Dispersion-corrected extracorporeal arterial input functions in PET studies of mice: a comparison to intracorporeal microprobe measurements

Abstract

Background Kinetic modelling of dynamic PET typically requires knowledge of the arterial radiotracer concentration (arterial input function, AIF). Its accurate determination is very difficult in mice. AIF measurements in an extracorporeal shunt can be performed; however, this introduces catheter dispersion. We propose a framework for extracorporeal dispersion correction and validated it by comparison to invasively determined intracorporeal AIFs using implanted microprobes. Results The response of an extracorporeal radiation detector to radioactivity boxcar functions, characterised by a convolution-based dispersion model, gave best fits using double-gamma variate and single-gamma variate kernels compared to mono-exponential kernels for the investigated range of flow rates. Parametric deconvolution with the optimal kernels was performed on 9 mice that were injected with a bolus of 39 ± 25 MBq [18F]F-PSMA-1007 after application of an extracorporeal circulation for three different flow rates in order to correct for dispersion. Comparison with synchronous implantation of microprobes for invasive aortic AIF recordings showed favourable correspondence, with no significant difference in terms of area-under-curve after 300 s and 5000 s. One-tissue and two-tissue compartment model simulations were performed to investigate differences in kinetic parameters between intra- and extracorporeally measured AIFs. Results of the modelling study revealed kinetic parameters close to the chosen simulated values in all compartment models. Conclusion The high correspondence of simultaneously intra- and extracorporeally determined AIFs and resulting model parameters establishes a feasible framework for extracorporeal dispersion correction. This should allow more precise and accurate kinetic modelling in small animal experiments.

Validation of arterial input function measurements within an extracorporeal shunt driven by mouse blood pressure for preclinical dynamic PET-MRI

“…Ziel/Aim The dynamic arterial radiotracer concentration (arterial input function, AIF) is difficult to determine accurately in PET of mice. We already successfully performed AIF measurements using a pump-driven extracorporeal shunt 1 . We here investigate AIF measurements using the same setup without the pump, driven by mouse blood pressure alone, as the usage of a pump may not be possible in some cases, e.g.…”

“…Methodik/Methods The proposed setup involved extracorporeal shunting from the femoral artery to the tail vein for seven mice experiments using F-18-PSMA-1007, incorporating a blood radioactivity detector (Twilite, SwissTrace). Determination of the AIF was conducted in accordance to the previous study 1 , with dispersion, introduced by the catheters in the setup, being characterized as a sum of two gamma variates 2 . Parametric deconvolution involved fitting AIF and the unknown dispersion kernel simultaneously.…”