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At least 1,351 records · Page 75Linked to original sources
PubMed2005

A computer model of intracranial pressure dynamics during traumatic brain injury that explicitly models fluid flows and volumes.

A model of intracranial pressure (ICP) dynamics that uses fluid volumes as primary state variables is presented, along with clinical data for two subjects with elevated ICP. The data includes annotations to indicate the precise timing of clinical changes in cerebral spinal fluid drainage, head of bed elevation, and minute ventilation. The response to changes in the clinical parameters was used to calibrate the model to correspond to specific subjects by estimating values for key characteristics such as hematoma volume and CSF uptake resistance. The error in mean ICP predicted by the model was less than 2 mmHg when cerebral spinal fluid is drained and the head of bed elevation was increased. The error in mean ICP predicted by the model exceeded 5 mmHg during an episode when the head of bed was decreased and also during a reduction in minute ventilation. The estimated values for hematoma volume and other subject characteristics were plausible but could not be verified empirically.

Blood Pressure↗
PubMed2001

Quantification of aortic regurgitation by real-time 3-dimensional echocardiography in a chronic animal model: computation of aortic regurgitant volume as the difference between left and right ventricular stroke volumes.

BACKGROUND: The accuracy of conventional 2-dimensional echocardiographic and Doppler techniques for the quantification of valvular regurgitation remains controversial. In this study, we examined the ability of real-time 3-dimensional (RT3D) echocardiography to quantify aortic regurgitation by computing aortic regurgitant volume as the difference between 3D echocardiographic-determined left and right ventricular stroke volumes in a chronic animal model. METHODS: Three to 6 months before the study, 6 sheep underwent surgical incision of one aortic valve cusp to create aortic regurgitation. During the subsequent open chest study session, a total of 25 different steady-state hemodynamic conditions were examined. Electromagnetic (EM) flow probes were placed around the main pulmonary artery and ascending aorta and balanced against each other to provide reference right and left ventricular stroke volume (RVSV and LVSV) data. RT3D imaging was performed by epicardial placement of a matrix array transducer on the volumetric ultrasound system, originally developed at the Duke University Center for Emerging Cardiovascular Technology. During each hemodynamic steady state, the left and right ventricles were scanned in rapid succession and digitized image loops stored for subsequent measurement of end-diastolic and end-systolic volumes. Left and right ventricular stroke volumes and aortic regurgitant volumes were then calculated and compared with reference EM-derived values. RESULTS: There was good correlation between RT3D left and right ventricular stroke volumes and reference data (r = 0.83, y = 0.94x + 2.6, SEE = 9.86 mL and r = 0.63, y = 0.8x - 1.0, SEE = 5.37 mL, respectively). The resulting correlation between 3D- and EM-derived aortic regurgitant volumes was at an intermediate level between that for LVSV and that for RVSV (r = 0.80, y = 0.88x + 7.9, SEE = 10.48 mL). RT3D tended to underestimate RVSV (mean difference -4.7 +/- 5.4 mL per beat, compared with -0.03 +/- 9.7 mL per beat for the left ventricle). There was therefore a small overestimation of aortic regurgitant volume (4.7 +/- 10.4 mL per beat). CONCLUSION: Quantification of aortic regurgitation through the computation of ventricular stroke volumes by RT3D is feasible and shows good correlation with reference flow data. This method should also be applicable to the quantification of other valvular lesions or single site intracardiac shunts where a difference between right and left ventricular cavity stroke volumes is produced.

Animals↗
PubMed2004

Ultrasound image-based computer model of a common carotid artery with a plaque.

Ultrasound scans were acquired from a common carotid artery in a patient with an early atherosclerotic plaque forming a mild asymmetrical stenosis. The 3D vascular geometry of the diseased arterial segment was reconstructed from a series of 2D cross-sectional images, and computational meshes for the flow and wall domains were developed. Numerical flow simulations incorporating coupled fluid-solid interaction were implemented using flow and pressure waveforms measured in vivo. The effects of wall distensibility were investigated by comparing the predictions obtained with different wall compliance, one with 'natural' compliance and another with a stiffer wall. Limited flow separation was predicted in the post-stenotic zone. The non-uniform thickness of the diseased wall restricted the wall motion locally and re-distributed the stress, giving raised concentrations at the plaque shoulders.

Blood Flow Velocity↗
PubMed2006

Reply to comment on "Auditory-nerve first-spike latency and auditory absolute threshold: a computer model".

Krisha [J. Acoust. Soc. Am., in press (2006)] has commented that an explanation based on presynaptic calcium accumulation at the inner hair cell is an incorrect explanation for the success of a model of the auditory periphery [Meddis, R., J. Acoustic. Soc. Am. 119, 406-417 (2006)] in explaining data on first-spike auditory nerve latency. This reply accepts the criticism and accepts the strength of an alternative explanation based on expected latencies in random sequences of low-probability events. This reply also goes on briefly to explore the application of this argument to other phenomena, including the dependence of absolute auditory threshold on the duration of the stimulus. This has wide-ranging implications for the concept of "temporal integration" in psychophysics.

Action Potentials↗
PubMed2001

Computer modeling implicates stem cell overproduction in colon cancer initiation.

On the basis of our investigation of the premalignant crypt phenotype in familial adenomatous polyposis patients, the hypothesis is developed that tumor initiation in the colon is caused by crypt stem cell overproduction. A novel kinetic model for the colonic crypt was used to investigate how the earliest tissue abnormality (altered crypt labeling index) arises in these patients who have a mutant APC genotype. Only an increase in crypt stem cell number, not changes in the rate of cell cycle proliferation, differentiation, or apoptosis of the non-stem cell population, simulated this abnormality. This suggests that APC regulates the number of stem cells in the colonic crypt and when the cells become mutant, an expansion of the crypt stem cell population results.

Adenomatous Polyposis Coli↗
PubMed1991

A computational model of semantic memory impairment: modality specificity and emergent category specificity.

It is demonstrated how a modality-specific semantic memory system can account for category-specific impairments after brain damage. In Experiment 1, the hypothesis that visual and functional knowledge play different roles in the representation of living things and nonliving things is tested and confirmed. A parallel distributed processing model of semantic memory in which knowledge is subdivided by modality into visual and functional components is described. In Experiment 2, the model is lesioned, and it is confirmed that damage to visual semantics primarily impairs knowledge of living things, and damage to functional semantics primarily impairs knowledge of nonliving things. In Experiment 3, it is demonstrated that the model accounts naturally for a finding that had appeared problematic for a modality-specific architecture, namely, impaired retrieval of functional knowledge about living things. Finally, in Experiment 4, it is shown how the model can account for a recent observation of impaired knowledge of living things only when knowledge is probed verbally.

Amnesia↗
PubMed1987

Computer model analysis of the radial artery pressure waveform.

Simultaneous measurements of aortic and radial artery pressures are reviewed, and a model of the cardiovascular system is presented. The model is based on resonant networks for the aorta and axillo-brachial-radial arterial system. The model chosen is a simple one, in order to make interpretation of the observed relationships clear. Despite its simplicity, the model produces realistic aortic and radial artery pressure waveforms. It demonstrates that the resonant properties of the arterial wall significantly alter the pressure waveform as it is propagated from the aorta to the radial artery. Although the mean and end-diastolic radial pressures are usually accurate estimates of the corresponding aortic pressures, the systolic pressure at the radial artery is often much higher than that of the aorta due to overshoot caused by the resonant behavior of the radial artery. The radial artery dicrotic notch is predominantly dependent on the axillo-brachial-radial arterial wall properties, rather than on the aortic valve or peripheral resistance. Hence the use of the radial artery dicrotic notch as an estimate of end systole is unreliable. The rate of systolic upstroke, dP/dt, of the radial artery waveform is a function of many factors, making it difficult to interpret. The radial artery waveform usually provides accurate estimates for mean and diastolic aortic pressures; for all other measurements it is an inadequate substitute for the aortic pressure waveform. In the presence of low forearm peripheral resistance the mean radial artery pressure may significantly underestimate the mean aortic pressure, as explained by a voltage divider model.

Blood Pressure↗
PubMed1989

[Dynamic computer models of xenobiotics].

On the basis of the physical substance transport in the circulatory system a dynamic pharmacokinetic model is developed. The method describes the behaviour of xenobiotics and their metabolites by direct simulation of the transport and the distribution in the bloodstream and tissues by suitable algorithms in discrete steps. The cardiovascular system represented by a 2-(or 3-)dimensional array is connected to other kinetic relevant components, likewise represented by arrays of suitable dimensions and acting as transport-, storage, distribution-, exchange- and reaction areas. (Bio-)chemical transformation is accounted for by introducing an identical new set of arrays, one set for each metabolite. The overall characterisation of a model needs a great variety of coefficients, thus creating a highly flexible tool for the study of kinetic processes. The result being a time- and position-dependent discrete distribution of substance reflects the heterogeneity and complexity of a real biological system. The compartmental (deterministic and stochastic) models are of course a subset of the DVM.

Algorithms↗
PubMed1993

Explaining glomerular pores with fiber matrices. A visualization study based on computer modeling.

The extracellular space of the glomerular capillary wall is occupied by a complex meshwork of fibrous molecules. Little is understood about how the size, shape, and charge recognition properties of glomerular ultrafiltration arise from this space-filling fiber matrix. We studied the problem of size recognition by visualizing the void volume accessible to hard spheres in computer-generated three-dimensional homogeneous random fiber matrices. The spatial organization of the void volume followed a complex "blob-and-throat" pattern in which circumscribed cavities of free space within the matrix ("blobs") were joined to adjacent cavities by narrower throats of void space. For sufficiently small solutes, chains of blobs and throats traversed the matrix, providing pathways for trans-matrix permeation. The matrices showed threshold or gating properties with respect to permeation: solutes whose radius exceeded a critical value, at which a throat on the last connected trans-matrix pathway pinched off, could not cross, whereas smaller solutes had nonzero permeability. The thresholds may give the glomerular fiber matrix porelike response properties and explain why pore models have been such a useful means of treating permselectivity.

Capillaries↗
PubMed2005

Computational model of blood flow in the aorto-coronary bypass graft.

BACKGROUND: Coronary artery bypass grafting surgery is an effective treatment modality for patients with severe coronary artery disease. The conduits used during the surgery include both the arterial and venous conduits. Long- term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded and many of them are diseased. Why do the saphenous vein grafts fail the test of time? Many causes have been proposed for saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non-modifiable causes include different histological structure of the vein compared to artery, size disparity between coronary artery and saphenous vein. However, researches are more interested in the modifiable causes, such as graft flow dynamics and wall shear stress distribution at the anastomotic sites. Formation of intimal hyperplasia at the anastomotic junction has been implicated as the root cause of long- term graft failure. Many researchers have analyzed the complex flow patterns in the distal sapheno-coronary anastomotic region, using various simulated model in an attempt to explain the site of preferential intimal hyperplasia based on the flow disturbances and differential wall stress distribution. In this paper, the geometrical bypass models (aorto-left coronary bypass graft model and aorto-right coronary bypass graft model) are based on real-life situations. In our models, the dimensions of the aorta, saphenous vein and the coronary artery simulate the actual dimensions at surgery. Both the proximal and distal anastomoses are considered at the same time, and we also take into the consideration the cross-sectional shape change of the venous conduit from circular to elliptical. Contrary to previous works, we have carried out computational fluid dynamics (CFD) study in the entire aorta-graft-perfused artery domain. The results reported here focus on (i) the complex flow patterns both at the proximal and distal anastomotic sites, and (ii) the wall shear stress distribution, which is an important factor that contributes to graft patency. METHODS: The three-dimensional coronary bypass models of the aorto-right coronary bypass and the aorto-left coronary bypass systems are constructed using computational fluid-dynamics software (Fluent 6.0.1). To have a better understanding of the flow dynamics at specific time instants of the cardiac cycle, quasi-steady flow simulations are performed, using a finite-volume approach. The data input to the models are the physiological measurements of flow-rates at (i) the aortic entrance, (ii) the ascending aorta, (iii) the left coronary artery, and (iv) the right coronary artery. RESULTS: The flow field and the wall shear stress are calculated throughout the cycle, but reported in this paper at two different instants of the cardiac cycle, one at the onset of ejection and the other during mid-diastole for both the right and left aorto-coronary bypass graft models. Plots of velocity-vector and the wall shear stress distributions are displayed in the aorto-graft-coronary arterial flow-field domain. We have shown (i) how the blocked coronary artery is being perfused in systole and diastole, (ii) the flow patterns at the two anastomotic junctions, proximal and distal anastomotic sites, and (iii) the shear stress distributions and their associations with arterial disease. CONCLUSION: The computed results have revealed that (i) maximum perfusion of the occluded artery occurs during mid-diastole, and (ii) the maximum wall shear-stress variation is observed around the distal anastomotic region. These results can enable the clinicians to have a better understanding of vein graft disease, and hopefully we can offer a solution to alleviate or delay the occurrence of vein graft disease.

Animals↗
PubMed2005

Computational modeling of human natural killer cell development suggests a selection process regulating coexpression of KIR with CD94/NKG2A.

Natural killer cells fail to lyse target cells expressing sufficient levels of self MHC class I molecules, providing one mechanism to secure self tolerance. Inhibition of lysis is mediated by inhibitory receptors expressed by NK cells, such as the murine Ly49 receptors, human KIR receptors and CD94/NKG2A, expressed by both species. To ensure that most, if not all, NK cells express at least one inhibitory receptor for self MHC class I, selection processes have been postulated for murine NK cells regulating the number and identity of inhibitory receptors expressed by each cell. The presence of similar selection processes in human NK cells has not been demonstrated. In previous studies using mathematical modeling we have shown that, in the Ly49 system, the sequential model (in which gene expression and selection operate simultaneously) is most likely to explain the observed expression frequencies. We also predicted the parameters (such as receptor-ligand binding affinity levels) under which the models fit with the observed frequencies. This study aims to evaluate whether these models may be valid in the human system. Our data suggest that if selection operates during human NK cell development, it affects the co-expression of CD94/NKG2A and KIR rather than KIR expression alone, and is more likely to be governed by the two-step selection model.

Animals↗
PubMed1986

A computer model for simulating reflected ultrasound signals.

This letter describes a model for simulating an ultrasound signal reflected from a medium composed of randomly distributed scatterers, as typified by soft biological tissue, such as liver. The model is specified in terms of the effective transducer beam radius B and the mean scatterer spacing S. The novel feature of the model is that the transducer field is partitioned by packing cylinders, called microbeams, into concentric annular regions that lie parallel to the transducer axis. The radii of the microbeams and the annuli are related to S. An independent reflector sequence is generated for each microbeam, the microbeam sequences in each annulus are summed and convolved with the impulse response of a point reflector. The reflected waveform sequence is then generated by summing the annular contributions and convolving with a band-limited pulse waveform. Simulated signals were generated for different values of B and S and compared with actual signals reflected from two in vivo livers and a tissue-equivalent phantom. Estimates of the kurtosis for the simulated signals indicate the range of signals that can be generated by varying the values for S and B.

Computer Simulation↗