Molecular Imaging and Biology

, Volume 13, Issue 3, pp 573–576 | Cite as

Clinical Utility of Positron Emission Tomography/Computed Tomography in Inflammatory Bowel Disease

  • Robert T. Lapp
  • Bret J. Spier
  • Scott B. Perlman
  • Christine J. Jaskowiak
  • Mark Reichelderfer
Research Article

Abstract

Purpose

The clinical utility of positron emission tomography/computed tomography (PET/CT) in comparison to standard workup in patients with known or suspected inflammatory bowel disease (IBD) is unknown.

Procedures

Clinical data were collected on seven patients with known or suspected IBD undergoing PET/CT. Standard workup included history, physical exam, laboratory tests, colonoscopy and/or cross-sectional imaging. We divided the intestine into five regions [small bowel and four colon (ascending, transverse, descending and rectosigmoid)] and graded relative standard uptake values 0, 1, 2 or 3 by comparison to the liver, using a region-of-interest analysis (0 = no activity, 1 = liver, 2 and 3 = significant inflammation).

Results

In patients 1 and 2, PET/CT demonstrated more activity than we thought clinically present. The other patients avoided unnecessary escalation or initiation of IBD therapy based on PET/CT results. Compared with standard workup, all seven patients had superior results when therapeutic decisions were based on PET/CT.

Conclusions

We found PET/CT to be very useful in diagnosis and management in patients with known or suspected IBD.

Key words

Inflammatory Bowel Disease Pet/CT Clinical Crohn's colitis Ulcerative Colitis 

Introduction

Assessment of disease activity is crucial to therapeutic success in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), but current clinical activity scoring systems are indirect and endoscopic evaluation is invasive [1, 2, 3]. Positron emission tomography (PET) scanning has shown promise as a reliable noninvasive test for evaluation of active inflammation in IBD patients, with PET integrated with computed tomography (PET/CT) improving spatial resolution [4, 5, 6, 7, 8, 9]. We have previously shown PET/CT to be accurate in terms of quantifying inflammation [10, 11, 12]. However, the clinical utility of PET/CT has not been studied. Thus, we performed a prospective analysis of our initial clinical experience with PET/CT in consecutive patients. Our aim was to investigate the clinical utility of PET/CT in comparison to standard techniques.

Methods

Study Design

PET/CT imaging was performed in seven patients [six males (age, 33–70) and one female (age 34)] with known or suspected IBD if the disease process was undiagnosed or therapy decisions remained after the standard workup was completed. All patients who participated in the study signed a consent form, with the protocol approved by the University of Wisconsin Health Sciences Institutional Review Board. Exclusion criteria were pregnancy, blood sugar greater than 200 mg/dl [as hyperglycemia interferes with the uptake of 2-deoxy-2-[18F]fluoro-d-glucose (FDG)], age less than 18 years old and the presence of other inflammatory conditions known to show activity on PET/CT. No patients were excluded for blood glucose greater than 200 mg/dl.

Each patient had a PET/CT after fasting for a minimum of 6 h. Images of only the abdomen and pelvis were acquired using a GE Discovery LS PET/CT multislice scanner (GE Healthcare, Waukesha, WI, USA). We then administered intravenous FDG at a dose of 0.14 mCi/kg (minimum of 10 mCi). After 45 min, the patients were asked to void and were then positioned in the PET/CT scanner for image acquisition. A low-dose, noncontrast CT scan with 120 mA was then performed, the scanner bed advanced. Image acquisition time was 10 and 5 min per bed position in 2D mode and 3 min per bed position in 3D mode with images from 2D mode used for interpretation. The software automatically fuses PET and CT images.

PET/CT Scan Image Acquisition and Analysis

PET/CT scans were interpreted by a nuclear medicine physician blinded to the clinical data. As previously, we scored results selected from the CT component of the PET/CT in five bowel regions representing small bowel, ascending, transverse, descending and rectosigmoid [8]. We compared bowel segment activity to liver activity using relative standardized uptake values (rSUV) based on the ratio of bowel to liver. We graded rSUV 0, 1, 2 or 3 in each segment of bowel using a region-of-interest (ROI) analysis. The liver was chosen as a reference organ for the bowel, as it was always in the field of view and less likely to be abnormal in patients with IBD (excluding primary sclerosing cholangitis). A grade of 0 indicated that the bowel had no FDG-PET activity or was less than the liver. A grade of 1 was equal to the liver. FDG-PET activity three times the liver or greater was recorded as grade 3 with grade 2 being less than 3 but greater than the liver. An rSUV of <1 was grade 0, rSUV = 1 was grade 1, rSUV = 2 was grade 2 and rSUV = 3 was grade 3. We used rSUV to measure disease activity rather than absolute SUV as the normal range of metabolic activity of the bowel is not well defined. Mild metabolic activity is often observed in the bowel in normal patients. Therefore, as we have previously shown, significant bowel metabolism (grade 2 or 3) is defined as abnormal for this investigation [11].

Standard Workup

Modified Harvey–Bradshaw (MHB) scores were calculated for each CD patient and our patient with suspected IBD before obtaining PET/CT scans (score >4 is active) [13]. Similarly, pouchitis disease activity index (PDAI) scores were calculated for the two pouch patients (score >6 is active) [14]. We also recorded laboratory markers of inflammation. The clinical team made decisions on specific procedures performed in addition to PET/CT scans, including colonoscopy and/or other cross-sectional imaging. Each patient’s gastroenterologist interpreted the colonoscopy and capsule studies. Other cross-sectional imaging performed in individual patients was reviewed by the investigators.

Results

Patient Characteristics

Our study included four patients with CD, two patients with ileal pouch-anal anastomosis surgery for UC and one patient with suspected IBD. All patients were at least moderately ill based on their MHB score or PDAI calculated on presentation. Additional studies were available in most patients (Table 1).
Table 1

Patient characteristics

Patient

MHB score

CRP (nl <1 mg/dl)

ESR (nl <15 mm/h)

Plt (nl <370,000/ul)

Colon/pouch

Study

1

8

0

N/A

285,000

Neg

N/A

2

6

2

43

377,000

Neg

MRI:TI wall thickening

3

12

1

17

272,000

Neg

CTE, capsule neg

4

5

0

7

355,000

N/A

N/A

      

CT: dilated SB

5

PDAI = 7

1

7

144,000

Pouchitis

Capsule: pouch inflammation

6

PDAI = 9

0

7

331,000

Pouchitis

Capsule: pouch inflammation

7

7

0

2

291,000

Neg

CT: colon wall thickening

CRP C-Reactive Protein; ESR Erythrocyte Sedimentation Rate; Plt Platelets; CTE Computed Tomography Enterography; SB Small Bowel

PET/CT Scan Results

There were 14 abnormally active segments identified (grade 2 or 3) of a total 35 segments (Table 2).
Table 2

PET/CT scan results

Patient

Indication

PET/CT

ROI grade

Outcome

Sb

Asc

Trans

Dsc

Rs

1

?CD flare

Pos

3

2

2

2

2

Biologics

2

?CD flare

Pos

2

2

2

1

2

Steroids

3

GI bleed, ? SB Crohn's

Pos

0

2

0

2

3

Not CD

4

?CD flare

Pos

1

2

0

1

2

Flare

5

Pouchitis

Neg

0

NA

NA

NA

NA

Not CD

6

Pouchitis

Neg

0

NA

NA

NA

NA

Not CD

7

FUO

Neg

0

0

0

0

0

Not CD

Patient Outcomes

  • Patient 1 (69 years old/male/CD): The patient presented with diarrhea and abdominal pain suggestive of a flare with colonoscopy being negative and normal inflammatory markers; previous small bowel evaluation was negative years previously. Immunosuppression was held based on results of colonoscopy and inflammatory markers. PET/CT scan showed very significant increased uptake in both the small bowel and the colon. Anti-TNF therapy was initiated with good response. The patient has continued in remission since starting biologics.

  • Patient 2 (63 years old/male/CD): The patient presented with increased bowel movements with increased inflammatory markers, but only mild terminal ileum thickening on MRI. Subsequent colonoscopy was negative; therefore, immunosuppression was held. PET/CT scan showed increased uptake diffusely in the small intestine and colon (Fig. 1). He was started on prednisone with excellent response and has continued in remission on budesonide.
    Fig. 1

    Patient 2 with marked PET small bowel activity present diffusely (coronal 2D image). Small bowel demonstrated an rSUV = 2 and grade = 2. All sections of colon demonstrated an rSUV = 2 and grade = 2, except for the descending colon demonstrating an rSUV = 1 and grade = 1.

  • Patient 3 (68 years old/male/CD): The patient presented with gastrointestinal bleeding with his known ileal CD being suggested as a source and increased immunosuppression being contemplated for treatment of his gastrointestinal bleed. Initial workup including inflammatory markers, colonoscopy, CT enterography and capsule endoscopy was negative. PET/CT showed no significant small bowel uptake. The patient was not treated with drug escalation and improved with conservative treatment.

  • Patient 4 (66 years old/male/CD): The patient presented with an obstruction with CT showing a distal ileal stricture. He had had previous surgery demonstrating moderately severe adhesions with the issue being whether or not his CD was active; he was already on high-level immunosuppression with azathioprine and budesonide. Based on CT scan results, his immunosuppression was continued. PET/CT showed no significant small bowel activity and only mild colon activity. Immunosuppression was tapered, particularly important as he had an active fungal infection. The patient did well until a flare 14 months later.

  • Patient 5 (58 years old/male/pouch): The patient presented with increased stool output through his pouch and abdominal pain raising the possibility of small bowel CD. Pouch endoscopy, CT and capsule endoscopy were positive for active pouch inflammation. These results led to the initiation of steroids on admission. PET/CT did not demonstrate active inflammation above the pouch. Inflammation in the pouch on pouch endoscopy, CT and capsule endoscopy was secondary to pouch volvulus. Therefore, steroids started on admission were tapered and the patient did well.

  • Patient 6 (40 years old/male/pouch): The patient presented with bloody stools and abdominal pain, raising the possibility of CD. Pouch endoscopy and capsule endoscopy of the pouch were positive for active pouch inflammation. Initiation of immunosuppression was planned when results of pouch endoscopy and capsule returned. However, PET/CT showed no evidence of active inflammation above the pouch; therefore, unneeded immunosuppression was avoided.

  • Patient 7 [34 years old/female/fever of unknown origin (FUO)]: The patient presented with FUO concerning for IBD with initial CT scan of abdomen showing colon wall thickening. Patient had negative colonoscopy and normal inflammatory markers. Immunosuppressants were planned based on CT scan results. PET/CT was negative in all ROI (Fig. 2). Unnecessary treatments were avoided and the patient was ultimately diagnosed with Munchausen.
    Fig. 2

    Patient 7 with no PET activity in small bowel or colon (coronal 2D image). Colon and small bowel demonstrated an rSUV = 0 and grade = 0 in all sections.

Discussion

Our study demonstrates PET/CT to be useful clinically in selected patients with known or suspected IBD. Although used in a heterogeneous group of patients (four with CD, two with pouches, and one without IBD), PET/CT contributed significantly to clinical decision-making in each patient and proved superior to currently available modalities.

CD activity was underestimated by standard tests in patients 1 and 2; PET/CT activity was surprisingly impressive in each, leading directly to increased immune suppression and control of disease activity. Patients 3 and 4 presented with gastrointestinal bleeding and obstruction, respectively, which are common complications of CD; however, PET/CT showed absence of significant activity thereby avoiding drug escalation with both patients subsequently doing well with conservative therapy. The pouch patients (5 and 6) were both quite ill with CD being raised as a probable explanation; surprisingly no significant inflammation in patient 5, indicating the need for further evaluation which resulted in the diagnosis of a pouch volvulus and PET/CT showed absence of inflammation proximal to the pouch in patient 6 (PET/CT having the advantage of being able to evaluate transmural inflammation, rather than mucosal inflammation only, as seen in endoscopy). PET/CT was very useful in patient 7, representing strong evidence for the lack of active IBD, and helped contribute to the diagnosis of Munchausen syndrome.

In our patients, standard methods of disease quantification were inaccurate. CD activity was significantly underestimated in patients 1 and 2. Patients 3 and 4 presented with complications possibly related to CD, and standard methods were unable to resolve this dilemma (both being common clinical problems in the management of CD). Post-pouch inflammation crossing over between standard pouchitis and CD extending above the pouch is also a common problem; PET/CT appears to have utility in this area and seems more definitive than standard radiologic or endoscopic pouch evaluations. Finally, PET/CT was the definitive test in defining lack of IBD in our seventh patient and was more helpful than radiology, endoscopy or lab evaluation of this very difficult patient.

Thus, while we have clinically demonstrated usefulness in PET/CT, we have also demonstrated the difficulties that currently rest with our standard techniques for quantifying disease activity accurately. Although our cohort size is small, each case demonstrates a commonly occurring diagnostic dilemma faced in IBD. In addition, the diagnostic workup was not identical in each patient reflecting the clinical nature of our current study. Further large-scale, controlled, prospective, blinded studies using a comparative effectiveness model are warranted if the true impact of PET/CT as a noninvasive measurement of disease activity in IBD is to be ascertained.

Notes

Acknowledgements

This study was funded in part by an unrestricted grant from Proctor & Gamble Pharmaceuticals.

Disclosure

None of the authors have conflicts to disclose.

References

  1. 1.
    Xavier RJ, Podolsky DK (2007) Unraveling the pathogenesis of inflammatory bowel disease. Nature 448:427–434PubMedCrossRefGoogle Scholar
  2. 2.
    Abraham C, Cho J (2009) Inflammatory bowel disease. N Engl J Med 361:2066–2078PubMedCrossRefGoogle Scholar
  3. 3.
    Bernstein CN, Fried M, Krabshuis JH et al (2010) World gastroenterology organization practice guidelines for the diagnosis and management of IBD in 2010. Inflamm Bowel Dis 16:112–124PubMedGoogle Scholar
  4. 4.
    Spier BJ, Perlman SB, Reichelderfer MX (2009) FDG-PET in inflammatory bowel disease. QJ Nucl Med Mol Imaging 53:64–71Google Scholar
  5. 5.
    Bick I, Bauerfeind P, BreitBach T et al (1997) Inflammatory bowel disease activity measured by positron-emission tomography. Lancet 350:262CrossRefGoogle Scholar
  6. 6.
    Lemberg DA, Issenman RM, Cawdron R et al (2005) Positron emission tomography in the investigation of pediatric inflammatory bowel disease. Inflamm Bowel Dis 11:733–738PubMedCrossRefGoogle Scholar
  7. 7.
    Loffler M, Weckesser M, Franzius C et al (2006) High diagnostic value of 18F-FDG-PET in pediatric patients with chronic inflammatory bowel disease. Ann N Y Acad Sci 1072:379–385PubMedCrossRefGoogle Scholar
  8. 8.
    Neurath MF, Vehling D, Schunk K et al (2002) Noninvasive assessment of Crohn's disease activity: a comparison of 18F-fluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging, and granulocyte scintigraphy with labeled antibodies. Am J Gastroenterol 97:1978–1985PubMedCrossRefGoogle Scholar
  9. 9.
    Adler J, Stidham RW, Higgins PDR (2009) Bringing the inflamed and fibrotic bowel into focus: imaging in inflammatory bowel disease. Gastroenterology & Hepatology 5:705–715Google Scholar
  10. 10.
    Louis E, G. Ancion A, Colard V et al (2007) Noninvasive assessment of Crohn's disease intestinal lesions with (18)F-FDG PET/CT. J Nucl Med 48:1053–1059, Google Scholar
  11. 11.
    Meisner, Randall S, Bret J Spier, Sigurdur Einarsson et al (2007) Pilot study using PET/CT as a novel, noninvasive assessment of disease activity in inflammatory bowel disease. Inflammatory Bowel Disease 13:993–1000Google Scholar
  12. 12.
    Spier BJ, Perlman SB, Jaskowiak CJ et al (2009) PET/CT in the evaluation of inflammatory bowel disease: studies in patients before and after treatment. Molecular Imaging and BiologyGoogle Scholar
  13. 13.
    Harvey RF, Bradshaw JM (1980) A simple index of Crohn's-disease activity. Lancet 1:514PubMedCrossRefGoogle Scholar
  14. 14.
    Sandborn WJ, Tremaine WJ, Batts KP et al (1994) Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc 69:409–415PubMedGoogle Scholar

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Robert T. Lapp
    • 1
  • Bret J. Spier
    • 1
  • Scott B. Perlman
    • 2
  • Christine J. Jaskowiak
    • 2
  • Mark Reichelderfer
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Department of Radiology, University of Wisconsin School of Medicine and Public HealthMadisonUSA

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