title: Assessment of DCE-MRI parameters for brain tumors through implementation of physiologically-based pharmacokinetic model approaches for Gd-DOTA.
abstract: Dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI) is used for detailed characterization of pathology of lesions sites, such as brain tumors, by quantitative analysis of tracer's data through the use of pharmacokinetic (PK) models. A key component for PK models in DCE-MRI is the estimation of the concentration-time profile of the tracer in a nearby vessel, referred as Arterial Input Function (AIF). The aim of this work was to assess through full body physiologically-based pharmacokinetic (PBPK) model approaches the PK profile of gadoteric acid (Gd-DOTA) and explore potential application for parameter estimation in DCE-MRI based on PBPK-derived AIFs. The PBPK simulations were generated through Simcyp(®) platform and the predicted PK parameters for Gd-DOTA were compared with available clinical data regarding healthy volunteers and renal impairment patients. The assessment of DCE-MRI parameters was implemented by utilizing similar virtual profiles based on gender, age and weight to clinical profiles of patients diagnosed with glioblastoma multiforme. The PBPK-derived AIFs were then used to compute DCE-MRI parameters through the Extended Tofts Model and compared with the corresponding ones derived from image-based AIF computation. The comparison involved: (i) image measured AIF of patients vs AIF of in silico profile, and, (ii) population average AIF vs in silico mean AIFs. The results indicate that PBPK-derived AIFs allowed the estimation of comparable imaging biomarkers with those calculated from typical DCE-MRI image analysis. The incorporation of PBPK models and potential utilization of in silico profiles to real patient data, can provide new perspectives in DCE-MRI parameter estimation and data analysis.
authors.affiliation: Institute of Computer Science, Computational BioMedicine Lab, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete, Greece. marspan@ics.forth.gr.
authors.forename: Marios
authors.identifier: 0000-0003-2163-0653
authors.initials: M
authors.lastname: Spanakis
authors.affiliation: Institute of Computer Science, Computational BioMedicine Lab, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete, Greece.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Kontopodis
authors.affiliation: Department of Radiology, University Hospitals Leuven, Louvain, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Cauter
authors.affiliation: Institute of Computer Science, Computational BioMedicine Lab, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete, Greece.
authors.forename: Vangelis
authors.initials: V
authors.lastname: Sakkalis
authors.affiliation: Institute of Computer Science, Computational BioMedicine Lab, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Marias
mesh_terms: D001921:Brain / Q000098:blood supply; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000502:physiology; D064368:Healthy Volunteers; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
keywords: AIF; DCE–MRI; Gd-DOTA; Glioblastoma; PBPK; Pharmacokinetics; Simcyp; Tumor