Image-derived input function in dynamic human PET/CT: methodology and validation with 11C-acetate and 18F-fluorothioheptadecanoic acid in muscle and 18F-fluorodeoxyglucose in brain
Despite current advances in PET/CT systems, blood sampling still remains the standard method to obtain the radiotracer input function for tracer kinetic modelling. The purpose of this study was to validate the use of image-derived input functions (IDIF) of the carotid and femoral arteries to measure the arterial input function (AIF) in PET imaging. The data were obtained from two different research studies, one using 18F-FDG for brain imaging and the other using 11C-acetate and 18F-fluoro-6-thioheptadecanoic acid (18F-FTHA) in femoral muscles.
The method was validated with two phantom systems. First, a static phantom consisting of syringes of different diameters containing radioactivity was used to determine the recovery coefficient (RC) and spill-in factors. Second, a dynamic phantom built to model bolus injection and clearance of tracers was used to establish the correlation between blood sampling, AIF and IDIF. The RC was then applied to the femoral artery data from PET imaging studies with 11C-acetate and 18F-FTHA and to carotid artery data from brain imaging with 18F-FDG. These IDIF data were then compared to actual AIFs from patients.
With 11C-acetate, the perfusion index in the femoral muscle was 0.34±0.18 min−1 when estimated from the actual time–activity blood curve, 0.29±0.15 min−1 when estimated from the corrected IDIF, and 0.66±0.41 min−1 when the IDIF data were not corrected for RC. A one-way repeated measures (ANOVA) and Tukey’s test showed a statistically significant difference for the IDIF not corrected for RC (p<0.0001). With 18F-FTHA there was a strong correlation between Patlak slopes, the plasma to tissue transfer rate calculated using the true plasma radioactivity content and the corrected IDIF for the femoral muscles (vastus lateralis r=0.86, p=0.027; biceps femoris r=0.90, p=0.017). On the other hand, there was no correlation between the values derived using the AIF and those derived using the uncorrected IDIF. Finally, in the brain imaging study with 18F-FDG, the cerebral metabolic rate of glucose (CMRglc) measured using the uncorrected IDIF was consistently overestimated. The CMRglc obtained using blood sampling was 13.1±3.9 mg/100 g per minute and 14.0±5.7 mg/100 g per minute using the corrected IDIF (r 2 =0.90).
Correctly obtained, carotid and femoral artery IDIFs can be used as a substitute for AIFs to perform tracer kinetic modelling in skeletal femoral muscles and brain analyses.
- Logan J, Alexoff D, Kriplani A. Simplifications in analyzing positron emission tomography data: effects on outcome measures. Nucl Med Biol 2007;34:743–56. CrossRef
- van der Weerdt AP, Klein LJ, Boellaard R, Visser CA, Visser FC, Lammertsma AA. Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans. J Nucl Med 2001;42:1622–9.
- Wu HM, Hoh CK, Choi Y, et al. Factor analysis for extraction of blood time-activity curves in dynamic FDG-PET studies. J Nucl Med 1995;36:1714–22.
- Phillips RL, Chen CY, Wong DF, London ED. An improved method to calculate cerebral metabolic rates of glucose using PET. J Nucl Med 1995;36:1668–79.
- Graham MM, Peterson LM, Hayward RM. Comparison of simplified quantitative analyses of FDG uptake. Nucl Med Biol 2000;27:647–55. CrossRef
- Huang SC. Anatomy of SUV. standardized uptake value. Nucl Med Biol 2000;27:643–6. CrossRef
- Ogden RT. Estimation of kinetic parameters in graphical analysis of PET imaging data. Stat Med 2003;22:3557–68. CrossRef
- Chen K, Bandy D, Reiman E, et al. Noninvasive quantification of the cerebral metabolic rate for glucose using positron emission tomography, 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function. J Cereb Blood Flow Metab 1998;18:716–23. CrossRef
- Brock CS, Young H, Osman S, Luthra SK, Jones T, Price PM. Glucose metabolism in brain tumours can be estimated using [18F]2-fluorodeoxyglucose positron emission tomography and a population-derived input function scaled using a single arterialised venous blood sample. Int J Oncol 2005;26:1377–83.
- Brun E, Kjellen E, Tennvall J, et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 2002;24:127–35. CrossRef
- Bentourkia M, Croteau E, Langlois R, et al. Cardiac studies in rats with 11C-acetate and PET: a comparison with 13N-ammonia. IEEE Trans Nucl Sci 2002;49:2322–7. CrossRef
- Maki MT, Haaparanta M, Nuutila P, et al. Free fatty acid uptake in the myocardium and skeletal muscle using fluorine-18-fluoro-6-thia-heptadecanoic acid. J Nucl Med 1998;39:1320–7.
- Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 1979;6:371–88. CrossRef
- Logan J. Graphical analysis of PET data applied to reversible and irreversible tracers. Nucl Med Biol 2000;27:661–70. CrossRef
- van der Weerdt AP, Klein LJ, Visser CA, Visser FC, Lammertsma AA. Use of arterialised venous instead of arterial blood for measurement of myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping. Eur J Nucl Med Mol Imaging 2002;29:663–9. CrossRef
- Syvanen S, Blomquist G, Appel L, Hammarlund-Udenaes M, Langstrom B, Bergstrom M. Predicting brain concentrations of drug using positron emission tomography and venous input: modeling of arterial-venous concentration differences. Eur J Clin Pharmacol 2006;62:839–48. CrossRef
- Meyer PT, Circiumaru V, Cardi CA, Thomas DH, Bal H, Acton PD. Simplified quantification of small animal [18F]FDG PET studies using a standard arterial input function. Eur J Nucl Med Mol Imaging 2006;33:948–54. CrossRef
- Laforest R, Sharp TL, Engelbach JA, et al. Measurement of input functions in rodents: challenges and solutions. Nucl Med Biol 2005;32:679–85. CrossRef
- Litton JE, Hall H, Blomqvist G. Improved receptor analysis in PET using a priori information from in vitro binding assays. Phys Med Biol 1997;42:1653–60. CrossRef
- Chen K, Chen X, Renaut R, et al. Characterization of the image-derived carotid artery input function using independent component analysis for the quantitation of [18F] fluorodeoxyglucose positron emission tomography images. Phys Med Biol 2007;52:7055–71. CrossRef
- Su KH, Wu LC, Liu RS, Wang SJ, Chen JC. Quantification method in [18F]fluorodeoxyglucose brain positron emission tomography using independent component analysis. Nucl Med Commun 2005;26:995–1004. CrossRef
- Mourik JE, Lubberink M, Schuitemaker A, et al. Image-derived input functions for PET brain studies. Eur J Nucl Med Mol Imaging 2009;36:463–71. CrossRef
- Mourik JE, van Velden FH, Lubberink M, et al. Image derived input functions for dynamic high resolution research tomograph PET brain studies. Neuroimage. 2008;43:676–86. CrossRef
- Gregory R, Partridge M, Flower MA. Performance evaluation of the Philips “Gemini” PET. IEEE Trans Nucl Sci 2006;53:93–101. CrossRef
- Surti S, Kuhn A, Werner ME, Perkins AE, Kolthammer J, Karp JS. Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities. J Nucl Med 2007;48:471–80.
- Prevost S, Lavallee E, Croteau E, et al. Partial volume effects on SUV measurements: impact of acquisition methods, reconstruction modes and image filtering for 2 dedicated PET scanners. J Nucl Med 2003;44:985.
- Blake JR, Meagher S, Fraser KH, Easson WJ, Hoskins PR. A method to estimate wall shear rate with a clinical ultrasound scanner. Ultrasound Med Biol 2008;34:760–74. CrossRef
- Radegran G, Saltin B. Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake. Am J Physiol Heart Circ Physiol 2000;278:H162–7.
- Williams MA, Nicolaides AN. Predicting the normal dimensions of the internal and external carotid arteries from the diameter of the common carotid. Eur J Vasc Surg 1987;1:91–6. CrossRef
- Olufsen MS, Peskin CS, Kim WY, Pedersen EM, Nadim A, Larsen J. Numerical simulation and experimental validation of blood flow in arteries with structured-tree outflow conditions. Ann Biomed Eng 2000;28:1281–99. CrossRef
- Sandgren T, Sonesson B, Ahlgren R, Lanne T. The diameter of the common femoral artery in healthy human: influence of sex, age, and body size. J Vasc Surg 1999;29:503–10. CrossRef
- Hussain ST, Smith RE, Wood RF, Bland M. Observer variability in volumetric blood flow measurements in leg arteries using duplex ultrasound. Ultrasound Med Biol 1996;22:287–91. CrossRef
- Bartlett ES, Walters TD, Symons SP, Fox AJ. Carotid stenosis index revisited with direct CT angiography measurement of carotid arteries to quantify carotid stenosis. Stroke 2007;38:286–91. CrossRef
- Buck A, Wolpers HG, Hutchins GD, et al. Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET. J Nucl Med 1991;32:1950–7.
- Gambhir SS, Schwaiger M, Huang SC, et al. Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose. J Nucl Med 1989;30:359–66.
- Maki MT, Haaparanta MT, Luotolahti MS, et al. Fatty acid uptake is preserved in chronically dysfunctional but viable myocardium. Am J Physiol 1997;273:H2473–80.
- Sokoloff L, Reivich M, Kennedy C, et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977;28:897–916. CrossRef
- Reivich M, Alavi A, Wolf A, et al. Glucose metabolic rate kinetic model parameter determination in humans: the lumped constants and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab 1985;5:179–92.
- Sun KT, Yeatman LA, Buxton DB, et al. Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate. J Nucl Med 1998;39:272–80.
- van den Hoff J, Burchert W, Borner AR, et al. [1-(11)C]acetate as a quantitative perfusion tracer in myocardial PET. J Nucl Med 2001;42:1174–82.
- Kessler RM, Ellis JR Jr, Eden M. Analysis of emission tomographic scan data: limitations imposed by resolution and background. J Comput Assist Tomogr 1984;8:514–22. CrossRef
- Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med 2007;48:932–45. CrossRef
- Zanotti-Fregonara P, Maroy R, Comtat C, et al. Comparison of 3 methods of automated internal carotid segmentation in human brain PET studies: application to the estimation of arterial input function. J Nucl Med 2009;50:461–7. CrossRef
- Herrero P, Kim J, Sharp TL, et al. Assessment of myocardial blood flow using 15O-water and 1-11C-acetate in rats with small-animal PET. J Nucl Med 2006;47:477–85.
- van Hall G, Sacchetti M, Radegran G. Whole body and leg acetate kinetics at rest, during exercise and recovery in humans. J Physiol (Lond) 2002;542:263–72. CrossRef
- de Geus-Oei LF, Visser EP, Krabbe PF, et al. Comparison of image-derived and arterial input functions for estimating the rate of glucose metabolism in therapy-monitoring 18F-FDG PET studies. J Nucl Med 2006;47:945–9.
- Image-derived input function in dynamic human PET/CT: methodology and validation with 11C-acetate and 18F-fluorothioheptadecanoic acid in muscle and 18F-fluorodeoxyglucose in brain
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
European Journal of Nuclear Medicine and Molecular Imaging
Volume 37, Issue 8 , pp 1539-1550
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Positron emission tomography
- Tracer kinetic modelling
- Image-derived input function
- Industry Sectors
- Author Affiliations
- 1. Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada
- 2. Sherbrooke Molecular Imaging Center, Centre de recherche clinique Étienne-LeBel, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
- 4. Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
- 3. Research Center on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada
- 5. Mécanismes Adaptatifs et Évolution, MNHN-CNRS, Brunoy, France
- 6. Division of Nuclear Medicine, Department of Radiology, University of British Columbia, Vancouver, BC, Canada
- 7. BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada