technetium leukocyte imaging in inflammatory bowel disease

Technetium Leukocyte Imaging in Inflammatory Bowel Disease

Martin Charron, MD, FRCP (C)

AddressChildren’s Hospital of Pittsburgh, Department of Radiology, University of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.

Current Gastroenterology Reports 1999, 1:245–252Current Science Inc. ISSN 1522-8037Copyright © 1999 by Current Science Inc.

IntroductionInflammatory bowel disease (IBD) frequently begins inlate childhood or in adolescence. Usually it is diagnosed inchildren aged between 5 and 16 years (less than 5% ofcases are diagnosed in children younger than 5 years). Theetiologies of Crohn’s disease and ulcerative colitis areunknown, but positive family history of either is an impor-tant contributing association because as many as 20% ofpatients have an affected relative. Some features that distin-guish IBD in children and IBD in the adult population arehigher frequency of pancolonic involvement, likelihood ofproximal extension of distal disease, and risk for colec-tomy. Unpredictable exacerbation and remission and vari-able response to therapy characterize ulcerative colitis andCrohn’s disease. Current methods used for diagnosis andmonitoring of therapy are imperfect.

Diagnosis of inflammatory bowel disease in childrenThe approach to the child thought to have IBD has beenchallenging. Because children may not have had serioushealth problems before the onset of IBD, it is essential torecognize the emotional impact of intrusive routine diag-nostic studies such as rectal examinations, radiographs,and endoscopy [1]. For many years, the barium enema wasthe cornerstone of diagnostic testing; recently, colonoscopyhas been used more often. Colonoscopic diagnoses of IBDare not 100% accurate [2–4].

Monitoring responses to medical therapyIn addition to initial diagnosis, monitoring disease inresponse to therapy has been difficult. Complex clinicaltools such as the Disease Activity Index of Lloyd-Still andGreen [5] and the Pediatric Disease Activity Index [6] havebeen developed to quantify disease activity. Erythrocytesedimentation rate (ESR) is abnormal in approximately85% of patients at diagnosis and in 35% of patients duringthe course of the disease, therefore impeding the accuracyand clinical value of these indices.

There is poor correlation between the anatomic find-ings depicted by computed tomography (CT) or contraststudies and the disease activity in patients with IBD [7,8].Radiographic findings of patients with mild to moderatecolitis are usually normal and require more radiation thanTechnetium imaging [9]. Endoscopy is more sensitive thanradiology, and allows for the histologic evaluation of tissue.

Evaluation with Technetium-99m White Blood Cell ImagingTechnetium has recently been shown to radiolabel leuko-cytes in vitro. Technetium labeling has many theoreticaladvantages over 111In oxime-labeled white blood cell (WBC)imaging, including better image quality, briefer acquisitiontime, lower radiation dose, and lower cost [10,11]. Radiationexposure with technetium labeling is approximately onethird what it is with 111In-WBC imaging. Pragmatic consider-ation of the biodistribution of 99mTc-WBC imaging includeslung activity that is partially cleared by 4 hours, incompleteelution of 99mTc (excreted in the urine), and visualization ofthe gallbladder in approximately 4% to 10% of patients. Thenormal distribution with 99mTc-WBC imaging is character-ized by uptake in the lungs, liver, spleen, bone marrow, kid-neys, and bladder (Fig. 1).

Technetium-99m white blood cell (99mTc-WBC) imaging has been part of the initial evaluation and follow-up of more than 400 children presenting with inflammatory bowel disease (IBD) at Children’s Hospital of Pittsburgh. Studies have sug-gested that 99mTc-WBC imaging is superior to contrast radi-ology in assessing the extent and activity of IBD. With only one examination, 99mTc-WBC imaging is ideally suited to obtain a precise temporal snapshot of the distribution and intensity of inflammation, whereas radiography tends to detect more chronic changes. There is a high correlation between 99mTc-WBC imaging findings and those of endos-copy. When total colonoscopy cannot be completed satisfac-torily or when contrast radiography findings are negative or equivocal, scintigraphy can confirm the presence of ileitis or right-sided colitis. Occasionally, 99mTc-WBC imaging is use-ful in differentiating Crohn’s disease from ulcerative colitis. Some studies have suggested that 99mTc-WBC imaging is useful as an initial screening modality to exclude IBD. Techne-tium-99m WBC imaging is noninvasive, practical, safe, requires no bowel preparation, and entails less radiation exposure than contrast radiology or computed tomography.

246 Pediatric Gastroenterology

Imaging protocolTechnetium-99m labeling of leukocytes from 20 to 45 mL ofvenous blood has been described [12]. Imaging is performedwith a gamma camera at 0.5 to 1 hour and at 2 to 3 hoursafter the intravenous injection of 99mTc-WBC. Anterior 8-minute and posterior 5-minute images of the abdomen andpelvis are recorded in digital form at 30 minutes. In our expe-rience [13], most studies (88%) are positive by 30 minutes,and the test can be terminated if necessary. Perianal and rec-tal diseases are easily detected by the caudal projection or bysingle photon emission CT, which separates the perianal andrectal areas from the bladder and can cause them to overlapwith the anterior projection (three-dimensional 99mTc-WBCimages are available for review at the website HTTP://128.147.46.201) [12,14••]. An anterior view of the abdo-men with the patient in a standing position is obtained todistinguish the liver from the transverse colon. The patientshould void before any imaging technique.

Timing of imagingBecause the exact timing of the first and second sets ofimages is controversial, timing varies from institution toinstitution [15]. In a series of 87 patients, Lantto et al. [11]found 88% sensitivity for detecting IBD and abdominalinfection at 30 minutes and 95% sensitivity for detectingthem at 2 hours. However, delayed imaging is associatedwith the late physiologic excretion of 99mTc-WBC in theright lower quadrant (Fig. 2). This was thought to affectadversely the accuracy of abdominal imaging [11,16–18].These concerns led to the suggestion by many to havepatients undergo imaging early after the injection of 99mTc-WBC to decrease the number of false-positive findings. Inother reports, physiologic bowel uptake was not notedbefore 2 hours and was rarely seen at 3 hours [12,19–23].Late accumulation (seen in 19% of our control group[24•]) is probably caused by the biliary excretion of non-cell–bound, 99mTc-labeled secondary hydrophilic com-plexes. With time, because of bowel peristalsis, these com-plexes eventually accumulate and concentrate sufficientlyto be visualized only on the late 4-hour scans. We have

characterized the patterns that permit identification of thislate physiologic excretion and its differentiation fromactive inflammation [24•]. One essential criterion to iden-tify this physiologic activity is its migration to distal seg-ments. Obviously, this does not apply to segmentsinvolved in acute inflammatory exacerbation of IBD. Addi-tionally, the intensity of uptake in IBD is higher than thephysiologic excretion of 99mTc-WBC [24•]. Our experiencewith more than 400 children suggests that in most patientsthis free activity is in the distal small bowel at 2 to 3 hoursand that it migrates to the cecum at approximately 4 hours.When these free complexes are in the distal small bowel, adistinct shape that indicates a bowel segment cannot beidentified because of the amalgam of segments. In sum-mary, the physiologic late accumulation of 99mTc-WBC inthe right lower quadrant is characterized by accumulationat 3 hours or sooner, no accumulation in other segments ofthe bowel, faint accumulation of lesser intensity than inthe iliac crest, diffuse accumulation pattern, and migrationof 99mTc-WBC to the cecum. Recognition of this excretionpattern assures the accurate differentiation of activeCrohn’s disease of the small bowel from the migration andaccumulation of 99mTc-WBC in the right lower quadrant ofthe abdomen.

Technetium-99m WBC scintigraphy versus colonoscopy in children with inflammatory bowel diseaseThe outcome for patients with inflammatory bowel diseasedepends on the severity of disease and the extent of coloninvolvement. Thus, colonoscopy with biopsy has been thecriterion by which to evaluate IBD. However, it has manylimitations. In a large series of 606 patients, Pera et al. [4]found colonoscopy to be 89% accurate for the assessmentof IBD. Moreover, there is no role for repeat colonoscopybased on the severity of inflammation in Crohn’s diseasebecause endoscopic appearance correlates poorly withclinical remission, either in response to drug therapy [3] orafter surgery [25]. Additionally, endoscopic methodsrequire sedation, involve some instrumentation risks, andonly evaluate a finite length of the terminal ileum.

We evaluated retrospectively the sensitivity and speci-ficity of 99mTc-WBC scintigraphy for detecting colonicinflammation in 215 children with and without IBD[14••]. We reviewed the 99mTc-WBC scans and analyzeduptake in 3440 bowel segments. The 99mTc-WBC scanswere interpreted blindly and were compared withcolonoscopy results and biopsy specimens (Fig. 3). In 78children who did not recently undergo colonoscopy,99mTc-WBC findings were compared with long-term clini-cal follow-up, laboratory values, and the gastroenterolo-gist’s initial clinical assessment. Histology and 99mTc-WBCscans correlated in 128 of 137 children with availablebiopsy specimens. There were seven false-negative and twofalse-positive results; sensitivity was 90%, specificity was97%, positive predictive value was 97%, negative predic-

Figure 1. Normal biodistribution of 99mTc-WBC. Anterior and poste-rior images of the abdomen.

Technetium Leukocyte Imaging in Inflammatory Bowel Disease • Charron 247

tive value was 93%, prevalence of disease was 53%, andoverall accuracy was 93%. Table 1 summarizes the data inthese patients. The false-negative 99mTc-WBC results thatunderestimated the amount of inflammation were seen ina few patients with early-stage Crohn’s disease, small aph-toid ulcers, or autoimmune colitis. There were no false-positive results in 79 control subjects. We concluded that99mTc-WBC imaging is a useful noninvasive diagnostic testto determine the extent and distribution of inflammationin children with IBD. Similar rates of accuracy of 99mTc-WBC scintigraphy in children with IBD were reported byother groups [26••, 27••,28,29•].

Assessment of the small bowelIn approximately 30% to 40% of patients, Crohn’s dis-ease involves the terminal ileum alone and spares thelarge bowel [30]. Current techniques to evaluate the ter-minal ileum have limitations. In approximately 20% ofpatients, the terminal ileum is inaccessible to evaluationeven by an experienced endoscopist because of technicallimitations such as scars, strictures, inflammation, andtechnical difficulty [31].

Endoscopic and radiologic methods of disease localiza-tion produce discomfort related to instrumentation or topreparation for the procedure (eg, bowel cleansing), andseveral studies are needed to analyze the entire bowel. Flu-oroscopic methods show only indirect evidence of inflam-mation (edema, fibrosis, and ulceration) and entail

considerable radiation exposure. The effective dose equiva-lent for 99mTc-WBC imaging is approximately 3 mSv,whereas it is approximately 6 mSv for barium small bowelfollow-through or 8.5 mSv for barium enema.

An alternative technique to assess inflammation lim-ited to the terminal ileum would be valuable. 99mTc-WBCimaging quantifies and localizes inflammation directlywhile it overcomes the disadvantages of fluoroscopy andendoscopy, and it provides information about the colon orthe small bowel that cannot be visualized directly bycolonoscopy.

Figure 2. A, Late accumulation of 99mTc-WBC on the 3-hour image in the right lower quadrant (see text for criteria). B, Image from a 14-year-old boy with Crohn's disease under hospital care for pain and diarrhea. His medi-cation regimen included 30 mg prednisone daily and 1 g Pentasa three times a day. His white blood cell count was normal at 4.2. The image, at 30 minutes, shows increased uptake; it is shaped like a bowel segment (ter-minal ileum) and is easy to differentiate from false-positive activity (a).

Figure 3. Image from a 14-year-old girl with ulcerative colitis who came to the emer-gency room with bloody stool and hypovolemia. Her erythrocyte sedimen-tation rate was 20, hematocrit level was 20, and albumin count was 2.4.The patient underwent a colectomy that revealed complete colitis in association with the diffuse colonic increased uptake of 99mTc-WBC noted in this image.

Table 1. Accuracy of Technetium-99m White Blood Cell Imaging for Inflammatory Bowel Disease

Crohn's disease Ulcerative colitis Indeterminate colitis Total*

No. biopsies 41 22 12 137Sensitivity (%) 93 95 67 93Specificity (%) 98 95 92 98

*PN and controls: 58


We evaluated the value of 99mTc-WBC scintigraphy foridentifying the terminal ileum in children with Crohn’sdisease who underwent colonoscopy a few days beforeimaging [32•]. It detected inflammation in the terminalileum of 21 patients in whom the endoscopist did not can-nulate the terminal ileum. Of the 19 patients in whom theterminal ileum was visualized endoscopically or surgically,99mTc-WBC scintigraphy revealed similar degrees ofinflammation in 17. In 10 of these 21 children in whomthe gastroenterologist did not reach the terminal ileum,findings on 99mTc-WBC imaging were abnormal. In chil-dren who did not undergo ileoscopy, results of 99mTc-WBCimaging were consistent with laboratory values, clinicalassessment, and long-term clinical follow-up. When totalcolonoscopy or ileoscopy cannot be satisfactorily com-pleted, scintigraphy can confirm the presence of ileitis orright-sided colitis.

Technetium-99m WBC scintigraphy versus upper gastrointestinal seriesThe accuracy of radiographic studies to evaluate the inten-sity of inflammation of the small bowel is poor [7,8]. In aprospective study of 110 patients with radiologic confirma-tion of ileitis, suspicion of inflammation was rejected in 28patients [33]. In one series [34], lymphoid nodular hyper-plasia was found in 24% of patients after barium smallbowel follow-through examinations to investigate IBD[34]. This finding can be confused diagnostically withCrohn’s disease [33–36]. Although Crohn’s disease maybecome progressively more severe within the confines ofits site of origin, its anatomic extent rarely changes. For thisreason, there is no need for follow-up barium studies.Careful endoscopic and histologic evaluations of a radio-graphically normal bowel frequently reveal signs of inflam-mation [37,38]. Radiologic findings tend to persist forweeks after the acute flare-up of inflammation. Thus,radiologic findings have a poor correlation with the inten-sity of inflammation in children with IBD.

In a retrospective evaluation of 35 children with IBD,Jewell et al. [39•] compared 99mTc-WBC imaging to endos-copy and barium study and found the imaging sensitive forthe presence or flare-up of IBD in children; in fact, 99mTc-WBC imaging performance exceeded that of barium stud-ies. Jobling et al. [27••] prospectively compared 99mTc-WBC imaging to endoscopy and to barium enema andfound a greater sensitivity with 99mTc-WBC scintigraphy(90%) than with barium enema (42%). They concludedthat there was no role for barium studies in the initialwork-up of patients thought to have IBD. In our experi-ence, 99mTc-WBC imaging is superior to radiology for eval-uating the intensity and location of inflammation. In asubgroup of children studied at our institution, 19 of 26(73%) abnormal findings on 99mTc-WBC imaging (docu-mented by biopsy specimens) were normal on upper gas-trointestinal (UGI) studies (Charron, Unpublishedobservations). In children with true-negative results of

99mTc-WBC imaging, there were 24 true-negative results ofUGI-small bowel follow-through and four equivocalresults (lymphoid nodular hyperplasia vs Crohn’s disease).In adults, studies have also suggested that 99mTc-WBCimaging is superior to contrast radiology in assessing theextent and activity of IBD [20,40].

The radiation dose from a 99mTc-WBC study is half thedose from a barium small bowel follow-through study [9].The 99mTc-WBC scan seems ideally suited as a precise tem-poral snapshot of the distribution [41] and intensity ofinflammation in the large and small bowels, whereasradiographic modalities of investigation tend to representmore chronic changes [42–44]. Occasionally, 99mTc-WBCimaging can help characterize equivocal findings on theUGI-small bowel follow-through study [33].

Disease intensityAssessment of inflammation intensity in patients with IBDhas been the object of complex clinical and laboratoryscores. Because it labels the child’s own leukocytes, 99mTc-WBC imaging is a good indicator of the intensity of inflam-mation, and it provides a precise snapshot of the amountof inflammation at a precise moment. Other markers ofinflammation, such as radiology studies and ESR values,are indicative of more chronic changes.

An early report scrutinized disease intensity in 27 chil-dren with IBD [45••]. Scan score was calculated by com-paring tracer uptake in five bowel segments with iliac crestbone marrow activity. The clinical scoring system forchronic IBD described by Lloyd-Still and Green [5] wasused for children with Crohn’s disease and for control sub-jects without IBD, with some modifications. The clinicalactivity score for the 17 patients with Crohn’s disease andthe four control patients was correlated with the overallscan score. The scan score correlated more accurately withclinical disease activity (r = 0.62) than with ESR value (r =0.24). This excellent correlation between imaging scoreand clinical activity index indicates that 38% of the vari-ability of the clinical score is related to the variability of theimaging score. From this small series, it appeared that99mTc-WBC scintigraphy was useful for the evaluation ofdisease intensity in children with IBD. These results wereduplicated by Papos et al. [28], who reported that scinti-graphic activity correlated well with laboratory parameters(r = 0.82; P < 0.001), and by others [27••,39•].

Differentiation of ulcerative colitis from Crohn’s diseaseOnce a diagnosis of inflammatroy bowel disease has beenestablished, the differentiation between Crohn’s diseaseand ulcerative colitis can be a challenging, sometimesimpossible, chore. Ulcerative colitis and Crohn’s diseasecan usually be distinguished from one another by histo-logic characteristics, radiographic features, endoscopic fea-tures, and clinical presentation. However, as many as 20%to 25% of cases defy classification. It is essential to establish


a precise diagnosis because of the clinical issues of long-term prognosis and, more importantly, because of decisionsregarding colectomy.

We reviewed our data to validate the ability of 99mTc-WBC imaging to differentiate Crohn’s disease from ulcer-ative colitis [46•]. Blinded to the diagnoses, we interpretedthe scans as showing continuous colitis, discontinuous coli-tis, or no colitis. In 76 children with Crohn’s disease, thescans correctly revealed discontinuous colitis in 65 patientsand continuous colitis in 11. For the 29 patients with activeulcerative colitis, four scans (showing mild uptake) incor-rectly revealed discontinuous uptake of 99mTc-WBC. Allcontrol scans were interpreted as showing no colitis. Insummary, our experience suggests that unless inflammationis mild, 99mTc-WBC imaging is often reliable in distinguish-ing discontinuous colitis from continuous colitis.

Technetium-99m WBC as a screening modality for inflammatory bowel diseaseHow to screen for the presence of a specific disease in a dis-crete patient population can be debated epidemiologicallyand epistemologically ad infinitum. Because of some well-delineated limitations of colonoscopy, we believed there wasa role for a noninvasive technique. Therefore, we conducted aretrospective study (Charron, Unpublished data) to assesswhether 99mTc-WBC scintigraphy can exclude inflammationin children without IBD. The population studied consisted of303 children who underwent 99mTc-WBC imaging, including129 children who underwent it to exclude IBD and 46 con-trol subjects. Of the 129 children studied to exclude IBD, thefinal diagnoses (based on colonoscopy and biopsy speci-mens) were Crohn’s disease in 27, ulcerative colitis in nine,miscellaneous colitis in 13, and probably no disease in 80.The 99mTc-WBC scans indicated IBD in 45 of 129 (35%) chil-dren thought to have IBD. They were positive in all but threepatients newly diagnosed with Crohn’s disease, ulcerativecolitis, or miscellaneous colitis. In children with suspectedIBD, 99mTc-WBC imaging, when compared to endoscopyand biopsy, had a sensitivity of 93%, a specificity of 97%, apositive predictive value of 98%, a negative predictive valueof 98%, and an accuracy of 96%. These results suggest that99mTc-WBC imaging is useful as an initial screening modalityto exclude IBD. A negative 99mTc-WBC imaging result in apatient with bowel symptoms virtually excludes IBD. Con-versely, a positive 99mTc-WBC result suggests IBD. When the99mTc-WBC scintigraphy result is positive, the patient shouldundergo colonoscopy for additional characterization of thehistopathologic nature of the colitis. We proposed that99mTc-WBC scintigraphy be one of the initial diagnosticmodalities used for any patient with suspected IBD.

In a retrospective study [29•], 99mTc-WBC scintigraphywas assessed as an initial imaging investigation in evaluat-ing children with suspected IBD. Forty-two new patientscame for evaluation of suspected IBD. Seven scan resultswere abnormal. Combination histology and barium exam-inations confirmed IBD. Of the remaining 35 scans, three

results were abnormal and 32 were normal. None of thepatients were subsequently confirmed to have IBD. Theseresults show that in detecting active IBD, a positive 99mTc-WBC scan has 100% sensitivity (24 of 24) and 91% speci-ficity (32 of 35) for the diagnosis of IBD.

Distribution of diseaseDetermining the extent of inflammation in patients withinflammatory bowel disease is important for several reasons.The intensity of therapy can be customized according to dis-ease. Retention enemas of 5-aminosalicylic acid can be usedfor disease that does not extend beyond the splenic flexure.The risk for carcinoma is higher in a patient with ulcerativecolitis than in a patient with pancolitis. A localized segment isamenable to localized surgery and eliminates the need forextensive resection. Farmer et al. [30], in their initial report,stressed the importance of disease localization as a predictorof the clinical pattern that patients could expect. Patients withCrohn’s ileocolitis have poorer responses to pharmacother-apy than do those with only involvement of the small bowel[41]. Patients with small bowel involvement often require a 5-aminosalicylic acid preparation, such as Pentasa (HoechstMarion Roussel, Kansas City, MO), that is activated in thesmall bowel and provides an anti-inflammatory effectthroughout the intestinal tract. Although both Crohn’s dis-ease and ulcerative colitis are chronic diseases amenable topharmacotherapy, surgery is only curative for ulcerative coli-tis. Previous reports of patterns of anatomic gastrointestinalinvolvement in children with Crohn’s disease were based onradiographic evaluation [41] and underestimated the extentof active inflammation.

The distribution of 99mTc-WBC uptake in bowel seg-ments of many children with IBD was studied (Table 2)[41]. In children with Crohn’s disease, uptake involved thesmall bowel alone in 18% of patients, the large bowel alonein 44% of patients, and large and small bowels in 38% ofpatients. In children with ulcerative colitis, uptake involvedthe entire colon in 50% of patients, extended farther thanthe sigmoid in 27% of patients, and was limited to the sig-moid colon–rectum in 23% of patients (Fig. 4). The distri-bution of 99mTc-WBC uptake in different bowel segmentsin patients with IBD was similar to what had been reportedhistologically and endoscopically [41]. In 18% of childrenonly the small bowel was involved, roughly half of whathad been reported in adults [41]. More than half the chil-dren with Crohn’s disease had abnormal accumulations of99mTc- WBC uptake in the ascending colon.

Miscellaneous applicationsThe clinical role of Technetium-99m WBC scintigraphywas recently examined in the treatment of children withinflammatory bowel disease [26••]. For 20 of 24 chil-dren, 99mTc-WBC scans were abnormal, prompting moreaggressive management in 15 (75%) of them. Six of the15, who were receiving maximum medical therapy,underwent surgical resection of severely affected bowel


segments, and medical treatment was intensified in theother nine. The remaining five patients were receivingoptimal medical therapy, instituted at their recent visit,and did not require additional medication adjustments.The author concluded that 99mTc-WBC imaging is a safeand useful diagnostic adjunct for the subsequent evalua-tion of patients known to have IBD [26••].

Technetium-99m WBC imaging is useful in definingthe degree of inflammation in narrowed bowel seg-ments. Determining whether inflammation or strictureis the cause for narrowing is helpful in patient manage-ment because medical management is more likely to besuccessful with the former [45••]. Occasionally, 99mTc-WBC imaging reveals active disease limited to precisesegments of the bowel that are amenable to surgicalresection. Similarly, in patients with terminal ileumresection and diarrhea, 99mTc-WBC imaging can deter-mine whether the diarrhea is caused by bile salt loss or arecurrence of IBD. Rates of postsurgical recurrence maybe as high as 100% [31]. Identifying the complicationsof IBD, such as abscesses and fistulas, is possible. Itappears likely that 99mTc-WBC imaging can be used as amonitoring tool for inflammatory activity in lieu ofcomplex scores [15]. Scintigraphy can also be used todocument the proximal extension of ulcerative proc-tosigmoiditis [47] or the postoperative recurrence ofCrohn’s disease [48].

Advantages and disadvantagesTechnetium-99m WBC imaging is noninvasive and can beused to evaluate the entire bowel in one study. It producesless radiation exposure than barium radiography and, thus,is useful when repeat evaluations are necessary [9]. The over-all cost for endoscopy in children is higher than that for99mTc-WBC imaging ($3500 vs $800 at our institution)[45••]. Even in acutely ill patients who may not tolerateendoscopic or radiologic studies, 99mTc-WBC imaging ispractical and safe. The correlation between colonoscopy and99mTc-WBC imaging for the localization and evaluation ofthe extent of inflammation is excellent, and 99mTc-WBCimaging is superior to radiology procedures at showing thecorrect intensity and location of inflammation. 99mTc-WBCimaging seems ideally suited for obtaining a precise tempo-ral snapshot of the distribution [41] and intensity of inflam-mation in the large and small bowels, whereas radiographicmodalities of investigation tend to represent more chronicchanges [42–44]. An additional advantage of 99mTc-WBCscintigraphy is high patient acceptability, especially amongchildren (Fig. 5). The images are easy to interpret, they showthe continuity of structures, and they allow better differenti-ation between the small and large bowels. 99mTc-WBC imag-ing can be performed easily and should be readily availablein any of the 5000 facilities with nuclear medicine equip-ment in the United States.

However, 99mTc-WBC scintigraphy has well-docu-mented limitations. It is not useful for defining anatomicdetails seen in strictures, prestenotic dilations, or fistulas,which are best evaluated by barium radiography. Scans donot allow for histologic evaluation, which may be neces-sary to confirm a diagnosis and exclude entities such aseosinophilic gastroenteritis, lymphoma, adenocarci-noma, or cytomegalovirus colitis. If a gastrointestinalbleed occurs simultaneously with 99mTc-WBC imaging, itcan confound the interpretation of the findings. In rareinstances a repeat study may be necessary if a patient hashad massive gastrointestinal bleeding.

ConclusionsAfter evaluating more than 400 children through the use of99mTc-WBC scintigraphy, our pediatric gastroenterologistconsiders this modality to be the criterion by which toestablish or exclude the diagnosis of inflammatory boweldisease. At Children’s Hospital of Pittsburgh, we often use99mTc-WBC imaging in the initial work-up of the childthought to have IBD. It is highly useful in the child withsubtle signs suggestive of IBD (such as abdominal pain,mild diarrhea, and decreased oral intake) in whom labora-tory test results are either normal or slightly abnormal. Inthose cases, a negative 99mTc-WBC scan may be reassuringfor family and physician and may avert unnecessary endo-scopic investigations. In addition, in the child in whom fullcolonoscopy may not be completed successfully, we rou-

Table 2. Distribution of Uptake of Technetium-99m White Blood Cell Imaging in Bowel Segment

Crohn's disease (%)

Ulcerative colitis (%)

Terminal ileum 56 0Ascending colon 53 50Transverse colon 44 69Descending 54 73Rectum 36 81

Figure 4. Anterior planar images of the abdomen show increased activity in the transverse and descending colon in a child with ulcer-ative colitis. It is diffi-cult to assess whether there is activity in the rectum because of overlap-ping bladder activity.


tinely use the 99mTc-WBC imaging to clarify the extent ofinflammation in the proximal part of the bowel.

Among the other compelling advantages of imagingwith 99mTc-WBC scintigraphy are the lack of need for spe-cial patient or bowel preparation, the ability to evaluate thesmall bowel and the large bowel simultaneously, and thesafety of this imaging technique in acutely ill children. It isrelatively noninvasive and economical compared withendoscopy. In conclusion, 99mTc-WBC imaging is a highlyuseful tool to evaluate IBD in children, and it should beadded to the clinician’s investigative armamentarium.

References and Recommended ReadingPapers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

1. Kirschner BS: Ulcerative colitis and Crohn’s's disease in chil-dren: diagnosis and management. Gastroenterol Clin North Am 1995, 24:99–117.

2. Gomes P, du Boulay C, Smith CL, Holdstock G: Relationship between disease activity indices and colonoscopic findings in patients with colonic inflammatory bowel disease. Gut 1986, 27:92–95.

3. Landi B, Anh TN, Cortot A, et al.: Endoscopic monitoring of Crohn’s's disease treatment: a prospective, randomized clini-cal trial: the Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Gastroenterology 1992, 102:1647–1653.

4. Pera A, Bellando P, Caldera D, et al.: Colonoscopy in inflam-matory bowel disease: diagnostic accuracy and proposal of an endoscopic score. Gastroenterology 1987, 92:181–185.

5. Lloyd-Still JD, Green OC: A clinical scoring system for chronic inflammatory bowel disease in children. Dig Dis Sci 1979, 24:620–624.

6. Hyams JS, Ferry GD, Mandel FS, et al.: Development and vali-dation of a pediatric Crohn’s's disease activity index. J Pediatr Gastroenterol Nutr 1991, 12:439–447.

7. Kjeldsen J, Schaffalitzky de Muckadell OB: Assessment of dis-ease severity and activity in inflammatory bowel disease. Scand J Gastroenterol 1993, 28:1–9.

8. Macfarlane PI, Miller V, Ratcliffe JF: Clinical and radiological diagnosis of Crohn’s's disease in children. J Pediatr Gastroen-terol Nutr 1986, 5:87–92.

9. Shields RA, Lawson RS: Effective dose equivalent. Nucl Med Commun 1987, 8: 851–855.

10. Lantto E, Jarvi K, Krekela I, et al.: Technetium-99m hexamethyl propylene amine oxine leucocytes in the assessment of dis-ease activity in inflammatory bowel disease. Eur J Nucl Med 1992, 19:14–18.

11. Lantto EH, Lantto TJ, Vorne M: Fast diagnosis of abdominal infections and inflammations with technetium-99m-HMPAO labeled leukocytes. J Nucl Med 1991, 32:2029–2034.

12. Charron M, Orenstein SR, Bhargava S: Detection of inflamma-tory bowel disease in pediatric patients with technetium-99m-HMPAO-labeled leukocytes. J Nucl Med 1994, 35:451–455.

13. Charron M, Del Rosario JF, Kocoshis S: Comparison of the sen-sitivity of early versus delayed imaging with Tc-99m HMPAO WBC in children with inflammatory bowel disease. Clin Nucl Med 1998, 23:649–653.

14.•• Charron M, Del Rosario JF, Kocoshis S: Assessment of pediatric inflammatory bowel disease with 99mTc-WBC. Radiology 1999, in press.

This series evaluates retrospectively the accuracy of 99mTc-WBC scin-tigraphy in 215 children and compares it with colonoscopy and biopsy. The three-dimensional technique is discussed in detail.15. Kipper S: Radiolabeled leukocyte imaging of the abdomen. In

Nuclear Medicine Annual 1995. Edited by Freeman L. New York: Raven Press; 1995:81–128.

16. Roddie ME, Peters AM, Danpure HJ, et al.: Inflammation: imaging with Tc-99m HMPAO-labeled leukocytes. Radiology 1988, 166:767–772.

17. Hotze A, Briele B, Wolf F, et al.: Localization and activity of inflammatory bowel disease using 111In leukocyte imaging. Nuklearmedizin 1988, 27:83–86.

Figure 5. Three-dimensional images show separation of the bladder from the rectum on frames A through F.


18. Peters AM, Roddie ME, Danpure HJ, et al.: 99Tcm-HMPAO labelled leucocytes: comparison with 111In-tropolonate labelled granulocytes. Nucl Med Commun 1988, 9:449–463.

19. Arndt JW, van der Sluys Veer A, Blok D, et al.: Prospective com-parative study of technetium-99m-WBCs and indium-111-granulocytes for the examination of patients with inflamma-tory bowel disease. J Nucl Med 1993, 34:1052–1057.

20. Kennan N, Hayward M: Tc HMPAO-labelled white cell scintig-raphy in Crohn’s's disease of the small bowel. Clin Radiol 1992, 45:331–334.

21. Laitinen R, Tahtinen J, Lantto T, Vorne M: Tc-99m labeled leu-kocytes in imaging of patients with suspected acute abdomi-nal inflammation. Clin Nucl Med 1990, 15:597–602.

22. Li DJ, Middleton SJ, Wraight EP: 99Tcm and 111In leucocyte scintigraphy in inflammatory bowel disease. Nucl Med Com-mun 1992, 13:867–870.

23. Vilien M, Nielsen SL, Jorgensen M, et al.: Leucocyte scintigra-phy to localize inflammatory activity in ulcerative colitis and Crohn’s's disease. Scand J Gastroenterol 1992, 27:582–586.

24.• Charron M, Del Rosario JF, Kocoshis SA: Characterization of late abdominal accumulation of 99Tcm-HMPAO leukocytes in a large population of children. Nucl Med Commun 1998, 19:753–759.

This study establishes criteria to identify false-positive excretions of 99mTc-WBC in the right lower quadrant at 4 hours.25. Olaison G, Smedh K, Sjodahl R: Natural course of Crohn’s's

disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms [see comments]. Gut 1992, 33:331–335.

26.•• Del Rosario MA, Fitzgerald JF, Siddiqui AR, et al.: Clinical appli-cations of technetium Tc 99m hexamethyl propylene amine oxime leukocyte scan in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1999, 28:63–70.

Experience with 99mTc-WBC imaging is examined and its clinical applications are evaluated in this study of the treatment of 35 patients with inflammatory bowel disease.27.•• Jobling JC, Lindley KJ, Yousef Y, et al.: Investigating inflamma-

tory bowel disease: white cell scanning, radiology, and colonoscopy. Arch Dis Child 1996, 74:22–26.

This study evaluates prospectively the different methods of bowel examination for patients thought to have inflammatory bowel dis-ease. 99mTc-WBC imaging proved to be sensitive, specific, and nonin-vasive and was recommended as the first line of investigation. The role of barium imaging, with its high radiation burden and relatively low sensitivity, must be redefined. Colonoscopy, combined with endoscopic biopsy, has a high detection rate at facilities with the nec-essary expertise.28. Papos M, Varkonyi A, Lang J, et al.: HM-PAO-labeled leukocyte

scintigraphy in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1996, 23:547–552.

29.• Shah DB, Cosgrove M, Rees JI, Jenkins HR: The technetium white cell scan as an initial imaging investigation for evaluat-ing suspected childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1997, 25:524–528.

In this retrospective study to examine 99mTc-WBC imaging as an ini-tial tool to evaluate children with suspected inflammatory bowel dis-ease, results showed that it is very useful for select patients.30. Farmer RG, Hawk WA, Turnbull RB Jr: Clinical patterns in

Crohn’s's disease: a statistical study of 615 cases. Gastroenter-ology 1975, 68:627–635.

31. Quinn PG, Binion DG, Connors PJ: The role of endoscopy in inflammatory bowel disease. Med Clin North Am 1994, 78:1331–1352.

32.• Charron M, Del Rosario JF, Kocoshis S: Assessment of terminal ileal and colonic inflammation in Crohn’s's disease with tc99m-wbc. Acta Paediatrica 1999, 88:193–198.

This article reviews the limitations of ileoscopy and demonstrates the role of 99mTc-WBC scintigraphy to assess the terminal ileum.

33. Coremans G, Rutgeerts P, Geboes K, et al.: The value of ileoscopy with biopsy in the diagnosis of intestinal Crohn’s's disease. Gastrointest Endosc 1984, 30:167–172.

34. Lipson A, Bartram CI, Williams CB, et al.: Barium studies and ileoscopy compared in children with suspected Crohn’s's dis-ease. Clin Radiol 1990, 41:5–8.

35. Bartram CI, Halligan S: Radiological investigation of chronic inflammatory bowel disease in childhood. Baillieres Clin Gas-troenterol 1994, 8:101–119.

36. Hyams JS: Crohn’s's disease in children. Pediatr Clin North Am 1996, 43:255–277.

37. Elliott PR, Williams CB, Lennard-Jones JE, et al.: Colonoscopic diagnosis of minimal change colitis in patients with a nor-mal sigmoidoscopy and normal air-contrast barium enema. Lancet 1982, 8273:650–651.

38. Heyman MB, Perman JA, Ferrell LD, Thaler MM: Chronic non-specific inflammatory bowel disease of the cecum and proxi-mal colon in children with grossly normal-appearing colonic mucosa: diagnosis by colonoscopic biopsies. Pediatrics 1987, 80:255–261.

39.• Jewell FM, Davies A, Sandhu B, et al.: Technetium-99m-HMPAO labelled leucocytes in the detection and monitoring of inflammatory bowel disease in children. Br J Radiol 1996, 69:508–514.

This study of 35 children compares imaging findings with the results of endoscopy/biopsy, barium studies, and antinuclear cytoplasm anti-body serology. The 99mTc technique is recommended as a first-line investigation to detect inflammatory bowel disease, with a resultant reduction in the use of endoscopy and barium imaging.40. Kolkman JJ, Falke TH, Roos JC, et al.: Computed tomography

and granulocyte scintigraphy in active inflammatory bowel disease: comparison with endoscopy and operative findings. Dig Dis Sci 1996, 41:641–650.

41. Charron M, Fernando del Rosario J, Kocoshis S: Distribution of acute bowel inflammation determined by technetium- labeled white blood cells in children with inflammatory bowel disease. Inflamm Bowel Dis 1998, 4:84–88.

42. Balthazar EJ: CT of the gastrointestinal tract: principles and interpretation. AJR Am J Roentgenol 1991, 156:23–32.

43. Meuwissen SG, Pape KS, Agenant D, et al.: Crohn’s's disease of the colon: analysis of the diagnostic value of radiology, endo-scopy, and histology. Am J Dig Dis 1976, 21:81–88.

44. Prantera C, Luzi C, Olivotto P, et al.: Relationship between clinical and laboratory parameters and length of lesion in Crohn’s's disease of small bowel. Dig Dis Sci 1984, 29:1093–1097.

45.•• Bhargava SA, Orenstein SR, Charron M: Technetium-99m hex-amethylpropyleneamine-oxime-labeled leukocyte scintigra-phy in inflammatory bowel disease in children. J Pediatr 1994, 125:213–217.

In this study of a small number of children, the imaging score is cor-related to clinical indexes of disease activity.46.• Charron M, del Rosario JF, Kocoshis S: Use of technetium-

tagged white blood cells in patients with Crohn’s's disease and ulcerative colitis: is differential diagnosis possible? Pediatr Radiol 1998, 28:871–877.

Pattern recognition and skip lesions are used to differentiate between continuous and discontinuous colitis.47. Almers S, Granerus G, Franzen L, Strom M: Technetium-99m

scintigraphy: more accurate assessment of ulcerative colitis with exametazime-labelled leucocytes than with antigranulo-cyte antibodies. Eur J Nucl Med 1996, 23:247–255.

48. Biancone L, Scopinaro F, Ierardi M, et al.: 99mTc-HMPAO gran-ulocyte scintigraphy in the early detection of postoperative asymptomatic recurrence in Crohn’s's disease. Dig Dis Sci 1997, 42:1549–1556.

technetium leukocyte imaging in inflammatory bowel disease

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