Abstract
Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility.Thirteen healthy volunteers (28.7 ± 1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n = 9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland–Altman analysis of agreement.Maximum percent change relative to parameters obtained using zero delays, were −31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and −10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p = 0.0085) and HA fraction (p < 0.0001), but not other parameters. Improved mean differences and Bland–Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling.CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.
Highlights
Dynamic contrast enhanced (DCE) MRI is an established technique for quantification of liver perfusion
contrast agent (CA) boluses arrival times differ between the arterial input function (AIF), portal venous (PV) input function (PVIF) and the liver parenchyma—to correct for this, terms for vascular input function (VIF)-tissue bolus arrival delays are included in the model (Materne et al 2000, 2002, Miyazaki et al 2008)
Because of small hepatic arterial (HA) fraction estimates obtained when assuming zero VIF CA bolus arrival delays, introduction of CA bolus delays for both AIF and PVIFs resulted in increases of as much as 3247% (13.40 s AIF delay, 10.05 s PVIF delay, figure 3(c))
Summary
Dynamic contrast enhanced (DCE) MRI is an established technique for quantification of liver perfusion. SI measurements are converted to CA concentration, before pharmacokinetic modelling of the uptake and washout of CA from the tissues is used to characterise tissue perfusion (Tofts and Kermode 1991, Materne et al 2002, Pandharipande et al 2005). These measurements have been used both in the assessment of microvascular changes in fibrosis/cirrhosis (Annet et al 2003, Hagiwara et al 2008, Kim et al 2008) and for assessment of lesional vascularity and tumour angiogenesis (Jackson et al 2002). CA boluses arrival times differ between the arterial input function (AIF), PV input function (PVIF) and the liver parenchyma—to correct for this, terms for VIF-tissue bolus arrival delays are included in the model (Materne et al 2000, 2002, Miyazaki et al 2008)
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