[en] PURPOSE: The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn's disease (CD) activity by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach. METHODS: A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUVmean), partial volume-corrected SUVmean (PVC-SUVmean), SUVmax, uncorrected total lesion glycolysis (TLG = MAV x SUVmean), and PVC total lesion glycolysis (PVC-TLG = MAV x PVC-SUVmean) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated. RESULTS: SUVmax, PVC-SUVmean, and PVC-TLG significantly correlated with segment CDEIS subscores (r = 0.50, r = 0.69, and r = 0.31, respectively; p < 0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r = 0.64 and r = 0.51, respectively; p < 0.05). CONCLUSION: By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD.
Disciplines :
Gastroenterology & hepatology Radiology, nuclear medicine & imaging
Author, co-author :
SABOURY, BABAK; University of Pennsylvania School of Medicine > Department of Radiology
SALAVATI, ALI; University of Pennsylvania School of Medicine > Department of Radiology
BROTHERS, ALEX; University of Pennsylvania School of Medicine > Department of Radiology
BASU, SANDIP; University of Pennsylvania School of Medicine > Department of Radiology
KWEE, THOMAS; university medical center Utrecht - Netherlands > Department of Radiology and Nuclear Medicine
LAM, MARNIX; university medical center Utrecht - Netherlands > department of Radiology and Nuclear Medicine
HUSTINX, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Service médical de médecine nucléaire et imagerie onco
LOUIS, Edouard ; Centre Hospitalier Universitaire de Liège - CHU > Gastro-Entérologie-Hépatologie
TORIGIAN, DREW; University of Pennsylvania School of Medicine > Department of Radiology
ALAVI, ABASS; Hospital of the University of Pennsylvania > Department of Radiology
Language :
English
Title :
FDG PET/CT in Crohn's disease : correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity
Publication date :
2014
Journal title :
European Journal of Nuclear Medicine and Molecular Imaging
Meuwis MA, Fillet M, Chapelle JP, Malaise M, Louis E, Merville MP. New biomarkers of Crohn's disease: serum biomarkers and development of diagnostic tools. Expert Rev Mol Diagn 2008;8(3): 327-37. doi:10.1586/14737159.8.3.327. (Pubitemid 351724711)
Louis E, Belaiche J, Reenaers C. Anti-tumor necrosis factor nonresponders in Crohn 's disease: therapeutic strategies. Dig Dis 2009;27(3):351-7. doi:10.1159/000228573.
Masselli G, Gualdi G. MR imaging of the small bowel. Radiology 2012;264(2):333-48. doi:10.1148/radiol.12111658.
Chiorean MV, Sandrasegaran K, Saxena R,Maglinte DD, Nakeeb A,Johnson CS. Correlation of CT enteroclysis with surgical pathologyin Crohn's disease. Am J Gastroenterol 2007;102(11):2541-50. doi:10.1111/j.1572-0241.2007.01537.x. (Pubitemid 47631798)
Bettenworth D, Reuter S, Hermann S, Weckesser M, Kerstiens L,Stratis A, et al. Translational 18F-FDG PET/CT imaging to monitorlesion activity in intestinal inflammation. J Nucl Med 2013;54(5):748-55. doi:10.2967/jnumed.112. 112623.
Gotthardt M, Bleeker-Rovers CP, Boerman OC, Oyen WJ. Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. J Nucl Med 2010;51(12):1937-49. doi:10.2967/jnumed.110.076232.
Groshar D, Bernstine H, Stern D, Sosna J, Eligalashvili M, Gurbuz EG, et al. PET/CT enterography in Crohn disease: correlation of disease activity on CT enterography with 18F-FDG uptake. J Nucl Med 2010;51(7):1009-14. doi:10.2967/jnumed.109.073130.
Jacene HA, Ginsburg P, Kwon J, Nguyen GC, Montgomery EA,Bayless TM, et al. Prediction of the need for surgical intervention inobstructive Crohn's disease by 18F-FDG PET/CT. J Nucl Med2009;50(11):1751-9. doi:10.2967/jnumed.109. 065466.
Louis E, Ancion G, Colard A, Spote V, Belaiche J, Hustinx R.Noninvasive assessment of Crohn's disease intestinal lesions with(18)F-FDG PET/CT. J Nucl Med 2007;48(7):1053-9. doi:10.2967/jnumed.107.040436. (Pubitemid 47052642)
Vucelic B. Inflammatory bowel diseases: controversies in the use of diagnostic procedures. Dig Dis 2009;27(3):269-77. doi:10.1159/000228560.
Basu S, Zhuang H, Torigian DA, Rosenbaum J, Chen W, Alavi A.Functional imaging of inflammatory diseases using nuclear medicine techniques. Semin Nucl Med 2009;39(2):124-45. doi:10.1053/j.semnuclmed.2008.10.006.
Shyn PB. 18F-FDG positron emission tomography: potential utilityin the assessment of Crohn's disease. Abdom Imaging 2012;37(3):377-86. doi:10.1007/s00261-011-9793-y.
Treglia G, Quartuccio N, Sadeghi R, Farchione A, Caldarella C,Bertagna F, et al. Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in patients with chronic inflammatory bowel disease: a systematic review and ametaanalysis.J Crohns Colitis 2013;7(5):345-54. doi:10.1016/j.crohns.2012.08.005.
Neurath MF, Vehling D, Schunk K, Holtmann M, Brockmann H,Helisch A, et al. 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 2002;97(8):1978-85. doi:10.1111/j.1572-0241.2002.05836.x.
Kresnik E, Mikosch P, Gallowitsch HJ, Heinisch M, Lind P. F-18fluorodeoxyglucose positron emission tomography in the diagnosisof inflammatory bowel disease. Clin Nucl Med 2001;26(10):867. (Pubitemid 32916833)
Pio BS, Byrne FR, Aranda R, Boulay G, Spicher K, Song MH, et al.Noninvasive quantification of bowel inflammation through positronemission tomography imaging of 2-deoxy-2-[18F]fluoro-D-glucoselabeledwhite blood cells. Mol Imaging Biol 2003;5(4):271-7. (Pubitemid 37074878)
Lemberg DA, Issenman RM, Cawdron R, Green T, Mernagh J,Skehan SJ, et al. Positron emission tomography in the investigationof pediatric inflammatory bowel disease. Inflamm Bowel Dis2005;11(8):733-8. (Pubitemid 41271177)
Löffler M, Weckesser M, Franzius C, Schober O, Zimmer KP. High diagnostic value of 18F-FDG-PET in pediatric patients with chronicinflammatory bowel disease. Ann N YAcad Sci 2006;1072:379-85.doi:10.1196/annals.1326.014. (Pubitemid 44448470)
Meisner RS, Spier BJ, Einarsson S, Roberson EN, Perlman SB,Bianco JA, et al. Pilot study using PET/CT as a novel, noninvasiveassessment of disease activity in inflammatory bowel disease.Inflamm Bowel Dis 2007;13(8):993-1000. doi:10.1002/ibd.20134. (Pubitemid 47309971)
Rubin DT, Surma BL, Gavzy SJ, Schnell KM, Bunnag AP, Huo D,et al. Positron emission tomography (PET) used to image subclinical inflammation associated with ulcerative colitis (UC) in remission. Inflamm Bowel Dis 2009;15(5):750-5. doi:10.1002/ibd.20819.
Spier BJ, Perlman SB, Jaskowiak CJ, Reichelderfer M. PET/CT inthe evaluation of inflammatory bowel disease: studies in patients before and after treatment. Mol Imaging Biol 2010;12(1):85-8. doi:10.1007/s11307-009-0232-1.
Ahmadi A, Li Q, Muller K, Collins D, Valentine JF, Drane W, et al.Diagnostic value of noninvasive combined fluorine-18 labeledfluoro-2-deoxy-D- glucose positron emission tomography and computedtomography enterography in active Crohn's disease. Inflamm Bowel Dis 2010;16(6):974-81. doi:10.1002/ibd.21153.
Halpenny DF, Burke JP, Lawlor GO, O'Connell M. Role of PET and combination PET/CT in the evaluation of patients with inflammatory bowel disease. Inflamm Bowel Dis 2009;15(6):951-8. doi:10.1002/ibd.20817.
Däbritz J, Jasper N, Loeffler M,Weckesser M, Foell D. Noninvasive assessment of pediatric inflammatory bowel disease with (18)F- fluorodeoxyglucose-positron emission tomography and computed tomography. Eur J Gastroenterol Hepatol 2011;23(1):81-9. doi:10.1097/MEG.0b013e3283410222.
Spier BJ, Perlman SB, Reichelderfer M. FDG-PET in inflammatory bowel disease. Q J Nucl Med Mol Imaging 2009;53(1):64-71.
Horsthuis K, Bipat S, Bennink RJ, Stoker J. Inflammatory bowel disease diagnosed with US,MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology 2008;247(1):64-79. doi:10.1148/radiol.2471070611.
Henriksen M, Jahnsen J, Lygren I, Stray N, Sauar J, Vatn MH, et al.C-reactive protein: a predictive factor and marker of inflammation ininflammatory bowel disease. Results from a prospective population-based study. Gut 2008;57(11):1518-23. doi:10.1136/gut.2007.146357.
Alavi A, Newberg AB, Souder E, Berlin JA. Quantitative analysis of PETand MRI data in normal aging and Alzheimer's disease: atrophyweighted total brain metabolism and absolute whole brain metabolismas reliable discriminators. J Nucl Med 1993;34(10):1681-7. (Pubitemid 23295377)
Torigian DA, Lopez RF, Alapati S, Bodapati G, Hofheinz F, van den Hoff J, et al. Feasibility and performance of novel software to quantify metabolically active volumes and 3D partial volume corrected SUV and metabolic volumetric products of spinal bone marrow metastaseson 18F-FDG-PET/CT. Hell J Nucl Med 2011;14(1):8-14.
Fonti R, Larobina M, Del Vecchio S, De Luca S, Fabbricini R,Catalano L, et al. Metabolic tumor volume assessed by 18F-FDGPET/CT for the prediction of outcome in patients with multiplemyeloma. J Nucl Med 2012;53(12):1829-35. doi:10.2967/jnumed.112.106500.
Lim R, Eaton A, Lee NY, Setton J, Ohri N, Rao S, et al. 18F-FDGPET/CT metabolic tumor volume and total lesion glycolysis predict outcome in oropharyngeal squamous cell carcinoma. J Nucl Med 2012;53(10):1506-13. doi:10.2967/jnumed.111.101402.
Berkowitz A, Basu S, Srinivas S, Sankaran S, Schuster S, Alavi A.Determination of whole-body metabolic burden as a quantitativemeasure of disease activity in lymphoma: a novel approach withfluorodeoxyglucose-PET. Nucl Med Commun 2008;29(6):521-6.doi:10.1097/MNM.0b013e3282f813a4. (Pubitemid 351643419)
Hernandez-Martinez A, Marin-Oyaga VA, Salavati A, Saboury B, Codreanu I, Lam MG, et al. Quantitative assessment of global hepaticglycolysis in patients with cirrhosis and normal controls using 18F-FDG-PET/CT: a pilot study. Ann Nucl Med 2013. doi:10.1007/s12149-013-0780-y.
Liao S, Penney BC,Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDGPET in nonsurgical patients with non-small cell lung cancer.Eur J Nucl Med Mol Imaging 2012;39(1):27-38. doi:10.1007/s00259-011-1934-6.
Francis RJ, Byrne MJ, van der Schaaf AA, Boucek JA, Nowak AK,Phillips M, et al. Early prediction of response to chemotherapy andsurvival in malignant pleural mesothelioma using a novelsemiautomated 3-dimensional volume-based analysis of serial 18FFDGPET scans. J Nucl Med 2007;48(9):1449-58. doi:10.2967/jnumed.107.042333. (Pubitemid 47397395)
Dibble EH, Alvarez AC, Truong MT, Mercier G, Cook EF, Subramaniam RM. 18F-FDG metabolic tumor volume and totalglycolytic activity of oral cavity and oropharyngeal squamous cellcancer: adding value to clinical staging. J Nucl Med 2012;53(5):709-15. doi:10.2967/jnumed.111.099531.
Mary JY, Modigliani R. Development and validation of an endoscopicindex of the severity for Crohn's disease: a prospective multicentrestudy. Groupe d ' Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut 1989;30(7):983-9.
Best WR, Becktel JM, Singleton JW, Kern Jr F. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology 1976;70(3):439-44.
Hofheinz F, Langner J, Petr J, Beuthien-Baumann B, Oehme L, Steinbach J, et al. A method for model-free partial volume correction in oncological PET. EJNMMI Res 2012;2(1):16.doi:10.1186/2191-219X-2-16.
Hofheinz F, Dittrich S, Pötzsch C, Hoff J. Effects of cold sphere walls in PET phantom measurements on the volume reproducing threshold. Phys Med Biol 2010;55(4):1099-113. doi:10.1088/0031-9155/55/4/013.
Schaefer A, Kim YJ, Kremp S, Mai S, Fleckenstein J, Bohnenberger H, et al. PET-based delineation of tumour volumes in lung cancer: comparison with pathological findings. Eur J Nucl Med Mol Imaging 2013;40(8):1233-44. doi:10.1007/s00259-013-2407-x.
Schaefer A, Kremp S, Hellwig D, Rübe C, Kirsch CM, Nestle U. A contrast-oriented algorithm for FDG-PET-based delineation of tumourvolumes for the radiotherapy of lung cancer: derivation from phantommeasurements and validation in patient data. Eur J Nucl Med Mol Imaging 2008;35(11):1989-99. doi:10.1007/s00259-008-0875-1.
Musiek ES, Saboury B,Mishra S, Chen Y, Reddin JS, Newberg AB, et al. Feasibility of estimation of brain volume and 2-deoxy-2-(18)F-fluoro-D-glucose metabolism using a novel automated image analysis method: application in Alzheimer 's disease. Hell J Nucl Med 2012;15(3):190-6. doi:10.1967/ s002449910052.
Abdulla S, Salavati A, Saboury B, Basu S, Torigian DA, Alavi A. Quantitative assessment of global lung inflammation following radiationtherapy using FDG PET/CT: a pilot study. Eur J Nucl Med Mol Imaging 2013. doi:10.1007/s00259-013-2579-4.
Toriihara A, Yoshida K, Umehara I, Shibuya H. Normal variants ofbowel FDG uptake in dual-time-point PET/CT imaging. Ann Nucl Med 2011;25(3):173-8. doi:10.1007/s12149-010-0439-x.
Kozuch PL, Hanauer SB. Treatment of inflammatory bowel disease: areview of medical therapy. World J Gastroenterol 2008;14(3):354-77. (Pubitemid 351320845)
Bitton A, Peppercorn MA, Antonioli DA, Niles JL, Shah S,Bousvaros A, et al. Clinical, biological, and histologic parametersas predictors of relapse in ulcerative colitis. Gastroenterology2001;120(1):13-20. (Pubitemid 32061864)
Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A.Review article: Crohn's disease: monitoring disease activity. Aliment Pharmacol Ther 2003;17 Suppl 2:11-7. (Pubitemid 36831453)
Holtmann MH, Uenzen M, Helisch A, Dahmen A, Mudter J, Goetz M, et al. 18F-Fluorodeoxyglucose positron-emission tomography(PET) can be used to assess inflammation non-invasively in Crohn's disease. Dig Dis Sci 2012;57(10):2658-68. doi:10.1007/s10620-012-2190-8.
Hindryckx P, Staelens S, Devisscher L, Deleye S,De Vos F, Delrue L, et al. Longitudinal quantification of inflammation in the murinedextran sodium sulfate-induced colitis model using ìPET/CT. Inflamm Bowel Dis 2011;17(10):2058-64. doi:10.1002/ibd.21578.
Brewer S, Mc Pherson M, Fujiwara D, Turovskaya O, Ziring D, Chen L, et al.Molecular imaging of murine intestinal inflammation with 2-deoxy-2-[18F] fluoro-D-glucose and positron emission tomography. Gastroenterology 2008;135(3):744-55. doi:10.1053/j.gastro.2008.06.040.
Wang H, Machtaler S, Bettinger T, Lutz AM, Luong R, Bussat P,et al. Molecular imaging of inflammation in inflammatory bowel disease with a clinically translatable dual-selectin-targeted US contrast agent: comparison with FDG PET/CT in a mouse model. Radiology 2013;267(3):818-29. doi:10.1148/radiol.13122509.
Basu S, Zaidi H, Houseni M, Bural G, Udupa J, Acton P, et al. Novelquantitative techniques for assessing regional and global function andstructure based on modern imaging modalities: implications for normalvariation, aging and diseased states. Semin Nucl Med2007;37(3):223-39. (Pubitemid 46533824)
Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med 2007;48(6):932-45. doi:10.2967/jnumed.106.035774.
Dewaraja YK, Ljungberg M, Koral KF. Monte Carlo evaluation ofobject shape effects in iodine-131 SPET tumor activity quantification.Eur J Nucl Med 2001;28(7):900-6.Acknowledgments and conflicts of interest This work was supported by a FIRS grant from the CHU of Liège and by an unrestricted research grant from Astra Zeneca Belgium. Edouard Louis is Senior Research Associate at the FNRS of Belgium. (Pubitemid 32662553)
