title: Mathematical analysis of the influence of brain metabolism on the BOLD signal in Alzheimer's disease.
abstract: Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) is a standard clinical tool for the detection of brain activation. In Alzheimer's disease (AD), task-related and resting state fMRI have been used to detect brain dysfunction. It has been shown that the shape of the BOLD response is affected in early AD. To correctly interpret these changes, the mechanisms responsible for the observed behaviour need to be known. The parameters of the canonical hemodynamic response function (HRF) commonly used in the analysis of fMRI data have no direct biological interpretation and cannot be used to answer this question. We here present a model that allows relating AD-specific changes in the BOLD shape to changes in the underlying energy metabolism. According to our findings, the classic view that differences in the BOLD shape are only attributed to changes in strength and duration of the stimulus does not hold. Instead, peak height, peak timing and full width at half maximum are sensitive to changes in the reaction rate of several metabolic reactions. Our systems-theoretic approach allows the use of patient-specific clinical data to predict dementia-driven changes in the HRF, which can be used to improve the results of fMRI analyses in AD patients.
authors.affiliation: 1 ASD Advanced Simulation and Design GmbH, Rostock, Germany.|2 Department of Systems Biology and Bioinformatics, Rostock University, Rostock, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Winter
authors.affiliation: 1 ASD Advanced Simulation and Design GmbH, Rostock, Germany.
authors.forename: Catrin
authors.initials: C
authors.lastname: Bludszuweit-Philipp
authors.affiliation: 2 Department of Systems Biology and Bioinformatics, Rostock University, Rostock, Germany.|3 Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wolkenhauer
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001923:Brain Chemistry; D001931:Brain Mapping; D002560:Cerebrovascular Circulation; D003198:Computer Simulation; D006019:Glycolysis; D006439:Hemodynamics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008962:Models, Theoretical; D010100:Oxygen / Q000097:blood*
chemical_list: D010100:Oxygen
keywords: BOLD contrast; energy metabolism; hemodynamics; kinetic modelling; mathematical modelling