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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.

Ernest Starling first presented a hypothesis about the absorption of tissue fluid to the plasma within tissue capillaries in 1896. In this Chapter we trace the evolution of Starling's hypothesis to a principle and an equation, and then look in more detail at the extension of the Starling principle in recent years. In 2012 Thomas Woodcock and his son proposed that experience and experimental observations surrounding clinical practices involving the administration of intravenous fluids were better explained by the revised Starling principle. In particular, the revised or extended Starling principle can explain why crystalloid resuscitation from the abrupt physiologic insult of hypovolaemia is much more effective than the pre-revision Starling principle had led clinicians to expect. The authors of this chapter have since combined their science and clinical expertise to offer clinicians a better basis for their practice of rational fluid therapy.