title: Target-specific contrast agents for magnetic resonance microscopy.
abstract: High-resolution ex vivo magnetic resonance (MR) imaging can be used to delineate prominent architectonic features in the human brain, but increased contrast is required to visualize more subtle distinctions. To aid MR sensitivity to cell density and myelination, we have begun the development of target-specific paramagnetic contrast agents. This work details the first application of luxol fast blue (LFB), an optical stain for myelin, as a white matter-selective MR contrast agent for human ex vivo brain tissue. Formalin-fixed human visual cortex was imaged with an isotropic resolution between 80 and 150 microm at 4.7 and 14 T before and after en bloc staining with LFB. Longitudinal (R1) and transverse (R2) relaxation rates in LFB-stained tissue increased proportionally with myelination at both field strengths. Changes in R1 resulted in larger contrast-to-noise ratios (CNR), per unit time, on T1-weighted images between more myelinated cortical layers (IV-VI) and adjacent, superficial layers (I-III) at both field strengths. Specifically, CNR for LFB-treated samples increased by 229 +/- 13% at 4.7 T and 269 +/- 25% at 14 T when compared to controls. Also, additional cortical layers (IVca, IVd, and Va) were resolvable in 14 T-MR images of LFB-treated samples but not in control samples. After imaging, samples were sliced in 40-micron sections, mounted, and photographed. Both the macroscopic and microscopic distributions of LFB were found to mimic those of traditional histological preparations. Our results suggest target-specific contrast agents will enable more detailed MR images with applications in imaging pathological ex vivo samples and constructing better MR atlases from ex vivo brains.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129, USA.mlb@nmr.mgh.harvard.edu
authors.forename: Megan L
authors.initials: ML
authors.lastname: Blackwell
authors.forename: Christian T
authors.initials: CT
authors.lastname: Farrar
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosen
mesh_terms: D003287:Contrast Media / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007211:Indoles / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014793:Visual Cortex / Q000166:cytology*
chemical_list: D003287:Contrast Media; D007211:Indoles; C018588:Luxol Fast Blue MBS