Modelling the arterial input function for blood pool agents in dynamic contrast enhanced-MRI
Authors: Dieter De Naeyer, Wim Ceelen, Sunny Eloot
Journal: Clinical Cancer Research (2008)

B31    Introduction:  Dynamic contrast enhanced-MRI (DCE-MRI) in combination with pharmacokinetic modelling can serve as a biomarker for angiogenic activity and treatment response in tumours. Though difficult to determine, the arterial input function (AIF), the plasma tracer concentration in the tumoral vascular network, is of crucial importance for the accuracy of the technique. The aim of this work is to validate a model able to predict the functional form of the AIF for the blood pool agent (BPA) P792 at different locations throughout the organism.   Materials and Methods:  The proposed model for the distribution of BPA through the bloodstream subdivides the latter into three compartments: an aortic compartment (AC), a central vascular compartment (CVC) and peripheral vascular compartment (PVC). Between compartments, tracer is exchanged through a blood flow F. In the central vascular compartment, containing the main excretion organs for P792, a linear excretion flux with clearance time constant K was accounted for. The model was validated by measuring the concentration-time curve of P792 after bolus injection (6 rats) or continuous infusion (1 rat, 30 s) in the renal artery (CVC) and the femoral artery (PVC) in a DCE-MRI experiment (Turbo-Flash sequence). Secondly, the normalised signal intensity vs. time curve in a manually selected region of interest after bolus injection of P792 was analysed according to the Tofts model with 2 different AIF’s in 3 rats with induced CC531 tumours. Fitted parameters were K trans *T 10t /T 10p , the product of the endothelial transfer constant and the ratio of the native T 1 -relaxation time in tissue and plasma respectively, and k ep , the ratio of K trans  and the fractional interstitial volume ν e .  The first AIF was measured in the femoral artery, nearby the tumour. The second AIF is the simulated CVC-concentration, produced by fitting the measured one to the PVC-compartment. Both AIF’s were compared by means of the R²-values for the Tofts modelling.   Results:  The model performed well from a mathematical point of view, and it was able to fit the identifiable parameters from the 7 curves with acceptable standard errors (  2 -values ( > 95 %). Physiologically, fitted blood flow values (0.693 - 1.1 ml s -1 ) and P792 clearance time constants (0.561 -0.995 ms -1 ) were in good accordance with literature. Furthermore it was shown that for both the renal and the femoral artery a sum of three degrading exponentials is needed to describe the AIF accurately. For the AC however, the model impulse response can be redimensionalized to a sum of two degrading exponentials, as can be expected from the global pharmacokinetic behaviour of P792. Finally, the pharmacokinetic modelling of the 3 rats with induced tumours shows an average increase in R 2  of 6% (over the ROI) when the simulated AIF is applied instead of the measured one.   Conclusion:  The model is physiologically relevant and able to predict the functional form of the AIF of P792 at different locations at the body. This functional form is a sum of three degrading exponentials. The use of the aortic plasma concentration as AIF can introduce errors in the pharmacokinetic modelling. The model can be used to adapt the measured AIF to accord more correctly to the real AIF in the tissue of interest, thereby improving the accuracy of the pharmacokinetic modelling.