title: Kinetic modeling in the context of cerebral blood flow quantification by H2(15)O positron emission tomography: the meaning of the permeability coefficient in Renkin-Crone׳s model revisited at capillary scale.
abstract: One the one hand, capillary permeability to water is a well-defined concept in microvascular physiology, and linearly relates the net convective or diffusive mass fluxes (by unit area) to the differences in pressure or concentration, respectively, that drive them through the vessel wall. On the other hand, the permeability coefficient is a central parameter introduced when modeling diffusible tracers transfer from blood vessels to tissue in the framework of compartmental models, in such a way that it is implicitly considered as being identical to the capillary permeability. Despite their simplifying assumptions, such models are at the basis of blood flow quantification by H2(15)O Positron Emission Tomgraphy. In the present paper, we use fluid dynamic modeling to compute the transfers of H2(15)O between the blood and brain parenchyma at capillary scale. The analysis of the so-obtained kinetic data by the Renkin-Crone model, the archetypal compartmental model, demonstrates that, in this framework, the permeability coefficient is highly dependent on both flow rate and capillary radius, contrarily to the central hypothesis of the model which states that it is a physiological constant. Thus, the permeability coefficient in Renkin-Crone׳s model is not conceptually identical to the physiologic permeability as implicitly stated in the model. If a permeability coefficient is nevertheless arbitrarily chosen in the computed range, the flow rate determined by the Renkin-Crone model can take highly inaccurate quantitative values. The reasons for this failure of compartmental approaches in the framework of brain blood flow quantification are discussed, highlighting the need for a novel approach enabling to fully exploit the wealth of information available from PET data.
authors.affiliation: CNRS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France; Université de Toulouse, INPT, UPS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France. Electronic address: Sylvie.Lorthois@imft.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lorthois
authors.affiliation: Université de Toulouse, INPT, UPS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France; CNRS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Duru
authors.affiliation: Université de Toulouse, INPT, UPS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France; CNRS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France.
authors.forename: Ian
authors.initials: I
authors.lastname: Billanou
authors.affiliation: CNRS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France; Université de Toulouse, INPT, UPS, IMFT (Institut de Mécanique des Fluides de Toulouse), Allée Camille Soula, F-31400 Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Quintard
authors.affiliation: INSERM, UMR 825, Cerebral Imaging and Neurological Handicaps, Toulouse F-31000, France; Université Toulouse III Paul Sabatier, UMR 825, Toulouse F-31000, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Celsis
mesh_terms: D002196:Capillaries / Q000000981:diagnostic imaging* / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009716:Numerical Analysis, Computer-Assisted; D010104:Oxygen Radioisotopes; D049268:Positron-Emission Tomography; D012015:Reference Standards; D014867:Water / Q000378:metabolism*
chemical_list: D010104:Oxygen Radioisotopes; D014867:Water
keywords: Brain microcirculation; Compartmental approach; Diffusible tracer; Numerical simulation; Permeability-surface product