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Precision analysis of kinetic modelling estimates in dynamic contrast enhanced MRI

Dieter De Naeyer (UGent) , Yves De Deene (UGent) , Wim Ceelen (UGent) , Patrick Segers (UGent) and Pascal Verdonck (UGent)
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Abstract
Dynamic contrast enhanced MRI and pharmacokinetic modelling provide a powerful tool for tumour diagnosis and treatment evaluation. However, several studies show low reproducibility of the technique and poor precision of the transendothelial transfer constant K (trans). This work proposes a theoretical framework describing how finite signal-noise-ratio (SNR) in the MR images is propagated throughout the measurement protocol to uncertainty on the kinetic parameter estimates. After deriving a distribution for the contrast agent concentration, a maximum likelihood estimator (MLM) is proposed that exhibits Cramer-Rao lower bounds (CRLB). An analytical expression is derived for the CRLB that can be used to determine confidence intervals for kinetic parameters and to investigate the influence of protocol parameters as scan time and temporal resolution on K (trans)-precision. K (trans)-uncertainty can be reduced up to 30% by using MLM in comparison with least square estimator. K (trans)-precision is proportional to the SNR and depends strongly on the kinetic parameter values themselves. Minimal scan time and temporal resolution were found to be 15 min and 15 s, respectively, for Gd-DTPA. Temporal resolution should be enhanced by decreasing the NEX parameter (NEX a parts per thousand currency sign 1). CRLB provide a golden standard to construct 95% confidence intervals, which can be used to perform protocol optimization and to test the statistical significance of K (trans)-changes in treatment evaluation.
Keywords
Experiment design, Precision analysis, Confidence interval, TRACER KINETICS, PHARMACOKINETIC PARAMETERS, FLIP ANGLES, DCE-MRI, AGENT CONCENTRATION, SIGNAL INTENSITY, T-1-WEIGHTED MRI, REPRODUCIBILITY, UNCERTAINTY, PERFUSION, Kinetic modelling

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Chicago
De Naeyer, Dieter, Yves De Deene, Wim Ceelen, Patrick Segers, and Pascal Verdonck. 2011. “Precision Analysis of Kinetic Modelling Estimates in Dynamic Contrast Enhanced MRI.” Magnetic Resonance Materials in Physics Biology and Medicine 24 (2): 51–66.
APA
De Naeyer, D., De Deene, Y., Ceelen, W., Segers, P., & Verdonck, P. (2011). Precision analysis of kinetic modelling estimates in dynamic contrast enhanced MRI. MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE, 24(2), 51–66.
Vancouver
1.
De Naeyer D, De Deene Y, Ceelen W, Segers P, Verdonck P. Precision analysis of kinetic modelling estimates in dynamic contrast enhanced MRI. MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE. 2011;24(2):51–66.
MLA
De Naeyer, Dieter, Yves De Deene, Wim Ceelen, et al. “Precision Analysis of Kinetic Modelling Estimates in Dynamic Contrast Enhanced MRI.” MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE 24.2 (2011): 51–66. Print.
@article{1984666,
  abstract     = {Dynamic contrast enhanced MRI and pharmacokinetic modelling provide a powerful tool for tumour diagnosis and treatment evaluation. However, several studies show low reproducibility of the technique and poor precision of the transendothelial transfer constant K (trans). This work proposes a theoretical framework describing how finite signal-noise-ratio (SNR) in the MR images is propagated throughout the measurement protocol to uncertainty on the kinetic parameter estimates. 
After deriving a distribution for the contrast agent concentration, a maximum likelihood estimator (MLM) is proposed that exhibits Cramer-Rao lower bounds (CRLB). An analytical expression is derived for the CRLB that can be used to determine confidence intervals for kinetic parameters and to investigate the influence of protocol parameters as scan time and temporal resolution on K (trans)-precision. 
K (trans)-uncertainty can be reduced up to 30\% by using MLM in comparison with least square estimator. K (trans)-precision is proportional to the SNR and depends strongly on the kinetic parameter values themselves. Minimal scan time and temporal resolution were found to be 15 min and 15 s, respectively, for Gd-DTPA. Temporal resolution should be enhanced by decreasing the NEX parameter (NEX a parts per thousand currency sign 1). 
CRLB provide a golden standard to construct 95\% confidence intervals, which can be used to perform protocol optimization and to test the statistical significance of K (trans)-changes in treatment evaluation.},
  author       = {De Naeyer, Dieter and De Deene, Yves and Ceelen, Wim and Segers, Patrick and Verdonck, Pascal},
  issn         = {0968-5243},
  journal      = {MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE},
  keyword      = {Experiment design,Precision analysis,Confidence interval,TRACER KINETICS,PHARMACOKINETIC PARAMETERS,FLIP ANGLES,DCE-MRI,AGENT CONCENTRATION,SIGNAL INTENSITY,T-1-WEIGHTED MRI,REPRODUCIBILITY,UNCERTAINTY,PERFUSION,Kinetic modelling},
  language     = {eng},
  number       = {2},
  pages        = {51--66},
  title        = {Precision analysis of kinetic modelling estimates in dynamic contrast enhanced MRI},
  url          = {http://dx.doi.org/10.1007/s10334-010-0235-6},
  volume       = {24},
  year         = {2011},
}

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