Dispersion of input function
The measured blood curve after a radiotracer bolus is smeared out, because of inhomogeneous velocity fields in the vessels and in the catheter and detector assemblies. Also sticking of radiotracer to the tubing may add to this dispersion effect. Dispersion affects the shape of the blood curve, especially at the bolus infusion peak time, but at late times the AUC of blood curve is not biased. Therefore, dispersion correction is necessary only when very fast kinetics are measured, for example perfusion measurement with radiowater.
In theory, input function is the same for all organs and can be measured from arterial blood, but since dispersion effect differs for the measured and true input function to the region of interest, this is not strictly true, unless dispersion correction is applied. Venous blood sampling causes additional dispersion and biases.
Figure 1. Physiological processes cause distortion (dispersion and delay) of plasma TAC. Sample withdrawal and measurement apparatus may distort the TAC even more.
Dispersion correction with traditional methods adds noise to the blood curve. Regardless of that, dispersion correction should not be accompanied by smoothing (Wollenweber et al., 1997). Munk et al. (2004 and 2008) proposed a dispersion correction method with less noise problem. Although certain automatic blood sampling systems are MR-compatible (Breuer et al., 2010), most are not, requiring long tubing with PET-MR systems. Long tubing increases the dispersion error; O’Doherty et al. (2015) have shown that dispersion correction can be successful even with 3 m arterial sampling tubing.
Dispersion in the detector system
External dispersion of the input function can be determined by measuring the rising/falling edges of the detector system’s response to an input step function (Iida et al., 1986; Senda et al., 1988; Weinberg et al., 1988).
A separate β-microprobe placed close to the arterial catheter could be used to measure the shape of the blood curve without most of the dispersion effects of the main detector system and blood tubing (Seki et al., 1998). Microprobe system could also work without the pump, relying only on the impedance of the system to control the blood flow (Wollenweber et al., 1996).
The internal (physiological) dispersion (caused by human vascular system) between the radial artery and the brain is 4-6 sec (Iida et al., 1986). Liver is especially difficult case with dual input (Keiding, 2012).
In Turku PET Centre, when the dispersion correction is necessary, it is usually done automatically by the blood data processing software: first, the external dispersion is corrected, and secondly the internal dispersion is corrected, if an estimate of internal dispersion time constant is available.
In Turku PET Centre, the external dispersion time constant has been estimated to be 2.5 sec for the assemblies that are currently in use. If tubing is changed, the dispersion time constant should be measured again.
Internal dispersion time constant of 5 sec has been used for the brain studies.
The corrections are done using disp4dft.
To continue with the above example, the command would be:
disp4dft off uo268blo.kbq 2.5 uo268ab.kbq
Bassingthwaighte JB. Dispersion of indicator in the circulation. Proc IBM Med Symp. 1963; 5: 57-76. PMID: 21577275.
Bol A, Vanmelckenbeke P, Michel C, Cogneau M, Goffinet AM. Measurement of cerebral blood flow with a bolus of oxygen-15-labelled water: comparison of dynamic and integral methods. Eur J Nucl Med. 1990; 17: 234-241.
Iida H, Higano S, Tomura N, Shishido F, Kanno I, Miura S, Murakami M, Takahashi K, Sasaki H, Uemura K. Evaluation of regional difference of tracer appearance time in cerebral tissues using [15O]water and dynamic positron emission tomography. J Cereb Blood Flow Metab. 1988; 8: 285-288. doi: 10.1038/jcbfm.1988.60.
Iida H, Kanno I, Miura S, Murakami M, Takahashi K, Uemura K. Error analysis of a quantitative cerebral blood flow measurement using H215O autoradiography and positron emission tomography, with respect to the dispersion of the input function. J Cereb Blood Flow Metab. 1986; 6: 536-545. doi: 10.1038/jcbfm.1986.99.
Keiding S. Bringing physiology into PET of the liver. J Nucl Med. 2012; 53(3): 425-433.
Litton J-E, Eriksson L. Transcutaneous measurement of the arterial input function in positron emission tomography. IEEE Trans Nucl Sci. 1990; 37: 627-628. doi: 10.1109/23.106688.
Meyer E. Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H215O autoradiographic method and dynamic PET. J Nucl Med. 1989; 30:1069-1078.
Munk OL, Keiding S, Bass L. A method to estimate catheter dispersion and to calculate dispersion-free blood time-activity curves. J Nucl Med. 2004; 45(5): 392P-393P.
Munk OL, Keiding S, Bass L. A method to estimate dispersion in sampling catheters and to calculate dispersion-free blood time-activity curves. Med Phys. 2008; 35(8): 3471-3481. doi: 10.1118/1.2948391.
O’Doherty J, Chilcott A, Dunn J. Effect of tubing length on the dispersion correction of an arterially sampled input function for kinetic modeling in PET. Nucl Med Commun. 2015; 36(11): 1143-1149. doi: 10.1097/MNM.0000000000000374.
Oikonen V. Model equations for the dispersion of the input function in bolus infusion PET studies. TPCMOD0003.
Seki C, Okada H, Mori S, Kakiuchi T, Yoshikawa E, Nishiyama S, Tsukada H, Yamashita T. Application of a beta microprobe for quantification of regional cerebral blood flow with 15O-water and PET in rhesus monkeys. Ann Nucl Med. 1998; 12(1): 7-14.
van den Hoff J, Burchert W, Müller-Schauenburg W, Meyer G-J, Hundeshagen H. Accurate local blood flow measurements with dynamic PET: fast determination of input function delay and dispersion by multilinear minimization. J Nucl Med. 1993; 34:1770-1777.
Walker MD, Feldmann M, Matthews JC, Anton-Rodriguez JM, Wang S, Koepp MJ, Asselin M-C. Optimization of methods for quantification of rCBF using high-resolution [15O]H2 PET images. Phys Med Biol. 2012; 57: 2251-2271. doi: 10.1088/0031-9155/57/8/2251.
Wollenweber SD, Hichwa RD, Ponto LLB. A Simple on-line arterial time-activity curve detector for [O-15]water PET studies. IEEE Trans Nucl Sci. 1997; 44(4): 1613-1617. doi: 10.1109/23.597022.
Updated at: 2018-11-24
Written by: Vesa Oikonen