Blood flow using [15O]H2O and dynamic PET
Radiowater bolus-injection studies can be analyzed with kinetic model fitting or autoradiographic (ARG) method. Both methods are based on the same model for [15O]H2O, and both can be applied to dynamic PET scan data, but static PET data can only be analyzed with the ARG method.
Separate instructions are available for
and the instructions on this page apply to perfusion measurements in other organs.
The results from parametric images should always be validated against results from regional average curves (Lodge et al., 2000). Noise in dynamic image may lead into biased results with distorted variance. Filtering of dynamic images may be needed to achieve the same quantitative results as in the regional analysis. To prevent artefacts and excessive loss of image resolution, the strength of filtering must not exceed the level that is required to achieve comparable results. If input function is derived from the image, dynamic image should be filtered as little as possible.
Water content, and thus also the partition coefficient of water, can be very low and variable in white adipose tissue (Thomas, 1962), and even more so in brown adipose tissue (Raiko et al., 2015; U Din et al., 2017). Therefore the kinetic model fitting is recommended over ARG method for WAT and BAT data analysis, although ARG method is still useful in carefully controlled experimental settings (Iozzo et al., 2012; Heinonen et al., 2012 and 2014). Partition coefficient 0.19 has been used for white adipose tissue (Virtanen et al., 2001). See also breast tissue. Kinetic model has been used in the perfusion assessment of BAT for example by Orava et al. (2011) and Lahesmaa et al. (2014).
PET is used to measure changes in tumour blood flow in response to treatment with new anticancer drugs (Anderson and Price, 2002). ARG method can be used to estimate the perfusion in tumours, but the result may be biased, because the partition coefficient (Vd) for water in tumours is unknown and may be variable in different tumour types, and inside the tumour. Partition coefficient of water may be equally important as blood flow in studying treatment responses (Kötz et al., 2009). Also vascular volume in tumours may be variable and very high. Therefore kinetic model fitting is recommended over ARG method, at least as a gold standard method, for validation of simpler methods.
Perfusion of breast tumours has been measured in numerous PET studies (Wilson et al., 1992; Mankoff et al., 2002 and 2003; Tseng et al., 2004), and also with MRI (Brix et al., 2004). Substituting K1 from dynamic [18F]FDG PET studies for [15O]H2O studies has been proposed for sites which do not have possibility to produce radiowater (Zasadny et al., 2003; Tseng et al., 2004; Dunnwald et al., 2008; Eby et al., 2008). In addition to oncological PET studies, breast tissue perfusion has also been measured after plastic surgery for breast reconstruction (Schrey et al., 2006, 2008, and 2010).
Distribution volume of water (partition coefficient) is higher in breast tumours than in normal breast tissue because of the high fat content of normal breast tissue (0.56 ± 0.15 vs 0.14 ± 0.05 mL/mL by Wilson et al., 1992).
Anderson H, Price P. Clinical measurement of blood flow in tumours using positron emission tomography: A review. Nucl Med Commun. 2002; 23: 131-138. doi: 10.1097/00006231-200202000-00004.
Boellaard R, Knaapen P, Rijbroek A, Luurtsema GJ, Lammertsma AA. Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15O-water and positron emission tomography. Mol Imaging Biol. 2005; 7(4): 273-285. doi: 10.1007/s11307-005-0007-2.
Lahesmaa M, Orava J, Schalin-Jäntti C, Soinio M, Hannukainen JC, Noponen T, Kirjavainen A, Iida I, Kudomi H, Enerbäck S, Virtanen KA, Nuutila P. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab. 2014; 99: E28-E35. doi: 10.1210/jc.2013-2312.
de Langen Aj, Lubberink M, Boellaard R, Spreeuwenberg MD, Smit EF, Hoekstra OS, Lammertsma AA. Reproducibility of tumor perfusion measurements using 15O-labeled water and PET. J Nucl Med. 2008; 49(11): 1763-1768. doi: 10.2967/jnumed.108.053454.
Lehtiö K, Oikonen V, Grönroos T, Eskola O, Kalliokoski K, Bergman J, Solin O, Grénman R, Nuutila P, Minn H. Imaging of blood flow and hypoxia in head and neck cancer: Initial evaluation with [15O]H2O and [18F]Fluoroerythronitroimidazole PET. J Nucl Med. 2001; 42: 1645–1652. PMID: 11696633.
Lodge MA, Carson RE, Carrasquillo JA, Whatley M, Libutti SK, Bacharach SL. Parametric images of blood flow in oncology PET studies using [15O]water. J Nucl Med 2000; 41:1784-1792. PMID: 11079484.
Perlmutter JS, Powers WJ, Herscovitch P, Fox PT, Raichle ME. Regional asymmetries of cerebral blood flow, blood volume, oxygen utilization and extraction in normal subjects. J Cereb Blood Flow Metab. 1987; 7: 64-67. doi: 10.1038/jcbfm.1987.9.
Raichle ME. Quantitative in vivo autoradiography with positron emission tomography. Brain Res Rev. 1979; 1: 47-68. doi: 10.1016/0165-0173(79)90016-x.
Rosell S, Belfrage E. Blood circulation in adipose tissue. Physiol Rev. 1979; 59(4): 1078-1104. doi: 10.1152/physrev.19184.108.40.2068.
Ruotsalainen U, Raitakari M, Nuutila P, Oikonen V, Sipilä H, Teräs M, Knuuti J, Bloomfield PM, Iida H. Quantitative blood flow measurement of skeletal muscle using oxygen-15-water and PET. J Nucl Med. 1997; 38: 314-319. PMID: 9025761.
Wells P, Jones T, Price P. Assessment of inter- and intrapatient variability in C15O2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers. Clin Cancer Res. 2003; 9: 6350-6356. PMID: 14695134.
Wilson CBJH, Lammertsma AA, McKenzie CG, Sikora K, Jones T. Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method. Cancer Res. 1992; 52: 1592-1597. PMID: 1540969.
Updated at: 2019-09-26
Created at: 2007-09-17
Written by: Vesa Oikonen