title: Development of a MR-visible compound for tracing neuroanatomical connections in vivo.
abstract: Traditional studies of neuroanatomical connections require injection of tracer compounds into living brains, then histology of the postmortem tissue. Here, we describe and validate a compound that reveals neuronal connections in vivo, using MRI. The classic anatomical tracer CTB (cholera-toxin subunit-B) was conjugated with a gadolinium-chelate to form GdDOTA-CTB. GdDOTA-CTB was injected into the primary somatosensory cortex (S1) or the olfactory pathway of rats. High-resolution MR images were collected at a range of time points at 11.7T and 7T. The transported GdDOTA-CTB was visible for at least 1 month post-injection, clearing within 2 months. Control injections of non-conjugated GdDOTA into S1 were not transported and cleared within 1-2 days. Control injections of Gd-Albumin were not transported either, clearing within 7 days. These MR results were verified by classic immunohistochemical staining for CTB, in the same animals. The GdDOTA-CTB neuronal transport was target specific, monosynaptic, stable for several weeks, and reproducible.
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA. carolyn.wu@cea.fr
authors.forename: Carolyn W-H
authors.initials: CW
authors.lastname: Wu
authors.forename: Olga
authors.initials: O
authors.lastname: Vasalatiy
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.forename: Sarah
authors.initials: S
authors.lastname: Cheal
authors.forename: Der-Yow
authors.initials: DY
authors.lastname: Chen
authors.forename: Alan P
authors.initials: AP
authors.lastname: Koretsky
authors.forename: Gary L
authors.initials: GL
authors.lastname: Griffiths
authors.forename: Roger B H
authors.initials: RB
authors.lastname: Tootell
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Ungerleider
mesh_terms: D000818:Animals; D002772:Cholera Toxin / Q000378:metabolism / Q000493:pharmacokinetics; D005682:Gadolinium / Q000378:metabolism / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D009445:Neuroanatomy / Q000295:instrumentation / Q000379:methods; D009833:Olfactory Pathways / Q000033:anatomy & histology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000033:anatomy & histology*; D013788:Thalamus / Q000033:anatomy & histology / Q000378:metabolism; D013997:Time Factors
chemical_list: D002772:Cholera Toxin; D005682:Gadolinium