title: Biocytin-derived MRI contrast agent for longitudinal brain connectivity studies.
abstract: To investigate the connectivity of brain networks noninvasively and dynamically, we have developed a new strategy to functionalize neuronal tracers and designed a biocompatible probe that can be visualized in vivo using magnetic resonance imaging (MRI). Furthermore, the multimodal design used allows combined ex vivo studies with microscopic spatial resolution by conventional histochemical techniques. We present data on the functionalization of biocytin, a well-known neuronal tract tracer, and demonstrate the validity of the approach by showing brain networks of cortical connectivity in live rats under MRI, together with the corresponding microscopic details, such as fibers and neuronal morphology under light microscopy. We further demonstrate that the developed molecule is the first MRI-visible probe to preferentially trace retrograde connections. Our study offers a new platform for the development of multimodal molecular imaging tools of broad interest in neuroscience, that capture in vivo the dynamics of large scale neural networks together with their microscopic characteristics, thereby spanning several organizational levels.
authors.affiliation: Department for Physiology of Cognitive Processes and ‡High-Field MR Center, Max-Planck Institute for Biological Cybernetics,Spemannstrasse 38, 72076 T€ubingen, Germany.
authors.forename: Anurag
authors.initials: A
authors.lastname: Mishra
authors.forename: Almut
authors.initials: A
authors.lastname: Schüz
authors.forename: Jörn
authors.initials: J
authors.lastname: Engelmann
authors.forename: Michael
authors.initials: M
authors.lastname: Beyerlein
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.forename: Santiago
authors.initials: S
authors.lastname: Canals
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives*; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development*; D001931:Brain Mapping; D001932:Brain Neoplasms / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015195:Drug Design; D005682:Gadolinium / Q000737:chemistry; D008024:Ligands; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009434:Neural Pathways / Q000033:anatomy & histology / Q000254:growth & development*; D009447:Neuroblastoma / Q000473:pathology; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D008024:Ligands; D011522:Protons; D001710:Biotin; D005682:Gadolinium; C013411:biocytin; D008239:Lysine