Evaluation of the Glymphatic System in Rabbits Using Gadobutrol-Enhanced MR Cisternography With T1 and T2 Mapping

We aimed to characterize and further understand CSF circulation and outflow of rabbits. To our knowledge, there is no research on contrast material-enhanced MR cisternography (CE-MRC) with T1 and T2 mapping in the rabbit model using a clinical 3-T MR unit without a stereotaxic frame.

Twenty-one rabbits were included in the study. The CE-MRC exams with T1/T2 mappings were categorized into approximate time points based on an intention-to-scan approach: precontrast, less than 4 h after contrast, 24 h after contrast, and 24 to 120 h after gadobutrol. The presence of contrast media in the head and neck structures was scored with a 3-point scale (present, score: 2; absent, score: 0; and inconsistent, score: 1). T1 and T2 estimates were directly derived by drawing regions of interest on the corresponding maps.

Gadobutrol accumulation was detected in the CSF near the cribriform plate and nasal areas on early-phase postcontrast images of all animals. These contrast material accumulations completely disappeared on the images obtained in postcontrast ≥ 24 h. The lowest T1 and T2 estimates in olfactory and cerebral areas were observed on early-phase images. Significant correlations were observed between the enhancement of the bladder and the medial portion of the sclera and the enhancement of inner ear structures, olfactory regions, turbinates, nasal cavities, and cranial subarachnoid spaces. The T1 and T2 estimates of the septum and olfactory bulb were generally lower than those measured in the frontal and parietal lobes on early-phase images.

Our findings, which indicate an absence of clearly visible arachnoid granulations in rabbits, support the significance of olfactory outflow and the glymphatic system as highlighted in recent literature. Glymphatic transport can be more effectively demonstrated using T1 mapping in rabbits. The anatomical and physiological differences between human and rodent central nervous systems must be considered when translating experimental results from rabbits to humans.