title: A comparison of two methods for estimating DCE-MRI parameters via individual and cohort based AIFs in prostate cancer: a step towards practical implementation.
abstract: Multi-parametric Magnetic Resonance Imaging, and specifically Dynamic Contrast Enhanced (DCE) MRI, play increasingly important roles in detection and staging of prostate cancer (PCa). One of the actively investigated approaches to DCE MRI analysis involves pharmacokinetic (PK) modeling to extract quantitative parameters that may be related to microvascular properties of the tissue. It is well-known that the prescribed arterial blood plasma concentration (or Arterial Input Function, AIF) input can have significant effects on the parameters estimated by PK modeling. The purpose of our study was to investigate such effects in DCE MRI data acquired in a typical clinical PCa setting. First, we investigated how the choice of a semi-automated or fully automated image-based individualized AIF (iAIF) estimation method affects the PK parameter values; and second, we examined the use of method-specific averaged AIF (cohort-based, or cAIF) as a means to attenuate the differences between the two AIF estimation methods. Two methods for automated image-based estimation of individualized (patient-specific) AIFs, one of which was previously validated for brain and the other for breast MRI, were compared. cAIFs were constructed by averaging the iAIF curves over the individual patients for each of the two methods. Pharmacokinetic analysis using the Generalized kinetic model and each of the four AIF choices (iAIF and cAIF for each of the two image-based AIF estimation approaches) was applied to derive the volume transfer rate (K(trans)) and extravascular extracellular volume fraction (ve) in the areas of prostate tumor. Differences between the parameters obtained using iAIF and cAIF for a given method (intra-method comparison) as well as inter-method differences were quantified. The study utilized DCE MRI data collected in 17 patients with histologically confirmed PCa. Comparison at the level of the tumor region of interest (ROI) showed that the two automated methods resulted in significantly different (p<0.05) mean estimates of ve, but not of K(trans). Comparing cAIF, different estimates for both ve, and K(trans) were obtained. Intra-method comparison between the iAIF- and cAIF-driven analyses showed the lack of effect on ve, while K(trans) values were significantly different for one of the methods. Our results indicate that the choice of the algorithm used for automated image-based AIF determination can lead to significant differences in the values of the estimated PK parameters. K(trans) estimates are more sensitive to the choice between cAIF/iAIF as compared to ve, leading to potentially significant differences depending on the AIF method. These observations may have practical consequences in evaluating the PK analysis results obtained in a multi-site setting.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. Electronic address: fedorov@bwh.harvard.edu.
authors.forename: Andriy
authors.initials: A
authors.lastname: Fedorov
authors.affiliation: Department of Radiology, Northwestern University, Chicago, Illinois 60611.
authors.forename: Jacob
authors.initials: J
authors.lastname: Fluckiger
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37212.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ayers
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37212; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37212.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: General Electric Global Research, Niskayuna, New York 12309.
authors.forename: Sandeep N
authors.initials: SN
authors.lastname: Gupta
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Clare
authors.initials: C
authors.lastname: Tempany
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Department of Radiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Robert
authors.initials: R
authors.lastname: Mulkern
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37212; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37212; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37212; Department of Physics, Vanderbilt University, Nashville, Tennessee 37212; Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37212.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Fennessy
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015331:Cohort Studies; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000378:metabolism*; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA
keywords: Arterial Input Function; DCE-MRI; Pharmacokinetic modeling; Prostate cancer; Quantitative imaging