Mapping human brain capillary water lifetime: high-resolution metabolic neuroimaging.

Shutter-speed analysis of dynamic-contrast-agent (CA)-enhanced normal, multiple sclerosis (MS), and glioblastoma (GBM) human brain data gives the mean capillary water molecule lifetime ((b)) and blood volume fraction (v(b); capillary density-volume product (V-dagger)) in a high-resolution (H2O)-H-1 MRI voxel (40 L) or ROI. The equilibrium water extravasation rate constant, k(po) ((-1)(b)), averages 3.2 and 2.9 s(-1) in resting-state normal white matter (NWM) and gray matter (NGM), respectively (n = 6). The results (italicized) lead to three major conclusions. (A) k(po) differences are dominated by capillary water permeability (P-W(dagger)), not size, differences. NWM and NGM voxel k(po)and v(b) values are independent. Quantitative analyses of concomitant population-averaged k(po), v(b) variations in normal and normal-appearing MS brain ROIs confirm P(W)(dagger)dominance. (B) P-W(dagger) is dominated (>95%) by a trans(endothelial)cellular pathway, not the P-CA(dagger) paracellular route. In MS lesions and GBM tumors, P(CA)(dagger)increases but P(W)(dagger)decreases. (C) k(po) tracks steady-state ATP production/consumption flux per capillary. In normal, MS, and GBM brain, regional k(po)correlates with literature MRSI ATP (positively) and Na+ (negatively) tissue concentrations. This suggests that the P(W)(dagger)pathway is metabolically active. Excellent agreement of the relative NGM/NWM k(po)v(b) product ratio with the literature (PMRSI)-P-31-MT CMRoxphos ratio confirms the flux property. We have previously shown that the cellular water molecule efflux rate constant (k(io)) is proportional to plasma membrane P-type ATPase turnover, likely due to active trans-membrane water cycling. With synaptic proximities and synergistic metabolic cooperativities, polar brain endothelial, neuroglial, and neuronal cells form gliovascular units. We hypothesize that a chain of water cycling processes transmits brain metabolic activity to k(po), letting it report neurogliovascular unit Na+,K+-ATPase activity. Cerebral k(po) maps represent metabolic (functional) neuroimages. The NGM 2.9 s(-1)k(po) means an equilibrium unidirectional water efflux of similar to 10(15) H2O molecules s(-1) per capillary (in 1 L tissue): consistent with the known ATP consumption rate and water co-transporting membrane symporter stoichiometries. (c) 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.