Cerebral hunger maps in rodents and humans by diffusion weighted MRI

We design, implement and validate a novel image processing strategy to obtain in vivo maps of hunger stimulation in the brain of mice, rats and humans, combining Diffusion Weighted Magnetic Resonance Imaging (DWI) datasets from fed and fasted subjects. Hunger maps were obtained from axial/coronal (rodents/humans) brain sections containing the hypothalamus and coplanar cortico-limbic structures using Fisher's Discriminant Analysis of the combined voxel ensembles from both feeding situations. These maps were validated against those provided by the classical mono-exponential diffusion model as applied over the same subjects and conditions. Mono-exponential fittings revealed significant Apparent Diffusion Coefficient (ADC) decreases through the brain regions stimulated by hunger, but rigorous parameter estimations imposed the rejection of considerable number of pixels. The proposed approach avoided pixel rejections and provided a representation of the combined DWI dataset as a pixel map of the “Hunger Index” (HI), a parameter revealing the hunger score of every pixel. The new methodology proved to be robust both, by yielding consistent results with classical ADC maps and, by reproducing very similar HI maps when applied to newly acquired rodent datasets. ADC and HI maps demonstrated similar patterns of activation by hunger in hypothalamic and cortico-limbic structures of the brain of rodents and humans, albeit with different relative intensities, rodents showing more intense activations by hunger than humans, for similar fasting periods. The proposed methodology may be easily extended to other feeding paradigms or even to alternative imaging methods.
This work was supported in part by Grants, SAF-2014-53739-R and SAF-2017-83043-R to SC and PLL, S2017/BMD-3688 to SC, PLL and MSM and grant CAM/UAM (CCG10-UAM/TIC-5864) to LFLF. AB held a predoctoral fellowship from the Spanish Agency for International Cooperation and Development and predoctoral contracts from CSIC and UAM. BL held predoctoral (BES-2009-02765) and postdoctoral contracts from the Spanish Ministry of Economy and Competitiveness and CSIC. IG held a predoctoral contract from the Spanish contracts from the Ministry of Economy and Competitiveness (BES-2015-075202).