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PURPOSE To investigate the feasibility of simultaneously estimating cellular water efflux rate (kie ), intracellular longitudinal relaxation rate (R10i ) and intracellular volume fraction (vi ) of a cell suspension using multiple samples with different gadolinium concentrations. METHODS Numerical simulation studies were conducted to assess the uncertainty in estimation of kie , R10i , and vi from saturation recovery data using single (SC) or multiple concentrations (MC) of gadolinium-based contrast agent (GBCA). In vitro experiments with 4T1 murine breast cancer and SCCVII squamous cell cancer models were conducted at 11T to compare parameter estimation using the SC protocol with that using the MC protocol. The cell lines were challenged with a Na+ /K+ -ATPase inhibitor Digoxin to assess the treatment response in terms of kie , R10i , and vi . Data analysis was conducted using the two-compartment exchange model for parameter estimation. RESULTS The simulation study data demonstrate that the MC method compared with the SC method reduces the uncertainty of the estimated kie by decreasing the inter-quartile ranges of 27.3±3.7% to 18.8±5.1% and the median differences from ground truth from 15.0±6.3% to 7.2±4.2%, while estimating R10i and vi simultaneously. In the cell studies, the MC method demonstrated reduced uncertainty in overall parameter estimation compared with the SC approach. MC method measured parameter changes in cells treated with Digoxin increased R10i by 11.7% (P = 0.218) and kie by 5.9 % (P = 0.234) for 4T1 cells, respectively, and decreases R10i by 28.8 % (P = 0.226) and kie by 1.6 % (P = 0.751) for SCCVII cells, respectively. vi did not change noticeably by the treatment. CONCLUSION The results of this study substantiate the feasibility of using saturation recovery data of multiple samples with different GBCA concentrations for simultaneous measurement of cellular water efflux rate, intracellular volume fraction, and intracellular longitudinal relaxation rate in cancer cells.