title: Multiscale modeling of intracranial aneurysms: cell signaling, hemodynamics, and remodeling.
abstract: The genesis, growth, and rupture of intracranial aneurysms (IAs) involve physics at the molecular, cellular, blood vessel, and organ levels that occur over time scales ranging from seconds to years. Comprehensive mathematical modeling of IAs, therefore, requires the description and integration of events across length and time scales that span many orders of magnitude. In this letter, we outline a strategy for mulstiscale modeling of IAs that involves the construction of individual models at each relevant scale and their subsequent combination into an integrative model that captures the overall complexity of IA development. An example of the approach is provided using three models operating at different length and time scales: 1) shear stress induced nitric oxide production; 2) smooth muscle cell apoptosis; and 3) fluid-structure-growth modeling. A computational framework for combining them is presented. We conclude with a discussion of the advantages and challenges of the approach.
authors.affiliation: Auckland Bioengineering Institute, The University of Auckland, Auckland 1142, New Zealand. harvey.ho@auckland.ac.nz
authors.forename: Harvey
authors.initials: H
authors.lastname: Ho
authors.forename: Vinod
authors.initials: V
authors.lastname: Suresh
authors.forename: Wendy
authors.initials: W
authors.lastname: Kang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Cooling
authors.forename: Paul N
authors.initials: PN
authors.lastname: Watton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hunter
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001696:Biomechanical Phenomena; D020013:Calcium Signaling; D002560:Cerebrovascular Circulation; D002941:Circle of Willis; D006801:Humans; D002532:Intracranial Aneurysm / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction