| Summary: | 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 (K<sup>trans</sup>), was solved in COMSOL Multiphysics software to generate IFP and IFV maps. Tumor volume (V<sub>t</sub>), K<sup>trans</sup>, IFP, and IFV values were compared (Wilcoxon and Spearman) between the time- points. D2-TX K<sup>trans</sup> values were significantly different from pre-TX and D1-TX (<i>p</i> < 0.05). The D1-TX and pre-TX mean IFV values exhibited a borderline significant difference (<i>p</i> = 0.08). The IFP values varying <3.0% between the three time-points were not significantly different (<i>p</i> > 0.05). V<sub>t</sub> and IFP values were strongly positively correlated at pre-TX (ρ = 0.90, <i>p</i> = 0.005), while IFV exhibited a strong negative correlation at D1-TX (ρ = −0.74, <i>p</i> = 0.045). V<sub>t</sub>, K<sup>trans</sup>, IFP, and IFV hold promise as imaging biomarkers of early response to therapy in PDAC.
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