Fluids and Barriers of the CNS最新文献

Background and purpose: Dysregulation of cerebrospinal fluid (CSF) volume results in hydrocephalus, a disease that leads to over 30,000 surgical shunt-valve implantations annually in the US. These shunt-valves require a trial-and-error process to determine optimal settings for each individual, sometimes resulting in implantation of multiple valves in series. This work sought to evaluate two mathematical models of the relationship between valve opening pressure settings in series and resultant drainage using a benchtop system to aid clinicians in determination of optimal shunt-valve settings.

Methods: A gravity-driven in-vitro flow system at 37 °C with a simulated ICP of 22 cmH₂O + 60 cmH₂O from valve to simulated peritoneal cavity was built. Differential pressure and gravitational valves were tested in isolation and series at various settings. The relationship between flow rate and the pressure drop across a valve is expressed with a valve coefficient. Results of isolated valve trials were used to calculated valve coefficients for each valve, which were then used to calculate combined valve coefficients to predict flowrate of valves in series. Flowrate predictions were compared to experimental results to evaluate each mathematical model presented here.

Results: In isolation, differential pressure and gravitational valves had low intra- and inter-valve variability (p > 0.05). Valves in series had highly variable flowrates across trials and sets of valves in both supine and upright positions (p < 0.05). Using calculated combined valve coefficients to predict flowrates of valves in series, the average percent error was 15 ± 7% and 23 ± 18% in the supine and upright positions, respectively.

Conclusions: In all, neither of the two models outperformed the other and both were insufficient to properly characterize the relationship between drainage and opening pressures of valves in series. These results indicate low flowrate variability of isolated valves but high variability of valves placed in series. Without a consistent model from which opening pressure setting of valves in series can be determined, physicians must rely on a trial-and-error method in optimal opening pressure determination which directly impacts patient outcomes. These findings underscore the difficulties faced by physicians in determination of optimal valve settings for shunted patients.

Altered glymphatic function is observed for many neurological diseases. Glioma, one of the most common brain cancers, is known to have altered fluid dynamics in terms of edema and blood-brain barrier breakdown, both features potentially impacting the glymphatic function. To study glioma and its fluid dynamics, we propose a flexible mathematical model, including the tumor, the peri-tumoral edema and the healthy tissue. From a mechanical point of view, we consider the brain as a multicompartment porous medium and model both the fluid movement and the clearance of solutes within the brain. Our results indicate that the impairment of the glymphatic system due to glioma growth is two-fold. First, edema resulting from the leakage of fluid at the blood-brain barrier and/or the occlusion of the interstitial fluid exit routes (notably the perivascular spaces) due to migratory tumor cells result in a slight localized increase of pressure, consequently impairing negatively glymphatic clearance. Second, local changes of porosity (i.e. the volume fraction of certain compartments such as perivascular or extracellular spaces), result in a disruption of the transport of solutes in the brain. Our results indicate that an effect similar to the enhanced permeability and retention is obtained using biologically relevant changes of parameter values of our model. Our mathematical model is the first step towards a digital twin for drug or contrast product delivery within the cerebro-spinal fluid directly (e.g. from intrathecal injection) for patients suffering from gliomas.