By contrast, manganese enhancement at the transport zones, within a few hours after injection, rapidly spread into neighboring regions, including different subfields

of the same nucleus, and even into different nuclei (Figure 7B, right panels, Figure 7C, lower panel, and Figure 7D, Small molecule library lower right panel). Thus, compared with the GdDOTA-CTB, it is more difficult to use manganese to reveal the precise zones that are directly connected with the injection site, if transport results are not timed precisely. This can be especially challenging if transport is faster for some targets (e.g., closer targets) compared to others (further away from the injection site). In such cases, perhaps no single transport time is optimal. To test for transport in a peripheral neural pathway, we

injected GdDOTA-CTB unilaterally into the nostril cavity (n = 2). Strong signal enhancement was observed in the olfactory epithelium, exclusively ipsilateral to the injection, as early learn more as 12 hr following the injection (i.e., the second MRI time point). By day 2, robust enhancement was clearly detected throughout the olfactory epithelium and along the olfactory tract ipsilateral to the injection (Figure 8A). Weaker enhancement was also found in the outer layer of the inferior olfactory bulb (OB, i.e., the glomeruli layer). Some individual glomeruli in the specific region of the OB could be easily identified

based on the MRI enhancement patterns (Figure 8B). Enhancement in these regions lasted up to 7 days. The injection of GdDOTA-CTB into one nostril did not enhance signal in the contralateral nostril pathway, consistent with the known anatomical evidence (for review, see Imai and Sakano, 2008; also see Kikuta et al., 2008, Figure 1). Together, these results suggest that GdDOTA-CTB can be used to trace peripheral anatomical pathways, in addition to central ones. Following Isotretinoin unilateral injection of the OB, MR signal enhancement was found on day 7 in other regions of the OB, and in part of the ipsilateral anterior olfactory nucleus (AON; Figure 8C). Weaker enhancement could also be detected in the ipsilateral projection of the central olfactory pathway to pyriform cortex (Figure 8C). The location and pattern of GdDOTA-CTB transport is consistent with known olfactory pathways using conventional tracers (Smithson et al., 1989). To our knowledge, this study is the first to demonstrate brain connections in vivo, using a purpose-designed compound combining a classic neuroanatomical tracer (here, cholera-toxin subunit-B, CTB) with a known MRI-visible label (gadolinium-chelate, GdDOTA).