Targeted delivery of large therapeutic macromolecules to desired locations inside the brain via systemic delivery is hampered by the function of the blood-brain barrier (BBB), which is formed by tight junctions of the epithelium that lines capillaries in the brain. Recently, direct injection methods such as the so-called Convection-enhanced delivery (CED) are pursued to effectively bypass this vascular barrier and using an infusion catheter whose tip is placed close to the target site. In this technique, a cannula is inserted directly into the area of the brain to be treated, and the therapeutic agent is delivered through the cannula via bulk flow, circumventing the BBB. The efficacy of direct injection methods is assessed by achievable penetration depth and drug distribution volume defined as the region of the brain dosed above a certain therapeutic concentration threshold. In the scope of this paper, the threshold was set at 10% of the inlet drug concentration.
The dynamic interaction between the solid brain, cerebrospinal fluid and blood flow within the cranial vault have previously been described only qualitatively. In this study, computational analysis using the finite element method and physiological parameters was used to describe cerebrospinal fluid-tissue interactions in a quantitative manner. By describing the soft tissue deformations and fluid flow under both normal and pathological conditions, we were able to quantify human intracranial dynamics with the hope of allowing prediction of pathophysiological conditions leading to hydrocephalus or other cerebral disease states.
Urinary tract obstruction is a common clinical problem involving the narrowing of the ureters or urethra. Current diagnostic methods are invasive and costly, and urologists are constantly seeking new, inexpensive, non-invasive measures to diagnose obstruction. The present study investigates diagnostic applications of computational fluid dynamics (CFD) to urinary tract obstruction for the first time.