title: 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.
  
  
  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 (ve). From the three-parameter ETM, additionally the plasma volume fraction (vp) could be extracted. From the three-parameter C-TU it was possible to extract information about the blood flow (Fp), permeability-surface area product (PS) and vp. Finally, the four-parameter 2CXM extended the C-TU to include ve. 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 Fp(2CXM), ρ = 0.91.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Physics, Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Jesper Folsted
authors.initials: JF
authors.lastname: Kallehauge
authors.forename: Kari
authors.initials: K
authors.lastname: Tanderup
authors.forename: Chong
authors.initials: C
authors.lastname: Duan
authors.forename: Søren
authors.initials: S
authors.lastname: Haack
authors.forename: Erik Morre
authors.initials: EM
authors.lastname: Pedersen
authors.forename: Jacob Christian
authors.initials: JC
authors.lastname: Lindegaard
authors.forename: Lars Ulrik
authors.initials: LU
authors.lastname: Fokdal
authors.forename: Sandy Mohamed Ismail
authors.initials: SM
authors.lastname: Mohamed
authors.forename: Thomas
authors.initials: T
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D055806:Microvessels; D008875:Middle Aged; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000473:pathology
chemical_list: D003287:Contrast Media