title: A method for pharmacokinetic modelling of dynamic contrast enhanced MRI studies of rapidly enhancing lesions acquired in a clinical setting.
abstract: Abnormal microcirculation is a feature of many neoplastic and non-neoplastic diseases. Physiological variables that characterize tissue microcirculation (capillary permeability and the volume of the extravascular extracellular fluid) are altered in pathological states. Pharmacokinetic analysis of dynamic contrast enhanced MRI (DCE-MRI) has found a widespread use in the assessment of abnormal microcirculation due to the direct link between the contrast agent kinetics and underlying microcirculatory properties. A representation of temporal variation of contrast agent concentration in blood plasma (C(p)(t)) is central to this analysis. In clinical applications of DCE-MRI, signal intensity curves derived from rapidly enhancing lesions often display a sigmoid shape during the initial phase of contrast uptake and rapid arrival at the equilibrium phase. In this work, the features of two principal methods for pharmacokinetic analysis of DCE-MRI which allow for theoretical representation of C(p)(t) are examined and combined to improve analysis of this particular class of DCE-MRI curves. The proposed method allows the representation of the initial sigmoid part of the enhancement profiles whilst retaining a realistic representation of C(p)(t) based on previously published measurements obtained in healthy volunteers. The results of the computer simulations indicate that in rapidly enhancing lesions, with the transfer constant K(trans) greater than 0.1 min(-1), the DCE-MRI acquisition can be restricted to 5 min post-injection and a mono-exponential representation of C(p)(t) decay is sufficient. Furthermore, non-ideal bolus delivery can be represented as a short constant rate infusion when the tissue under investigation exhibits a sigmoid pattern of contrast uptake.
authors.affiliation: Academic Unit of Medical Physics, University of Leeds, The Wellcome Wing, Leeds General Infirmary, Leeds LS1 3EX, UK. sasha@medphysics.leeds.ac.uk
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Radjenovic
authors.forename: John P
authors.initials: JP
authors.lastname: Ridgway
authors.forename: Michael A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media