Abstract
Entorhinal cortex (EC) is a potential target of deep brain stimulation in Alzheimer's disease (AD) rodent models. Studies reported that the lateral EC is the earliest forebrain area affected by AD, as shown by neurofibrillary tangles. However, it remains challenging to study the EC-based fMRI connectivity in rats due to image signal loss and the lower sensitivity of the surface coil ring or array coil for the deep brain areas, in particular, EC. The fMRI image signal loss at EC is due to its proximity to the air-tissue interface in the ears which introduces a high level of magnetic field inhomogeneity. To reduce the signal loss issue, we introduced baby cream (Baby Healing Ointment, Meijer) into the middle ear. To address the sensitivity issue of the coil, we implemented two inductively coupled ear-bars (ICEs) in the 7T Bruker scanner to relay locally detected MR signals to the external coil array with a nearly 2-fold signal-to-noise in EC over the conventional surface array increase. We now can acquire high-quality functional images of the rat brains with restored fMRI signal in the EC (spatial resolution: 0.5 mm × 0.5 mm × 0.5 mm, TR: 1s), along with high-quality high-resolution structural images in dexmedetomidine-anesthetized dementia rats. We evaluated this setup by measuring the fMRI signal over the whole brain first using task fMRI with electrical stimulation on the left forepaw (3 Hz, 4 s, 3 mA stimulation) and then using resting-state fMRI (rs-fMRI). In the task fMRI, we observed a robust evoked BOLD signal along with the ascending projection to the motor cortex from the thalamus. In the rs-fMRI, we observed a strong default-mode network, including prelimbic cortex, cingulate cortex, auditory cortex, posterior parietal cortex, and retrosplenial cortex. Finally, we analyzed the seed-based rs-fMRI connectivity maps based on the left EC and observed strong connectivity in the hippocampus, piriform cortex, septal nuclei, and prefrontal cortex. In summary, our optimized ICE-based procedure enables and facilitates EC-driven brain fMRI studies with a simplified experimental setup and provides the possibility to further study EC in AD rat models.
