Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging of locally advanced cervical cancer

Abstract

Background. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a unique capability to probe tumour microvasculature. Different analysis of the acquired data will possibly lead to different conclusions. Therefore, the objective of this study was to investigate under which conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer.

Material and methods. Ten patients with locally advanced cervical cancer (FIGO: IIA/IIB/IIIB/IVA – 1/5/3/1) underwent DCE-MRI prior to radiotherapy. From the two-parameter TM it was possible to extract the forward volume transfer constant (K^trans) and the extracellular-extravascular volume fraction (v_e). From the three-parameter ETM, additionally the plasma volume fraction (v_p) could be extracted. From the three-parameter C-TU it was possible to extract information about the blood flow (F_p), permeability-surface area product (PS) and v_p. Finally, the four-parameter 2CXM extended the C-TU to include v_e. For each voxel, corrected Akaike information criterion (AICc) values were calculated, taking into account both the goodness-of-fit and the number of model parameters. The optimal model was defined as the model with the lowest AICc.

Results. All four TKMs were the optimal model in different contiguous regions of the cervical tumours. For the 24 999 analysed voxels, the TM was optimal in 17.0%, the ETM was optimal in 2.2%, the C-TU in 23.4% and the 2CXM was optimal in 57.3%. Throughout the tumour, a high correlation was found between K^trans(TM) and F_p(2CXM), ρ = 0.91.

Conclusion. The 2CXM was most often optimal in describing the contrast agent enhancement of pre-treatment cervical cancers, although this model broke down in a subset of the tumour voxels where overfitting resulted in non-physiological parameter estimates. Due to the possible overfitting of the 2CXM, the C-TU was found more robust and when 2CXM was excluded from comparison the C-TU was the preferred model.

Acknowledgments

The authors will like to acknowledge Drs. J. R. Garbow and J. J. H. Ackerman, Washington University, St. Louis (MO), USA for a critical reading of the manuscript and for useful comments regarding content and presentation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

The study was supported by research grants from CIRRO – the Lundbeck Foundation Centre for Interventional Research in Radiation Oncology, founding from the Danish Research Council, the European Programme (FP7/2013–2016) under grant agreement no. [ICT-2011.5.2] (DrTherapat).