title: In vivo imaging of optic nerve fiber integrity by contrast-enhanced MRI in mice.
abstract: The rodent visual system encompasses retinal ganglion cells and their axons that form the optic nerve to enter thalamic and midbrain centers, and postsynaptic projections to the visual cortex. Based on its distinct anatomical structure and convenient accessibility, it has become the favored structure for studies on neuronal survival, axonal regeneration, and synaptic plasticity. Recent advancements in MR imaging have enabled the in vivo visualization of the retino-tectal part of this projection using manganese mediated contrast enhancement (MEMRI). Here, we present a MEMRI protocol for illustration of the visual projection in mice, by which resolutions of (200 µm)3 can be achieved using common 3 Tesla scanners. We demonstrate how intravitreal injection of a single dosage of 15 nmol MnCl2 leads to a saturated enhancement of the intact projection within 24 hr. With exception of the retina, changes in signal intensity are independent of coincided visual stimulation or physiological aging. We further apply this technique to longitudinally monitor axonal degeneration in response to acute optic nerve injury, a paradigm by which Mn2+ transport completely arrests at the lesion site. Conversely, active Mn2+ transport is quantitatively proportionate to the viability, number, and electrical activity of axon fibers. For such an analysis, we exemplify Mn2+ transport kinetics along the visual path in a transgenic mouse model (NF-κB p50KO) displaying spontaneous atrophy of sensory, including visual, projections. In these mice, MEMRI indicates reduced but not delayed Mn2+ transport as compared to wild type mice, thus revealing signs of structural and/or functional impairments by NF-κB mutations. In summary, MEMRI conveniently bridges in vivo assays and post mortem histology for the characterization of nerve fiber integrity and activity. It is highly useful for longitudinal studies on axonal degeneration and regeneration, and investigations of mutant mice for genuine or inducible phenotypes.
authors: Hans Berger Department of Neurology, Jena University Hospital.
authors: Stefanie
authors: S
authors: Fischer
authors: Immunology, Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena.
authors: Christian
authors: C
authors: Engelmann
authors: Institute of Diagnostic and Interventional Radiology, Medical Physics Group, Jena University Hospital.
authors: Karl-Heinz
authors: KH
authors: Herrmann
authors: Institute of Diagnostic and Interventional Radiology, Medical Physics Group, Jena University Hospital.
authors: Jürgen R
authors: JR
authors: Reichenbach
authors: Hans Berger Department of Neurology, Jena University Hospital.
authors: Otto W
authors: OW
authors: Witte
authors: Immunology, Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena.
authors: Falk
authors: F
authors: Weih
authors: Hans Berger Department of Neurology, Jena University Hospital.
authors: Alexandra
authors: A
authors: Kretz
authors: Immunology, Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena; rhaenold@fli-leibniz.de.
authors: Ronny
authors: R
authors: Haenold
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D003287:Contrast Media; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000473:pathology; D009900:Optic Nerve / Q000033:anatomy & histology* / Q000166:cytology; D009901:Optic Nerve Diseases / Q000473:pathology; D020221:Optic Nerve Injuries / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000166:cytology; D014795:Visual Pathways / Q000033:anatomy & histology / Q000166:cytology
chemical_list: D003287:Contrast Media