Brain Tissue Water Comes in 2 Pools: Evidence from Diffusion & R2 Measurements with USPIOs in Non Human Primates

Denis Le Bihan^1,2, Olivier Joly³, Toshihiko Aso², Lynn Uhrig³, Cyril Poupon¹, Naoki Tani³, H. Iwamuro³, Shin-Ichi Urayama², Bechir Jarraya³

Water diffusion in biological tissues is not free, as the signal attenuation is not monoexponential with diffusion-weigthing (b value). Some groups have successfully characterize this attenuation with a biexponential model, which suggests the presence of 2 water pools (fast and slow) in slow or intermediate exchange. However, this model is still controversial and the nature of the 2 remains elusive. Here we show that this 2 pools model also explains the T2 behavior of USPIO contrast agents in the non-human primate brain. This mechanism which also applies to blood deoxyhemoglobin may have implications for the interpretation of BOLD experiments. Finally, the possibility to target USPIO effects to a specific water pool using diffusion-weighting might offer new contrast avenues, especially for molecular imaging.