title: Multimodality imaging and mathematical modelling of drug delivery to glioblastomas.
abstract: Patients diagnosed with glioblastoma, an aggressive brain tumour, have a poor prognosis, with a median overall survival of less than 15 months. Vasculature within these tumours is typically abnormal, with increased tortuosity, dilation and disorganization, and they typically exhibit a disrupted blood-brain barrier (BBB). Although it has been hypothesized that the 'normalization' of the vasculature resulting from anti-angiogenic therapies could improve drug delivery through improved blood flow, there is also evidence that suggests that the restoration of BBB integrity might limit the delivery of therapeutic agents and hence their effectiveness. In this paper, we apply mathematical models of blood flow, vascular permeability and diffusion within the tumour microenvironment to investigate the effect of these competing factors on drug delivery. Preliminary results from the modelling indicate that all three physiological parameters investigated-flow rate, vessel permeability and tissue diffusion coefficient-interact nonlinearly to produce the observed average drug concentration in the microenvironment.
authors.affiliation: School of Petroleum Engineering , Heriot-Watt University , Edinburgh EH14 4AS , UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Boujelben
authors.affiliation: School of Petroleum Engineering , Heriot-Watt University , Edinburgh EH14 4AS , UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Watson
authors.affiliation: School of Petroleum Engineering , Heriot-Watt University , Edinburgh EH14 4AS , UK.
authors.forename: Steven
authors.initials: S
authors.lastname: McDougall
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown, MA 02129 , USA.
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.affiliation: Department of Neurology, Massachusetts General Hospital , Harvard Medical School , Boston, MA , USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gerstner
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown, MA 02129 , USA.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown, MA 02129 , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Deisboeck
authors.affiliation: Department of Neurology, Massachusetts General Hospital , Harvard Medical School , Boston, MA , USA.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown, MA 02129 , USA.
authors.forename: David
authors.initials: D
authors.lastname: Boas
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown, MA 02129 , USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Rosen
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown, MA 02129 , USA.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Kalpathy-Cramer
authors.affiliation: School of Mathematics and Statistics , University of St Andrews , St Andrews KY16 9SS , UK.
authors.forename: Mark A J
authors.identifier: 0000-0001-5727-2160
authors.initials: MA
authors.lastname: Chaplain
keywords: computational modelling and simulation; drug delivery; glioblastoma; multimodality imaging; perfusion