title: Efficacy of positive contrast imaging techniques for molecular MRI of tumor angiogenesis.
abstract: Superparamagnetic iron oxide particles (SPIOs) are promising contrast agents for molecular MRI. To improve the in vivo detection of iron-based contrast media, positive contrast imaging techniques have been developed. Here, the efficacy of two positive contrast techniques, white marker and susceptibility gradient mapping (SGM), were evaluated for molecular MRI of tumor angiogenesis and compared with conventional negative contrast gradient echo (GE) imaging. In vitro, cylindrical phantoms containing varying iron oxide concentrations were used to measure the response of positive contrast techniques. In vivo, tumor bearing mice were used as a model for tumor angiogenesis. Mice were injected with unlabeled SPIOs (n = 5) or SPIOs labeled with cyclic NGR peptide (cNGR) (n = 5), which homes specifically to angiogenic microvessels. Pre- and post-contrast GE and white marker images were acquired. Subsequently, SGM images and R(2)(*) maps were calculated. For image analysis, the contrast-to-noise ratio (CNR) and the percentage of enhanced voxels (EVs) in the tumor rim and core were calculated. In vitro, the linear increases in MRI signal response for increasing iron oxide concentration were much stronger for SGM than white marker. In vivo, the CNR of GE, white marker and SGM imaging was 5.7, 1.2 and 6.2, respectively, with equal acquisition times. Significant differences in the percentage of EVs between the tumor rim and core were found using R(2)(*) mapping, GE and SGM (p < 0.05). The two contrast agents had significantly different percentages of EVs by R(2)(*) mapping and SGM in the rim (p < 0.001). The in vivo efficacy of white marker and SGM was evaluated for molecular MRI relative to GE imaging and R(2)(*) mapping. Only SGM, and not white marker, can be used to transfer the negative contrast from targeted SPIOs in a positive contrast signal without loss of CNR.
authors.affiliation: Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Wolters
authors.forename: M
authors.initials: M
authors.lastname: Oostendorp
authors.forename: B F
authors.initials: BF
authors.lastname: Coolen
authors.forename: M J
authors.initials: MJ
authors.lastname: Post
authors.forename: J M H
authors.initials: JM
authors.lastname: Janssen
authors.forename: G J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: M E
authors.initials: ME
authors.lastname: Kooi
authors.forename: K
authors.initials: K
authors.lastname: Nicolay
authors.forename: W H
authors.initials: WH
authors.lastname: Backes
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D017352:Echo-Planar Imaging; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D019047:Phantoms, Imaging; D012815:Signal Processing, Computer-Assisted; D059629:Signal-To-Noise Ratio
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide