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Bayesian estimation of pharmacokinetic parameters for DCE-MRI with a robust treatment of enhancement onset time

Matthew R Orton1, David J Collins1, Simon Walker-Samuel1, James A d'Arcy1, David J Hawkes2, David Atkinson2 and Martin O Leach1

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When applying pharmacokinetic (PK) models to dynamic contrast enhanced MRI (DCE-MRI) data it is important to appropriately deal with the enhancement onset time, because errors in the onset time will affect the PK parameter estimates. This paper presents a Bayesian approach to the estimation of the PK parameters kep and Ktrans that robustly treats the onset time. This approach involves the computation of an analytically intractable integral, so two approximate methods are developed. The first uses adaptive numerical quadrature, which produces results accurate to a given tolerance, and the other a simple approximation with a summation. These approaches are compared with each other, and with the standard least-squares (LS) approach. The results of a Monte Carlo experiment show that the LS approach produces biased estimates when kep is large and Ktrans is small, whereas both the Bayesian methods are unbiased. The two Bayesian methods produce very similar estimates, but the simple summation method requires less than half the computation time of either the LS, or the quadrature approximation. The standard deviation of the LS estimates is shown to be larger than either of the Bayesian estimates, while uncertainty estimates based around a Hessian approximation are shown to be too small for all three methods. A more detailed method of assessing the uncertainty of the Bayesian approach is described, and the results show that this is a more accurate description of the estimation uncertainty.


PACS

87.61.Tg Clinical applications

02.50.Ng Distribution theory and Monte Carlo studies

02.60.Jh Numerical differentiation and integration

87.10.-e General theory and mathematical aspects

02.70.Rr General statistical methods

Subjects

Computational physics

Biological physics

Medical physics

Dates

Issue 9 (7 May 2007)

Received 8 September 2006, in final form 6 February 2007

Published 10 April 2007



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