Zinc Nanoparticles Enhance Brain Connectivity in the Canine Olfactory Network: Evidence From an fMRI Study in Unrestrained Awake Dogs.

Prior functional Magnetic Resonance Imaging (fMRI) studies have indicated increased neural activation when zinc nanoparticles are added to odorants in canines. Here we demonstrate that zinc nanoparticles up-regulate directional brain connectivity in parts of the canine olfactory network. This provides an explanation for previously reported enhancement in the odor detection capability of the dogs in the presence of zinc nanoparticles. In this study, we obtained fMRI data from awake and unrestrained dogs while they were being exposed to odorants with and without zinc nanoparticles, zinc nanoparticles suspended in water vapor, as well as just water vapor alone. We obtained directional connectivity between the brain regions of the olfactory network that were significantly stronger for the condition of odorant + zinc nanoparticles compared to just odorants, water vapor + zinc nanoparticles and water vapor alone. We observed significant strengthening of the paths of the canine olfactory network in the presence of zinc nanoparticles. This result indicates that zinc nanoparticles could potentially be used to increase canine detection capabilities in the environments of very low concentrations of the odorants, which would have otherwise been undetected.

Enhancement of Odor-Induced Activity in the Canine Brain by Zinc Nanoparticles: A Functional MRI Study in Fully Unrestrained Conscious Dogs.

Using noninvasive in vivo functional magnetic resonance imaging (fMRI), we demonstrate that the enhancement of odorant response of olfactory receptor neurons by zinc nanoparticles leads to increase in activity in olfaction-related and higher order areas of the dog brain. To study conscious dogs, we employed behavioral training and optical motion tracking for reducing head motion artifacts. We obtained brain activation maps from dogs in both anesthetized state and fully conscious and unrestrained state. The enhancement effect of zinc nanoparticles was higher in conscious dogs with more activation in higher order areas as compared with anesthetized dogs. In conscious dogs, voxels in the olfactory bulb and hippocampus showed higher activity to odorants mixed with zinc nanoparticles as compared with pure odorants, odorants mixed with gold nanoparticles as well as zinc nanoparticles alone. These regions have been implicated in odor intensity processing in other species including humans. If the enhancement effect of zinc nanoparticles observed in vivo are confirmed by future behavioral studies, zinc nanoparticles may provide a way for enhancing the olfactory sensitivity of canines for detection of target substances such as explosives and contraband substances at very low concentrations, which would otherwise go undetected.

Functional MRI of the olfactory system in conscious dogs.

We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology.

Improving optical contact for functional near­infrared brain spectroscopy and imaging with brush optodes.

A novel brush optode was designed and demonstrated to overcome poor optical contact with the scalp that can occur during functional near infrared spectroscopy (fNIRS) and imaging due to light obstruction by hair. The brush optodes were implemented as an attachment to existing commercial flat-faced (conventional) fiber bundle optodes. The goal was that the brush optodes would thread through hair and improve optical contact on subjects with dense hair. Simulations and experiments were performed to assess the magnitude of these improvements. FNIRS measurements on 17 subjects with varying hair colors (blonde, brown, and black) and hair densities (0-2.96 hairs/mm(2)) were performed during a finger tapping protocol for both flat and brush optodes. In addition to reaching a study success rate of almost 100% when using the brush optode extensions, the measurement setup times were reduced by a factor of three. Furthermore, the brush optodes enabled improvements in the activation signal-to-noise ratio (SNR) by up to a factor of ten as well as significant (p < 0.05) increases in the detected area of activation (dAoA). The measured improvements in SNR were matched by Monte Carlo (MC) simulations of photon propagation through scalp and hair. In addition, an analytical model was derived to mathematically estimate the observed light power losses due to different hair colors and hair densities. Interestingly, the derived analytical formula produced excellent estimates of the experimental data and MC simulation results despite several simplifying assumptions. The analytical model enables researchers to readily estimate the light power losses due to obstruction by hair for both flat-faced fiber bundles and individual fibers for a given subject.

Single-camera motion measurement and monitoring for magnetic resonance applications.

An optically based rigid-body six-degrees of freedom (DOF) measurement system optimized for prospective (real-time) motion correction in magnetic resonance imaging (MRI) applications is described. By optimizing system capabilities to the specific applications requirements, the six-DOF measurement is accomplished using a single camera and simple three-disc fiducial at rates of 50 Hz. The algorithm utilizes successive approximation to solve the three point pose problem for angles close to the origin. Convergence to submicroradian levels occurs within 20 iterations for angles in an approximate half-radian (29°) arc centered on the origin. The overall absolute accuracy of the instrument is 10-100 µm for translational and <100 µrad (0.005°) for rotational motions. Results for head nodding and speech tasks are presented for subjects in the MR scanner, and the instrument results are compared to standard prospective acquisition correction.

fMRI headtracking using a single camera and a lightweight fiducial.

A single CCD/DSP camera based optical system affords six degree of freedom motion tracking for MRI applications with resolutions in the range of < 50 microradians and 10-100 microns. The fiducial target is a lightweight compact three dimensional pattern that allows efficient, centroid based algorithms to determine distance translation and angle rotation at rates of 30Hz. In-magnet tests measure the inherent magnet vibration as well as subject signatures such as those for respiration, speech, swallow and nod.