Patient-specific computational analysis of the influence of a stent on the unsteady flow in cerebral aneurysms

We present a patient-specific computational analysis of the influence of a stent on the unsteady flow in cerebral aneurysms. The analysis is based on four different arterial models extracted form medical images, and the stent is placed across the neck of the aneurysm to reduce the flow circulation in the aneurysm. The core computational technique used in the analysis is the space–time (ST) version of the variational multiscale (VMS) method and is called “DSD/SST-VMST”. The special techniques developed for this class of cardiovascular fluid mechanics computations are used in conjunction with the DSD/SST-VMST technique. The special techniques include NURBS representation of the surface over which the stent model and mesh are built, mesh generation with a reasonable resolution across the width of the stent wire and with refined layers of mesh near the arterial and stent surfaces, modeling the double-stent case, and quantitative assessment of the flow circulation in the aneurysm. We provide a brief overview of the special techniques, compute the unsteady flow patterns in the aneurysm for the four arterial models, and investigate in each case how those patterns are influenced by the presence of single and double stents.     

One-dimensional models for blood flow in arteries

In this paper a family of one-dimensional nonlinear systems which model the blood pulse propagation in compliant arteries is presented and investigated. They are obtained by averaging the Navier-Stokes equation on each section of an arterial vessel and using simplified models for the vessel compliance. Different differential operators arise depending on the simplifications made on the structural model. Starting from the most basic assumption of pure elastic instantaneous equilibrium, which provides a well-known algebraic relation between intramural pressure and vessel section area, we analyse in turn the effects of terms accounting for inertia, longitudinal pre-stress and viscoelasticity. The problem of how to account for branching and possible discontinuous wall properties is addressed, the latter aspect being relevant in the presence of prosthesis and stents. To this purpose a domain decomposition approach is adopted and the conditions which ensure the stability of the coupling are provided. The numerical method here used in order to carry out several test cases for the assessment of the proposed models is based on a finite element Taylor-Galerkin scheme combined with operator splitting techniques.     

Fluid–structure interaction modeling of a patient-specific cerebral aneurysm: influence of structural modeling

Fluid–structure interaction (FSI) simulations of a cerebral aneurysm with the linearly elastic and hyper-elastic wall constitutive models are carried out to investigate the influence of the wall-structure model on patient-specific FSI simulations. The maximum displacement computed with the hyper-elastic model is 36% smaller compared to the linearly elastic material model, but the displacement patterns such as the site of local maxima are not sensitive to the wall models. The blood near the apex of an aneurysm is likely to be stagnant, which causes very low wall shear stress and is a factor in rupture by degrading the aneurysmal wall. In this study, however, relatively high flow velocities due to the interaction between the blood flow and aneurysmal wall are seen to be independent of the wall model. The present results indicate that both linearly elastic and hyper-elastic models can be useful to investigate aneurysm FSI.     

Comparison of regional cerebral blood flow in Parkinson's disease with depression and major depression

Diagnosis of depression in Parkinson's disease (PD) patients is complicated due to the overlapping symptoms of the two disorders. We investigated regional cerebral blood flow (rCBF) in patients with only major depression (MD) and PD patients with (PDMD) and without MD (PDNMD) using ^99mTc hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO‐SPECT). A total of 103 patients (38 PDMD, 46 PDNMD, and 19 MD patients) underwent brain HMPAO‐SPECT scans. Voxel‐wise whole‐brain analysis was conducted to compare rCBF of the PDMD group with that of the PDNMD and MD groups. The scores of the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI) were significantly higher in the PDMD group than in the PDNMD group. The PDMD group showed significant hypoperfusion in the subcallosal cortex than the PDNMD group. The MD group showed significant hypoperfusion in the brainstem and inferomedial frontal region compared with the PDMD group. Our findings suggest that dysfunction of the inferomedial frontal cortex may be involved in the pathogenesis of depression in PD patients.     

Numerical modeling and simulation of pulsatile blood flow in rigid vessel using gradient smoothing method

Computer modeling and simulation is an effective tool to investigate, analyze, and understand the homodynamic, mechanical behavior of blood flow. The detailed information on shear stress, pressure drops, recirculation, stagnation, and turbulence can be applied in the medical practice to establish a direct linkage between flow characteristic and disease. In this paper, a novel gradient smoothing method is proposed to simulate the blood flow in the common artery, vessel with stenosis, and abdominal aortic aneurysm. Compared with the standard finite volume method, the gradient smoothing method is originated from the gradient smoothing operation to approximate the spatial derivatives at various locations based on irregular cells regardless its physical background. The dual time stepping scheme and point-implicit five-stage Runge-Kutta (RK5) method are implemented to enhance the efficiency and stability in iterative solution procedures. The numerical results have demonstrated that the model obtained from gradient smoothing method is more accurate than the standard finite volume method using commercial software of Fluent.     

便携式脐血流多普勒信号多参数分析系统

文章在笔记本计算机的硬件基础上建立了脐血流多普勒信号多参数分析的便携式系统。通过计算机声卡采集脐血流音频多普勒信号，然后进行传统的声谱参数分析、零极点模型分析、Teager算子分析和分形特征分析，应用Fisher多元判据法对四类特征参数进行分类决策，从而判断胎儿的生长情况。流速实验和临床试用的结果表明，该系统是有效的，可以应用于产科的临床诊断。     

Effects of nicergoline treatment on regional cerebral blood flow in early Alzheimer's disease

Alzheimer's disease (AD) is associated with reduction of regional cerebral blood flow (rCBF) in various brain regions. Although nicergoline has been used to treat cognitive impairment in various types of dementia, the effect of nicergoline on brain perfusion in AD has not been elucidated. The aim of the study was to examine the effect of nicergoline on rCBF in patients with early AD using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). For 1.7 years on average, 22 patients with early AD received nicergoline (30 mg twice daily) and acetylcholinesterase inhibitors (AChEI), whereas other 22 patients received AChEI only. All patients underwent assessment of dementia severity and SPECT scans at baseline and follow-up. We compared baseline rCBF and annual percent change of rCBF between the two groups. There were no significant differences in rCBF between the groups at baseline. Although changes in dementia severity was not statistically different, the annual percent changes of rCBF were higher in the left temporal pole (−0.12 ± 3.95 vs −3.38 ± 3.30, P = 0.002) and middle cingulate gyrus (1.91 ± 3.58 vs −1.34 ± 3.17, P = 0.002) among the nicergoline group. Our study demonstrated that nicergoline treatment combined with AChEI either better preserves or further improves cerebral perfusion in the temporal and cingulate cortices in patients with early AD compared to AChEI treatment alone. These results may indicate potential beneficial effects of nicergoline on brain functions in AD.     

Parameter calibration and inadequacy modeling in a computer experiment

Deterministic simulation is a popular tool used to numerically solve complex mathematical models in engineering applications. These models often involve parameters in the form of numerical values that can be calibrated when real‐life observations are available. This paper presents a systematic approach in parameter calibration using Response Surface Methodology (RSM). Additional modeling by considering correlation in error structure is suggested to compensate the inadequacy of the computer model and improve prediction at untried points. Computational Fluid Dynamics (CFD) model for manure storage ventilation is used for illustration. A simulation study shows that in comparison to likelihood‐based parameter calibration, the proposed parameter calibration method performs better in accuracy and consistency of the calibrated parameter value. The result from sensitivity analysis leads to a guideline in setting up factorial distance in relation to initial parameter values. The proposed calibration method extends RSM beyond its conventional use of process yield improvement and can also be applied widely to calibrate other types of models when real‐life observations are available. Moreover, the proposed inadequacy modeling is useful to improve the accuracy of simulation output, especially when a computer model is too expensive to run at its finest level of detail. Copyright © 2011 John Wiley and Sons Ltd.     

Absorbing boundary conditions for a 3D non-Newtonian fluid-structure interaction model for blood flow in arteries

Blood flow in arteries is characterized by pulse pressure waves due to the interaction with the vessel walls. A 3D fluid-structure interaction (FSI) model in a compliant vessel is used to represent the pressure wave propagation. The 3D fluid is described through a shear-thinning generalized Newtonian model and the structure by a nonlinear hyperelastic model. In order to cope with the spurious reflections due to the truncation of the computational domain, several absorbing boundary conditions are analyzed. First, a 1D hyperbolic model that effectively captures the wave propagation nature of blood flow in arteries is coupled with the 3D FSI model. Extending previous results, an energy estimate is derived for the 3D FSI-1D coupling in the case of generalized Newtonian models. Secondly, absorbing boundary conditions obtained from the 1D model are imposed directly on the outflow sections of the 3D FSI model, and numerical results comparing the different absorbing conditions in an idealized vessel are presented. Results in a human carotid bifurcation reconstructed from medical images are also provided in order to show that the proposed methodology can be applied to anatomically realistic geometries.     

Automation cueing modulates cerebral blood flow and vigilance in a simulated air traffic control task

Automation cueing of impending hazards or critical signals can have both beneficial and deleterious effects on the human operator, depending on automation reliability. To assess these effects, transcranial Doppler sonography (TCD), a low-cost non-invasive procedure that allows continuous monitoring of blood flow in the left and right cerebral hemispheres, was used to examine the influence of automation cues of varying reliability on vigilance performance in a 40-min simulated air traffic control task. Four levels of automation cue reliability (100, 80 and 40% reliable cueing and a no-cue control) were combined factorially with two levels of critical signal salience (high and low). For both levels of signal salience, the detection rate of critical signals was very high and remained stable over time with 100% cue-reliability, but declined over time in the remaining cue conditions, so that, by the end of the task, performance efficiency was best in the 100% condition followed in order by the 80%, 40%, and no-cue conditions. These performance effects for cueing were very closely mirrored by changes in cerebral blood flow in the right (but not the left) hemisphere in conjunction with low salience signals. The results fit well with an attentional resource model of vigilance and show that cerebral blood flow provides a metabolic index of the utilization of information-processing resources during sustained attention. The demonstration of systematic modulation of cerebral blood flow with time on task, automation cueing and signal salience also provides strong evidence for a right hemispheric brain system that is involved in the functional control of vigilance performance over time. Measurement of the activation of this system, as a reflection of operator mental workload, can, therefore, inform the design of optimal automation cueing.     

Three-dimensional computer modeling of slag cement hydration

A newly developed version of a three-dimensional computer model for simulating the hydration and microstructure development of slag cement pastes is presented in this study. It is based on a 3-D computer model for Portland cement hydration (CEMHYD3D) which was originally developed at NIST, taken over in the authors’ group and further developed. Features like the digitized 3-D microstructure, the cellular automata (CA) algorithm for simulating the random walking, phase transformation for simulating the chemical reactions, are retained. But, the 3-D microstructure was reconstructed allowing for slag particles as binder in the system. Algorithms and rules are developed to account for the interaction between Portland cement hydration and slag reaction in the paste, of which the mechanisms were revealed in the studies by Chen and Brouwers [(2007) J Mater Sci 42(2):428; (2007) J Mater Sci 42(2):444] Methods for considering the various factors on the reactivity of slag in hydrating slag cement pastes are proposed, mainly for the oxide composition of slag and the alkalinity in the pore solution composition. A comparison between the model predictions and the experimental results in literature shows that the presented computer model can successfully predict the hydration process and the microstructure development of hydrating slag cement paste.     

Polytomous modeling of cognitive errors in computer adaptive testing

In the past two decades of psychometric research, an array of extended item response models has been proposed to capture the complex nature of human cognition. While the literature abounds in model fit analysis, the debate on model selection in different testing conditions continues. This study examines the problems of model selection in computer adaptive testing (CAT) of cognitive errors by comparing the relative measurement efficiency of polytomous modeling over dichotomous modeling under different scoring schemes and termination criteria. Monte Carlo simulation was adopted as the inquiry paradigm to generate 1000 subjects and 100 items in the calibration sample and 200 simulees in the CAT sample. The results suggest that polytomous CAT yields marginal gains over dichotomous CAT when termination criteria are more stringent (shorter test length or smaller standard error of ability estimate). When the conventional dichotomous scoring scheme is adopted, in which all partially correct answers are scored as incorrect, polytomous CAT cannot prevent the non-uniform gain in test information as was observed in paper-and-pencil testing.     

Alterations of regional cerebral blood flow after NMDA receptor antagonist administration in patients with alcohol‐related dementia

Although N‐methyl‐d ‐aspartate (NMDA) receptor antagonists may have beneficial influences on cognition in patients with alcohol‐related dementia (ARD), their effects on regional cerebral blood flow (rCBF) remain unknown. This study evaluated changes in rCBF in ARD patients after administration of NMDA receptor antagonist for 12 weeks using technetium‐99m ethyl cysteinate dimer (Tc‐99m ECD) single‐photon emission computed tomography (SPECT). Twenty‐eight ARD patients were administered memantine for 12 weeks and underwent clinical evaluations and brain SPECT scans at baseline and follow‐up. Whole‐brain changes in perfusion were examined on a voxel‐by‐voxel basis. At follow‐up, the patients showed reduced rCBF in the left medial frontal gyrus, left cingulate gyrus, left claustrum, right brainstem, left superior temporal gyrus, bilateral fusiform gyrus, and left cerebellum. On the other hand, increased rCBF was found in the bilateral uncus, left parahippocampal gyrus, bilateral superior frontal gyrus, right inferior parietal lobule, left cuneus, and left superior temporal gyrus. Perfusion increases in various brain areas including the superior frontal, parahippocampal, and inferior parietal areas, which may play important roles in the pathophysiology of ARD, suggest potential benefits of NMDA receptor antagonists on brain functions in patients with ARD.     

Hyperosmotic chemical agent's effect on in vivo cerebral blood flow revealed by laser speckle

We investigated the influence of a hyperosmotic agent (glycerol) on the normal physiological function of tissue by applying the glycerol in vitro and in vivo to rabbit dura mater to assess the changes in the tissue's optical properties. We used a laser speckle imaging technique to study the effect of epidurally applied glycerol on resting cerebral blood flow (CBF). Our results showed that resting CBF decreased as the transparency of the dura mater increased. The challenges for the design of an optical clearing technique were not only the clearing effects and the duration of the action of the chemical agents but also the influence of the glycerol on the tissue's normal physiological function.     

SWNT-DNA and SWNT-polyC hybrids: AFM study and computer modeling

Hybrids of carbon single-walled nanotubes (SWNT) with fragmented single or double-stranded DNA (fss- or fds-DNA) or polyC were studied by Atom Force Microscopy (AFM) and computer modeling. It was found that fragments of the polymer wrap in several layers around the nanotube, forming a strand-like spindle. In contrast to the fss-DNA, the fds-DNA also forms compact structures near the tube surface due to the formation of self-assembly structures consisting of a few DNA fragments. The hybrids of SWNT with wrapped single-, double- or triple strands of the biopolymer were simulated, and it was shown that such structures are stable. To explain the reason of multi-layer polymeric coating of the nanotube surface, the energy of the intermolecular interactions between different components of polyC was calculated at the MP2/6-31++G** level as well as the interaction energy in the SWNT-cytosine complex.     

Analysis of cerebral blood flow in Parkinson's disease with dementia versus subcortical ischemic vascular dementia using single photon emission computed tomography

Since both Parkinson's disease with dementia (PDD) and subcortical ischemic vascular dementia (SIVaD) are subcortical dementia syndromes and have similar patterns of cognitive dysfunction, it is difficult to accurately differentiate between these in their early phases using neuropsychological tests. The purpose of this study was to investigate differences in the cerebral perfusion pattern of patients with SIVaD and PDD at the earliest stages using single photon emission computed tomography (SPECT). We, consecutively, recruited 24 patients with mild PDD, 28 patients with mild probable AD, and 33 age‐matched healthy subjects. All subjects underwent Tc‐99m HMPAO perfusion SPECT and general neuropsychological tests. Brain SPECT images were analyzed using the statistical parametric mapping program. There was more significant hypoperfusion in the right cuneus, fusiform gyrus and lingual gyrus in the occipital lobe, right middle temporal gyrus, right postcentral gyrus, and right cerebellar tonsil in PDD compared with the SIVaD group. Conversely, significant hypoperfusion was observed in the bilateral brain stem, limbic system and posterior cingulate gyrus in SIVaD compared with the PDD group. This study suggests that parieto‐occipital hypoperfusion in PDD and hypoperfusion of the brain stem and limbic system in SIVaD are likely useful to differentiate between mild PDD and SIVaD.     

Quantitative real-time blood flow estimation with intravascular ultrasound in the presence of in-plane flow

Previously, we showed a source of error in blood flow estimation introduced by in-plane flow using a slow-time finite-impulse response (FIR) filter-bank method measuring blood flow through the image plane of an intravascular ultrasound (IVUS) catheter array. There is a monotonic relationship between flow velocity and the normalized second moment of the slow-time spectrum when flow is orthogonal to the image plane of a side-looking catheter array. However, this relationship changes in the presence of in-plane flow, as slow-time spectra shift and spread with varying in-plane and out-of-plane components. These two effects increase the normalized spectral second moment, resulting in flow overestimates. However, by resampling the received signal with variable time delay from pulse to pulse (i.e., tilting the slow-time signals), the slow-time spectrum shifts back to direct current (DC), and the orthogonal estimation method can be used. We present a method to correct this overestimation and accurately estimate blood flow through the image plane in real time. Initially, the tilt delay needed to shift the slow-time spectrum back to DC at each point within the flow field is calculated. Knowing this tilt delay, a tilted slow-time signal is obtained for the velocity component normal to the image plane, and its spectrum is estimated using a filter-bank. That spectrum then is used to estimate the flow speed using a mapping function closely related to the monotonic relationship between the slow-time spectrum and flow speed observed for orthogonal flow. To accurately estimate flow angles, we modified the filter-bank algorithm, applying slow-time filter coefficients in a tilted arrangement and studying the slow-time spectral energy as a function of tilt. The slow-time spectral estimate is constructed with the tilted output of eight narrow, band-pass filters from a filter-bank. Independent simulations show that, for blood slowing at angles between +/-6 degrees and +/-15 degrees at a speed of 300 mm/s, flow velocity would be overestimated by as much as 38.79% and 249%, respectively, using the direct filter-bank approach. However, this error can be corrected using the modified method presented here, reducing the maximum overestimation error by a factor of 2.69 and 10.88 for those angles, respectively. Although the remaining error is not negligible, the volume flow rate, calculated by integrating the flow velocity over the entire vessel lumen, differs by only 3% or less from the true value over the angular range considered here. This represents an improvement of a factor of 40 over uncompensated estimates at maximum flow angles. Consequently, the modified real-time method can quantitatively measure flow in most IVUS applications in which the catheter's image plane is not precisely orthogonal to the flow direction.     

Predicting gas chromatographic separation and stationary-phase selectivity using computer modeling

A computer modeling technique has been developed which allows for the prediction of chromatographic separation and stationary-phase selectivity. This technique enables development of application-specific gas chromatographic columns by allowing for the simultaneous optimization of physical dimensions, flow and temperature programs, and stationary-phase composition. Stationary-phase selectivity is the most powerful tool available to achieve a separation; however most commercially available columns were not designed to have a selectivity specific to the separations for which they are used. The techniques described in this paper were developed to address this need.