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Large cerebral aneurysms are considered more dangerous than their smaller counterparts, with higher risk of subarachnoid hemorrhage. Understanding the hemodynamics of large aneurysms has potential to predict their response to treatment.Digital subtraction angiography images for patients with intracranial aneurysms over a seven-year period were reviewed. Unruptured solitary aneurysms of the internal carotid artery (ICA) proximal to the terminus and posterior communicating artery were included. Contrast intensity over time was analyzed at the center of the M1 segment of the middle cerebral artery distal to the aneurysm and compared to the contralateral side. Analysis included time to peak (TP)10%–100% (time needed for contrast to change from 10% intensity to 100%), washout time (WT)100%–10% (time for 100% intensity to 10%), and quartile time (QT)25%–25% (time for 25% intensity during vessel filling to 25% during emptying).Fifty patients met the inclusion criteria. Analysis over the ipsilateral M1 segment revealed a significant increase in QT25%–25% (8.5 vs 7.6 seconds, p = 0.006) compared to the contralateral side. There was a correlation between TP10%–100% and QT25%–25% with aneurysm size (Pearson’s r = 0.37, p = 0.007 and r = 0.43, p = 0.001, respectively).Larger ICA aneurysms were associated with delayed contrast intensity times. A plausible mechanism is that large aneurysms act as a capacitance chamber (Windkessel effect) that slow the arrival of contrast distal to the aneurysm. This may be of significance for large aneurysms after treatment, where the loss of the Windkessel effect places the distal circulation at greater risk for hemorrhage, and warrants further study. [ABSTRACT FROM AUTHOR]

Classical reaction kinetics based on deterministic rates laws are not valid for the description of cellular events in which the small number of molecules introduces stochasticity with discrete instead of continuous state transitions. Stochastic models are suitable for simulating transcriptional and translational events inside biological cells, but are impractical for solving inverse problems, which aim to estimate unknown reaction propensities from experimental observations. We introduce a new mathematical framework of Ito stochastic differential equations for the modeling of discrete cellular events and the robust and consistent parameter estimation of cellular dynamics where classical reaction kinetics is invalid. The results supported by case studies on gene expression in B. subtilis cells and viral gene transcription and translation inside non-lytic viral cells demonstrate that the proposed methodology performs as reliable as the gold standard Gillespie algorithm for simulating cellular events. More importantly, the new Ito process framework is ideal for estimating unknown reaction propensities from data as readily as in deterministic parameter estimation by using the novel ‘SPE – simulation free parameter estimation’ approach. Also, the computation time for the stochastic differential equation models is significantly low when compared to discrete event simulations. [ABSTRACT FROM AUTHOR]

The article focuses on regulation of water permeability by aquaporin-4 water channels in neurological diseases and opposing roles of the channels in vasogenic and cytotoxic edema. Topics include the role of the channels in brain homeostasis which is related to survival of neurons, the channels playing detrimental role in cytotoxic edema and beneficial role in vasogenic edema, decline in AQP4 post traumatic brain injury (TBI) and accumulation of cerebrospinal fluid (CSF) in brain ventricles.

The article focuses on a computational model of cerebrospinal fluid (CSF) production and reabsorption driven by starling forces. Topics include the model investigating the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), and perivascular space, the osmolarity of the serum effecting the bulk flow rate of nascent fluid into the ventricles, and the model supporting the exchange of water from choroid capillaries to the ventricles.

This work illuminates a practical design approach for developing economically viable and thermodynamically feasible metallurgical manufacturing processes. Successively refined economic potential estimators serve as the driving force for systematically advancing the design effort. The focus on process economics aims at identifying design inferior options and discarding process configurations with marginal economic performance early in the development cycle. In the proposed approach, novel process ideas evolve gradually as prescribed by the decision hierarchy by Douglas [AIChE J. 31 (1985) 353] modified to address metallurgical processes. Due to lack of heuristics in modeling reaction networks, a bi-level mathematical program for the simultaneous optimization of economic performance and complex multi-phase thermodynamic equilibrium is developed. The discussion includes the derivation of a thermodynamically consistent framework for integrating empirical atom interaction coefficients into the total Gibbs free energy model. The article demonstrates the beneficial use of mathematical modeling and non-linear mathematical programming within a systematic design framework. [Copyright &y& Elsevier]

This paper presents a mathematical model of the global, arterio‐venous circulation in the entire human body, coupled to a refined description of the cerebrospinal fluid (CSF) dynamics in the craniospinal cavity. The present model represents a substantially revised version of the original Müller‐Toro mathematical model. It includes one‐dimensional (1D), non‐linear systems of partial differential equations for 323 major blood vessels and 85 zero‐dimensional, differential‐algebraic systems for the remaining components. Highlights include the myogenic mechanism of cerebral blood regulation; refined vasculature for the inner ear, the brainstem and the cerebellum; and viscoelastic, rather than purely elastic, models for all blood vessels, arterial and venous. The derived 1D parabolic systems of partial differential equations for all major vessels are approximated by hyperbolic systems with stiff source terms following a relaxation approach. A major novelty of this paper is the coupling of the circulation, as described, to a refined description of the CSF dynamics in the craniospinal cavity, following Linninger et al. The numerical solution methodology employed to approximate the hyperbolic non‐linear systems of partial differential equations with stiff source terms is based on the Arbitrary DERivative Riemann problem finite volume framework, supplemented with a well‐balanced formulation, and a local time stepping procedure. The full model is validated through comparison of computational results against published data and bespoke MRI measurements. Then we present two medical applications: (i) transverse sinus stenoses and their relation to Idiopathic Intracranial Hypertension; and (ii) extra‐cranial venous strictures and their impact in the inner ear circulation, and its implications for Ménière's disease. [ABSTRACT FROM AUTHOR]

Recent advancements in multiphoton imaging and vascular reconstruction algorithms have increased the amount of data on cerebrovascular circulation for statistical analysis and hemodynamic simulations. Experimental observations offer fundamental insights into capillary network topology but mainly within a narrow field of view typically spanning a small fraction of the cortical surface (less than 2%). In contrast, larger‐resolution imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), have whole‐brain coverage but capture only larger blood vessels, overlooking the microscopic capillary bed. To integrate data acquired at multiple length scales with different neuroimaging modalities and to reconcile brain‐wide macroscale information with microscale multiphoton data, we developed a method for synthesizing hemodynamically equivalent vascular networks for the entire cerebral circulation. This computational approach is intended to aid in the quantification of patterns of cerebral blood flow and metabolism for the entire brain. In part I, we described the mathematical framework for image‐guided generation of synthetic vascular networks covering the large cerebral arteries from the circle of Willis through the pial surface network leading back to the venous sinuses. Here in part II, we introduce novel procedures for creating microcirculatory closure that mimics a realistic capillary bed. We demonstrate our capability to synthesize synthetic vascular networks whose morphometrics match empirical network graphs from three independent state‐of‐the‐art imaging laboratories using different image acquisition and reconstruction protocols. We also successfully synthesized twelve vascular networks of a complete mouse brain hemisphere suitable for performing whole‐brain blood flow simulations. Synthetic arterial and venous networks with microvascular closure allow whole‐brain hemodynamic predictions. Simulations across all length scales will potentially illuminate organ‐wide supply and metabolic functions that are inaccessible to models reconstructed from image data with limited spatial coverage. [ABSTRACT FROM AUTHOR]

Departures of normal blood flow and metabolite distribution from the cerebral microvasculature into neuronal tissue have been implicated with age-related neurodegeneration. Mathematical models informed by spatially and temporally distributed neuroimage data are becoming instrumental for reconstructing a coherent picture of normal and pathological oxygen delivery throughout the brain. Unfortunately, current mathematical models of cerebral blood flow and oxygen exchange become excessively large in size. They further suffer from boundary effects due to incomplete or physiologically inaccurate computational domains, numerical instabilities due to enormous length scale differences, and convergence problems associated with condition number deterioration at fine mesh resolutions. Our proposed simple finite volume discretization scheme for blood and oxygen microperfusion simulations does not require expensive mesh generation leading to the critical benefit that it drastically reduces matrix size and bandwidth of the coupled oxygen transfer problem. The compact problem formulation yields rapid and stable convergence. Moreover, boundary effects can effectively be suppressed by generating very large replica of the cortical microcirculation in silico using an image-based cerebrovascular network synthesis algorithm, so that boundaries of the perfusion simulations are far removed from the regions of interest. Massive simulations over sizeable portions of the cortex with feature resolution down to the micron scale become tractable with even modest computer resources. The feasibility and accuracy of the novel method is demonstrated and validated with in vivo oxygen perfusion data in cohorts of young and aged mice. Our oxygen exchange simulations quantify steep gradients near penetrating blood vessels and point towards pathological changes that might cause neurodegeneration in aged brains. This research aims to explain mechanistic interactions between anatomical structures and how they might change in diseases or with age. Rigorous quantification of age-related changes is of significant interest because it might aide in the search for imaging biomarkers for dementia and Alzheimer's disease. Author summary: Brain function critically depends on the maintenance of physiological blood supply and metabolism in the cortex. Disturbances to adequate perfusion have been linked to age-related neurodegeneration. However, the precise correlation between age-related hemodynamic changes and the resulting decline in oxygen delivery is not well understood and has not been quantified. Therefore, we introduce a new compact, and therefore highly scalable, computational method for predicting the physiological relationship between hemodynamics and cortical oxygen perfusion for large sections of the cortical microcirculation. We demonstrate the novel mesh generation-free (MGF), multi-scale simulation approach through realistic in vivo case studies of cortical microperfusion in the mouse brain. We further validate mechanistic correlations and a quantitative relationship between blood flow and brain oxygenation using experimental data from cohorts of young, middle aged and old mouse brains. Our computational approach overcomes size and performance limitations of previous unstructured meshing techniques to enable the prediction of oxygen tension with a spatial resolution of least two orders of magnitude higher than previously possible. Our simulation results support the hypothesis that structural changes in the microvasculature induce hypoxic pockets in the aged brain that are absent in the healthy, young mouse. [ABSTRACT FROM AUTHOR]

Objective: Indications for the treatment of cerebral aneurysms with flow diversion stents are expanding. The current aneurysm occlusion rate at six months ranges between 60 and 80%. Predictability of complete vs. partial aneurysm occlusion is poorly defined. Here, we evaluate the angiographic contrast time-density as a predictor of aneurysm occlusion rate at six months' post-flow diversion stents. Methods: Patients with unruptured cerebral aneurysms proximal to the internal carotid artery terminus treated with single flow diversion stents were included. 2D parametric parenchymal blood flow software (Siemens-Healthineers, Forchheim, Germany) was used to calculate contrast time-density within the aneurysm and in the proximal adjacent internal carotid artery. The area under the curve ratio between the two regions of interests was assessed at baseline and after flow diversion stents deployment. The area under the curve ratio between completely vs. partially occluded aneurysms at six months' follow-up was compared. Results: Thirty patients with 31 aneurysms were included. Mean aneurysm diameter was 8 mm (range 2–28 mm). Complete occlusion was obtained in 19 aneurysms. Younger patients (P = 0.006) and smaller aneurysms (P = 0.046) presented higher chance of complete obliteration. Incomplete occlusion of the aneurysm was more likely if the area under the curve contrast time-density ratio showed absolute (P = 0.001) and relative percentage (P = 0.001) decrease after flow diversion stents deployment. Area under ROC curve was 0.85. Conclusion: Negative change in the area under the curve ratio indicates less contrast stagnation in the aneurysm and lower chance of occlusion. These data provide a real-time analysis after aneurysm treatment. If validated in larger datasets, this can prompt input to the surgeon to place a second flow diversion stents. [ABSTRACT FROM AUTHOR]

Objective: It is commonly believed that in intrathecal (IT) drug delivery, agent distribution is confined to a narrow region close to the injection site, thereby undermining the efficacy of the method. Methods: To test the claim, multimodal in vivo imaging was used to experimentally observe the effects of IT infusion in cynomolgus monkey, looking at cerebrospinal fluid flow, anatomy, and dispersion of a radiolabeled tracer. Results: At high infusion rates, the tracer reached the cervical region after only 2 h, demonstrating rapid and wide distribution. The same in vivo nonhuman primate imaging data also provided evidence in support of a computational fluid dynamic model for the prediction of drug distribution following IT injection. Tracer dispersion was predicted in two specimens matching the distribution acquired with positron emission tomography (PET). For the third specimen, tracer dispersion simulations were conducted as a blind study: predictions were made before in vivo biodistribution data was known. In all cases, the computational fluid dynamics (CFD) predictions of drug dispersion after IT administration showed close spatio-temporal agreement with tracer biodistribution in vivo. Conclusion: Validation by in vivo nonhuman primate data confirms our ability to predict the biodistribution of intrathecally administered agents in subject-specific models of the central nervous system from first principles. Significance: The experiments reinstate IT delivery as a viable administration method when targeting molecules to the whole spine or the brain. The proposed computational methodology enables rational design of novel therapies for neurological diseases that require reliable, efficient, and safe delivery of therapeutic agents to specific target sites in the central nervous system. [ABSTRACT FROM AUTHOR]

The development of venous outflow stenosis in cerebral arteriovenous malformation (AVM) is poorly understood. The location of stenosis within the AVM draining vein in relation to the adjacent venous sinus and the hypothesis that the ratio of draining vein to adjacent sinus diameter might predict the development of venous stenosis were explored. Patients with supratentorial AVMs (1997–2018) were reviewed (N = 290). AVM draining vein and adjacent venous sinus diameters, degree of draining vein stenosis, and distance from the maximal stenotic point to the junction of the adjacent draining sinus were recorded. Correlation between percentage of AVM draining vein stenosis and the ratio of AVM draining vein to venous sinus diameters was analyzed. A total of 360 draining veins in 243 AVMs with complete angiographic data were measured. Venous stenosis (in 131 draining veins) was observed within 20 mm of the junction to the adjacent draining sinus in 85% of our sample. The ratio of draining vein to adjacent sinus diameter correlated positively with the percentage of venous stenosis (P < 0.01, r = 0.21). The ratio between 0.51–1.0 and >1.0 showed significant tighter stenosis compared with the ratio ≤0.5 (25.9% and 28.9% vs. 10.0%, respectively; P < 0.01). AVM venous outflow stenosis is observed close to the adjacent venous sinus junction. The degree of venous stenosis is greater when the ratio of AVM draining vein/adjacent venous sinus diameter is >0.5. This may be related to more turbulent flow at the junction of the draining vein and venous sinus, especially in larger draining veins, which causes venous stenosis to develop over time. [ABSTRACT FROM AUTHOR]

Abstract A computationally inexpensive mathematical solution approach using orthogonal collocations for space discretization with temporal Fourier series is proposed to compute subject-specific blood flow in distensible vessels of large cerebral arterial networks. Several models of wall biomechanics were considered to assess their impact on hemodynamic predictions. Simulations were validated against in vivo blood flow measurements in six human subjects. The average root-mean-square relative differences were found to be less than 4.3% for all subjects with a linear elastic wall model. This discrepancy decreased further in a viscoelastic Kelvin-Voigt biomechanical wall. The results provide support for the use of collocation-Fourier series approach to predict clinically relevant blood flow distribution and collateral blood supply in large portions of the cerebral circulation at reasonable computational costs. It thus opens the possibility of performing computationally inexpensive subject-specific simulations that are robust and fast enough to predict clinical results in real time on the same day. [ABSTRACT FROM AUTHOR]

Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain. [ABSTRACT FROM AUTHOR]

Objective: Proximal obstruction due to cellular material is a major cause of shunt failure in hydrocephalus management. The standard approach to treat such cases involves surgical intervention which unfortunately is accompanied by inherent surgical risks and a likelihood of future malfunction. We report a prototype design of a proximal ventricular catheter capable of noninvasively clearing cellular obstruction. Methods: In-vitro cell-culture methods show that low-intensity ac signals successfully destroy a cellular layer in a localized manner by means of Joule heating induced hyperthermia. A detailed electrochemical model for determining the temperature distribution and ionic current density for an implanted ventricular catheter supports our experimental observations. Results: In-vitro experiments with cells cultured in a plate as well as cells seeded in mock ventricular catheters demonstrated that localized heating between 43 °C and 48 °C caused cell death. This temperature range is consistent with hyperthermia. The electrochemical model verified that Joule heating due to ionic motion is the primary contributor to heat generation. Conclusion: Hyperthermia induced by Joule heating can clear cellular material in a localized manner. This approach is feasible to design a noninvasive self-clearing ventricular catheter system. Significance: A shunt system capable of clearing cellular obstruction could significantly reduce the need for future surgical interventions, lower the cost of disease management, and improve the quality of life for patients suffering from hydrocephalus. [ABSTRACT FROM AUTHOR]

Convection-enhanced delivery (CED) is an invasive drug delivery technique used to target specific regions of the brain for the treatment of cancer and neurodegenerative diseases while bypassing the blood-brain barrier. In order to prevent the possibility of backflow, low volumetric flow rates are applied which limit the achievable drug distribution volumes from CED. This can render CED treatment ineffective since a small convective flow produces narrow drug distribution inside the treatment region. Novel catheter designs and CED protocols are needed to improve the drug distribution inside the treatment region. This is especially important when administering toxic chemotherapeutics which could adversely affect other organs if backflow occurred and these drugs entered the circulating blood stream. In order to help elucidate the causes of backflow and to design backflow-free catheters, we have studied the impact that microfluid flow has on deformable brain phantom gels experimentally as well as numerically. We found that fluid injections into porous media have considerable effects on local transport properties such as porosity and hydraulic conductivity. These phenomena not only alter the bulk flow velocity distribution of the microfluid flow due to the changing porosity, but significantly modify flow direction and even volumetric flow distribution due to induced local hydraulic conductivity anisotropy. These studies led us to the development of novel backflow-free catheters with safe volumetric flow rates up to 10 µL/min. The catheter designs, numerical simulations and experimental results are described throughout this article. [ABSTRACT FROM AUTHOR]

Nanotechnology is being increasingly applied for developing drug delivery options for specific treatments. Magnetic nanoparticles have drawn attention as drug delivery vehicles due to their stability, biocompatibility and ability to be non-invasively guided to desired target areas using magnetic fields. In this paper, we describe a new delivery vehicle for magnetic drug targeting. In magnetic drug targeting, drug functionalized magnetic nanoparticles are guided and localized at specific sites using external magnetic fields. Magnetic nanoparticles act as contrast agents for magnetic resonance imaging. However, it cannot be visualized via this technique during drug delivery. This is between magnetic fields used for imaging and delivery can interference with each other. Our laboratory has synthesized a magnetic drug targeting vehicle conjugated with quantum dots that can be imaged during the drug delivery process with in vivo imaging techniques such as fluorescence molecular tomography. These nanocomposites can be used as drug delivery vehicles for the central nervous system, where drug targeting is especially difficult and minimizing side effects is critical. [ABSTRACT FROM AUTHOR]

Purpose The aim of this prospective multicenter study was to determine 50:50% perceptibility threshold ( PT) and 50:50% acceptability threshold ( AT) of dental ceramic under simulated clinical settings. Materials and Methods The spectral radiance of 63 monochromatic ceramic specimens was determined using a non-contact spectroradiometer. A total of 60 specimen pairs, divided into 3 sets of 20 specimen pairs (medium to light shades, medium to dark shades, and dark shades), were selected for psychophysical experiment. The coordinating center and seven research sites obtained the Institutional Review Board (IRB) approvals prior the beginning of the experiment. Each research site had 25 observers, divided into five groups of five observers: dentists- D, dental students- S, dental auxiliaries- A, dental technicians- T, and lay persons- L. There were 35 observers per group (five observers per group at each site ×7 sites), for a total of 175 observers. Visual color comparisons were performed using a viewing booth. Takagi- Sugeno- Kang ( TSK) fuzzy approximation was used for fitting the data points. The 50:50% PT and 50:50% AT were determined in CIELAB and CIEDE2000. The t-test was used to evaluate the statistical significance in thresholds differences. Results The CIELAB 50:50% PT was Δ Eab = 1.2, whereas 50:50% AT was Δ Eab = 2.7. Corresponding CIEDE2000 (Δ E00) values were 0.8 and 1.8, respectively. 50:50% PT by the observer group revealed differences among groups D, A, T, and L as compared with 50:50% PT for all observers. The 50:50% AT for all observers was statistically different than 50:50% AT in groups T and L. Conclusion A 50:50% perceptibility and ATs were significantly different. The same is true for differences between two color difference formulas Δ E00/Δ Eab. Observer groups and sites showed high level of statistical difference in all thresholds. Clinical Significance Visual color difference thresholds can serve as a quality control tool to guide the selection of esthetic dental materials, evaluate clinical performance, and interpret visual and instrumental findings in clinical dentistry, dental research, and subsequent standardization. The importance of quality control in dentistry is reinforced by increased esthetic demands of patients and dental professionals. [ABSTRACT FROM AUTHOR]

Objective Convection-enhanced delivery (CED) has emerged as a promising technique for bypassing the blood–brain barrier to deliver therapeutic agents. However, animal studies and clinical trials that utilize the technique suggest that it may require further optimization before it can be safely used in humans. In particular, while volume of distribution in the target tissue can be controlled, the geometrical spread into a desired target region is highly variable from experiment to experiment. In the present paper we have sought to characterize the non-uniform distribution geometry using fluorescent nanoparticles in both a rat model and computer simulations. Methods Using diffusion tensor imaging MRI data of the rat brain, we performed computer simulations of a 0.5 μL/min CED infusion. A step design catheter targeting the striatum was simulated to infuse 20 μL of infusate. Using the same infusion parameters, we then performed in vivo CED experiments where we infused fluorescently labeled polyethylene glycol-polylactide-polycaprolactone nanoparticles (FPNPs) into the rat striatum. Fluorescence microscopy was used to examine the distribution geometry histologically. Results The computer simulations demonstrated large variations in distribution patterns when catheter placement was shifted by only 1 mm. Animal infusions also exhibited highly irregular and variable distribution geometries despite the use of relatively small flow rates. Conclusion Computer simulations and repeated in vivo infusions demonstrate the difficulty of achieving desired drug distribution in target tissue. We have proposed a calculation for sphericity which, along with the ubiquitous volume of distribution measure, may prove helpful in describing distribution geometry. Taken together, our results suggest that CED's limitations must be considered and further optimization may be required before the technique sees widespread use in humans. [ABSTRACT FROM AUTHOR]

Background and Purpose Digital subtraction angiography (DSA) provides an excellent anatomic characterization of cerebral vasculature, but hemodynamic assessment is often qualitative and subjective. Various clinical algorithms have been produced to semiquantify flow from the data obtained from DSA, but few have tested them against reliable flow values. Methods An arched flow model was created and injected with contrast material. Seventeen injections were acquired in anterior–posterior and lateral DSA projections, and 4 injections were acquired in oblique projection. Image intensity change over the angiogram cycle of each DSA run was analyzed through a custom MATLAB code. Time–density plots obtained were divided into 3 components (time–density times, TDTs): TDT 10%-100% (time needed for contrast material to change image intensity from 10% to 100%), TDT 100%-10% (time needed for contrast material to change image intensity from 100% to 10%), and TDT 25%-25% (time needed for contrast material to change from 25% image intensity to 25%). Time–density index (TDI) was defined as model cross-sectional area to TDT ratio, and it was measured against different flow rates. Results TDI 10%-100% , TDI 100%-10% , and TDI 25%-25% all correlated significantly with flow ( P < 0.001). TDI 10%-100% , TDI 100%-10% , and TDI 25%-25% showed, respectively, a correlation coefficient of 0.91, 0.91, and 0.97 in the anterior–posterior DSA projections ( P < 0.001). In the lateral DSA projection, TDI 100%-10% showed a weaker correlation ( r = 0.57; P = 0.03). Also in the oblique DSA projection, TDIs correlated significantly with flow. Conclusions TDI on DSA correlates significantly with flow. Although in vitro studies might overlook conditions that occur in patients, this method appears to correlate with the flow and could offer a semiquantitative method to evaluate the cerebral blood flow. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) mostly occurs following the rupture of cerebral aneurysm causing blood to leak into the cranial subarachnoid space (SAS). Hemorrhage volume has been linked to the development of secondary vasospasm. Therefore, eliminating blood contaminants from the cerebrospinal fluid (CSF) space after the initial hemorrhage could improve patient outcomes and prevent the development of vasospasm. A number of clinical trials demonstrate that lumbar drainage effectively clears hemorrhagic debris from the cranial compartment. The benefits of optimal lumbar drainage rate and patient orientation are difficult to determine by trial-and-error in live patients, because of the invasive nature, limited subject availability and ethical considerations. Therefore, there is a lack of consensus about clinical guidelines for the use of continuous lumbar drainage following the ictus of SAH. A realistic bench-top model which reproduces the anatomy and CSF dynamics of the human central nervous system (CNS) was built to experimentally study contaminant clearance scenarios under lumbar drainage. To mimic a hemorrhagic event, porcine blood was injected at the basal cistern level of the bench-top model and the efficacy of lumbar drains was assessed experimentally for different drainage rates and patient orientations. In addition, the efficacy of blood clearance was predicted with a computational fluid dynamics (CFD) model. Bench-top experiments and CFD simulations identify body position and drainage rates as key parameters for effective blood clearance. The study findings suggest the importance of treatment in upright position to maximize contaminant diversion from the cranial CSF compartment. The bench-top CNS model together with the validated CFD predictions of lumbar drainage systems can serve to optimize subject-specific treatment options for SAH patients.