title: Molecular MRI approaches to the detection of CNS inflammation.
abstract: Inflammation is a key component of many neurological diseases, yet our understanding of the contribution of these processes to tissue damage remains poor. For many such diseases, magnetic resonance imaging (MRI) has become the method of choice for clinical diagnosis. However, many of the MRI parameters that enable disease detection, such as passive contrast enhancement across a compromised blood-brain barrier, are weighted towards late-stage disease. Moreover, whilst these methods may report on disease severity, they are not able to provide information on either disease activity or the underlying molecular processes. There is a need, therefore, to develop methods that enable earlier disease detection, potentially long before clinical symptoms become apparent, together with identification of specific molecular processes that may guide specific therapy. This chapter describes the methodology for the synthesis and validation of two novel, functional MRI-detectable probes, based on microparticles of iron oxide (MPIO), which target endothelial adhesion molecules. These contrast agents enable the detection of acute brain inflammation in vivo, at a time when pathology is undetectable by conventional MRI. Such molecular MRI methods are opening new vistas for the acute diagnosis of CNS disease, together with the possibility for individually tailored therapy and earlier, more sensitive assessment of the efficacy of novel therapies.
authors.affiliation: CR-UK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK. nicola.sibson@rob.ox.ac.uk
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Sibson
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
authors.forename: Sander
authors.initials: S
authors.lastname: van Kasteren
authors.forename: Alex
authors.initials: A
authors.lastname: Dickens
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Balderas
authors.forename: Martina A
authors.initials: MA
authors.lastname: McAteer
authors.forename: Robin P
authors.initials: RP
authors.lastname: Choudhury
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Davis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism; D007249:Inflammation / Q000175:diagnosis*; D016256:Lewis X Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D051381:Rats; D000080506:Sialyl Lewis X Antigen; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000906:Antibodies; D005290:Ferric Compounds; D016256:Lewis X Antigen; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C000499:ferric oxide