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The present study aims to monitor longitudinal changes in simulated tumor interstitial fluid pressure (IFP) and velocity (IFV) values using dynamic contrast-enhanced (DCE)-MRI-based computational fluid modeling (CFM) in pancreatic ductal adenocarcinoma (PDAC) patients. Nine PDAC patients underwent MRI, including DCE-MRI, on a 3-Tesla MRI scanner at pre-treatment (TX (0)), after the first fraction of stereotactic body radiotherapy (SBRT, (D1-TX)), and six weeks post-TX (D2-TX). The partial differential equation of IFP formulated from the continuity equation, incorporating the Starling Principle of fluid exchange, Darcy velocity, and volume transfer constant (Ktrans), was solved in COMSOL Multiphysics software to generate IFP and IFV maps. Tumor volume (Vt), Ktrans, IFP, and IFV values were compared (Wilcoxon and Spearman) between the time- points. D2-TX Ktrans values were significantly different from pre-TX and D1-TX (p &lt, 0.05). The D1-TX and pre-TX mean IFV values exhibited a borderline significant difference (p = 0.08). The IFP values varying &lt, 3.0% between the three time-points were not significantly different (p &gt, 0.05). Vt and IFP values were strongly positively correlated at pre-TX (r = 0.90, p = 0.005), while IFV exhibited a strong negative correlation at D1-TX (r = −0.74, p = 0.045). Vt, Ktrans, IFP, and IFV hold promise as imaging biomarkers of early response to therapy in PDAC.