December 12, 1996.

Diagnoses in 132 of the 215 patients were based on standard colonoscopic, histologic, or radiologic criteria (5,6) and included Crohn disease (CD) in 80 patients, ulcerative colitis (UC) in 34, and miscellaneous colitis in 18 (indeterminate colitis in 11, infectious colitis in three, autoimmune colitis in three, and toxic colitis in one).

In the 132 patients with IBD, a 99mTc WBC study was performed to assess the intensity of inflammation in 113, and/or the extent of disease in 98, and/or the presence of small-bowel disease in 72.

Fifty-two of the 215 children had a very low probability of IBD (low-probability group) on the basis of nonspecific gastrointestinal symptoms and no demonstrable findings of IBD with conventional diagnostic methods (ie, radiography, colonoscopy, clinical follow-up). Final diagnoses in this group included lactose intolerance, anal fissure, postviral gastroparesis, gastritis, mesenteric adenitis, duodenogastric reflux, hepatitis, protein-losing enteropathy, duodenitis, chronic constipation, appendicitis, ulcer, irritable bowel syndrome, rectal polyp, and gluten enteropathy. Colonoscopy was performed in 29 of these children and surgery in one. Colonoscopic results were normal in this group, and we arbitrarily chose not to reclassify them into the control group.

Thirty-one control subjects (20 boys and 11 girls; average age, 10 years; median age, 11 years) underwent 99mTc WBC scanning for nonabdominal problems (the final diagnoses included osteomyelitis, cellulitis, trauma, myocarditis, fever of unknown origin, painful hip, and peritonitis).

The medication regimen of each patient in the week before 99mTc WBC scintigraphy was recorded, but not that of each control subject. Laboratory values (eg, sedimentation rate and levels of WBC, hemoglobin, hematocrit, platelets, serum albumin, protein, amylase, alanine aminotransferase, aspartate aminotransferase, and {gamma}-glutamyl transpeptidase) were recorded when available. The time between initial diagnosis of IBD and performance of the imaging examination was as long as 62 months (mean, 277 days).

Colonoscopy and Surgery
Colonoscopy and endoscopic biopsy were performed within 30 days (average, 10 days; mode, 7 days) of 99mTc WBC scintigraphy in 137 of the 215 patients. Diagnoses in 106 of the 137 patients included CD in 41, UC in 23, miscellaneous colitis in 12, and low probability of IBD in 30. Table 1 shows the number of children who underwent surgery, endoscopic biopsy, or both.


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  		TABLE 1. Number of Children Who Underwent Various Examinations
 
Total colonoscopy (models CF100TL or PCF20; Olympus Optical, Tokyo, Japan) was performed by an experienced endoscopist to assess the extent and activity of the mucosal inflammatory changes in eight intestinal segments (rectum, sigmoid, descending, transverse, ascending, cecum, terminal ileum, and small bowel). The endoscopic findings of inflammatory activity were classified as absent (noninflamed mucosa), mild (granularity, edema, invisible vascular pattern), moderate (hyperemia, friability, and all features of mild inflammatory activity), or severe (ulcerations, in addition to features of moderate inflammatory activity) (7).

Surgery was performed in 12 of the 137 patients, within an average of 15 days before 99mTc WBC scintigraphy. Six of the patients who underwent surgery also underwent colonoscopy. Macroscopic findings at surgery and microscopic details at biopsy of resected segments were compared with the grade for the 99mTc WBC scan.

Patients without Colonoscopic Data: Clinical Follow-up
The remaining 78 children (22 with low probability, 56 with IBD [CD in 39, UC in 11, and miscellaneous colitis in six]) underwent colonoscopy longer than 1 month before 99mTc scintigraphy. Findings on the 99mTc WBC scans were compared with laboratory values, the gastroenterologist's initial assessment, and findings at clinical follow-up in the 56 children with IBD (average follow-up, 398 days) and in the 22 low-probability patients (average follow-up, 336 days).

Scanning Examinations
Venous blood (20–45 mL) was withdrawn into a 60-mL syringe containing 7 mL of acid citrate dextrose solution. Six percent hetastarch (5 mL) was added and mixed. The syringe was inverted and allowed to settle for 40–60 minutes. The leukocyte-rich plasma was collected and centrifuged at 300 g for 5 minutes. A vial with 0.5 mg of hexamethyl-propylene- amine oxime (HMPAO) (Cerentec; Nycomed Amersham, Princeton, NJ) was reconstituted with 1,110 MBq 99mTc (3 mL), and radiochemical purity was tested. The 99mTc HMPAO (2.5 mL [925 MBq]) was added to the leukocyte button, mixed gently, and incubated for 15 minutes. Platelet-rich plasma (5 mL) was added, and the entire preparation was centrifuged for 5 minutes. The 99mTc leukocyte button was reconstituted in 5 mL platelet-rich plasma and assayed in a dose calibrator. The adult dose of 740 MBq per kilogram of body weight was adjusted for children to 20 MBq/kg. The average efficiency of labeling was 62%. The blood was then reinjected intravenously.

In all patients, imaging was performed at 1/2 to 1 hour after injection, with a gamma camera (Large Field of View; Siemens Orbiter, Des Plaines, Ill) fitted with a low-energy, high-resolution collimator. Anterior and posterior 8-minute images of the abdomen and pelvis were recorded in analog and digital form. Pelvic outlet, or caudal, views were also obtained to distinguish bladder from rectal inflammation activities. Anterior views of the abdomen were obtained with the patient standing, to separate the liver from the transverse colon. At 2–4 hours after injection in all patients, an 8-minute anterior view of the abdomen was acquired.

Also at 2–4 hours after injection in 97 patients, single photon emission computed tomography (SPECT) was performed with a newly purchased double-headed camera (model dst-xl; SMV, Twinsburgh, Ohio). SPECT was performed with the following acquisition parameters: 30 seconds per stop; 60 stops; 120 projections; 1.6 magnification; Hanning-Nyquist prefilter, 1.515; cut-off, 1.315; Nyquist ramp filter, 1.515; cut-off, 1.31. SPECT was not performed in the 31 control subjects. Volume-rendered images were derived from the SPECT data by means of the maximum-activity-projection technique. When scan findings were equivocal, delayed imaging was performed at 6–8 hours and, rarely, at 24 hours, to differentiate active CD from late accumulation of 99mTc WBC in the right lower quadrant. Cinematic representations of some of the maximum-activity-projection 99mTc WBC images are available for review at our Internet site: http://128.147.46.201.

Analysis of Scans
To assess the sensitivity and specificity of 99mTc WBC scintigraphy with each set of scans (1/2 to 1 hour and 2–4 hours) in the 215 patients, the bowel was divided into eight segments (rectum, sigmoid, descending, transverse, ascending, cecum, terminal ileum, and small bowel). This resulted in 3,440 bowel segments to be scored (ie, eight segments x two images x 215 patients = 3,440 segments). The inflammatory activity in each segment on the planar images was graded semiquantitatively by one reviewer (M.C.) by comparing the uptake in the bowel with that in the liver and the bone marrow in the iliac crest (8–11). The following grading scale was used: grade 0, no inflammatory activity; grade 1, inflammatory activity less than that in the iliac crest; grade 2, activity similar to that in the iliac crest; grade 3, activity greater than that in the iliac crest; grade 4, activity equal to that in the liver; grade 5, activity greater than that in the liver; grade 6, activity equal to that in the spleen.

The grade of uptake on the planar images was compared with the endoscopic biopsy result. Planar, orthogonal SPECT, and maximum-activity-projection images were reviewed together on a workstation with ad lib manipulation of intensity scale, contrast, color scale, and cine display. Maximum-activity-projection images were used to help interpret the SPECT images (12–14).

A 99mTc WBC scintigram was considered false-negative if there was a difference in the degree of inflammation depicted and the result at endoscopic biopsy (ie, mild inflammation [grade 1 or 2] depicted but severe inflammation seen at colonoscopy). A 99mTc WBC scintigram was considered false-positive if it depicted increased uptake of 99mTc WBC in an area that was seen to be normal at endoscopic biopsy. Thus, 99mTc WBC scans in one patient with active gastrointestinal bleeding were considered to be false-positive despite movement of inflammatory activity over time at colonoscopy. Inflammatory activity seen at a colostomy or ileostomy site was excluded from analysis.


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Findings at 99mTc WBC Scintigraphy and Biopsy
In the 137 children with endoscopic biopsy results, the sensitivity of 99mTc WBC scintigraphy was 90%, the specificity 97%, the positive predictive value 97%, and the negative predictive value 93% (Table 2). The prevalence of disease was 53%, and the accuracy of 99mTc WBC scintigraphy was 93%. When children with miscellaneous colitis were excluded from analysis, the sensitivity of 99mTc WBC scintigraphy was 93% (57 of 61 patients). The number of normal (Fig 1) and positive and negative scans is also given in Table 2.


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  		TABLE 2. Results with 99mTc WBC Scintigraphy
 


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  		Figure 1a. Normal 99mTc WBC studies at (a) 30 minutes and (b) 3 hours.

 


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  		Figure 1b. Normal 99mTc WBC studies at (a) 30 minutes and (b) 3 hours.

 
In 128 of the 137 patients with a biopsy specimen, the intensity and location of inflammation were consistent with those on the 99mTc WBC scan (Figs 2, 3). In this group, there were two false-positive studies and seven false-negative studies (two in patients with CD, two with UC, and three with miscellaneous colitis). Note that four of the children with a false-negative 99mTc WBC study had normal laboratory values and a visually normal colonic mucosa during colonoscopy, with mild chronic inflammation seen at biopsy. These findings suggest that minute microscopic inflammation may not be scintigraphically evident. The remaining three false-negative 99mTc WBC studies were seen in children with miscellaneous colitis (three with autoimmune colitis), who had moderately to severely abnormal laboratory values and moderate to severe inflammation at colonoscopy.



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  		Figure 2. Abnormal uptake of 99mTc WBC in the terminal ileum (arrow) in a child with CD. The uptake is intense, bowel-shaped, and appears early (at 30 minutes). On the late scan (not shown), the uptake did not move or change shape, which suggests active inflammation (proved at endoscopic biopsy).

 


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  		Figure 3. Skip areas of inflammation (arrows) are depicted on the 99mTc WBC scans obtained in four children with CD (proved at endoscopic biopsy).

 
In five patients (two with CD, one with low probability, one with miscellaneous colitis), the 99mTc WBC studies underestimated the amount of inflammation in one segment; other segments were positive in these patients. Labeling efficiency in the false-negative 99mTc WBC study was greater than 50% and thus did not account for the lack of uptake. False-positive 99mTc WBC studies were seen in a child who was actively bleeding from the gastrointestinal tract and in a child with a new surgical anastomosis. In the patient with gastrointestinal bleeding, delayed images revealed movement of inflammatory activity in the distal bowel, a finding not suggestive of active inflammation.

No false-positive 99mTc WBC studies were seen in the 31 control subjects or in the 30 children in the low-probability group (SPECT images were normal) who had undergone biopsy. One child in the low-probability group had a rectal polyp with associated acute and chronic inflammation seen at biopsy, yet the 99mTc WBC scan was normal.

Surgery
The 99mTc WBC scan showed the same intensity and distribution of inflammation as was seen in the surgical specimens in all but one patient, in whom the scan underestimated the inflammation in the cecum while accurately showing inflammation in the rest of the colon.

One child's resected ileum and ascending colon showed an area of focal ulceration and increased lymphoid inflammatory cells within the lamina propria and inflammatory cells in the muscularis externa at the margin of resection. In this patient, the 99mTc WBC scan acquired after surgery correctly depicted increased accumulation of 99mTc WBC at the anastomotic site.

Another child underwent exploratory laparoscopy that revealed a macroscopically normal ileum, and 3 days later, a 99mTc WBC scan showed abnormal localization in the terminal ileum. Three days after the 99mTc WBC scan was acquired, colonoscopy revealed inflammation in the terminal ileum.

One of the children in the low-probability group underwent appendectomy, and both the pathologic specimen and the 99mTc WBC scan were normal.

Patients without Colonoscopic Data
In 75 (96%) of 78 children (39 with CD, 11 with UC, six with miscellaneous colitis, 22 with low probability [Table 1]) without recent endoscopic biopsy results, the laboratory values, gastroenterologist's initial assessment, and findings at clinical follow-up (average, 398 days) were consistent with the results at 99mTc WBC scintigraphy.

In the 39 children with CD and without recent endoscopic biopsy results, 38 studies were abnormal. In 37 of these children, the scan results were congruent with the laboratory values, gastroenterologist's initial assessment, and findings at clinical follow-up (average, 464 days). In the two children with positive 99mTc WBC studies that were not consistent with the findings at clinical follow-up, laboratory values were normal at presentation, and the prednisone dose was lowered. At clinical follow-up, however, these children did not experience any exacerbation of their symptoms. In three patients with CD, small-bowel uptake of 99mTc WBC was seen due to gastrointestinal bleeding. Uptake was also noted in an abdominal scar in a child who underwent surgery 9 days prior to scanning. In four different children, uptake of 99mTc WBC was seen at a stricture site, as documented at upper gastrointestinal and small-bowel follow-through examinations. Recent endoscopic biopsy results were not available to document the histologic nature of the strictured areas. Similarly, uptake was seen in a perirectal abscess and fistula in two children with CD. In four other children, uptake of 99mTc WBC was seen at an anastomotic site, and we could not differentiate active CD from normal inflammatory repair.

In all six children with miscellaneous colitis and 10 of the 11 children with UC, results at 99mTc WBC scintigraphy were congruent with laboratory values, the gastroenterologist's initial assessment, and clinical follow-up findings. In one child with UC, uptake of 99mTc WBC was seen in the right lower quadrant, and we could not exclude subclinical appendicitis or CD. In a 14-year-old girl with UC and known pancreatitis, the 99mTc WBC study did not show any uptake in the pancreas.

Twenty-one children in the low-probability group had a normal 99mTc WBC study, and there was no evidence of IBD on the basis of laboratory values or findings at clinical follow-up (average, 336 days). In one child in the low-probability group, 99mTc WBC uptake was seen in a loop of small bowel, but there was no clinical suggestion of IBD on the basis of findings at prolonged follow-up (558 days). In one child in this group, inflammatory activity was seen in a dilated ureter that could have been ascribed to small-bowel uptake.

Miscellaneous Colitis
The initial disease classification prior to 99mTc WBC scintigraphy was incorrect in two patients. The correct classifications were suggested by findings on the 99mTc WBC scan, and they were subsequently proved at surgery. One of these two patients was referred to our center with a diagnosis of UC, but the 99mTc WBC scan depicted small-intestine disease indicative of Crohn disease (Fig 4). Disease in the other patient was initially diagnosed as indeterminate colitis, but grade 3 rectosigmoid involvement and the lack of skip areas or small-intestine involvement helped correct prediction of the surgical diagnosis of UC.



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  		Figure 4a. CD depicted on 99mTc WBC scans. (a) At 3 hours after injection, inflammation is depicted in the terminal ileum (curved arrow) and small bowel (straight arrow). This pattern of uptake contrasts singularly with (b) the late physiologic excretion (mild ill-defined uptake) (arrowhead) seen in a different patient at 3 hours.

 


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  		Figure 4b. CD depicted on 99mTc WBC scans. (a) At 3 hours after injection, inflammation is depicted in the terminal ileum (curved arrow) and small bowel (straight arrow). This pattern of uptake contrasts singularly with (b) the late physiologic excretion (mild ill-defined uptake) (arrowhead) seen in a different patient at 3 hours.

 
In eight children, a segment with increased uptake of 99mTc WBC depicted on the SPECT and maximum-activity-projection images was depicted as normal on the planar images. In all these children, planar images depicted abnormal uptake of 99mTc WBC in other segments of the bowel (sum of scores for each segment, 24, 6, 9, 27, 18, 3, 12, 14, respectively). Three of these children underwent colonoscopy, which revealed very mild inflammation in the segment missed on the planar images.

In 11 other patients, SPECT and maximum-activity-projection images revealed uptake of 99mTc WBC at colostomy or ileostomy sites. We were able to identify all patients with active gastrointestinal bleeding on the basis of movement of inflammatory activity depicted over time, without interfering with the interpretation of inflammation in patients with IBD.

No side effect of 99mTc WBC was reported in any children. Among 120 of the 184 patients, 105 (88%) had abnormal 99mTc WBC studies at 30 minutes and 15 (12%) had abnormal studies only later.


   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
IBD is an important category of chronic gastrointestinal disease. The approach to treatment of a child with suspected IBD is intricate. The accuracy of colonoscopic diagnosis of IBD ranges from 80% to 90% (15–17). One weakness with colonoscopy and biopsy as the reference method is that the biopsy specimen may not be representative of an entire colorectal segment, particularly in patients with CD, in whom the inflammatory changes are often patchy. There appears to be no justification for repeated routine endoscopic assessment of colonic inflammation, since there is poor correlation between clinical symptoms and endoscopic and histologic findings (15,16). Endoscopic and radiologic methods of disease localization are more invasive than is 99mTc WBC scintigraphy, and they tend to produce more discomfort related to instrumentation and preparation for the procedure (eg, bowel cleansing). Moreover, several studies are needed to analyze the entire bowel, since colonoscopy cannot be used to analyze the entire small bowel.

A noninvasive technique is needed that can be used in the follow-up of pediatric patients. Scintigraphy with 99mTc WBC seems ideally suited to obtain a precise temporal snapshot of the distribution and intensity of inflammation, whereas radiographic modalities tend to depict more chronic changes. An additional advantage is high patient acceptability, especially in children. Patients prefer 99mTc WBC scintigraphy to barium follow-through study or enteroclysis. The effective dose equivalent for a 99mTc WBC study is approximately 3 mSv, whereas it is on the order of 6 mSv for a barium small-bowel follow-through study or 8.5 mSv for a barium enema examination (18). A positive 99mTc WBC study occurs by 30 minutes in most children (88%). The examination can be terminated if there is a clinical need.

Scintigraphy with 99mTc WBC has been reported to be sensitive for the detection of inflammation in adults (1,2,8–10,19–23) and small series of children (4,22,24,25). The correlation between scintigraphic and endoscopic findings is sufficiently close that scintigraphy can supplement left-side colonoscopy if total colonoscopy is technically impossible (2,8,10,26–30). Scintigraphy with 99mTc WBC may replace colonoscopy as a monitoring tool for inflammatory activity. Scintigraphy can also be used to document proximal extension of ulcerative proctosigmoiditis (31) (Fig 5) or postoperative recurrence of CD (32). Scintigraphy with 99mTc WBC is useful to assess the inflammatory component of a stricture seen on a small-bowel follow-through study.



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  		Figure 5. Multiple continuous 99mTc WBC projections from a three-dimensional cine display on our Internet site (see Materials and Methods) show separation of inflammatory activity in the rectum (arrow) from that in the bladder (arrowhead).

 
However, 99mTc WBC scintigraphy has limitations. It is not useful to define anatomic details such as strictures, prestenotic dilations, or fistulas, which are best evaluated with barium radiographic studies. In a patient with CD, distinction of the large from the small bowel can be difficult if the uptake is focal, since landmarks disappear. The presence of gastrointestinal bleeding during the 99mTc WBC study can complicate the interpretation of findings. Clearance of uptake from the initial site on the delayed images indicates the presence of gastrointestinal bleeding.

Our experience suggests that inflammation on a 99mTc WBC scan is bowel shaped, does not move on the late scan, and increases in intensity over time. Three-dimensional display of SPECT data by means of the maximum-activity-projection technique increases continuity of structures and facilitates understanding of spatial relationships (14). This technique, used routinely at our institution, has advantages and limitations that have been enumerated (12,13). Maximum-activity-projection images are not a substitute for SPECT images, and both sets of images should be reviewed together (12). In eight children, a segment of bowel with increased uptake of 99mTc WBC was depicted on only the SPECT and maximum-activity-projection images. On the planar images for these children, however, uptake of 99mTc WBC was abnormal in other bowel segments. Therefore, the routine use of SPECT is probably not indicated. The detection of one additional segment with minimal inflammation is unlikely to change patient treatment.

In this study, we found high accuracy for 99mTc WBC scintigraphy in the evaluation of inflammation in children with IBD. We compared the findings at 99mTc WBC scintigraphy to those at biopsy in three groups of children: patients with known IBD, control subjects, and patients with a low probability of IBD. This variation in pretest probability of disease allowed us to accurately calculate the positive and negative predictive values of 99mTc WBC scintigraphy in children with and children without IBD. Compared with the accuracy of colonoscopy (17), the accuracy of 99mTc WBC scintigraphy is more than 90%. Compared with the accuracy of laboratory values, the gastroenterologist's initial assessment, and clinical follow-up findings (15), the accuracy of 99mTc WBC scintigraphy is even higher, although in a small number of children there was no standard of reference that could corroborate the 99mTc WBC scan findings of uptake at fistulas and anastomoses. We had no false-positive 99mTc WBC scintigraphic findings in 79 control subjects, which helps confirm a high positive predictive value for 99mTc WBC scintigraphy. False-negative 99mTc WBC studies or scans that underestimated the amount of inflammation were seen in a few cases of early CD with a few small aphthoid ulcers and in cases of autoimmune colitis. In most of the children without recent endoscopic biopsy findings, laboratory values, the gastroenterologist's initial assessment, and clinical follow-up findings agreed with the 99mTc WBC scan findings.

In a few children, uptake of 99mTc WBC was depicted at anastomotic sites. Because of the lack of biopsy data at these sites, we could not document the nature of these findings. In a recent prospective study in 17 patients, Biancone et al (32) evaluated 99mTc WBC scintigraphy for the early detection of postoperative, asymptomatic recurrence of CD. They found the 99mTc WBC studies to be accurate. We observed focal uptake of 99mTc WBC in fistulas and in one polyp, as reported by others (33). Because of the punctiform nature of the findings, this is easily distinguishable from uptake in IBD. An exception is the presence of focal inflammatory activity near the cecum; the differential diagnosis then also includes appendicitis. Appendiceal involvement was recently reported (34–37) to occur in UC, and this could have been the case in one of our patients.

This study has three potential limitations. Colonoscopy is not a perfect standard of reference, and thus some discrepancies between 99mTc WBC scintigraphy and colonoscopy can be expected. Also, only one nuclear physician interpreted each scan blindly, albeit the scans are easy to interpret (Fig 6). Finally, SPECT data in this series were not obtained in control subjects. Since SPECT findings may decrease the specificity of 99mTc WBC scintigraphy, it is conceivable that we might have seen some false-positive results if SPECT had been performed in the control subjects. SPECT images were obtained in the low-probability group, however, and no false-positive results were seen.



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  		(a,b) Continuous uptake (arrows) is depicted on 99mTc WBC scans obtained in two different children with UC.

 


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  		(a,b) Continuous uptake (arrows) is depicted on 99mTc WBC scans obtained in two different children with UC.

 
In conclusion, 99mTc WBC scintigraphy is an accurate technique to assess inflammation in children with IBD. Scintigraphy should play an important role in the follow-up of IBD patients, especially in cases of suspected recurrence and in the monitoring of treatment, which would reduce the need for repeated colonoscopy. Scintigraphy with 99mTc WBC is a rapid, relatively painless test that requires no bowel preparation. The minimal invasiveness of 99mTc WBC scintigraphy makes it a practical modality for the evaluation of children with IBD. It is economical, and its diagnostic sensitivity is excellent.


   Acknowledgments
 
We thank Ricki Smith and Melanie Fitzgerald for their help with the manuscript. We also thank A. Delbert Bowen, MD, Thomas Foley, MD, Patty Murtha, PhD, David Townsend, PhD, and Nick Bohnen, MD, PhD, for their helpful comments about the manuscript.


   Footnotes
 
Abbreviations: CD = Crohn disease HMPAO = hexamethylpropylene- amine oxime IBD = inflammatory bowel disease UC = ulcerative colitis WBC = white blood cells

Author contributions: Guarantor of integrity of entire study, M.C.; study concepts and design, M.C., F.J.d.R., S.A.K.; definition of intellectual content, M.C., F.J.d.R., S.A.K.; literature research, M.C.; clinical studies, S.A.K., F.J.d.R.; data acquisition, M.C.; data analysis, M.C., F.J.d.R.; statistical analysis, M.C.; manuscript preparation, editing, and review, M.C., F.J.d.R., S.A.K.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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