Skip to main content
Top
Published in: EJNMMI Research 1/2013

Open Access 01-12-2013 | Original research

Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4–2008 image quality parameters

Authors: Charline Lasnon, Elske Quak, Mélanie Briand, Zheng Gu, Marie-Hélène Louis, Nicolas Aide

Published in: EJNMMI Research | Issue 1/2013

Login to get access

Abstract

Background

The use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT).

Methods

Firstly, a NEMA NU 4–2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media.

Results

There was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4–2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (−0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004).

Conclusions

The use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4–2008 IQ parameters.
Appendix
Available only for authorised users
Literature
1.
go back to reference Cullinane C, Dorow DS, Jackson S, Solomon B, Bogatyreva E, Binns D, Young R, Arango ME, Christensen JG, McArthur GA, Hicks RJ: Differential (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models. J Nucl Med 2011, 8: 1261–1267.CrossRef Cullinane C, Dorow DS, Jackson S, Solomon B, Bogatyreva E, Binns D, Young R, Arango ME, Christensen JG, McArthur GA, Hicks RJ: Differential (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models. J Nucl Med 2011, 8: 1261–1267.CrossRef
2.
go back to reference Zannetti A, Iommelli F, Speranza A, Salvatore M, Del Vecchio S: 3'-deoxy-3'-18 F-fluorothymidine PET/CT to guide therapy with epidermal growth factor receptor antagonists and Bcl-xL inhibitors in non-small cell lung cancer. J Nucl Med 2012, 3: 443–450.CrossRef Zannetti A, Iommelli F, Speranza A, Salvatore M, Del Vecchio S: 3'-deoxy-3'-18 F-fluorothymidine PET/CT to guide therapy with epidermal growth factor receptor antagonists and Bcl-xL inhibitors in non-small cell lung cancer. J Nucl Med 2012, 3: 443–450.CrossRef
3.
go back to reference Chow PL, Rannou FR, Chatziioannou AF: Attenuation correction for small animal PET tomographs. Phys Med Biol 2005, 8: 1837–1850.CrossRef Chow PL, Rannou FR, Chatziioannou AF: Attenuation correction for small animal PET tomographs. Phys Med Biol 2005, 8: 1837–1850.CrossRef
4.
go back to reference Graham KC, Detombe SA, MacKenzie LT, Holdsworth DW, MacDonald IC, Chambers AF, Drangova M: Contrast-enhanced microcomputed tomography using intraperitoneal contrast injection for the assessment of tumor-burden in liver metastasis models. Invest Radiol 2008, 7: 488–495.CrossRef Graham KC, Detombe SA, MacKenzie LT, Holdsworth DW, MacDonald IC, Chambers AF, Drangova M: Contrast-enhanced microcomputed tomography using intraperitoneal contrast injection for the assessment of tumor-burden in liver metastasis models. Invest Radiol 2008, 7: 488–495.CrossRef
5.
go back to reference Choquet P, Calon A, Breton E, Beck F, Domon-Dell C, Freund JN, Constantinesco A: Multiple-contrast X-ray micro-CT visualization of colon malformations and tumours in situ in living mice. C R Biol 2007, 11: 821–827.CrossRef Choquet P, Calon A, Breton E, Beck F, Domon-Dell C, Freund JN, Constantinesco A: Multiple-contrast X-ray micro-CT visualization of colon malformations and tumours in situ in living mice. C R Biol 2007, 11: 821–827.CrossRef
6.
go back to reference Almajdub M, Nejjari M, Poncet G, Magnier L, Chereul E, Roche C, Janier M: In-vivo high-resolution X-ray microtomography for liver and spleen tumor assessment in mice. Contrast Media Mol Imaging 2007, 2: 88–93. 10.1002/cmmi.130CrossRefPubMed Almajdub M, Nejjari M, Poncet G, Magnier L, Chereul E, Roche C, Janier M: In-vivo high-resolution X-ray microtomography for liver and spleen tumor assessment in mice. Contrast Media Mol Imaging 2007, 2: 88–93. 10.1002/cmmi.130CrossRefPubMed
7.
go back to reference Ford NL, Graham KC, Groom AC, Macdonald IC, Chambers AF, Holdsworth DW: Time-course characterization of the computed tomography contrast enhancement of an iodinated blood-pool contrast agent in mice using a volumetric flat-panel equipped computed tomography scanner. Invest Radiol 2006, 4: 384–390.CrossRef Ford NL, Graham KC, Groom AC, Macdonald IC, Chambers AF, Holdsworth DW: Time-course characterization of the computed tomography contrast enhancement of an iodinated blood-pool contrast agent in mice using a volumetric flat-panel equipped computed tomography scanner. Invest Radiol 2006, 4: 384–390.CrossRef
8.
go back to reference Suckow CE, Stout DB: MicroCT liver contrast agent enhancement over time, dose, and mouse strain. Mol Imaging Biol 2008, 2: 114–120.CrossRef Suckow CE, Stout DB: MicroCT liver contrast agent enhancement over time, dose, and mouse strain. Mol Imaging Biol 2008, 2: 114–120.CrossRef
9.
go back to reference Willekens I, Lahoutte T, Buls N, Vanhove C, Deklerck R, Bossuyt A, de Mey J: Time-course of contrast enhancement in spleen and liver with Exia 160, Fenestra LC, and VC. Mol Imaging Biol 2009, 2: 128–135.CrossRef Willekens I, Lahoutte T, Buls N, Vanhove C, Deklerck R, Bossuyt A, de Mey J: Time-course of contrast enhancement in spleen and liver with Exia 160, Fenestra LC, and VC. Mol Imaging Biol 2009, 2: 128–135.CrossRef
10.
go back to reference Aide N, Kinross K, Beauregard JM, Neels O, Potdevin T, Roselt P, Dorow D, Cullinane C, Hicks RJ: A dual radiologic contrast agent protocol for 18F-FDG and 18F-FLT PET/CT imaging of mice bearing abdominal tumors. Mol Imaging Biol 2011, 3: 518–525.CrossRef Aide N, Kinross K, Beauregard JM, Neels O, Potdevin T, Roselt P, Dorow D, Cullinane C, Hicks RJ: A dual radiologic contrast agent protocol for 18F-FDG and 18F-FLT PET/CT imaging of mice bearing abdominal tumors. Mol Imaging Biol 2011, 3: 518–525.CrossRef
11.
go back to reference Aschoff P, Plathow C, Beyer T, Lichy MP, Erb G, Oksuz MO, Claussen CD, Pfannenberg C: Multiphase contrast-enhanced CT with highly concentrated contrast agent can be used for PET attenuation correction in integrated PET/CT imaging. Eur J Nucl Med Mol Imaging 2012, 2: 316–325.CrossRef Aschoff P, Plathow C, Beyer T, Lichy MP, Erb G, Oksuz MO, Claussen CD, Pfannenberg C: Multiphase contrast-enhanced CT with highly concentrated contrast agent can be used for PET attenuation correction in integrated PET/CT imaging. Eur J Nucl Med Mol Imaging 2012, 2: 316–325.CrossRef
12.
go back to reference Berthelsen AK, Holm S, Loft A, Klausen TL, Andersen F, Hojgaard L: PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients. Eur J Nucl Med Mol Imaging 2005, 10: 1167–1175.CrossRef Berthelsen AK, Holm S, Loft A, Klausen TL, Andersen F, Hojgaard L: PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients. Eur J Nucl Med Mol Imaging 2005, 10: 1167–1175.CrossRef
13.
go back to reference Bunyaviroch T, Turkington TG, Wong TZ, Wilson JW, Colsher JG, Coleman RE: Quantitative effects of contrast enhanced CT attenuation correction on PET SUV measurements. Mol Imaging Biol 2008, 2: 107–113.CrossRef Bunyaviroch T, Turkington TG, Wong TZ, Wilson JW, Colsher JG, Coleman RE: Quantitative effects of contrast enhanced CT attenuation correction on PET SUV measurements. Mol Imaging Biol 2008, 2: 107–113.CrossRef
14.
go back to reference Mawlawi O, Erasmus JJ, Munden RF, Pan T, Knight AE, Macapinlac HA, Podoloff DA, Chasen M: Quantifying the effect of IV contrast media on integrated PET/CT: clinical evaluation. AJR Am J Roentgenol 2006, 2: 308–319.CrossRef Mawlawi O, Erasmus JJ, Munden RF, Pan T, Knight AE, Macapinlac HA, Podoloff DA, Chasen M: Quantifying the effect of IV contrast media on integrated PET/CT: clinical evaluation. AJR Am J Roentgenol 2006, 2: 308–319.CrossRef
15.
go back to reference Yau YY, Chan WS, Tam YM, Vernon P, Wong S, Coel M, Chu SK: Application of intravenous contrast in PET/CT: does it really introduce significant attenuation correction error? J Nucl Med 2005, 2: 283–291. Yau YY, Chan WS, Tam YM, Vernon P, Wong S, Coel M, Chu SK: Application of intravenous contrast in PET/CT: does it really introduce significant attenuation correction error? J Nucl Med 2005, 2: 283–291.
16.
go back to reference NEMA: NEMA Standards Publication NU 4–2008: Performance Measurements for Small Animal Positron Emission Tomographs. Rosslyn: NEMA; 2008. NEMA: NEMA Standards Publication NU 4–2008: Performance Measurements for Small Animal Positron Emission Tomographs. Rosslyn: NEMA; 2008.
17.
go back to reference Bao Q, Newport D, Chen M, Stout DB, Chatziioannou AF: Performance evaluation of the inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med 2009, 3: 401–408.CrossRef Bao Q, Newport D, Chen M, Stout DB, Chatziioannou AF: Performance evaluation of the inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med 2009, 3: 401–408.CrossRef
18.
go back to reference Aide N, Desmonts C, Briand M, Meryet-Figuiere M, Poulain L: High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously. Nucl Med Commun 2010, 10: 851–858. Aide N, Desmonts C, Briand M, Meryet-Figuiere M, Poulain L: High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously. Nucl Med Commun 2010, 10: 851–858.
19.
go back to reference Siepel F, van Lier MGTB, Chen M, Disselhorst JA, Meeuwis APW, Oyen WJ, Boerman OC, Visser EP: Scanning multiple mice in a small-animal PET scanner: influence on image quality. Nucl Instrum meth A 2010, 621: 605–610. 10.1016/j.nima.2010.05.057CrossRef Siepel F, van Lier MGTB, Chen M, Disselhorst JA, Meeuwis APW, Oyen WJ, Boerman OC, Visser EP: Scanning multiple mice in a small-animal PET scanner: influence on image quality. Nucl Instrum meth A 2010, 621: 605–610. 10.1016/j.nima.2010.05.057CrossRef
20.
go back to reference Aide N, Visser EP, Lheureux S, Heutte N, Szanda I, Hicks RJ: The motivations and methodology for high-throughput PET imaging of small animals in cancer research. Eur J Nucl Med Mol Imaging 2012,39(9):1497–1509. 10.1007/s00259-012-2177-xCrossRefPubMed Aide N, Visser EP, Lheureux S, Heutte N, Szanda I, Hicks RJ: The motivations and methodology for high-throughput PET imaging of small animals in cancer research. Eur J Nucl Med Mol Imaging 2012,39(9):1497–1509. 10.1007/s00259-012-2177-xCrossRefPubMed
21.
go back to reference Loening AM, Gambhir SS: AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2003, 3: 131–137.CrossRef Loening AM, Gambhir SS: AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2003, 3: 131–137.CrossRef
22.
go back to reference DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988, 3: 837–845.CrossRef DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988, 3: 837–845.CrossRef
23.
go back to reference Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986, 8476: 307–310.CrossRef Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986, 8476: 307–310.CrossRef
24.
go back to reference Disselhorst JA, Brom M, Laverman P, Slump CH, Boerman OC, Oyen WJ, Gotthardt M, Visser EP: Image-quality assessment for several positron emitters using the NEMA NU 4–2008 standards in the Siemens Inveon small-animal PET scanner. J Nucl Med 2010, 4: 610–617.CrossRef Disselhorst JA, Brom M, Laverman P, Slump CH, Boerman OC, Oyen WJ, Gotthardt M, Visser EP: Image-quality assessment for several positron emitters using the NEMA NU 4–2008 standards in the Siemens Inveon small-animal PET scanner. J Nucl Med 2010, 4: 610–617.CrossRef
25.
go back to reference Goertzen AL, Bao Q, Bergeron M, Blankemeyer E, Blinder S, Canadas M, Chatziioannou AF, Dinelle K, Elhami E, Jans HS, Lage E, Lecomte R, Sossi V, Surti S, Tai YC, Vaquero JJ, Vicente E, Williams DA, Laforest R: NEMA NU 4–2008 comparison of preclinical PET imaging systems. J Nucl Med 2012, 8: 1300–1309.CrossRef Goertzen AL, Bao Q, Bergeron M, Blankemeyer E, Blinder S, Canadas M, Chatziioannou AF, Dinelle K, Elhami E, Jans HS, Lage E, Lecomte R, Sossi V, Surti S, Tai YC, Vaquero JJ, Vicente E, Williams DA, Laforest R: NEMA NU 4–2008 comparison of preclinical PET imaging systems. J Nucl Med 2012, 8: 1300–1309.CrossRef
26.
go back to reference Antoch G, Jentzen W, Freudenberg LS, Stattaus J, Mueller SP, Debatin JF, Bockisch A: Effect of oral contrast agents on computed tomography-based positron emission tomography attenuation correction in dual-modality positron emission tomography/computed tomography imaging. Invest Radiol 2003, 12: 784–789. Antoch G, Jentzen W, Freudenberg LS, Stattaus J, Mueller SP, Debatin JF, Bockisch A: Effect of oral contrast agents on computed tomography-based positron emission tomography attenuation correction in dual-modality positron emission tomography/computed tomography imaging. Invest Radiol 2003, 12: 784–789.
27.
go back to reference Dizendorf E, Hany TF, Buck A, von Schulthess GK, Burger C: Cause and magnitude of the error induced by oral CT contrast agent in CT-based attenuation correction of PET emission studies. J Nucl Med 2003, 5: 732–738. Dizendorf E, Hany TF, Buck A, von Schulthess GK, Burger C: Cause and magnitude of the error induced by oral CT contrast agent in CT-based attenuation correction of PET emission studies. J Nucl Med 2003, 5: 732–738.
28.
go back to reference Dandekar M, Tseng JR, Gambhir SS: Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts. J Nucl Med 2007, 4: 602–607.CrossRef Dandekar M, Tseng JR, Gambhir SS: Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts. J Nucl Med 2007, 4: 602–607.CrossRef
29.
go back to reference Tseng JR, Dandekar M, Subbarayan M, Cheng Z, Park JM, Louie S, Gambhir SS: Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice. J Nucl Med 2005, 11: 1851–1857. Tseng JR, Dandekar M, Subbarayan M, Cheng Z, Park JM, Louie S, Gambhir SS: Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice. J Nucl Med 2005, 11: 1851–1857.
30.
go back to reference Chang E, Liu S, Gowrishankar G, Yaghoubi S, Wedgeworth JP, Chin F, Berndorff D, Gekeler V, Gambhir SS, Cheng Z: Reproducibility study of [(18)F]FPP(RGD)2 uptake in murine models of human tumor xenografts. Eur J Nucl Med Mol Imaging 2011, 4: 722–730.CrossRef Chang E, Liu S, Gowrishankar G, Yaghoubi S, Wedgeworth JP, Chin F, Berndorff D, Gekeler V, Gambhir SS, Cheng Z: Reproducibility study of [(18)F]FPP(RGD)2 uptake in murine models of human tumor xenografts. Eur J Nucl Med Mol Imaging 2011, 4: 722–730.CrossRef
Metadata
Title
Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4–2008 image quality parameters
Authors
Charline Lasnon
Elske Quak
Mélanie Briand
Zheng Gu
Marie-Hélène Louis
Nicolas Aide
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-3-5

Other articles of this Issue 1/2013

EJNMMI Research 1/2013 Go to the issue