LAUSR

Evidence mounts that the steady‐state cellular water efflux (unidirectional) first‐order rate constant (kio [s−1]) magnitude reflects the ongoing, cellular metabolic rate of the cytolemmal Na+, K+‐ATPase (NKA), cMRNKA (pmol [ATP consumed by NKA]/s/cell), perhaps biology's most vital enzyme. Optimal 1H2O MR kio determinations require paramagnetic contrast agents (CAs) in model systems. However, results suggest that the homeostatic metabolic kio biomarker magnitude in vivo is often too large to be reached with allowable or possible CA living tissue distributions. Thus, we seek a noninvasive (CA‐free) method to determine kio in vivo. Because membrane water permeability has long been considered important in tissue water diffusion, we turn to the well‐known diffusion‐weighted MRI (DWI) modality. To analyze the diffusion tensor magnitude, we use a parsimoniously primitive model featuring Monte Carlo simulations of water diffusion in virtual ensembles comprising water‐filled and ‐immersed randomly sized/shaped contracted Voronoi cells. We find this requires two additional, cytometric properties: the mean cell volume (V [pL]) and the cell number density (ρ [cells/μL]), important biomarkers in their own right. We call this approach metabolic activity diffusion imaging (MADI).