Imaging hypothalamic activity using diffusion weighted magnetic resonance imaging in the mouse and human brain

• Published in: NeuroImage (Orlando, Fla.) Vol. 64; pp. 448 - 457
• Main Authors: Lizarbe, Blanca, Benítez, Ania, Sánchez-Montañés, Manuel, Lago-Fernández, Luis F., Garcia-Martin, María L., López-Larrubia, Pilar, Cerdán, Sebastián
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-01-2013; Elsevier; Elsevier Limited
• Subjects: Action Potentials - physiology; Adult; Algorithms; Animals; Appetite - physiology; Appetite regulation; Biexponential diffusion; Biological and medical sciences; Body temperature; Brain Mapping - methods; Cerebral activation; Diet; Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion weighted MRI; Experiments; Fasting - physiology; Food; Functional imaging; Fundamental and applied biological sciences. Psychology; Humans; Hypothalamus - physiology; Image analysis; Image Enhancement - methods; Image Interpretation, Computer-Assisted - methods; Insulin; Male; Methods; Mice; Mice, Inbred C57BL; NMR; Nuclear magnetic resonance; Nutrition research; Reproducibility of Results; Rodents; Sensitivity and Specificity; Species Specificity; Studies; Vertebrates: nervous system and sense organs; Volunteers; Young Adult; Biexponential diffusion; Dslow; Appetite regulation; Image analysis; FDP; Cerebral activation; LDA; Diffusion weighted MRI; Dfast; SDP; Functional imaging; Appetite; Human; Rodentia; Central nervous system; Hypothalamus; Nuclear magnetic resonance imaging; Encephalon; Vertebrata; Mammalia; Mouse; Animal; Imaging
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2012.09.033

Hypothalamic appetite regulation is a vital homeostatic process underlying global energy balance in animals and humans, its disturbances resulting in feeding disorders with high morbidity and mortality. The objective evaluation of appetite remains difficult, very often restricted to indirect measurements of food intake and body weight. We report here, the direct, non‐invasive visualization of hypothalamic activation by fasting using diffusion weighted magnetic resonance imaging, in the mouse brain as well as in a preliminary study in the human brain. The brain of fed or fasted mice or humans were imaged at 7 or 1.5Tesla, respectively, by diffusion weighted magnetic resonance imaging using a complete range of b values (10<b<2000s.mm−2). The diffusion weighted image data sets were registered and analyzed pixel by pixel using a biexponential model of diffusion, or a model-free Linear Discriminant Analysis approach. Biexponential fittings revealed statistically significant increases in the slow diffusion parameters of the model, consistent with a neurocellular swelling response in the fasted hypothalamus. Increased resolution approaches allowed the detection of increases in the diffusion parameters within the Arcuate Nucleus, Ventromedial Nucleus and Dorsomedial Nucleus. Independently, Linear Discriminant Analysis was able to classify successfully the diffusion data sets from mice and humans between fed and fasted states. Present results are consistent with increased glutamatergic neurotransmission during orexigenic firing, a process resulting in increased ionic accumulation and concomitant osmotic neurocellular swelling. This swelling response is spatially extendable through surrounding astrocytic networks until it becomes MRI detectable. Present findings open new avenues for the direct, non‐invasive, evaluation of appetite disorders and other hypothalamic pathologies helping potentially in the development of the corresponding therapies.
We investigate the non‐invasive evaluation of the appetite impulse by diffusion weighted magnetic resonance imaging. We report that hypothalamic activation by fasting in mice (and humans) can be detected through increases in the slow diffusion phase (SDP) and the slow diffusion coefficient (Dslow) parameters of the hypothalamus and some hypothalamic nuclei. Model independent Linear Discriminant Analysis is able also to classify successfully all data sets between fed and fasted states. [Display omitted]
► DWI identifies hypothalamic activation by fasting in mice and humans. ► Increases in diffusion parameters can be observed in subhypothalamic nuclei. ► Fisher analysis discriminates DWI from fed and fasted states in mice and humans. ► Increases in diffusion may reveal osmotic changes associated with neuronal firing. ► DWI provides a useful tool to evaluate hypothalamic performance.