title: Modeling of pathophysiological coupling between brain electrical activation, energy metabolism and hemodynamics: insights for the interpretation of intracerebral tumor imaging.
abstract: Gliomas can display marked changes in the concentrations of energy metabolism molecules such as creatine (Cr), phosphocreatine (PCr) and lactate, as measured using magnetic resonance spectroscopy (MRS). Moreover, the BOLD (blood oxygen level dependent) contrast enhancement in functional magnetic resonance imaging (fMRI) can be reduced or missing within or near gliomas, while neural activity is not significantly reduced (so-called neurovascular decoupling), so that the location of functionally eloquent areas using fMRI can be erroneous. In this paper, we adapt a previously developed model of the coupling between neural activation, energy metabolism and hemodynamics, by including the venous dilatation "Balloon model" of Buxton and Frank. We show that decreasing the cerebral blood flow (CBF) baseline value, or the CBF increase fraction, results in a decrease of the BOLD signal and an increase of the lactate peak during a sustained activation. Baseline lactate and PCr levels are not significantly affected by CBF baseline reduction, but are altered even by a moderate decrease of mitochondrial respiration. Decreasing the total Cr and PCr concentration reduces the BOLD signal after the initial overshoot. In conclusion, we suggest that the coupled use of BOLD fMRI and MRS could contribute to a better understanding of the neurovascular and metabolic decoupling in gliomas.
authors.affiliation: INSERM U 483, Université Pierre et Marie Curie, Boîte 23, 9 quai Saint-Bernard, 75252 Paris 05, France. Agnes.Aubert@snv.jussieu.fr
authors.forename: Agnès
authors.initials: A
authors.lastname: Aubert
authors.forename: Robert
authors.initials: R
authors.lastname: Costalat
authors.forename: Hugues
authors.initials: H
authors.lastname: Duffau
authors.forename: Habib
authors.initials: H
authors.lastname: Benali
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008279:Magnetic Resonance Imaging; D008959:Models, Neurological; D010100:Oxygen / Q000097:blood; D010725:Phosphocreatine / Q000097:blood; D012964:Sodium / Q000493:pharmacokinetics
chemical_list: D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D012964:Sodium; D010100:Oxygen