In this study, we used mice, marmosets and humans to perform DTT on olfactory nerves within the nasal cavity and olfactory bulb. DTT virtually reconstructs neuronal pathways in three dimensions based on the diffusion and anisotropy of water molecules, and this technique is now commonly used in the field of neuroscience to estimate fiber pathways within the brain 5. The development and refinement of DTT during the past few decades has been made possible by advances in MRI technology (including increases in magnetic field intensity) and improvements in analytical techniques. Therefore, we conceived a new method of visualizing olfactory nerves using diffusion tensor tractography (DTT), which is based on magnetic resonance imaging (MRI). Additionally, the conventional techniques (e.g., neural tracers, immunostaining and transgenic animal models) used to evaluate the distribution of olfactory nerves are labor-intensive and require the use of tissue specimens to assess the continuity of nerves 4, which precludes their utilization in large numbers of people or animals. However, the neural pathways running from the nasal cavity to the olfactory bulb in humans have not been characterized in detail, and various theories exist regarding the distribution of olfactory mucosal epithelium in the human nasal cavity. Previous findings in mice have revealed a topographical correlation between the nasal cavity and olfactory bulb known as the odor map 3. These investigations have included a histological analysis of the types of epithelial tissue lining the nasal cavity 2, the use of transgenic animal models to visualize olfactory nerves expressing a single type of olfactory receptor 1, and mapping of nerve pathways using neural tracers 3. Most studies exploring the distribution of the olfactory nerves in the nasal cavity and the neuronal pathways projecting to the olfactory bulb have been conducted in rodents. Clarifying the distribution of the olfactory sensory neurons in the nasal cavity and the projections of these nerves to the olfactory bulb are essential to understanding the pathogenesis of olfactory dysfunction. Olfactory dysfunction can be caused by a variety of factors and is classified into three categories according to the anatomical location of the lesion: conductive (nasal disorders such as obstruction by polyps or inflammation), sensorineural (dysfunction of the olfactory sensory neurons themselves) and central (secondary to head trauma or conditions affecting the central nervous system such as brain tumors or neurodegenerative diseases). The surface of the olfactory bulb contains numerous glomeruli, and nerve fibers from olfactory neurons expressing the same olfactory receptor gene gather in a particular glomerulus 1. The chemical stimuli are transduced into electrical signals, and the projections of the olfactory neurons form nerve bundles that pass through the cribriform plate to reach the olfactory bulb, which is the primary center of olfaction. The first step in olfaction involves the binding of volatile small molecules to olfactory receptors on olfactory neurons in the nasal cavity. Further development of this technique might allow it to be used clinically to facilitate the diagnosis of olfactory dysfunction. The olfactory nerve maps revealed that the dorsal-ventral and medial-lateral axes were preserved between the olfactory epithelium and olfactory bulb in all three species. This technique allowed us to evaluate the olfactory sensory neuron projections from the nasal cavities to the olfactory bulbs and visualize the olfactory nerve maps of humans, marmosets and mice. ![]() ![]() ![]() Here, we demonstrate that high-field magnetic resonance imaging and diffusion tensor tractography can be used to visualize olfactory sensory neurons while maintaining their three-dimensional structures. However, the human olfactory nerve map remains unknown. Previous studies have constructed the olfactory nerve maps of rodents using histological analyses or transgenic animal models to investigate olfactory nerve pathways. The olfactory nerve map describes the topographical neural connections between the olfactory epithelium in the nasal cavity and the olfactory bulb.
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