Transmembrane dynamics of water exchange in human brain

Tracking arterial spin labeled (ASL) water in the human brain with magnetic resonance imaging can provide important information on the dynamics of the trans-capillary and trans-membrane water exchange. This information however, is not only important from a basic biological standpoint, but also is essential for deciphering positron emission tomography and MRI perfusion experiments based on the movement of labeled water. While substantial information exists on water exchange through cellular membranes in vitro, the in vivo information remains limited and controversial. In this MRI study, we use a combination of pulsed ASL and recently developed quantitative blood-oxygen-level-dependent technique to address this question. Our approach is based on the measurements of the intrinsic MR transverse relaxation (T2*) properties of the ASL-labeled water. We discovered that T2* of the ASL-labeled water in the extravascular space is 87 ms ± 10 ms while T2* of the corresponding tissue water is much shorter, 50 ms ± 4 ms. This suggests that the ASL-labeled water does not reach equilibrium with the extravascular tissue and is mostly localized to the extraneuronal space. We estimated that the water transport time through the neuronal membranes is on the order of several tens of seconds; a finding consistent with older PET tracer kinetic studies using (15)O-water.