title: In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE).
abstract: The infiltration of autoreactive T cells into the central nervous system (CNS) requires a complex molecular interplay between immune cells and the blood-brain barrier (BBB), especially involving adhesion molecules like intercellular adhesion molecule (ICAM)-1. Here we study the molecular expression at the BBB during adoptively transferred (AT) myelin basic protein (MBP)-experimental autoimmune encephalomyelitis (EAE) in vivo by sensitive particle acoustic quantification (SPAQ)-enhanced ultrasound after intravenous application of specific gas-filled MP (MP) targeted against ICAM-1 (ICAM-MP) as contrast agent. Our results reveal a clear periventricular and cerebellar upregulation of ICAM-1 expression at the disease maximum of AT-EAE. Moreover, SPAQ-enhanced ultrasound enables the sensitive quantification of ICAM-1 expression in vivo. This allows to monitor therapeutic changes as shown by suppression of ICAM-1 expression after pretreatment of rats with corticosteroids (P < 0.008). All imaging results were confirmed by parallel immunohistochemistry. In vivo magnetic resonance imaging and albumin staining of rat brains after sonification did not reveal a disturbance of the BBB, thereby proving the safety of the method. Subsequent application of specific MP did not influence follow-up measurements, a prerequisite for sequential measurements in longitudinal studies. Based on these data, quantitative molecular imaging of adhesion molecules by SPAQ-enhanced ultrasound proves to be a safe and reliable technology to monitor changes at the BBB in vivo.
authors.affiliation: Clinical Research Group for Multiple Sclerosis, Department of Neurology, Julius Maximilians-Universität Würzburg, Josef-Schneider-Strasse 11, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.forename: Michael
authors.initials: M
authors.lastname: Reinhardt
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.forename: Gesa
authors.initials: G
authors.lastname: Ladewig
authors.forename: Andreas
authors.initials: A
authors.lastname: Briel
authors.forename: Michael
authors.initials: M
authors.lastname: Schirner
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.forename: Peter
authors.initials: P
authors.lastname: Hauff
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003720:Densitometry; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D014463:Ultrasonography
chemical_list: D018799:Intercellular Adhesion Molecule-1; D008775:Methylprednisolone