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Sample records for perfusion model estimated

  1. Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability

    NASA Astrophysics Data System (ADS)

    Sourbron, S. P.; Buckley, D. L.

    2012-01-01

    The tracer-kinetic models developed in the early 1990s for dynamic contrast-enhanced MRI (DCE-MRI) have since become a standard in numerous applications. At the same time, the development of MRI hardware has led to increases in image quality and temporal resolution that reveal the limitations of the early models. This in turn has stimulated an interest in the development and application of a second generation of modelling approaches. They are designed to overcome these limitations and produce additional and more accurate information on tissue status. In particular, models of the second generation enable separate estimates of perfusion and capillary permeability rather than a single parameter Ktrans that represents a combination of the two. A variety of such models has been proposed in the literature, and development in the field has been constrained by a lack of transparency regarding terminology, notations and physiological assumptions. In this review, we provide an overview of these models in a manner that is both physically intuitive and mathematically rigourous. All are derived from common first principles, using concepts and notations from general tracer-kinetic theory. Explicit links to their historical origins are included to allow for a transfer of experience obtained in other fields (PET, SPECT, CT). A classification is presented that reveals the links between all models, and with the models of the first generation. Detailed formulae for all solutions are provided to facilitate implementation. Our aim is to encourage the application of these tools to DCE-MRI by offering researchers a clearer understanding of their assumptions and requirements.

  2. Comparison of blood flow models and acquisitions for quantitative myocardial perfusion estimation from dynamic CT.

    PubMed

    Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R; La Riviere, Patrick J; Alessio, Adam M

    2014-04-01

    Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This

  3. Comparison of blood flow models and acquisitions for quantitative myocardial perfusion estimation from dynamic CT

    NASA Astrophysics Data System (ADS)

    Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R.; La Riviere, Patrick J.; Alessio, Adam M.

    2014-04-01

    Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)-1, cardiac output = 3, 5, 8 L min-1). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that

  4. Perfusion CT estimates photosensitizer uptake and biodistribution in a rabbit orthotopic pancreas cancer model: a pilot study

    PubMed Central

    Elliott, Jonathan T.; Samkoe, Kimberley S.; Gunn, Jason R.; Stewart, Errol E.; Gardner, Timothy B.; Tichauer, Kenneth M.; Lee, Ting-Yim; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2015-01-01

    Objectives It was hypothesized that perfusion computed tomography (CT) blood flow (BF), blood volume (BV) and vascular permeability surface-area (PS) product parameters would be predictive of therapeutic anti-cancer agent uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of injected photosensitizer, vertepofin. Materials and Methods Nine New Zealand White rabbits underwent direct pancreas implantation of VX2 tumors and CT perfusion or endoscopic ultrasound was performed 10 days post-implantation. Verteporfin was injected during CT imaging and tissue was removed 1 h post-injection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathological staining were performed. Results DCE-CT showed enhanced BF, BV, and PS in the tumor rim, and decreased BF, BV and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. Conclusions The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a non-invasive method of mapping photosensitizer dose. PMID:25683500

  5. Transient finite element analysis of thermal methods used to estimate SAR and blood flow in homogeneously and nonhomogeneously perfused tumour models.

    PubMed

    Wong, T Z; Mechling, J A; Jones, E L; Strohbehn, J W

    1988-01-01

    A two-dimensional time-dependent finite element model was developed to evaluate thermal techniques for estimating blood flow and specific absorption rate (SAR). In these computer simulations, homogeneously and nonhomogeneously perfused tumour models were heated by a 915 MHz interstitial microwave antenna array. Representative blood flow values were assigned within the tumour, and the applied SAR distribution was based on a previously developed antenna theory. SAR values were estimated from the power-on transient temperatures, and blood flow values were estimated from thermal clearance data after power was discontinued. These estimated parameters were then compared to the known 'true' blood flow and SAR values throughout the treatment region. SAR values could be predicted with reasonable accuracy throughout most of the heated region independent of local blood flow. For a homogeneous model, thermal clearance was found to yield reasonably accurate blood flow estimates at high perfusion rates and less accurate estimates at lower perfusion rates. However, for the inhomogeneous model, the blood perfusion estimates were generally poor, and an average blood flow value for the tumour was obtained with little ability to resolve the differences in perfusion between regions. Using temperatures observed early in the cool-down curve resulted in improved spatial resolution, but increased the contribution of thermal conduction to the blood flow estimates. A single time-constant exponential thermal decay curve was found to be a necessary but not sufficient condition for reliable blood flow estimates using this technique. PMID:3171254

  6. Estimation of the parameter covariance matrix for aone-compartment cardiac perfusion model estimated from a dynamic sequencereconstructed using map iterative reconstruction algorithms

    SciTech Connect

    Gullberg, Grant T.; Huesman, Ronald H.; Reutter, Bryan W.; Qi,Jinyi; Ghosh Roy, Dilip N.

    2004-01-01

    In dynamic cardiac SPECT estimates of kinetic parameters ofa one-compartment perfusion model are usually obtained in a two stepprocess: 1) first a MAP iterative algorithm, which properly models thePoisson statistics and the physics of the data acquisition, reconstructsa sequence of dynamic reconstructions, 2) then kinetic parameters areestimated from time activity curves generated from the dynamicreconstructions. This paper provides a method for calculating thecovariance matrix of the kinetic parameters, which are determined usingweighted least squares fitting that incorporates the estimated varianceand covariance of the dynamic reconstructions. For each transaxial slicesets of sequential tomographic projections are reconstructed into asequence of transaxial reconstructions usingfor each reconstruction inthe time sequence an iterative MAP reconstruction to calculate themaximum a priori reconstructed estimate. Time-activity curves for a sumof activity in a blood region inside the left ventricle and a sum in acardiac tissue region are generated. Also, curves for the variance of thetwo estimates of the sum and for the covariance between the two ROIestimates are generated as a function of time at convergence using anexpression obtained from the fixed-point solution of the statisticalerror of the reconstruction. A one-compartment model is fit to the tissueactivity curves assuming a noisy blood input function to give weightedleast squares estimates of blood volume fraction, wash-in and wash-outrate constants specifying the kinetics of 99mTc-teboroxime for theleftventricular myocardium. Numerical methods are used to calculate thesecond derivative of the chi-square criterion to obtain estimates of thecovariance matrix for the weighted least square parameter estimates. Eventhough the method requires one matrix inverse for each time interval oftomographic acquisition, efficient estimates of the tissue kineticparameters in a dynamic cardiac SPECT study can be obtained with

  7. Tomographic digital subtraction angiography for lung perfusion estimation in rodents

    SciTech Connect

    Badea, Cristian T.; Hedlund, Laurence W.; De Lin, Ming; Boslego Mackel, Julie S.; Samei, Ehsan; Allan Johnson, G.

    2007-05-15

    In vivo measurements of perfusion present a challenge to existing small animal imaging techniques such as magnetic resonance microscopy, micro computed tomography, micro positron emission tomography, and microSPECT, due to combined requirements for high spatial and temporal resolution. We demonstrate the use of tomographic digital subtraction angiography (TDSA) for estimation of perfusion in small animals. TDSA augments conventional digital subtraction angiography (DSA) by providing three-dimensional spatial information using tomosynthesis algorithms. TDSA is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of {mu}L volumes of contrast at a series of different angles of rotation. The capabilities of TDSA are established in studies on lung perfusion in rats. Using an imaging system developed in-house, we acquired data for four-dimensional (4D) imaging with temporal resolution of 140 ms, in-plane spatial resolution of 100 {mu}m, and slice thickness on the order of millimeters. Based on a structured experimental approach, we optimized TDSA imaging providing a good trade-off between slice thickness, the number of injections, contrast to noise, and immunity to artifacts. Both DSA and TDSA images were used to create parametric maps of perfusion. TDSA imaging has potential application in a number of areas where functional perfusion measurements in 4D can provide valuable insight into animal models of disease and response to therapeutics.

  8. Estimating a regional ventilation-perfusion index

    PubMed Central

    Muller, P A; Li, T; Isaacson, D; Newell, J C; Saulnier, G J; Kao, Tzu-Jen; Ashe, Jeffrey

    2015-01-01

    This is a methods paper, where an approximation to the local ventilation-perfusion ratio is derived. This approximation, called the ventilation-perfusion index since it is not exactly the physiological ventilation-perfusion ratio, is calculated using conductivity reconstructions obtained using electrical impedance tomography. Since computation of the ventilation-perfusion index only requires knowledge of the internal conductivity, any conductivity reconstruction method may be used. The method is explained, and results are presented using conductivities obtained from two EIT systems, one using an iterative method and the other a linearization method. PMID:26006279

  9. TISSUE ENGINEERING PERFUSABLE CANCER MODELS

    PubMed Central

    Fong, E.L.; Santoro, M.; Farach-Carson, M.C.; Kasper, F.K.; Mikos, A.G.

    2014-01-01

    The effect of fluid flow on cancer progression is currently not well understood, highlighting the need for perfused tumor models to close this gap in knowledge. Enabling biological processes at the cellular level to be modeled with high spatiotemporal control, microfluidic tumor models have demonstrated applicability as platforms to study cell-cell interactions, effect of interstitial flow on tumor migration and the role of vascular barrier function. To account for the multi-scale nature of cancer growth and invasion, macroscale models are also necessary. The consideration of fluid dynamics within tumor models at both the micro- and macroscopic levels may greatly improve our ability to more fully mimic the tumor microenvironment. PMID:24634812

  10. Bayesian hemodynamic parameter estimation by bolus tracking perfusion weighted imaging.

    PubMed

    Boutelier, Timothé; Kudo, Koshuke; Pautot, Fabrice; Sasaki, Makoto

    2012-07-01

    A delay-insensitive probabilistic method for estimating hemodynamic parameters, delays, theoretical residue functions, and concentration time curves by computed tomography (CT) and magnetic resonance (MR) perfusion weighted imaging is presented. Only a mild stationarity hypothesis is made beyond the standard perfusion model. New microvascular parameters with simple hemodynamic interpretation are naturally introduced. Simulations on standard digital phantoms show that the method outperforms the oscillating singular value decomposition (oSVD) method in terms of goodness-of-fit, linearity, statistical and systematic errors on all parameters, especially at low signal-to-noise ratios (SNRs). Delay is always estimated sharply with user-supplied resolution and is purely arterial, by contrast to oSVD time-to-maximum TMAX that is very noisy and biased by mean transit time (MTT), blood volume, and SNR. Residue functions and signals estimates do not suffer overfitting anymore. One CT acute stroke case confirms simulation results and highlights the ability of the method to reliably estimate MTT when SNR is low. Delays look promising for delineating the arterial occlusion territory and collateral circulation. PMID:22410325

  11. Analytical estimation of ultrasound properties, thermal diffusivity, and perfusion using magnetic resonance-guided focused ultrasound temperature data

    NASA Astrophysics Data System (ADS)

    Dillon, C. R.; Borasi, G.; Payne, A.

    2016-01-01

    For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one.

  12. Analytical estimation of ultrasound properties, thermal diffusivity, and perfusion using magnetic resonance-guided focused ultrasound temperature data.

    PubMed

    Dillon, C R; Borasi, G; Payne, A

    2016-01-21

    For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one. PMID:26741344

  13. Modelling of temperature and perfusion during scalp cooling

    NASA Astrophysics Data System (ADS)

    Janssen, F. E. M.; Van Leeuwen, G. M. J.; Van Steenhoven, A. A.

    2005-09-01

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 °C to 18.3 °C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 °C to 21.8 °C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  14. Renal vascular perfusion index in a canine model.

    PubMed

    Shau, Yio-Wha; Pao, Sun-Hua; Chou, Nai-Kuan; Chang, King-Jen; Shyu, Jeou-Jong

    2009-01-01

    Decreased renal perfusion plays an important role in the progression toward renal failure. In this study, a novel measure was proposed to quantify renal perfusion using canine model. Serial renal vascular images at different vascular areas including the whole vascular tree, interlobar, arcuate and interlobular vessels were captured. Image processing software was designed to analyze the changes of power Doppler intensity of colored pixels within regions-of-interest (ROI). For a given ROI, the power Doppler vascular index (PDVI) was found to fluctuate with the cardiac cycle. It was also noted that the power Doppler signals generated by arterial vessels have different fluctuating waveforms and different phase compared with the signal derived from venous vessels. A power Doppler correlation-map was developed to differentiate the arteries and veins in the ROI. Using the serial power Doppler images and the derived flow direction information, the interlobular perfusion can be strongly quantified. The renal vascular perfusion index (RVPI) defined as the ratio of PDVI(max) versus PDVI(min) was significantly higher in the interlobular vessel areas than three other areas for seven healthy dogs. The RVPI resembles the systolic/diastolic (S/D) ratio that commonly reflects arterial hemodynamics. RVPI and power Doppler correlation-map reveal more "dynamic" sense of vascular perfusion and provide a novel approach for the examination of renal function in clinical practice. PMID:18805627

  15. Pancreas tumor model in rabbit imaged by perfusion CT scans

    NASA Astrophysics Data System (ADS)

    Gunn, Jason; Tichauer, Kenneth; Moodie, Karen; Kane, Susan; Hoopes, Jack; Stewart, Errol E.; Hadway, Jennifer; Lee, Ting-Yim; Pereira, Stephen P.; Pogue, Brian W.

    2013-03-01

    The goal of this work was to develop and validate a pancreas tumor animal model to investigate the relationship between photodynamic therapy (PDT) effectiveness and photosensitizer drug delivery. More specifically, this work lays the foundation for investigating the utility of dynamic contrast enhanced blood perfusion imaging to be used to inform subsequent PDT. A VX2 carcinoma rabbit cell line was grown in the tail of the pancreas of three New Zealand White rabbits and approximately 3-4 weeks after implantation the rabbits were imaged on a CT scanner using a contrast enhanced perfusion protocol, providing parametric maps of blood flow, blood volume, mean transit time, and vascular permeability surface area product.

  16. A fast nonlinear regression method for estimating permeability in CT perfusion imaging

    PubMed Central

    Bennink, Edwin; Riordan, Alan J; Horsch, Alexander D; Dankbaar, Jan Willem; Velthuis, Birgitta K; de Jong, Hugo W

    2013-01-01

    Blood–brain barrier damage, which can be quantified by measuring vascular permeability, is a potential predictor for hemorrhagic transformation in acute ischemic stroke. Permeability is commonly estimated by applying Patlak analysis to computed tomography (CT) perfusion data, but this method lacks precision. Applying more elaborate kinetic models by means of nonlinear regression (NLR) may improve precision, but is more time consuming and therefore less appropriate in an acute stroke setting. We propose a simplified NLR method that may be faster and still precise enough for clinical use. The aim of this study is to evaluate the reliability of in total 12 variations of Patlak analysis and NLR methods, including the simplified NLR method. Confidence intervals for the permeability estimates were evaluated using simulated CT attenuation–time curves with realistic noise, and clinical data from 20 patients. Although fixating the blood volume improved Patlak analysis, the NLR methods yielded significantly more reliable estimates, but took up to 12 × longer to calculate. The simplified NLR method was ∼4 × faster than other NLR methods, while maintaining the same confidence intervals (CIs). In conclusion, the simplified NLR method is a new, reliable way to estimate permeability in stroke, fast enough for clinical application in an acute stroke setting. PMID:23881247

  17. Modelling Brain Temperature and Perfusion for Cerebral Cooling

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2015-11-01

    Brain temperature relies heavily on two aspects: i) blood perfusion and porous heat transport through tissue and ii) blood flow and heat transfer through embedded arterial and venous vasculature. Moreover brain temperature cannot be measured directly unless highly invasive surgical procedures are used. A 3D two-phase fluid-porous model for mapping flow and temperature in brain is presented with arterial and venous vessels extracted from MRI scans. Heat generation through metabolism is also included. The model is robust and reveals flow and temperature maps in unprecedented 3D detail. However, the Karmen-Kozeny parameters of the porous (tissue) phase need to be optimised for expected perfusion profiles. In order to optimise the K-K parameters a reduced order two-phase model is developed where 1D vessels are created with a tree generation algorithm embedded inside a 3D porous domain. Results reveal that blood perfusion is a strong function of the porosity distribution in the tissue. We present a qualitative comparison between the simulated perfusion maps and those obtained clinically. We also present results studying the effect of scalp cooling on core brain temperature and preliminary results agree with those observed clinically.

  18. Estimation of the rate of Ca/sup 2 +/ influx in perfused rat liver using the multiple indicator dilution technique

    SciTech Connect

    Lapointe, D.S.; Olson, M.S.

    1987-05-01

    The multiple indicator dilution technique provides a useful mechanism for the determination of the rates of processes involved in the uptake and subsequent release of substances between an organ, such as the liver, and the vasculature. They have used this technique to investigate the uptake of /sup 45/Ca/sup 2 +/ into the perfused rat liver at a number of different perfusate Ca/sup 2 +/ concentrations. Each perfused liver is calibrated using reference injections of a mixture of /sup 3/H-sucrose and /sup 14/C-urea to determine parameters of a microcirculatory model of the liver, such as the characteristic transit times through vascular spaces and the ratio of tissue volume to extracellular volume. Using a single injection of a mixture of /sup 3/H-sucrose and /sup 45/Ca/sup 2 +/, the profiles of the efflux of the injected tracers are analyzed to estimate the rate constant for uptake of /sup 45/Ca/sup 2 +/. The estimated rate constant for uptake decreases with increasing perfusate Ca/sup 2 +/ concentration (kin = 0.155 +/- 0.036, 0.0896 +/- 0.024, 0.0713 +/- 0.009 for (Ca/sup 2 +/) = 0.05, 0.5, 1.25 mM; n=5). From these data, estimates for the maximum velocity of uptake of Ca/sup 2 +/ and the Ca/sup 2 +/ concentration for half maximal uptake are calculated to be 0.1208 mM/sec and 0.7278 mM respectively.

  19. A comparison of cost functions for data-driven motion estimation in myocardial perfusion SPECT imaging

    NASA Astrophysics Data System (ADS)

    Mukherjee, Joyeeta Mitra; Pretorius, P. H.; Johnson, K. L.; Hutton, Brian F.; King, Michael A.

    2011-03-01

    In myocardial perfusion SPECT imaging patient motion during acquisition causes severe artifacts in about 5% of studies. Motion estimation strategies commonly used are a) data-driven, where the motion may be determined by registration and checking consistency with the SPECT acquisition data, and b) external surrogate-based, where the motion is obtained from a dedicated motion-tracking system. In this paper a data-driven strategy similar to a 2D-3D registration scheme with multiple views is investigated, using a partially reconstructed heart for the 3D model. The partially-reconstructed heart has inaccuracies due to limited angle artifacts resulting from using only a part of the SPECT projections acquired while the patient maintained the same pose. The goal of this paper is to compare the performance of different cost-functions in quantifying consistency with the SPECT projection data in a registration-based scheme for motion estimation as the image-quality of the 3D model degrades. Six intensity-based metrics- Mean-squared difference (MSD), Mutual information (MI), Normalized Mutual information NMI), Pattern intensity (PI), normalized cross-correlation (NCC) and Entropy of the difference (EDI) were studied. Quantitative and qualitative analysis of the performance is reported using Monte-Carlo simulations of a realistic heart phantom including degradation factors such as attenuation, scatter and collimator blurring. Further the image quality of motion-corrected images using data-driven motion estimates was compared to that obtained using the external motion-tracking system in acquisitions of anthropomorphic phantoms and patient studies in a real clinical setting. Pattern intensity and Normalized Mutual Information cost functions were observed to have the best performance in terms of lowest average position error and stability with degradation of image quality of the partial reconstruction in simulations and anthropomorphic phantom acquisitions. In patient studies

  20. A corneal perfusion device for estimating ocular bioavailability in vitro.

    PubMed

    Richman, J B; Tang-Liu, D D

    1990-02-01

    An in vitro method for investigating drug penetration across the cornea from acute doses has been developed. The donor (epithelial or tear) side of a corneal chamber similar to those used by Edelhauser and co-workers was modified with a reduced-volume insert so that the donor side volume approximated 6% of the receiver (endothelial or aqueous humor) chamber volume. Fluid was pumped through the anterior chamber to simulate the physiologic tear turnover in vivo. The receiver chamber was bubbled with oxygen:carbon dioxide (95%:5%) to aerate and circulate the fluid. We investigated the in vitro ocular bioavailability of several marketed ophthalmic drug formulations using this model (0.03% flurbiprofen, 0.5% levobunolol, 0.1 and 0.25% fluorometholone, and 1% prednisolone acetate). At 1 min after the dose administration, drug was eluted from the donor chamber at a dose turnover rate of 12%/min. In all experiments, a small percentage of the applied dose penetrated the cornea. Using this chamber device, the ocular bioavailability via corneal absorption ranged between 5 and 16% for solution formulations, whereas the ocular bioavailability for the suspension formulations was less than 0.3%. The major portion of the administered dose was recovered from the donor side effluent. This observation was consistent with findings showing low ocular bioavailability of ophthalmic preparations due to the rapid precorneal washout in vivo. The extent of drug penetrating as its corneal metabolite in the model correlated well to in vitro corneal metabolism rate constants. The new model opens several potentially useful areas of research into ocular absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2324964

  1. Estimation of intra-operator variability in perfusion parameter measurements using DCE-US

    PubMed Central

    Gauthier, Marianne; Leguerney, Ingrid; Thalmensi, Jessie; Chebil, Mohamed; Parisot, Sarah; Peronneau, Pierre; Roche, Alain; Lassau, Nathalie

    2011-01-01

    AIM: To investigate intra-operator variability of semi-quantitative perfusion parameters using dynamic contrast-enhanced ultrasonography (DCE-US), following bolus injections of SonoVue®. METHODS: The in vitro experiments were conducted using three in-house sets up based on pumping a fluid through a phantom placed in a water tank. In the in vivo experiments, B16F10 melanoma cells were xenografted to five nude mice. Both in vitro and in vivo, images were acquired following bolus injections of the ultrasound contrast agent SonoVue® (Bracco, Milan, Italy) and using a Toshiba Aplio® ultrasound scanner connected to a 2.9-5.8 MHz linear transducer (PZT, PLT 604AT probe) (Toshiba, Japan) allowing harmonic imaging (“Vascular Recognition Imaging”) involving linear raw data. A mathematical model based on the dye-dilution theory was developed by the Gustave Roussy Institute, Villejuif, France and used to evaluate seven perfusion parameters from time-intensity curves. Intra-operator variability analyses were based on determining perfusion parameter coefficients of variation (CV). RESULTS: In vitro, different volumes of SonoVue® were tested with the three phantoms: intra-operator variability was found to range from 2.33% to 23.72%. In vivo, experiments were performed on tumor tissues and perfusion parameters exhibited values ranging from 1.48% to 29.97%. In addition, the area under the curve (AUC) and the area under the wash-out (AUWO) were two of the parameters of great interest since throughout in vitro and in vivo experiments their variability was lower than 15.79%. CONCLUSION: AUC and AUWO appear to be the most reliable parameters for assessing tumor perfusion using DCE-US as they exhibited the lowest CV values. PMID:21512654

  2. The prediction of radiation-induced liver dysfunction using a local dose and regional venous perfusion model

    SciTech Connect

    Cao Yue; Platt, Joel F.; Francis, Isaac R; Balter, James M.; Pan, Charlie; Normolle, Daniel; Ben-Josef, Edgar; Haken, Randall K. ten; Lawrence, Theodore S.

    2007-02-15

    We have shown that high dose conformal radiation combined with chemotherapy appears to prolong the survival of patients with unresectable intrahepatic cancers. The ability to safely deliver higher doses is primarily limited by the development of radiation-induced liver disease, characterized by venous occlusion. In this study, we investigated whether portal venous perfusion measured prior to the end of radiation therapy (RT) together with dose could predict liver venous perfusion dysfunction after treatment. Ten patients with unresectable intrahepatic cancer participated in an IRB-approved computer tomography (CT) perfusion study. Hepatic arterial and portal vein perfusion distributions were estimated by using dynamic contrast enhanced CT and the single compartmental model. Scans were obtained at four time points: prior to treatment, after 15 and 30 fractions of 1.5 Gy treatments, and one month following the completion of RT. Multivariant linear regression was used to determine covariances among the first three time point measurements plus dose for prediction of the post RT measurement. The reduction in the regional venous perfusion one month following RT was predicted by the local accumulated dose and the change in the regional venous perfusion after {approx}30 fractions (F=90.6,p<0.000 01). Each Gy produced an approximately 1.2% of reduction in the venous perfusion. This local dose and venous perfusion model has the potential to predict individual sensitivity to radiation. This is the first step toward developing a method to deliver higher and potentially more curative radiation doses to the patients who can safely receive these higher doses.

  3. Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

    PubMed

    Ahlgren, André; Wirestam, Ronnie; Petersen, Esben Thade; Ståhlberg, Freddy; Knutsson, Linda

    2014-09-01

    Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low-resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1 -based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high-resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra-subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low-resolution partial volume estimation in connection with ASL perfusion

  4. Uterine perfusion model for analyzing barriers to transport in fibroids.

    PubMed

    Stirland, Darren L; Nichols, Joseph W; Jarboe, Elke; Adelman, Marisa; Dassel, Mark; Janát-Amsbury, Margit-Maria; Bae, You Han

    2015-09-28

    This project uses an ex vivo human perfusion model for studying transport in benign, fibrous tumors. The uterine arteries were cannulated to perfuse the organ with a buffer solution containing blood vessel stain and methylene blue to analyze intratumoral transport. Gross examination revealed tissue expansion effects and a visual lack of methylene blue in the fibroids. Some fibroids exhibited regions with partial methylene blue penetration into the tumor environment. Histological analysis comparing representative sections of fibroids and normal myometrium showed a smaller number of vessels with decreased diameters within the fibroid. Imaging of fluorescently stained vessels exposed a stark contrast between fluorescence within the myometrium and relatively little within the fibroid tissues. Imaging at higher magnification revealed that fibroid blood vessels were indeed perfused and stained with the lipophilic membrane dye; however, the vessels were only the size of small capillaries and the blood vessel coverage was only 12% that of the normal myometrium. The majority of sampled fibroids had a strong negative correlation (Pearson's r=-0.68 or beyond) between collagen and methylene blue staining. As methylene blue was able to passively diffuse into fibroid tissue, the true barrier to transport in these fibroids is likely high interstitial fluid pressure, correlating with high collagen content and solid stress observed in the fibroid tissue. Fibroids had an average elevated interstitial fluid pressure of 4mmHg compared to -1mmHg in normal myometrium. Our findings signify relationships between drug distribution in fibroids and between vasculature characteristics, collagen levels, and interstitial fluid pressure. Understanding these barriers to transport can lead to developments in drug delivery for the treatment of uterine fibroids and tumors of similar composition. PMID:26184049

  5. Dynamic chest image analysis: model-based pulmonary perfusion analysis with pyramid images

    NASA Astrophysics Data System (ADS)

    Liang, Jianming; Haapanen, Arto; Jaervi, Timo; Kiuru, Aaro J.; Kormano, Martti; Svedstrom, Erkki; Virkki, Raimo

    1998-07-01

    The aim of the study 'Dynamic Chest Image Analysis' is to develop computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected at different phases of the respiratory/cardiac cycles in a short period of time. We have proposed a framework for ventilation study with an explicit ventilation model based on pyramid images. In this paper, we extend the framework to pulmonary perfusion study. A perfusion model and the truncated pyramid are introduced. The perfusion model aims at extracting accurate, geographic perfusion parameters, and the truncated pyramid helps in understanding perfusion at multiple resolutions and speeding up the convergence process in optimization. Three cases are included to illustrate the experimental results.

  6. Dynamic Chest Image Analysis: Model-Based Perfusion Analysis in Dynamic Pulmonary Imaging

    NASA Astrophysics Data System (ADS)

    Liang, Jianming; Järvi, Timo; Kiuru, Aaro; Kormano, Martti; Svedström, Erkki

    2003-12-01

    The "Dynamic Chest Image Analysis" project aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected with the dynamic pulmonary imaging technique. We have proposed and evaluated a multiresolutional method with an explicit ventilation model for ventilation analysis. This paper presents a new model-based method for pulmonary perfusion analysis. According to perfusion properties, we first devise a novel mathematical function to form a perfusion model. A simple yet accurate approach is further introduced to extract cardiac systolic and diastolic phases from the heart, so that this cardiac information may be utilized to accelerate the perfusion analysis and improve its sensitivity in detecting pulmonary perfusion abnormalities. This makes perfusion analysis not only fast but also robust in computation; consequently, perfusion analysis becomes computationally feasible without using contrast media. Our clinical case studies with 52 patients show that this technique is effective for pulmonary embolism even without using contrast media, demonstrating consistent correlations with computed tomography (CT) and nuclear medicine (NM) studies. This fluoroscopical examination takes only about 2 seconds for perfusion study with only low radiation dose to patient, involving no preparation, no radioactive isotopes, and no contrast media.

  7. Development of an Ex Vivo, Beating Heart Model for CT Myocardial Perfusion

    PubMed Central

    Pelgrim, Gert Jan; Das, Marco; Haberland, Ulrike; Slump, Cees; Handayani, Astri; van Tuijl, Sjoerd; Stijnen, Marco; Klotz, Ernst; Oudkerk, Matthijs; Wildberger, Joachim E.; Vliegenthart, Rozemarijn

    2015-01-01

    Objective. To test the feasibility of a CT-compatible, ex vivo, perfused porcine heart model for myocardial perfusion CT imaging. Methods. One porcine heart was perfused according to Langendorff. Dynamic perfusion scanning was performed with a second-generation dual source CT scanner. Circulatory parameters like blood flow, aortic pressure, and heart rate were monitored throughout the experiment. Stenosis was induced in the circumflex artery, controlled by a fractional flow reserve (FFR) pressure wire. CT-derived myocardial perfusion parameters were analysed at FFR of 1 to 0.10/0.0. Results. CT images did not show major artefacts due to interference of the model setup. The pacemaker-induced heart rhythm was generally stable at 70 beats per minute. During most of the experiment, blood flow was 0.9–1.0 L/min, and arterial pressure varied between 80 and 95 mm/Hg. Blood flow decreased and arterial pressure increased by approximately 10% after inducing a stenosis with FFR ≤ 0.50. Dynamic perfusion scanning was possible across the range of stenosis grades. Perfusion parameters of circumflex-perfused myocardial segments were affected at increasing stenosis grades. Conclusion. An adapted Langendorff porcine heart model is feasible in a CT environment. This model provides control over physiological parameters and may allow in-depth validation of quantitative CT perfusion techniques. PMID:26185756

  8. Dynamic CT myocardial perfusion imaging: detection of ischemia in a porcine model with FFR verification

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.

  9. Comparing model-based and model-free analysis methods for QUASAR arterial spin labeling perfusion quantification.

    PubMed

    Chappell, Michael A; Woolrich, Mark W; Petersen, Esben T; Golay, Xavier; Payne, Stephen J

    2013-05-01

    Amongst the various implementations of arterial spin labeling MRI methods for quantifying cerebral perfusion, the QUASAR method is unique. By using a combination of labeling with and without flow suppression gradients, the QUASAR method offers the separation of macrovascular and tissue signals. This permits local arterial input functions to be defined and "model-free" analysis, using numerical deconvolution, to be used. However, it remains unclear whether arterial spin labeling data are best treated using model-free or model-based analysis. This work provides a critical comparison of these two approaches for QUASAR arterial spin labeling in the healthy brain. An existing two-component (arterial and tissue) model was extended to the mixed flow suppression scheme of QUASAR to provide an optimal model-based analysis. The model-based analysis was extended to incorporate dispersion of the labeled bolus, generally regarded as the major source of discrepancy between the two analysis approaches. Model-free and model-based analyses were compared for perfusion quantification including absolute measurements, uncertainty estimation, and spatial variation in cerebral blood flow estimates. Major sources of discrepancies between model-free and model-based analysis were attributed to the effects of dispersion and the degree to which the two methods can separate macrovascular and tissue signal. PMID:22711674

  10. Whole ovine ovaries as a model for human: perfusion with cryoprotectants in vivo and in vitro.

    PubMed

    Isachenko, Vladimir; Rahimi, Gohar; Dattena, Maria; Mallmann, Peter; Baikoshkarova, Saltanat; Kellerwessel, Elisabeth; Otarbaev, Marat; Shalakhmetova, Tamara; Isachenko, Evgenia

    2014-01-01

    These experiments were performed to test the perfusion of ovine as a model for human ovaries by cryoprotectants in vivo at high temperature when the permeability of capillaries is high and when blood is insensibly replaced by the solution of cryoprotectants. By our hypothetical supposition, ovaries could be saturated by cryoprotectants before their surgical removal. The objective was to examine the effectiveness of perfusion of ovine ovaries with vascular pedicle in vivo and in vitro. Arteria ovarica was cannuled and ovaries were perfused by Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink in vivo and in vitro. In the first and second cycle of experiments, ovaries (n = 13 and n = 23) were perfused in vivo and in vitro, respectively, during 60 min with the rate of perfusion 50 mL/h (0.8 mL/min). It was established with in vivo perfusion that only about 10% of ovarian tissues were perfused due to an appearance of multiple anastomoses when the perfusion medium goes from arteria ovarica to arteria uterina without inflow into the ovaries. It was concluded that in vitro perfusion of ovine intact ovaries with vascular pedicle by freezing medium is more effective than this manipulation performed in vivo. PMID:24701576

  11. Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice

    PubMed Central

    Fushima, Tomofumi; Sekimoto, Akiyo; Minato, Takahiro; Ito, Takuya; Oe, Yuji; Kisu, Kiyomi; Sato, Emiko; Funamoto, Kenichi; Hayase, Toshiyuki; Kimura, Yoshitaka; Ito, Sadayoshi; Sato, Hiroshi; Takahashi, Nobuyuki

    2016-01-01

    Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE. PMID:27187738

  12. Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice.

    PubMed

    Fushima, Tomofumi; Sekimoto, Akiyo; Minato, Takahiro; Ito, Takuya; Oe, Yuji; Kisu, Kiyomi; Sato, Emiko; Funamoto, Kenichi; Hayase, Toshiyuki; Kimura, Yoshitaka; Ito, Sadayoshi; Sato, Hiroshi; Takahashi, Nobuyuki

    2016-01-01

    Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE. PMID:27187738

  13. Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity

    PubMed Central

    Horger, Marius; Buchgeister, Markus; Fenchel, Michael; Thomas, Christoph; Boehringer, Nadine; Schulze, Maximilian; Tsiflikas, Ilias; Claussen, Claus D.; Heuschmid, Martin

    2010-01-01

    Objective We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. Materials and Methods An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). Results Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. Conclusion Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans. PMID:20808699

  14. Optimization of arterial spin labeling MRI for quantitative tumor perfusion in a mouse xenograft model.

    PubMed

    Rajendran, Reshmi; Liang, Jieming; Tang, Mei Yee Annie; Henry, Brian; Chuang, Kai-Hsiang

    2015-08-01

    Perfusion is an important biomarker of tissue function and has been associated with tumor pathophysiology such as angiogenesis and hypoxia. Arterial spin labeling (ASL) MRI allows noninvasive and quantitative imaging of perfusion; however, the application in mouse xenograft tumor models has been challenging due to the low sensitivity and high perfusion heterogeneity. In this study, flow-sensitive alternating inversion recovery (FAIR) ASL was optimized for a mouse xenograft tumor. To assess the sensitivity and reliability for measuring low perfusion, the lumbar muscle was used as a reference region. By optimizing the number of averages and inversion times, muscle perfusion as low as 32.4 ± 4.8 (mean ± standard deviation) ml/100 g/min could be measured in 20 min at 7 T with a quantification error of 14.4 ± 9.1%. Applying the optimized protocol, heterogeneous perfusion ranging from 49.5 to 211.2 ml/100 g/min in a renal carcinoma was observed. To understand the relationship with tumor pathology, global and regional tumor perfusion was compared with histological staining of blood vessels (CD34), hypoxia (CAIX) and apoptosis (TUNEL). No correlation was observed when the global tumor perfusion was compared with these pathological parameters. Regional analysis shows that areas of high perfusion had low microvessel density, which was due to larger vessel area compared with areas of low perfusion. Nonetheless, these were not correlated with hypoxia or apoptosis. The results suggest that tumor perfusion may reflect certain aspect of angiogenesis, but its relationship with other pathologies needs further investigation. PMID:26104980

  15. A recapitulative three-dimensional model of breast carcinoma requires perfusion for multi-week growth

    PubMed Central

    Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R

    2016-01-01

    Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850

  16. A recapitulative three-dimensional model of breast carcinoma requires perfusion for multi-week growth.

    PubMed

    Goliwas, Kayla F; Marshall, Lauren E; Ransaw, Evette L; Berry, Joel L; Frost, Andra R

    2016-01-01

    Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter. PMID:27516850

  17. Ethanol-induced impairment of hepatic glycoprotein secretion in the isolated rat liver perfusion model

    SciTech Connect

    Volentine, G.D.; Ogden, K.A.; Tuma, D.J.; Sorrell, M.F.

    1987-05-01

    The authors have previously shown that acute administration of ethanol inhibits hepatic glycoprotein secretion in vivo. This ethanol-induced effect appears to be mediated by its reactive metabolite, acetaldehyde. Since hormonal influences and vascular changes can not be controlled in vivo during ethanol administration, they investigated the effect of ethanol in the isolated perfused liver model. Rat liver from fed animals was perfused with oxygenated KRB at 3 ml/min/g liver for 4 hrs. Since ethanol inhibits proteins synthesis in vitro, protein acceptor pool size was equalized in both ethanol and control perfused livers with 1 mM cycloheximide. /sup 3/H-glucosamine was used to label hepatic secretory glycoproteins in the perfusate. Colchicine, a known inhibitor of protein secretion, impaired the secretion of labeled glycoproteins with a concomitant retention of these export proteins in the liver; therefore, confirming the authors secretory model. Ethanol (50 mM) inhibited the appearance of glucosamine-labeled glycoproteins by 60% into the perfusate as compared to control livers. Pretreatment of animals with cyanamide (an aldehyde dehydrogenase inhibitor) further potentiated this effect of ethanol in the isolated perfused liver. These data suggest that ethanol inhibits hepatic glycoprotein secretion in the isolated liver perfusion model, and this ethanol-induced impairment appears to be mediated by acetaldehyde.

  18. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system.

    PubMed

    Fahmi, Rachid; Eck, Brendan L; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G; Wilson, David L

    2016-03-21

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR  <  0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR [Formula: see text] 0.65, the anterior-to-lateral flow ratio was 0.29  ±  0.01, over-estimating stenosis severity as compared to 0.42  ±  0.01 (p  <  0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50  ±  0.04 falsely indicating an actionable ischemic condition

  19. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2016-03-01

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR  <  0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR ≈ 0.65, the anterior-to-lateral flow ratio was 0.29  ±  0.01, over-estimating stenosis severity as compared to 0.42  ±  0.01 (p  <  0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50  ±  0.04 falsely indicating an actionable ischemic condition in a healthy

  20. Lumped-parameter tissue temperature-blood perfusion model of a cold-stressed fingertip.

    PubMed

    Shitzer, A; Stroschein, L A; Gonzalez, R R; Pandolf, K B

    1996-05-01

    A lumped-parameter model of a fingertip is presented. The semispherical model includes the effects of heat storage, heat exchange with the environment, and heat transport by blood perfusion. The thermal insulation on the surface of the fingertip is represented by the overall heat transfer coefficient that is calculated by common engineering formulas. The model is solved analytically for the simple case of constant blood perfusion rate. The general case of variable blood perfusion rates is solved by an Euler finite difference technique. At this stage, the model does not include active control mechanisms of blood perfusion. Thus the effects of cold-induced vasodilatation have to be superimposed and are modeled by symmetrical triangular waveforms because these were found to best depict the behavior of fingers exposed to cold environments. Results of this model were compared with experimental data obtained in two separate studies. One included 60-min infrared thermograms of the dorsal surface of bare hands of sedentary subjects horizontally suspended on a fish net in a 0 degree C environment. Another study, on gloved finger temperatures, involved 0 and -6.7 degrees C environments. Fingertip (nail bed) temperatures of both these studies were compared with model predictions. Blood perfusion rates were assumed and adjusted within physiologically reasonable limits. Comparison of measured and computed temperature records showed very good conformity in both cases studied. PMID:8727573

  1. A microfluidically perfused three dimensional human liver model.

    PubMed

    Rennert, Knut; Steinborn, Sandra; Gröger, Marko; Ungerböck, Birgit; Jank, Anne-Marie; Ehgartner, Josef; Nietzsche, Sandor; Dinger, Julia; Kiehntopf, Michael; Funke, Harald; Peters, Frank T; Lupp, Amelie; Gärtner, Claudia; Mayr, Torsten; Bauer, Michael; Huber, Otmar; Mosig, Alexander S

    2015-12-01

    Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation. PMID:26322723

  2. Radiation risk estimation models

    SciTech Connect

    Hoel, D.G.

    1987-11-01

    Cancer risk models and their relationship to ionizing radiation are discussed. There are many model assumptions and risk factors that have a large quantitative impact on the cancer risk estimates. Other health end points such as mental retardation may be an even more serious risk than cancer for those with in utero exposures. 8 references.

  3. [The isolated perfused porcine kidney model for investigations concerning surgical therapy procedures].

    PubMed

    Peters, Kristina; Michel, Maurice Stephan; Matis, Ulrike; Häcker, Axel

    2006-01-01

    Experiments to develop innovative surgical therapy procedures are conventionally conducted on animals, as crucial aspects like tissue removal and bleeding disposition cannot be investigated in vitro. Extracorporeal organ models however reflect these aspects and could thus reduce the use of animals for this purpose fundamentally in the future. The aim of this work was to validate the isolated perfused porcine kidney model with regard to its use for surgical purposes on the basis of histological and radiological procedures. The results show that neither storage nor artificial perfusion led to any structural or functional damage which would affect the quality of the organ. The kidney model is highly suitable for simulating the main aspects of renal physiology and allows a constant calibration of perfusion pressure and tissue temperature. Thus, with only a moderate amount of work involved, the kidney model provides a cheap and readily available alternative to conventional animal experiments; it allows standardised experimental settings and provides valid results. PMID:17086351

  4. Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.

    PubMed

    Koning, Nick J; de Lange, Fellery; Vonk, Alexander B A; Ahmed, Yunus; van den Brom, Charissa E; Bogaards, Sylvia; van Meurs, Matijs; Jongman, Rianne M; Schalkwijk, Casper G; Begieneman, Mark P V; Niessen, Hans W; Baufreton, Christophe; Boer, Christa

    2016-03-01

    Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury. PMID:26747506

  5. Effect of venous injection site on accuracy of fast computed tomography (CT) estimation of myocardial perfusion

    SciTech Connect

    Bell, M.R.; Rumberger, J.A.; Lerman, L.O.; Behrenbeck, T.; Sheedy, P.F.; Ritman, E.L. )

    1990-02-26

    Measurement of myocardial perfusion with fast CT, using venous injections of contrast, underestimates high flow rates. Accounting for intramyocardial blood volume improves the accuracy of such measurements but the additional influence of different contrast injection sites is unknown. To examine this, eight closed chest anesthetized dogs (18-24 kg) underwent fast CT studies of regional myocardial perfusion which were compared to microspheres (M). Dilute iohexol (0.5 mL/kg) was injected over 2.5 seconds, via, in turn, the pulmonary artery (PA), proximal inferior vena cava (IVC) and femoral vein (FV) during CT scans performed at rest and after vasodilation with adenosine (M flow range: 52-399 mL/100 g/minute). Correlations made with M were not significantly different for PA vs IVC (n = 24), PA vs FV (n = 22) and IVC vs FV (n = 44). To determine the relative influence of injection site on accuracy of measurements above normal flow rates (> 150mL/100g/minute), CT flow (mL/100g/minute; mean {+-}SD) was compared to M. Thus, at normal flow, some CT overestimation of myocardial perfusion occurred with PA injections but FV or IVC injections provided for accurate measurements. At higher flow rates only PA and IVC injections enabled accurate CT measurements of perfusion. This may be related to differing transit kinetics of the input bolus of contrast.

  6. Preliminary Study of Open Quotient in an Ex-Vivo Perfused Human Larynx Model

    PubMed Central

    Mendelsohn, Abie H.; Zhang, Zhaoyan; Luegmair, Georg; Orestes, Michael; Berke, Gerald S.

    2016-01-01

    Importance Scientific understanding human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. Due to its invasive nature, direct experimentation of human voice production has previously not been possible. The feasibility of an ex-vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. Objective In this study, the relationship between adductor muscle group stimulation and the open quotient (OQ) of vocal fold vibration was investigated using an ex-vivo perfused human larynx. Design Human perfused tissue study. Setting Physiology Laboratory. Participants Human larynx is recovered from research-consented organ donors within two hours of cardiac death. Interventions, Main Outcomes and Measures Perfusion with donated human blood is re-established shortly after cardiac death. Human perfused phonation is achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. The phonation resulting from the graded states of neuromuscular stimulations are evaluated through high-speed vibratory imaging. OQ is derived through digital kymography and glottal area waveform analysis. Results Under constant glottal flow, step-wise increase in adductor muscle group stimulation decreased OQ. Quantitatively, OQ values reached a lower limit of 0.42. Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. Conclusions and Relevance For the first time in a neuromuscularly activated human larynx, a negative relationship between adductor muscle group stimulation and phonatory OQ was demonstrated. Further experience with the ex-vivo perfused human phonatory model will work to systematically define this causal relationship. PMID:26181642

  7. A database for estimating organ dose for coronary angiography and brain perfusion CT scans for arbitrary spectra and angular tube current modulation

    SciTech Connect

    Rupcich, Franco; Badal, Andreu; Kyprianou, Iacovos; Schmidt, Taly Gilat

    2012-09-15

    Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360 Degree-Sign through anthropomorphic voxelized female chest and head (0 Degree-Sign and 30 Degree-Sign tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tables of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDI{sub vol} and multiplying by a physical CTDI{sub vol} measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30 Degree-Sign relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate

  8. Optical modeling toward optimizing monitoring of intestinal perfusion in trauma patients

    SciTech Connect

    Akl, Tony; Wilson, Mark A.; Ericson, Milton Nance; Cote, Gerard L.

    2013-01-01

    Trauma is the number one cause of death for people between the ages 1 and 44 years in the United States. In addition, according to the Centers of Disease Control and Prevention, injury results in over 31 million emergency department visits annually. Minimizing the resuscitation period in major abdominal injuries increases survival rates by correcting impaired tissue oxygen delivery. Optimization of resuscitation requires a monitoring method to determine sufficient tissue oxygenation. Oxygenation can be assessed by determining the adequacy of tissue perfusion. In this work, we present the design of a wireless perfusion and oxygenation sensor based on photoplethysmography. Through optical modeling, the benefit of using the visible wavelengths 470, 525 and 590nm (around the 525nm hemoglobin isobestic point) for intestinal perfusion monitoring is compared to the typical near infrared (NIR) wavelengths (805nm isobestic point) used in such sensors. Specifically, NIR wavelengths penetrate through the thin intestinal wall (~4mm) leading to high background signals. However, these visible wavelengths have two times shorter penetration depth that the NIR wavelengths. Monte-Carlo simulations show that the transmittance of the three selected wavelengths is lower by 5 orders of magnitude depending on the perfusion state. Due to the high absorbance of hemoglobin in the visible range, the perfusion signal carried by diffusely reflected light is also enhanced by an order of magnitude while oxygenation signal levels are maintained. In addition, short source-detector separations proved to be beneficial for limiting the probing depth to the thickness of the intestinal wall.

  9. A Phantom Tissue System for the Calibration of Perfusion Measurements

    PubMed Central

    Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Scott, Elaine P.; Diller, Thomas E.

    2008-01-01

    A convenient method for testing and calibrating surface perfusion sensors has been developed. A phantom tissue model is used to simulate the nondirectional blood flow of tissue perfusion. A computational fluid dynamics (CFD) model was constructed in Fluent® to design the phantom tissue and validate the experimental results. The phantom perfusion system was used with a perfusion sensor based on clearance of thermal energy. A heat flux gage measures the heat flux response of tissue when a thermal event (convective cooling) is applied. The blood perfusion and contact resistance are estimated by a parameter estimation code. From the experimental and analytical results, it was concluded that the probe displayed good measurement repeatability and sensitivity. The experimental perfusion measurements in the tissue were in good agreement with those of the CFD models and demonstrated the value of the phantom tissue system. PMID:19045509

  10. Polydimethylsiloxane embedded mouse aorta ex vivo perfusion model: proof-of-concept study focusing on atherosclerosis

    NASA Astrophysics Data System (ADS)

    Wang, Xueya; Wolf, Marc P.; Keel, Rahel Bänziger; Lehner, Roman; Hunziker, Patrick R.

    2012-07-01

    Existing mouse artery ex vivo perfusion models have utilized arteries such as carotid, uterine, and mesenteric arteries, but not the aorta. However, the aorta is the principal vessel analyzed for atherosclerosis studies in vivo. We have devised a mouse aorta ex vivo perfusion model that can bridge this gap. Aortas from apoE(-/-) mice are embedded in a transparent, gas-permeable, and elastic polymer matrix [polydimethylsiloxane (PDMS)] and artificially perfused with cell culture medium under cell culture conditions. After 24 h of artificial ex vivo perfusion, no evidence of cellular apoptosis is detected. Utilizing a standard confocal microscope, it is possible to image specific receptor targeting of cells in atherosclerotic plaques during 24 h. Imaging motion artifacts are minimal due to the polymer matrix embedding. Re-embedding of the aorta enables tissue sectioning and immuno-histochemical analysis. The ex vivo data are validated by comparison with in vivo experiments. This model can save animal lives via production of multiple endpoints in a single experiment, is easy to apply, and enables straightforward comparability with pre-existing atherosclerosis in vivo data. It is suited to investigate atherosclerotic disease in particular and vascular biology in general.

  11. A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging

    PubMed Central

    Cookson, A.N.; Lee, J.; Michler, C.; Chabiniok, R.; Hyde, E.; Nordsletten, D.; Smith, N.P.

    2014-01-01

    Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters

  12. A residence-time distribution analysis of the hydrodynamics within the intestine in man during a regional single-pass perfusion with Loc-I-Gut: in-vivo permeability estimation.

    PubMed

    Lennernäs, H; Lee, I D; Fagerholm, U; Amidon, G L

    1997-07-01

    The goal of this study was to determine the most appropriate hydrodynamic model for the Loc-I-Gut in-vivo perfusion system. The general mixing-tank-in-series model, which can approximate single mixing tank and laminar and plug-flow hydrodynamics, was fitted to the observed experimental residence-time distribution curves for the non-absorbable marker [14C]PEG 4000. The residence-time distribution analysis shows that the hydrodynamics of the perfusion solution within the jejunal segment in man is well approximately by a model containing on average between 1-2 mixing tanks in series. The solution is well mixed when using perfusion rates of 2.0, 3.0 and 6.0 mL min-1. The average mean residence time estimates from the fitted residence-time distribution were 12 +/- 7.6, 15 +/- 4.2 and 7.7 +/- 4.6 min, respectively, at these three perfusion rates. The mean volumes of the segment (Vs) were 25 +/- 15, 45 +/- 12 and 46 +/- 27 mL, respectively. There were no statistical differences between 2.0, 3.0 and 6.0 mL min-1 in respect of the number of mixing tanks (n) and mean residence times. This residence-time distribution analysis indicates that the luminal fluid in the Loc-I-Gut perfusion system is well-mixed, and that permeability calculations based on the well-mixed assumption most closely approximate the actual local (average) membrane permeability within the perfused segment. PMID:9255711

  13. Animal models of ex vivo lung perfusion as a platform for transplantation research

    PubMed Central

    Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Jr, Don Hayes; Black, Sylvester M; Whitson, Bryan A

    2014-01-01

    Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117

  14. Animal models of ex vivo lung perfusion as a platform for transplantation research.

    PubMed

    Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Hayes, Don; Black, Sylvester M; Whitson, Bryan A

    2014-05-20

    Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117

  15. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork

    PubMed Central

    Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.

    2016-01-01

    Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293

  16. In vivo perfusion assessment of an anastomosis surgery on porcine intestinal model (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Le, Hanh N. D.; Opferman, Justin; Decker, Ryan; Cheon, Gyeong W.; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2016-04-01

    Anastomosis, the connection of two structures, is a critical procedure for reconstructive surgery with over 1 million cases/year for visceral indication alone. However, complication rates such as strictures and leakage affect up to 19% of cases for colorectal anastomoses and up to 30% for visceral transplantation anastomoses. Local ischemia plays a critical role in anastomotic complications, making blood perfusion an important indicator for tissue health and predictor for healing following anastomosis. In this work, we apply a real time multispectral imaging technique to monitor impact on tissue perfusion due to varying interrupted suture spacing and suture tensions. Multispectral tissue images at 470, 540, 560, 580, 670 and 760 nm are analyzed in conjunction with an empirical model based on diffuse reflectance process to quantify the hemoglobin oxygen saturation within the suture site. The investigated tissues for anastomoses include porcine small (jejunum and ileum) and large (transverse colon) intestines. Two experiments using interrupted suturing with suture spacing of 1, 2, and 3 mm and tension levels from 0 N to 2.5 N are conducted. Tissue perfusion at 5, 10, 20 and 30 min after suturing are recorded and compared with the initial normal state. The result indicates the contrast between healthy and ischemic tissue areas and assists the determination of suturing spacing and tension. Therefore, the assessment of tissue perfusion will permit the development and intra-surgical monitoring of an optimal suture protocol during anastomosis with less complications and improved functional outcome.

  17. Modeling laser speckle imaging of perfusion in the skin (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Regan, Caitlin; Hayakawa, Carole K.; Choi, Bernard

    2016-02-01

    Laser speckle imaging (LSI) enables visualization of relative blood flow and perfusion in the skin. It is frequently applied to monitor treatment of vascular malformations such as port wine stain birthmarks, and measure changes in perfusion due to peripheral vascular disease. We developed a computational Monte Carlo simulation of laser speckle contrast imaging to quantify how tissue optical properties, blood vessel depths and speeds, and tissue perfusion affect speckle contrast values originating from coherent excitation. The simulated tissue geometry consisted of multiple layers to simulate the skin, or incorporated an inclusion such as a vessel or tumor at different depths. Our simulation used a 30x30mm uniform flat light source to optically excite the region of interest in our sample to better mimic wide-field imaging. We used our model to simulate how dynamically scattered photons from a buried blood vessel affect speckle contrast at different lateral distances (0-1mm) away from the vessel, and how these speckle contrast changes vary with depth (0-1mm) and flow speed (0-10mm/s). We applied the model to simulate perfusion in the skin, and observed how different optical properties, such as epidermal melanin concentration (1%-50%) affected speckle contrast. We simulated perfusion during a systolic forearm occlusion and found that contrast decreased by 35% (exposure time = 10ms). Monte Carlo simulations of laser speckle contrast give us a tool to quantify what regions of the skin are probed with laser speckle imaging, and measure how the tissue optical properties and blood flow affect the resulting images.

  18. Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange

    NASA Technical Reports Server (NTRS)

    Vidal Melo, M. F.; Loeppky, J. A.; Caprihan, A.; Luft, U. C.

    1993-01-01

    This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

  19. Dynamic CT perfusion measurement in a cardiac phantom.

    PubMed

    Ziemer, Benjamin P; Hubbard, Logan; Lipinski, Jerry; Molloi, Sabee

    2015-10-01

    Widespread clinical implementation of dynamic CT myocardial perfusion has been hampered by its limited accuracy and high radiation dose. The purpose of this study was to evaluate the accuracy and radiation dose reduction of a dynamic CT myocardial perfusion technique based on first pass analysis (FPA). To test the FPA technique, a pulsatile pump was used to generate known perfusion rates in a range of 0.96-2.49 mL/min/g. All the known perfusion rates were determined using an ultrasonic flow probe and the known mass of the perfusion volume. FPA and maximum slope model (MSM) perfusion rates were measured using volume scans acquired from a 320-slice CT scanner, and then compared to the known perfusion rates. The measured perfusion using FPA (P(FPA)), with two volume scans, and the maximum slope model (P(MSM)) were related to known perfusion (P(K)) by P(FPA) = 0.91P(K) + 0.06 (r = 0.98) and P(MSM) = 0.25P(K) - 0.02 (r = 0.96), respectively. The standard error of estimate for the FPA technique, using two volume scans, and the MSM was 0.14 and 0.30 mL/min/g, respectively. The estimated radiation dose required for the FPA technique with two volume scans and the MSM was 2.6 and 11.7-17.5 mSv, respectively. Therefore, the FPA technique can yield accurate perfusion measurements using as few as two volume scans, corresponding to approximately a factor of four reductions in radiation dose as compared with the currently available MSM. In conclusion, the results of the study indicate that the FPA technique can make accurate dynamic CT perfusion measurements over a range of clinically relevant perfusion rates, while substantially reducing radiation dose, as compared to currently available dynamic CT perfusion techniques. PMID:26156231

  20. Estimating multivariate similarity between neuroimaging datasets with sparse canonical correlation analysis: an application to perfusion imaging

    PubMed Central

    Rosa, Maria J.; Mehta, Mitul A.; Pich, Emilio M.; Risterucci, Celine; Zelaya, Fernando; Reinders, Antje A. T. S.; Williams, Steve C. R.; Dazzan, Paola; Doyle, Orla M.; Marquand, Andre F.

    2015-01-01

    An increasing number of neuroimaging studies are based on either combining more than one data modality (inter-modal) or combining more than one measurement from the same modality (intra-modal). To date, most intra-modal studies using multivariate statistics have focused on differences between datasets, for instance relying on classifiers to differentiate between effects in the data. However, to fully characterize these effects, multivariate methods able to measure similarities between datasets are needed. One classical technique for estimating the relationship between two datasets is canonical correlation analysis (CCA). However, in the context of high-dimensional data the application of CCA is extremely challenging. A recent extension of CCA, sparse CCA (SCCA), overcomes this limitation, by regularizing the model parameters while yielding a sparse solution. In this work, we modify SCCA with the aim of facilitating its application to high-dimensional neuroimaging data and finding meaningful multivariate image-to-image correspondences in intra-modal studies. In particular, we show how the optimal subset of variables can be estimated independently and we look at the information encoded in more than one set of SCCA transformations. We illustrate our framework using Arterial Spin Labeling data to investigate multivariate similarities between the effects of two antipsychotic drugs on cerebral blood flow. PMID:26528117

  1. Estimating multivariate similarity between neuroimaging datasets with sparse canonical correlation analysis: an application to perfusion imaging.

    PubMed

    Rosa, Maria J; Mehta, Mitul A; Pich, Emilio M; Risterucci, Celine; Zelaya, Fernando; Reinders, Antje A T S; Williams, Steve C R; Dazzan, Paola; Doyle, Orla M; Marquand, Andre F

    2015-01-01

    An increasing number of neuroimaging studies are based on either combining more than one data modality (inter-modal) or combining more than one measurement from the same modality (intra-modal). To date, most intra-modal studies using multivariate statistics have focused on differences between datasets, for instance relying on classifiers to differentiate between effects in the data. However, to fully characterize these effects, multivariate methods able to measure similarities between datasets are needed. One classical technique for estimating the relationship between two datasets is canonical correlation analysis (CCA). However, in the context of high-dimensional data the application of CCA is extremely challenging. A recent extension of CCA, sparse CCA (SCCA), overcomes this limitation, by regularizing the model parameters while yielding a sparse solution. In this work, we modify SCCA with the aim of facilitating its application to high-dimensional neuroimaging data and finding meaningful multivariate image-to-image correspondences in intra-modal studies. In particular, we show how the optimal subset of variables can be estimated independently and we look at the information encoded in more than one set of SCCA transformations. We illustrate our framework using Arterial Spin Labeling data to investigate multivariate similarities between the effects of two antipsychotic drugs on cerebral blood flow. PMID:26528117

  2. The isolated perfused equine distal limb as an ex vivo model for pharmacokinetic studies.

    PubMed

    Friebe, M; Stahl, J; Kietzmann, M

    2013-06-01

    Even though intra-articular injections play an important role in the treatment of joint-related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, an ex vivo model for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments (n = 11), which also included histological examinations of the joint capsule. As the model's first implementation, the articular efflux rate of betamethasone (BM), administered as BM disodium phosphate intra-articularly to the fetlock joint (4 mg BM/joint), was investigated. The concentration of BM in the venous perfusate of the radial vein was measured by means of high-performance liquid chromatography. The average BM efflux rate per minute was calculated to be 5.1 μg/min with values ranging from 9 μg/min to 2.9 μg/min. 7.5 h after i.a. application, 2.3 mg BM had left the joint via the radial vein. Using this inexpensive setup, the presented model allows studying a variety of pharmacological topics without the ethical limitations of animal studies. PMID:22913456

  3. Simultaneous detection of landmarks and key-frame in cardiac perfusion MRI using a joint spatial-temporal context model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoguang; Xue, Hui; Jolly, Marie-Pierre; Guetter, Christoph; Kellman, Peter; Hsu, Li-Yueh; Arai, Andrew; Zuehlsdorff, Sven; Littmann, Arne; Georgescu, Bogdan; Guehring, Jens

    2011-03-01

    Cardiac perfusion magnetic resonance imaging (MRI) has proven clinical significance in diagnosis of heart diseases. However, analysis of perfusion data is time-consuming, where automatic detection of anatomic landmarks and key-frames from perfusion MR sequences is helpful for anchoring structures and functional analysis of the heart, leading toward fully automated perfusion analysis. Learning-based object detection methods have demonstrated their capabilities to handle large variations of the object by exploring a local region, i.e., context. Conventional 2D approaches take into account spatial context only. Temporal signals in perfusion data present a strong cue for anchoring. We propose a joint context model to encode both spatial and temporal evidence. In addition, our spatial context is constructed not only based on the landmark of interest, but also the landmarks that are correlated in the neighboring anatomies. A discriminative model is learned through a probabilistic boosting tree. A marginal space learning strategy is applied to efficiently learn and search in a high dimensional parameter space. A fully automatic system is developed to simultaneously detect anatomic landmarks and key frames in both RV and LV from perfusion sequences. The proposed approach was evaluated on a database of 373 cardiac perfusion MRI sequences from 77 patients. Experimental results of a 4-fold cross validation show superior landmark detection accuracies of the proposed joint spatial-temporal approach to the 2D approach that is based on spatial context only. The key-frame identification results are promising.

  4. Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model

    PubMed Central

    Yang, Kwang Mo; Russell, James; Lupu, Mihaela E.; Cho, HyungJoon; Li, Xiao-Feng; Koutcher, Jason A.; Ling, C. Clifton

    2010-01-01

    The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first (pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone. PMID:19717985

  5. Comparison of TTP and Tmax estimation techniques in perfusion-weighted MR datasets for tissue-at-risk definition

    NASA Astrophysics Data System (ADS)

    Forkert, Nils Daniel; Kaesemann, Philipp; Fiehler, Jens; Thomalla, Götz

    2012-03-01

    Acute stroke is a major cause for death and disability among adults in the western hemisphere. Time-resolved perfusion-weighted (PWI) and diffusion-weighted (DWI) MR datasets are typically used for the estimation of tissue-at-risk, which is an important variable for acute stroke therapy decision-making. Although several parameters, which can be estimated based on PWI concentration curves, have been proposed for tissue-at-risk definition in the past, the time-to-peak (TTP) or time-to-max (Tmax) parameter is used most frequently in recent trials. Unfortunately, there is no clear consensus which method should be used for estimation of Tmax or TTP maps. Consequently, tissue-at-risk estimations and following treatment decision might vary considerably with the method used. In this work, 5 PWI datasets of acute stroke patients were used to calculate TTP or Tmax maps using 10 different estimation techniques. The resulting maps were segmented using a typical threshold of +4s and the corresponding PWI-lesions were calculated. The first results suggest that the TTP or Tmax method used has a major impact on the resulting tissue-at-risk volume. Numerically, the calculated volumes differed up to a factor of 3. In general, the deconvolution-based Tmax techniques estimate the ischemic penumbra rather smaller compared to direct TTP based techniques. In conclusion, the comparison of different methods for TTP or Tmax estimation revealed high variations regarding the resulting tissue-at-risk volume, which might lead to different therapy decisions. Therefore, a consensus how TTP or Tmax maps should be calculated seems necessary.

  6. The "kidney-liver" multiorgan ex vivo perfused model improves the circuit's biochemical milieu during perfusion compared to the "liver-kidney" counterpart.

    PubMed

    Chung, Wen Yuan; Gravante, Gianpiero; Eltweri, Amar; Sorge, Roberto; Ong, Seok Ling; Pollard, Cristina; Metcalfe, Mathew; Dennison, Ashley

    2015-06-01

    The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu. PMID:25557139

  7. Estimation of x-ray parameters in digital coronary angiography for compensation of myocardial perfusion measurements

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2008-03-01

    Coronary angiography is the primary technique for diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. However, the clinical relevance of an appearing stenosis is not that easy to assess. In previous work we have analyzed the myocardial perfusion by comparing basal and hyperemic coronary flow. This comparison is the basis of a Relative Coronary Flow Reserve (RCFR) measure. In a Region-of-Interest (ROI) on the angiogram the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In previous work we have presented the results of a small study of 20 patients. In this paper we present an analysis of the sensitivity of the method for variations in X-ray exposure between the two runs due to the Automatic Exposure Control (AEC) unit. The AEC is a system unit with the task to ensure a constant dose rate at the entrance of the detector by making the appropriate adaptations in X-ray factor settings for patients which range from slim to more obese. We have setup a phantom study to reveal the expected exposure variations. We present several of the developed phantoms together with a compensation strategy.

  8. Validation of a two-compartment model of ventilation/perfusion distribution.

    PubMed

    Loeppky, Jack A; Caprihan, Arvind; Altobelli, Stephen A; Icenogle, Milton V; Scotto, Pietro; Vidal Melo, Marcos F

    2006-03-28

    Ventilation (V (A)) to perfusion (Q ) heterogeneity (V (A)/Q ) analyses by a two-compartment lung model (2C), utilizing routine gas exchange measurements and a computer solution to account for O(2) and CO(2) measurements, were compared with multiple inert gas elimination technique (MIGET) analyses and a multi-compartment (MC) model. The 2C and MC estimates of V (A)/Q mismatch were obtained in 10 healthy subjects, 43 patients having chronic obstructive pulmonary disease (COPD) and in 14 dog experiments where hemodynamics and acid-base status were manipulated with gas mixtures, fluid loading and tilt-table stressors. MIGET comparisons with 2C were made on 6 patients and 32 measurements in healthy subjects before and after exercise at normoxia and altitude hypoxia. Statistically significant correlations for logarithmic standard deviations of V (A)/Q distributions (SD(V (A)/Q )) were obtained for all 2C comparisons, with similar values between 2C and both other methods in the 1.1-1.5 range, compatible with mild to moderate COPD. 2C tended to overestimate MC and MIGET values at low and underestimate them at high SD(V (A)/Q ) values. SD(V (A)/Q ) weighted by Q agreed better with MC and MIGET estimates in the normal range, whereas SD(V (A)/Q ) weighted by V (A) was closer to MC at higher values because the V (A)-weighted SD(V (A)/Q ) is related to blood-to-gas PCO(2) differences that are elevated in disease, thereby allowing better discrimination. The 2C model accurately described functional V (A)/Q characteristics in 26 normal and bronchoconstricted dogs during non-steady state rebreathing and could be used to quantify the effect of reduced O(2) diffusing capacity in diseased lungs. These comparisons indicate that 2C adequately describes V (A)/Q mismatch and can be useful in clinical or experimental situations where other techniques are not feasible. PMID:16024300

  9. Assessment of myocardial blood perfusion improved by CD151 in a pig myocardial infarction model

    PubMed Central

    Zuo, Hou-juan; Liu, Zheng-xiang; Liu, Xiao-chun; Yang, Jun; Liu, Tao; Wen, Sha; Wang, Dao-wen; Zhang, Xin

    2009-01-01

    Aim: To appraise the efficacy of CD151-induced myocardial therapeutic angiogenesis in a pig myocardial infarction model. Methods: CD151 and anti-CD151 were constructed into the recombinant adeno-associated virus (rAAV) vector. All 26 pigs were subjected to coronary artery ligation or no surgery. Eight weeks after coronary artery ligation, the expression of CD151 was measured by Western blot and immunostaining. Capillary density was evaluated using immunostaining for von Willebrand factor (vWF). 13N-labeled NH3 positron emission computed tomography ([13N]NH3 PET) was measured to assess regional myocardial perfusion and the defect area. Results: CD151 gene delivery could increase the expression of CD151 at protein level. Over-expression of CD151 increased the density of total capillaries in the ischemic myocardium, significantly improved the blood perfusion and reduced the defect area percentage. Conclusion: This study demonstrated that the rAAV-mediated CD151 gene delivery promoted efficient neovascularization and increased the blood perfusion after myocardial infarction in pigs. PMID:19079294

  10. Induction of Hepatic and Endothelial Differentiation by Perfusion in a Three-Dimensional Cell Culture Model of Human Fetal Liver

    PubMed Central

    Pekor, Christopher; Gerlach, Jörg C.; Nettleship, Ian

    2015-01-01

    The development of functional engineered tissue constructs depends on high cell densities and appropriate vascularization. In this study we implemented a four-compartment three-dimensional perfusion bioreactor culture model for studying the effects of medium perfusion on endothelial, hepatic, and hematopoietic cell populations of primary human fetal liver in an in vivo-like environment. Human fetal liver cells were cultured in bioreactors configured to provide either perfusion or diffusion conditions. Metabolic activities of the cultures were monitored daily by measuring glucose consumption and lactate production. Cell viability during culture was analyzed by lactate dehydrogenase activity. Hepatic functionality was determined by the release of albumin and alpha-fetoprotein (AFP) in culture medium samples. After 4 days of culture, cells were analyzed for the expression of a variety of endothelial, hepatic, and hematopoietic genes, as well as the surface marker expression of CD31 and CD34 in flow cytometry. We found that medium perfusion increased the gene expression of endothelial markers such as CD31, von Willebrand factor (vWF), CD140b, CD309, and CD144 while decreasing the gene expression of the erythrocyte-surface marker CD235a. Hepatic differentiation was promoted under perfusion conditions as demonstrated by lower AFP and higher albumin secretion compared with cultures not exposed to medium perfusion. Additionally, cultures exposed to medium perfusion gave higher rates of glucose consumption and lactate production, indicating increased metabolic activity. In conclusion, high-density bioreactors configured to provide constant medium perfusion significantly induced hepatic and endothelial cell differentiation and provided improved conditions for the culture of human fetal liver cells compared with cultures without perfusion. PMID:25559936

  11. Induction of Hepatic and Endothelial Differentiation by Perfusion in a Three-Dimensional Cell Culture Model of Human Fetal Liver.

    PubMed

    Pekor, Christopher; Gerlach, Jörg C; Nettleship, Ian; Schmelzer, Eva

    2015-07-01

    The development of functional engineered tissue constructs depends on high cell densities and appropriate vascularization. In this study we implemented a four-compartment three-dimensional perfusion bioreactor culture model for studying the effects of medium perfusion on endothelial, hepatic, and hematopoietic cell populations of primary human fetal liver in an in vivo-like environment. Human fetal liver cells were cultured in bioreactors configured to provide either perfusion or diffusion conditions. Metabolic activities of the cultures were monitored daily by measuring glucose consumption and lactate production. Cell viability during culture was analyzed by lactate dehydrogenase activity. Hepatic functionality was determined by the release of albumin and alpha-fetoprotein (AFP) in culture medium samples. After 4 days of culture, cells were analyzed for the expression of a variety of endothelial, hepatic, and hematopoietic genes, as well as the surface marker expression of CD31 and CD34 in flow cytometry. We found that medium perfusion increased the gene expression of endothelial markers such as CD31, von Willebrand factor (vWF), CD140b, CD309, and CD144 while decreasing the gene expression of the erythrocyte-surface marker CD235a. Hepatic differentiation was promoted under perfusion conditions as demonstrated by lower AFP and higher albumin secretion compared with cultures not exposed to medium perfusion. Additionally, cultures exposed to medium perfusion gave higher rates of glucose consumption and lactate production, indicating increased metabolic activity. In conclusion, high-density bioreactors configured to provide constant medium perfusion significantly induced hepatic and endothelial cell differentiation and provided improved conditions for the culture of human fetal liver cells compared with cultures without perfusion. PMID:25559936

  12. Noninvasive estimation of oxygen consumption in human calf muscle through combined NMR measurements of ASL perfusion and T₂ oxymetry.

    PubMed

    Decorte, Nicolas; Buehler, Tania; Caldas de Almeida Araujo, Ericky; Vignaud, Alexandre; Carlier, Pierre G

    2014-01-01

    The objective of this work was to demonstrate the feasibility of measuring muscle O2 consumption (V˙O2) noninvasively with a combination of functional nuclear magnetic resonance (NMR) imaging methods, and to verify that changes in muscle V˙O2 can be detected with a temporal resolution compatible with physiological investigation and patient ease. T2-based oxymetry of arterial and venous blood was combined with the arterial-spin labeling (ASL)-based determination of muscle perfusion. These measurements were performed on 8 healthy volunteers under normoxic and hypoxic conditions in order to assess the sensitivity of measurements over a range of saturation values. Blood samples were drawn simultaneously and used to titrate blood T2 measurements versus hemoglobin O2 saturation (%HbO2) in vitro. The in vitro calibration curve of blood T2 fitted very well with the %HbO2 (r(2): 0.95). The in vivo venous T2 measurements agreed well with the in vitro measurements (intraclass correlation coefficient 0.82, 95% confidence interval 0.61-0.91). Oxygen extraction at rest decreased in the calf muscles subjected to hypoxia (p = 0.031). The combination of unaltered muscle perfusion and pinched arteriovenous O2 difference (p = 0.038) pointed towards a reduced calf muscle V˙O2 during transient hypoxia (p = 0.018). The results of this pilot study confirmed that muscle O2 extraction and V˙O2 can be estimated noninvasively using a combination of functional NMR techniques. Further studies are needed to confirm the usefulness in a larger sample of volunteers and patients. PMID:25531648

  13. Cell death, perfusion and electrical parameters are critical in models of hepatic radiofrequency ablation

    PubMed Central

    Hall, Sheldon K.; Ooi, Ean H.; Payne, Stephen J.

    2015-01-01

    Abstract Purpose: A sensitivity analysis has been performed on a mathematical model of radiofrequency ablation (RFA) in the liver. The purpose of this is to identify the most important parameters in the model, defined as those that produce the largest changes in the prediction. This is important in understanding the role of uncertainty and when comparing the model predictions to experimental data. Materials and methods: The Morris method was chosen to perform the sensitivity analysis because it is ideal for models with many parameters or that take a significant length of time to obtain solutions. A comprehensive literature review was performed to obtain ranges over which the model parameters are expected to vary, crucial input information. Results: The most important parameters in predicting the ablation zone size in our model of RFA are those representing the blood perfusion, electrical conductivity and the cell death model. The size of the 50 °C isotherm is sensitive to the electrical properties of tissue while the heat source is active, and to the thermal parameters during cooling. Conclusions: The parameter ranges chosen for the sensitivity analysis are believed to represent all that is currently known about their values in combination. The Morris method is able to compute global parameter sensitivities taking into account the interaction of all parameters, something that has not been done before. Research is needed to better understand the uncertainties in the cell death, electrical conductivity and perfusion models, but the other parameters are only of second order, providing a significant simplification. PMID:26000972

  14. Noninvasive Blood Perfusion Measurements of an Isolated Rat Liver and an Anesthetized Rat Kidney

    PubMed Central

    Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Lee, Charles Y.; Diller, Thomas E.; Scott, Elaine P.

    2008-01-01

    A simple, cost effective, and noninvasive blood perfusion system is tested in animal models. The system uses a small sensor to measure the heat transfer response to a thermal event (convective cooling) imposed on the tissue surface. Heat flux data are compared with a mathematical model of the tissue to estimate both blood perfusion and thermal contact resistance between the tissue and the probe. The perfusion system was evaluated for repeatability and sensitivity using isolated rat liver and exposed rat kidney tests. Perfusion in the isolated liver tests was varied by controlling the flow of the perfusate into the liver, and the perfusion in the exposed kidney tests was varied by temporarily occluding blood flow through the renal artery and vein. The perfusion estimated by the convective perfusion probe was in good agreement with that of the metered flow of the perfusate into the liver model. The liver tests indicated that the probe can be used to detect small changes in perfusion (0.005 ml/ml/s). The probe qualitatively tracked the changes in the perfusion in the kidney model due to occlusion of the renal artery and vein. PMID:19045542

  15. Characterization of micro-invasive trabecular bypass stents by ex vivo perfusion and computational flow modeling

    PubMed Central

    Hunter, Kendall S; Fjield, Todd; Heitzmann, Hal; Shandas, Robin; Kahook, Malik Y

    2014-01-01

    Micro-invasive glaucoma surgery with the Glaukos iStent® or iStent inject® (Glaukos Corporation, Laguna Hills, CA, USA) is intended to create a bypass through the trabecular meshwork to Schlemm’s canal to improve aqueous outflow through the natural physiologic pathway. While the iStent devices have been evaluated in ex vivo anterior segment models, they have not previously been evaluated in whole eye perfusion models nor characterized by computational fluid dynamics. Intraocular pressure (IOP) reduction with the iStent was evaluated in an ex vivo whole human eye perfusion model. Numerical modeling, including computational fluid dynamics, was used to evaluate the flow through the stents over physiologically relevant boundary conditions. In the ex vivo model, a single iStent reduced IOP by 6.0 mmHg from baseline, and addition of a second iStent further lowered IOP by 2.9 mmHg, for a total IOP reduction of 8.9 mmHg. Computational modeling showed that simulated flow through the iStent or iStent inject is smooth and laminar at physiological flow rates. Each stent was computed to have a negligible flow resistance consistent with an expected significant decrease in IOP. The present perfusion results agree with prior clinical and laboratory studies to show that both iStent and iStent inject therapies are potentially titratable, providing clinicians with the opportunity to achieve lower target IOPs by implanting additional stents. PMID:24648713

  16. Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study

    SciTech Connect

    Donaldson, Stephanie B.; Betts, Guy; Bonington, Suzanne C.; Homer, Jarrod J.; Slevin, Nick J.; Kershaw, Lucy E.; Valentine, Helen; West, Catharine M.L.; Buckley, David L.

    2011-11-15

    Purpose: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. Methods and Materials: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. Results: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). Conclusions: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.

  17. Segmentation of the Left Ventricle in Myocardial Perfusion SPECT Using Active Shape Model

    NASA Astrophysics Data System (ADS)

    Tan, Wooi-Haw; Besar, Rosli

    In the quantification of myocardial perfusion SPECT (MPS), numerous processes are involved. Automation is desired as it will considerably reduce the laboriousness of the underlying tasks. In this paper, we propose a segmentation scheme for the delineation of left ventricle (LV) using the Active Shape Models. Our scheme will reduce the labour-intensiveness in MPS quantification, while still allowing interactive guidance from the medical experts. The proposed scheme has been applied on clinical MPS tomograms in which it has successfully delineated the LV in 94% of the test data. In addition, it has also shown to be more suitable for LV segmentation than the rivaling Active Contour Model.

  18. Blind estimation of compartmental model parameters.

    PubMed

    Di Bella, E V; Clackdoyle, R; Gullberg, G T

    1999-03-01

    Computation of physiologically relevant kinetic parameters from dynamic PET or SPECT imaging requires knowledge of the blood input function. This work is concerned with developing methods to accurately estimate these kinetic parameters blindly; that is, without use of a directly measured blood input function. Instead, only measurements of the output functions--the tissue time-activity curves--are used. The blind estimation method employed here minimizes a set of cross-relation equations, from which the blood term has been factored out, to determine compartmental model parameters. The method was tested with simulated data appropriate for dynamic SPECT cardiac perfusion imaging with 99mTc-teboroxime and for dynamic PET cerebral blood flow imaging with 15O water. The simulations did not model the tomographic process. Noise levels typical of the respective modalities were employed. From three to eight different regions were simulated, each with different time-activity curves. The time-activity curve (24 or 70 time points) for each region was simulated with a compartment model. The simulation used a biexponential blood input function and washin rates between 0.2 and 1.3 min(-1) and washout rates between 0.2 and 1.0 min(-1). The system of equations was solved numerically and included constraints to bound the range of possible solutions. From the cardiac simulations, washin was determined to within a scale factor of the true washin parameters with less than 6% bias and 12% variability. 99mTc-teboroxime washout results had less than 5% bias, but variability ranged from 14% to 43%. The cerebral blood flow washin parameters were determined with less than 5% bias and 4% variability. The washout parameters were determined with less than 4% bias, but had 15-30% variability. Since washin is often the parameter of most use in clinical studies, the blind estimation approach may eliminate the current necessity of measuring the input function when performing certain dynamic studies

  19. Error analysis of the quantification of hepatic perfusion using a dual-input single-compartment model

    NASA Astrophysics Data System (ADS)

    Miyazaki, Shohei; Yamazaki, Youichi; Murase, Kenya

    2008-11-01

    We performed an error analysis of the quantification of liver perfusion from dynamic contrast-enhanced computed tomography (DCE-CT) data using a dual-input single-compartment model for various disease severities, based on computer simulations. In the simulations, the time-density curves (TDCs) in the liver were generated from an actually measured arterial input function using a theoretical equation describing the kinetic behavior of the contrast agent (CA) in the liver. The rate constants for the transfer of CA from the hepatic artery to the liver (K1a), from the portal vein to the liver (K1p), and from the liver to the plasma (k2) were estimated from simulated TDCs with various plasma volumes (V0s). To investigate the effect of the shapes of input functions, the original arterial and portal-venous input functions were stretched in the time direction by factors of 2, 3 and 4 (stretching factors). The above parameters were estimated with the linear least-squares (LLSQ) and nonlinear least-squares (NLSQ) methods, and the root mean square errors (RMSEs) between the true and estimated values were calculated. Sensitivity and identifiability analyses were also performed. The RMSE of V0 was the smallest, followed by those of K1a, k2 and K1p in an increasing order. The RMSEs of K1a, K1p and k2 increased with increasing V0, while that of V0 tended to decrease. The stretching factor also affected parameter estimation in both methods. The LLSQ method estimated the above parameters faster and with smaller variations than the NLSQ method. Sensitivity analysis showed that the magnitude of the sensitivity function of V0 was the greatest, followed by those of K1a, K1p and k2 in a decreasing order, while the variance of V0 obtained from the covariance matrices was the smallest, followed by those of K1a, K1p and k2 in an increasing order. The magnitude of the sensitivity function and the variance increased and decreased, respectively, with increasing disease severity and decreased

  20. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    PubMed

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. PMID:25891783

  1. Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

    NASA Astrophysics Data System (ADS)

    Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

    2015-11-01

    Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

  2. Ocular Perfusion Pressure vs Estimated Trans–Lamina Cribrosa Pressure Difference in Glaucoma: The Central India Eye and Medical Study (An American Ophthalmological Society Thesis)

    PubMed Central

    Jonas, Jost B.; Wang, Ningli; Nangia, Vinay

    2015-01-01

    Purpose: To test the hypothesis that taking translamina pressure difference into consideration changes associations between ocular perfusion pressure and glaucomatous optic neuropathy. Methods: The population-based Central India Eye and Medical Study included 4711 subjects. Ocular perfusion pressure was calculated as follows: ⅔ [diastolic blood pressure + ⅓ × (systolic blood pressure – diastolic blood pressure)] – IOP. Cerebrospinal fluid pressure (mm Hg) was estimated as follows: 0.44 body mass index (kg/m2) + 0.16 diastolic blood pressure (mm Hg) − 0.18 × age (years) − 1.91. Translamina pressure difference was IOP minus cerebrospinal fluid pressure. Results: In multivariate analysis, higher open-angle glaucoma prevalence was associaed with higher IOP (P<.001; odds ratio [OR], 1.19; 95% CI, 1.15, 1.24) or with higher translamina pressure difference (P<.001; OR, 1.15; 95% CI, 1.10, 1.19), but not with ocular perfusion pressure (P<.37). A smaller neuroretinal rim area was correlated with higher IOP (P<.001; standardized coefficient beta −0.09) or larger translamina pressure difference (P<.001; β −0.10), but not with ocular perfusion pressure (P=.26). Greater prevalence of angle-closure glaucoma was associated with higher IOP (P<.001; OR, 1.22; 95% CI, 1.15, 1.28) or higher translamina pressure difference (P<.001; OR, 1.19; 95% CI, 1.13, 1.25) or lower ocular perfusion pressure (P<.04; OR, 0.95; 95% CI, 0.90, 0.996). Correlation coefficients were highest for the association with IOP and lowest for ocular perfusion pressure. A smaller rim area was correlated with higher IOP (P<.001; beta −0.08) and higher translamina pressure difference (P<.001; beta −0.08); rim area and ocular perfusion pressure were not significantly associated (P=.25). Conclusions: The present study provides information on the relationship of translamina pressure difference to the development of optic nerve damage in what is presently called glaucoma. It does not provide

  3. In-vivo regional myocardial perfusion measurements in a porcine model by ECG-gated multislice computed tomography

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Liang, Yun; Meyer, Cristopher A.; Teague, Shawn; Stecker, Michael; Hutchins, Gary; McLennan, Gordon; Persohn, Scott

    2003-05-01

    Purpose: To evaluate whether functional multi-slice computed tomography (MSCT) can identify regional areas of normally perfused and ischemic myocardium in a porcine model. Material and Methods: Three out bred pigs, two of which had ameroids surgically implanted to constrict flow within the LAD and LCx coronary arteries, were injected with 25 mL of iopromide (Isovue) at a rate of 5 mL/second via the femoral or jugular vein. Sixty axial scans along the short axis of the heart was acquired on a 16-slice CT scanner (Philips MX8000-IDT) triggered at end-diastole of the cardiac cycle and acquiring an image within 270 msec. A second series of scans were taken after an intravenous injection of a vasodilator, 150 μg/kg/min of adenosine. ROIs were drawn around the myocardial tissue and the resulting time-density curves were used to extract perfusion values. Results: Determination of the myocardial perfusion and fractional blood volume implementing three different perfusion models. A 5-point averaging or 'smoothing' algorithm was employed to effectively filter the data due to its noisy nature. The (preliminary) average perfusion and fractional blood volume values over selected axial slices for the pig without an artificially induced stenosis were measured to be 84 +/- 22 mL/min/100g-tissue and 0.17 +/- 0.04 mL/g-tissue, the former is consistent with PET scan and EBCT results. The pig with a stenosis in the left LAD coronary artery showed a reduced global perfusion value -- 45 mL/min/100g-tissue. Correlations in regional perfusion values relative to the stenosis were weak. During the infusion of adenosine, averaged perfusion values for the three subjects increased by 46 (+/-45) percent, comparable to increases measured with PET. Conclusion: Quantifying global perfusion values using MDCT appear encouraging. Future work will focus resolving the systematic effects from noise due to signal fluctuation from the porcine tachyardia (80-93 BPM) and provide a more robust measurement

  4. Collimator optimization and collimator-detector response compensation in myocardial perfusion SPECT using the ideal observer with and without model mismatch and an anthropomorphic model observer

    NASA Astrophysics Data System (ADS)

    Ghaly, Michael; Links, Jonathan M.; Frey, Eric C.

    2016-03-01

    The collimator is the primary factor that determines the spatial resolution and noise tradeoff in myocardial perfusion SPECT images. In this paper, the goal was to find the collimator that optimizes the image quality in terms of a perfusion defect detection task. Since the optimal collimator could depend on the level of approximation of the collimator-detector response (CDR) compensation modeled in reconstruction, we performed this optimization for the cases of modeling the full CDR (including geometric, septal penetration and septal scatter responses), the geometric CDR, or no model of the CDR. We evaluated the performance on the detection task using three model observers. Two observers operated on data in the projection domain: the Ideal Observer (IO) and IO with Model-Mismatch (IO-MM). The third observer was an anthropomorphic Channelized Hotelling Observer (CHO), which operated on reconstructed images. The projection-domain observers have the advantage that they are computationally less intensive. The IO has perfect knowledge of the image formation process, i.e. it has a perfect model of the CDR. The IO-MM takes into account the mismatch between the true (complete and accurate) model and an approximate model, e.g. one that might be used in reconstruction. We evaluated the utility of these projection domain observers in optimizing instrumentation parameters. We investigated a family of 8 parallel-hole collimators, spanning a wide range of resolution and sensitivity tradeoffs, using a population of simulated projection (for the IO and IO-MM) and reconstructed (for the CHO) images that included background variability. We simulated anterolateral and inferior perfusion defects with variable extents and severities. The area under the ROC curve was estimated from the IO, IO-MM, and CHO test statistics and served as the figure-of-merit. The optimal collimator for the IO had a resolution of 9-11 mm FWHM at 10 cm, which is poorer resolution than typical collimators

  5. Collimator optimization and collimator-detector response compensation in myocardial perfusion SPECT using the ideal observer with and without model mismatch and an anthropomorphic model observer.

    PubMed

    Ghaly, Michael; Links, Jonathan M; Frey, Eric C

    2016-03-01

    The collimator is the primary factor that determines the spatial resolution and noise tradeoff in myocardial perfusion SPECT images. In this paper, the goal was to find the collimator that optimizes the image quality in terms of a perfusion defect detection task. Since the optimal collimator could depend on the level of approximation of the collimator-detector response (CDR) compensation modeled in reconstruction, we performed this optimization for the cases of modeling the full CDR (including geometric, septal penetration and septal scatter responses), the geometric CDR, or no model of the CDR. We evaluated the performance on the detection task using three model observers. Two observers operated on data in the projection domain: the Ideal Observer (IO) and IO with Model-Mismatch (IO-MM). The third observer was an anthropomorphic Channelized Hotelling Observer (CHO), which operated on reconstructed images. The projection-domain observers have the advantage that they are computationally less intensive. The IO has perfect knowledge of the image formation process, i.e. it has a perfect model of the CDR. The IO-MM takes into account the mismatch between the true (complete and accurate) model and an approximate model, e.g. one that might be used in reconstruction. We evaluated the utility of these projection domain observers in optimizing instrumentation parameters. We investigated a family of 8 parallel-hole collimators, spanning a wide range of resolution and sensitivity tradeoffs, using a population of simulated projection (for the IO and IO-MM) and reconstructed (for the CHO) images that included background variability. We simulated anterolateral and inferior perfusion defects with variable extents and severities. The area under the ROC curve was estimated from the IO, IO-MM, and CHO test statistics and served as the figure-of-merit. The optimal collimator for the IO had a resolution of 9-11 mm FWHM at 10 cm, which is poorer resolution than typical collimators

  6. Four dimensional optoacoustic imaging of perfusion in preclinical breast tumor model in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Deán-Ben, Xosé Luís.; Ermolayev, Vladimir; Mandal, Subhamoy; Ntziachristos, Vasilis; Razansky, Daniel

    2016-03-01

    Imaging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models.

  7. Fluorescence-based enhanced reality (FLER) for real-time estimation of bowel perfusion in minimally invasive surgery

    NASA Astrophysics Data System (ADS)

    Diana, Michele

    2016-03-01

    Pre-anastomotic bowel perfusion is a key factor for a successful healing process. Clinical judgment has limited accuracy to evaluate intestinal microperfusion. Fluorescence videography is a promising tool for image-guided intraoperative assessment of the bowel perfusion at the future anastomotic site in the setting of minimally invasive procedures. The standard configuration for fluorescence videography includes a Near-Infrared endoscope able to detect the signal emitted by a fluorescent dye, more frequently Indocyanine Green (ICG), which is administered by intravenous injection. Fluorescence intensity is proportional to the amount of fluorescent dye diffusing in the tissue and consequently is a surrogate marker of tissue perfusion. However, fluorescence intensity alone remains a subjective approach and an integrated computer-based analysis of the over-time evolution of the fluorescence signal is required to obtain quantitative data. We have developed a solution integrating computer-based analysis for intra-operative evaluation of the optimal resection site, based on the bowel perfusion as determined by the dynamic fluorescence intensity. The software can generate a "virtual perfusion cartography", based on the "fluorescence time-to-peak". The virtual perfusion cartography can be overlapped onto real-time laparoscopic images to obtain the Enhanced Reality effect. We have defined this approach FLuorescence-based Enhanced Reality (FLER). This manuscript describes the stepwise development of the FLER concept.

  8. Single-pass intestinal perfusion to establish the intestinal permeability of model drugs in mouse.

    PubMed

    Escribano, Elvira; Sala, Xavier García; Salamanca, Jorge; Navarro, Claudia Roig; Regué, Josep Queralt

    2012-10-15

    The aim of the present work was to study the intestinal permeabilities (P(eff)) of five model drugs: furosemide, piroxicam, naproxen, ranitidine and amoxicillin in the in situ intestinal perfusion technique in mice and compare them with corresponding rat and human in vivo P(eff) values. The main experimental conditions were: mice CD1 30-35 g, test drug concentrations in perfusion experiments (the highest dose strength dissolved in 250 mL of PBS pH 6.2) and flow rate of 0.2 mL/min. The test compounds were assayed following a validated HPLC method. The effective permeability coefficients at steady-state were calculated after correcting the outlet concentration following the gravimetric correction method proposed by Sutton et al. (2001). The permeability coefficient values ranged from 0.1751±0.0756×10(-4) cm/s for ranitidine to 17.19±4.16×10(-4) cm/s for naproxen. The mouse method correctly assigned the BCS permeability classification of a given drug and a correlation between mouse permeability data and the fraction of an oral dose absorbed in humans was achieved (FA=1-exp(-34,745·P(eff(mouse))); R=0.9631). Based on the results obtained, we conclude that mouse can be considered a valuable tool in the evaluation of intestinal permeability in order to predict the extent of human gastrointestinal absorption following oral administration of a drug. PMID:22814225

  9. Diffusion-perfusion relationships in skeletal muscle: models and experimental evidence from inert gas washout.

    PubMed

    Piiper, J; Meyer, M

    1984-01-01

    In order to study the dependence of blood-tissue gas exchange upon diffusion, the simultaneous washout of two inert gases of differing diffusivity was investigated in isolated-perfused dog gastrocnemius preparations. The muscles were equilibrated with CH4 and SF6 via arterial blood. The washout kinetics were determined from venous blood samples analyzed by gas chromatography. The results revealed the following features: The washout of the test gases was pronouncedly multi-exponential, and could be described by three exponential components when analyzed to 5% of the initial value. The non-exponential washout was attributed to unequal distribution of capillary blood flow to tissue volume. The mean ratio of washout rate constants CH4/SF6 was within 1.10-1.25 and was even smaller than the ratio expected for pure perfusion limitation (1.46). Therefore, no evidence for effective tissue-blood diffusion limitation was obtained. The observed washout rate constant ratio could be explained by a model with veno-arterial back diffusion which more strongly retards washout kinetics of the better diffusible gas (CH4) as compared to the less diffusible gas (SF6). PMID:6731103

  10. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

    PubMed Central

    Medeiros, Israel L.; Pêgo-Fernandes, Paulo M.; Mariani, Alessandro W.; Fernandes, Flávio G.; Unterpertinger, Fernando V.; Canzian, Mauro; Jatene, Fabio B.

    2012-01-01

    OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex® was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p = 0.035). The mean pulmonary compliance was 46.8 cm H2O in Group 1 and 49.3 ml/cm H2O in Group 2 (p = 0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p = 0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm2 and 137.50/mm2, respectively (p = 0.71). CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation. PMID:23018310

  11. Tissue perfusability assessment from capillary velocimetry data via the multicompartment Windkessel model

    NASA Astrophysics Data System (ADS)

    Stiukhina, Elena S.; Kurochkin, Maxim A.; Klochkov, Victor A.; Fedosov, Ivan V.; Postnov, Dmitry E.

    2015-03-01

    A method is presented to obtain information on tissue perfusability from capillary velocimetry experiments coupled with venous occlusion probe. The method based on data fitting to developed mathematical model describing the blood flow redistribution caused by the introduced occlusion. Using mathematical modeling, we identify the segment of velocity time courses that corresponds to tissue swelling process and thus allows ones quantify it. We also compared the results of direct measurement of red blood cells (RBCs) velocity with time courses obtained from finger-placed sensors of two types: (i) photoplethysmographic sensor used in pulsometry and (ii) piezoelectric sensor for sphygmography. The obtained results suggest the measurable contribution of RBCs aggregation process in optical pulse signal formation.

  12. Comparative analysis of in situ versus ex situ perfusion on flow and microcirculation in kidney procurement: research on a porcine model

    PubMed Central

    2013-01-01

    Background The first crucial step in transplantation appears to be the effective rinsing of the graft during organ procurement. Even though there is strong suspicion that ex situ perfusion results in better rinsing of the graft, there is no proof for this hypothesis. The aim of this study was to analyse the differences of in situ and ex situ kidney perfusion in a porcine model. Methods Standardised multiorgan procurement was performed in 15 German landrace pigs. Perfusion was carried out using histidine–tryptophan–ketoglutarate solution (HTK) under the application of pressure. In one kidney, in situ perfusion via the aorta was carried out while the second kidney received ex situ perfusion via the renal artery (RA). Perfusate flow inside the aorta and the RA was recorded at different pressure steps. In order to visualise the effect on the microcirculation, different coloured microparticles (MPs; 10 μm) were administered via the aorta or RA. Subsequently, frozen sections of the explanted kidneys were analysed histologically and MPs were evaluated quantitatively. Results Ex situ kidney perfusion resulted in significantly improved flow rates (P<0.0001) compared with in situ perfusion. By applying ex situ perfusion it was even possible to attain physiological flow levels on the RA under the application of external pressure of 150 to 200 mmHg. The amount of MPs was able to highlight the positive impact of ex situ perfusion on microcirculation of the kidney graft (P<0.0001). Conclusions The use of MPs represents a valuable tool for quantitative investigation and illustration of kidney perfusion in experimental setups. Additional ex situ perfusion is able to improve the quality of kidney perfusion. PMID:23837545

  13. Effect of Extended CT Perfusion Acquisition Time on Ischemic Core and Penumbra Volume Estimation in Patients with Acute Ischemic Stroke due to a Large Vessel Occlusion

    PubMed Central

    Borst, Jordi; Marquering, Henk A.; Beenen, Ludo F. M.; Berkhemer, Olvert A.; Dankbaar, Jan Willem; Riordan, Alan J.; Majoie, Charles B. L. M.

    2015-01-01

    Background and Purpose It has been suggested that CT Perfusion acquisition times <60 seconds are too short to capture the complete in and out-wash of contrast in the tissue, resulting in incomplete time attenuation curves. Yet, these short acquisitions times are not uncommon in clinical practice. The purpose of this study was to investigate the occurrence of time attenuation curve truncation in 48 seconds CT Perfusion acquisition and to quantify its effect on ischemic core and penumbra estimation in patients with acute ischemic stroke due to a proximal intracranial arterial occlusion of the anterior circulation. Materials and Methods We analyzed CT Perfusion data with 48 seconds and extended acquisition times, assuring full time attenuation curves, of 36 patients. Time attenuation curves were classified as complete or truncated. Ischemic core and penumbra volumes resulting from both data sets were compared by median paired differences and interquartile ranges. Controlled experiments were performed using a digital CT Perfusion phantom to investigate the effect of time attenuation curve truncation on ischemic core and penumbra estimation. Results In 48 seconds acquisition data, truncation was observed in 24 (67%) cases for the time attenuation curves in the ischemic core, in 2 cases for the arterial input function and in 5 cases for the venous output function. Analysis of extended data resulted in smaller ischemic cores and larger penumbras with a median difference of 13.2 (IQR: 4.3–26.0)ml (P<0.001) and; 12.4 (IQR: 4.1–25.7)ml (P<0.001), respectively. The phantom data showed increasing ischemic core overestimation with increasing tissue time attenuation curve truncation. Conclusions Truncation is common in patients with large vessel occlusion and results in repartitioning of the area of hypoperfusion into larger ischemic core and smaller penumbra estimations. Phantom experiments confirmed that truncation results in overestimation of the ischemic core. PMID

  14. Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications--a systematic review of experimental models.

    PubMed

    Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Rohan; Mees, Soeren Torge; Dennison, Ashley; Maddern, Guy; Trochsler, Markus

    2016-01-01

    Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications. PMID:26253243

  15. A 3D porous media liver lobule model: the importance of vascular septa and anisotropic permeability for homogeneous perfusion.

    PubMed

    Debbaut, Charlotte; Vierendeels, Jan; Siggers, Jennifer H; Repetto, Rodolfo; Monbaliu, Diethard; Segers, Patrick

    2014-01-01

    The hepatic blood circulation is complex, particularly at the microcirculatory level. Previously, 2D liver lobule models using porous media and a 3D model using real sinusoidal geometries have been developed. We extended these models to investigate the role of vascular septa (VS) and anisotropic permeability. The lobule was modelled as a hexagonal prism (with or without VS) and the tissue was treated as a porous medium (isotropic or anisotropic permeability). Models were solved using computational fluid dynamics. VS inclusion resulted in more spatially homogeneous perfusion. Anisotropic permeability resulted in a larger axial velocity component than isotropic permeability. A parameter study revealed that results are most sensitive to the lobule size and radial pressure drop. Our model provides insight into hepatic microhaemodynamics, and suggests that inclusion of VS in the model leads to perfusion patterns that are likely to reflect physiological reality. The model has potential for applications to unphysiological and pathological conditions. PMID:23237543

  16. HIFU Therapy Compared with Other Thermal Ablation Methods in a Perfused Organ Model

    NASA Astrophysics Data System (ADS)

    Jenne, Jürgen W.; Risse, Frank; Häcker, Axel; Peters, Kristina; Siegler, Peter; Divkovic, Gabriela Wilzbach; Huber, Peter E.

    2007-05-01

    Therapy with high intensity focused ultrasound (HIFU) has been shown to be both safe and clinically practical in a growing number of patient studies for a variety of different target organs. Especially in cancer therapy there are comparable ablation methods like radio frequency (RFA) or laser (LITT) ablation, which are clinically more accepted. In an ongoing study we compare HIFU with RF- and laser ablation under MRI guidance in a perfused organ model. All evaluated techniques were appropriate to induce defined and localized ablation necrosis in the renal cortex. Our HIFU system and the laser system were completely MRI compatible. The tested RF- system showed local needle artefacts and disturbed the MR images during operation. The ablation rate of HIFU using a spot scanning technique was clearly lower compared to the other ablation techniques. However, advanced HIFU scanning methods might overcome this limitation. In addition HIFU is the only complete non-invasive ablation technique.

  17. Quantitative Myocardial Perfusion with Dynamic Contrast-Enhanced Imaging in MRI and CT: Theoretical Models and Current Implementation

    PubMed Central

    Handayani, A.; Dijkstra, H.; Prakken, N. H. J.; Slart, R. H. J. A.; Oudkerk, M.; Van Ooijen, P. M. A.; Vliegenthart, R.; Sijens, P. E.

    2016-01-01

    Technological advances in magnetic resonance imaging (MRI) and computed tomography (CT), including higher spatial and temporal resolution, have made the prospect of performing absolute myocardial perfusion quantification possible, previously only achievable with positron emission tomography (PET). This could facilitate integration of myocardial perfusion biomarkers into the current workup for coronary artery disease (CAD), as MRI and CT systems are more widely available than PET scanners. Cardiac PET scanning remains expensive and is restricted by the requirement of a nearby cyclotron. Clinical evidence is needed to demonstrate that MRI and CT have similar accuracy for myocardial perfusion quantification as PET. However, lack of standardization of acquisition protocols and tracer kinetic model selection complicates comparison between different studies and modalities. The aim of this overview is to provide insight into the different tracer kinetic models for quantitative myocardial perfusion analysis and to address typical implementation issues in MRI and CT. We compare different models based on their theoretical derivations and present the respective consequences for MRI and CT acquisition parameters, highlighting the interplay between tracer kinetic modeling and acquisition settings. PMID:27088083

  18. Quantitative Myocardial Perfusion with Dynamic Contrast-Enhanced Imaging in MRI and CT: Theoretical Models and Current Implementation.

    PubMed

    Pelgrim, G J; Handayani, A; Dijkstra, H; Prakken, N H J; Slart, R H J A; Oudkerk, M; Van Ooijen, P M A; Vliegenthart, R; Sijens, P E

    2016-01-01

    Technological advances in magnetic resonance imaging (MRI) and computed tomography (CT), including higher spatial and temporal resolution, have made the prospect of performing absolute myocardial perfusion quantification possible, previously only achievable with positron emission tomography (PET). This could facilitate integration of myocardial perfusion biomarkers into the current workup for coronary artery disease (CAD), as MRI and CT systems are more widely available than PET scanners. Cardiac PET scanning remains expensive and is restricted by the requirement of a nearby cyclotron. Clinical evidence is needed to demonstrate that MRI and CT have similar accuracy for myocardial perfusion quantification as PET. However, lack of standardization of acquisition protocols and tracer kinetic model selection complicates comparison between different studies and modalities. The aim of this overview is to provide insight into the different tracer kinetic models for quantitative myocardial perfusion analysis and to address typical implementation issues in MRI and CT. We compare different models based on their theoretical derivations and present the respective consequences for MRI and CT acquisition parameters, highlighting the interplay between tracer kinetic modeling and acquisition settings. PMID:27088083

  19. Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation

    PubMed Central

    Lofthouse, E. M.; Perazzolo, S.; Brooks, S.; Crocker, I. P.; Glazier, J. D.; Johnstone, E. D.; Panitchob, N.; Sibley, C. P.; Widdows, K. L.; Sengers, B. G.

    2015-01-01

    Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer. PMID:26676251

  20. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-01

    Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using compute unified device architecture-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, nonlinear least-squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626 400 voxels in a patient's liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10(-6). The method will be useful for generating liver perfusion images in clinical settings. PMID:22892645

  1. Prognostic Value of Major Cardiac Event Risk Score Estimated With Gated Myocardial Perfusion Imaging in Japanese Patients With Coronary Artery Disease.

    PubMed

    Yoda, Shunichi; Nakanishi, Kanae; Tano, Ayako; Hori, Yusuke; Hayase, Misa; Mineki, Takashi; Suzuki, Yasuyuki; Matsumoto, Naoya; Hirayama, Atsushi

    2016-07-27

    We published a cardiac event risk score (CERS) predicting the risk of major cardiac events (MCEs) within 3 years. The purpose of this study was to verify the prognostic value of the CERS before and after treatment in Japanese patients with coronary artery disease.We retrospectively investigated 612 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2013 and who had a significant stenosis with ≥ 75% narrowing of the arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia with the SPECT. The patients underwent treatment including revascularization and medication, and thereafter, were re-evaluated with SPECT during a chronic phase and followed-up to confirm prognosis for ≥ 1 year. The endpoint was the onset of MCEs during the follow-up.During the follow-up (36.7 ± 14.5 months), 50 patients (8.7%) experienced MCEs comprising cardiac death (n = 16), non-fatal myocardial infarction (n = 4), and unstable angina pectoris (n = 30). The multivariate Cox proportional hazards regression model analysis for the actual occurrence of MCEs showed the summed difference score % and MCE risks estimated with the CERS after treatment to be significant independent variables. Ischemic reduction after treatment contributed significantly to a decrease in the MCE risks. The MCE risks estimated with the CERS after treatment were generally consistent with the incidence of the MCEs actually observed.The CERS after treatment is a valuable formula for predicting prognosis in Japanese patients with coronary artery disease. PMID:27357436

  2. A comprehensive study on different modelling approaches to predict platelet deposition rates in a perfusion chamber

    PubMed Central

    Pallarès, Jordi; Senan, Oriol; Guimerà, Roger; Vernet, Anton; Aguilar-Mogas, Antoni; Vilahur, Gemma; Badimon, Lina; Sales-Pardo, Marta; Cito, Salvatore

    2015-01-01

    Thrombus formation is a multiscale phenomenon triggered by platelet deposition over a protrombotic surface (eg. a ruptured atherosclerotic plaque). Despite the medical urgency for computational tools that aid in the early diagnosis of thrombotic events, the integration of computational models of thrombus formation at different scales requires a comprehensive understanding of the role and limitation of each modelling approach. We propose three different modelling approaches to predict platelet deposition. Specifically, we consider measurements of platelet deposition under blood flow conditions in a perfusion chamber for different time periods (3, 5, 10, 20 and 30 minutes) at shear rates of 212 s−1, 1390 s−1 and 1690 s−1. Our modelling approaches are: i) a model based on the mass-transfer boundary layer theory; ii) a machine-learning approach; and iii) a phenomenological model. The results indicate that the three approaches on average have median errors of 21%, 20.7% and 14.2%, respectively. Our study demonstrates the feasibility of using an empirical data set as a proxy for a real-patient scenario in which practitioners have accumulated data on a given number of patients and want to obtain a diagnosis for a new patient about whom they only have the current observation of a certain number of variables. PMID:26391513

  3. Modeling of landslide volume estimation

    NASA Astrophysics Data System (ADS)

    Amirahmadi, Abolghasem; Pourhashemi, Sima; Karami, Mokhtar; Akbari, Elahe

    2016-06-01

    Mass displacement of materials such as landslide is considered among problematic phenomena in Baqi Basin located at southern slopes of Binaloud, Iran; since, it destroys agricultural lands and pastures and also increases deposits at the basin exit. Therefore, it is necessary to identify areas which are sensitive to landslide and estimate the significant volume. In the present study, in order to estimate the volume of landslide, information about depth and area of slides was collected; then, considering regression assumptions, a power regression model was given which was compared with 17 suggested models in various regions in different countries. The results showed that values of estimated mass obtained from the suggested model were consistent with observed data (P value= 0.000 and R = 0.692) and some of the existing relations which implies on efficiency of the suggested model. Also, relations that were created in small-area landslides were more suitable rather than the ones created in large-area landslides for using in Baqi Basin. According to the suggested relation, average depth value of landslides was estimated 3.314 meters in Baqi Basin which was close to the observed value, 4.609 m.

  4. Computational fluid dynamics modelling of perfusion measurements in dynamic contrast-enhanced computed tomography: development, validation and clinical applications

    NASA Astrophysics Data System (ADS)

    Peladeau-Pigeon, M.; Coolens, C.

    2013-09-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is an imaging tool that aids in evaluating functional characteristics of tissue at different stages of disease management: diagnostic, radiation treatment planning, treatment effectiveness, and monitoring. Clinical validation of DCE-derived perfusion parameters remains an outstanding problem to address prior to perfusion imaging becoming a widespread standard as a non-invasive quantitative measurement tool. One approach to this validation process has been the development of quality assurance phantoms in order to facilitate controlled perfusion ex vivo. However, most of these systems fail to establish and accurately replicate physiologically relevant capillary permeability and exchange performance. The current work presents the first step in the development of a prospective suite of physics-based perfusion simulations based on coupled fluid flow and particle transport phenomena with the goal of enhancing the understanding of clinical contrast agent kinetics. Existing knowledge about a controllable, two-compartmental fluid exchange phantom was used to validate the computational fluid dynamics (CFD) simulation model presented herein. The sensitivity of CFD-derived contrast uptake curves to contrast injection parameters, including injection duration and flow rate, were quantified and found to be within 10% accuracy. The CFD model was employed to evaluate two commonly used clinical kinetic algorithms used to derive perfusion parameters: Fick's principle and the modified Tofts model. Neither kinetic model was able to capture the true transport phenomena it aimed to represent but if the overall contrast concentration after injection remained identical, then successive DCE-CT evaluations could be compared and could indeed reflect differences in regional tissue flow. This study sets the groundwork for future explorations in phantom development and pharmaco-kinetic modelling, as well as the development of novel contrast

  5. Altered hepatic clearance and killing of Candida albicans in the isolated perfused mouse liver model.

    PubMed Central

    Sawyer, R T; Horst, M N; Garner, R E; Hudson, J; Jenkins, P R; Richardson, A L

    1990-01-01

    The adherence of Candida albicans was studied in situ by using the perfused mouse liver model. After exhaustive washing, 10(6) C. albicans were infused into mouse livers. At the time of recovery, 62 +/- 5% (mean +/- standard error of the mean) of the infused C. albicans were recovered from the liver and 14 +/- 3% were recovered from the effluent for a total recovery of 76 +/- 4%. This indicates that 86 +/- 3% of the original inoculum was trapped by the liver and that 24 +/- 4% was killed within the liver. Chemical pretreatment of C. albicans with 8 M urea, 12 mM dithiothreitol, 2% beta-mercaptoethanol, 1% sodium dodecyl sulfate, 10% Triton X-100, or 3 M potassium chloride or enzyme pretreatment with alpha-mannosidase, alpha-chymotrypsin, subtilisin, beta-N-acetyl-glucosaminidase, pronase, trypsin, papain, or lipase did not alter adherence of C. albicans to hepatic tissue. By contrast, pepsin pretreatment significantly decreased hepatic trapping. Simultaneous perfusion with either 100 mg of C. albicans glycoprotein per liter or 100 mg of C. albicans mannan per liter also decreased trapping. Furthermore, both substances eluted previously trapped C. albicans from hepatic tissue. Chemical pretreatment with 8 M urea, 12 mM dithiothreitol, or 3 M KCI or enzymatic pretreatment with alpha-mannosidase, subtilisin, alpha-chymotrypsin, or papain increased killing of C. albicans three- to fivefold within hepatic tissue. The data suggest that mannose-containing structures on the surface of C. albicans, for example. mannans or glucomannoproteins, mediate adherence of C. albicans within the liver. Indirectly, chemical and enzymatic pretreatment renders C. albicans more susceptible to hepatic killing. PMID:2117571

  6. The investigation of placental relaxation and estimation of placental perfusion using echo-planar magnetic resonance imaging.

    PubMed

    Duncan, K R; Gowland, P; Francis, S; Moore, R; Baker, P N; Johnson, I R

    1998-09-01

    Echo-planar imaging (EPI) is a form of magnetic resonance imaging (MRI) which acquires images in milliseconds rather than minutes as with conventional MRI. The images produced using EPI are affected by the physiological environment in which the hydrogen atoms producing the signals are found, a process referred to as relaxation. Also by producing images a matter of milliseconds apart, quantification of perfusion within the tissue being imaged is feasible. The objective of this study was to investigate T1 and T2 relaxation times along with perfusion in placentae from normal pregnancies at different gestations and also to compare these to pregnancies complicated by abnormal placental function. A cross-sectional study of normal and compromised pregnancies from 20 weeks to term and a longitudinal study of normal pregnancy were performed. Placental T1, T2 relaxation times, and perfusion were measured using echo-planar magnetic resonance imaging. Placental T1 and T2 relaxation times decreased in normal pregnancy (P<0.001). Relaxation times in pregnancies associated with placental pathology appeared to be reduced for that gestation although the numbers were too small to allow any statistical validation. No differences in placental perfusion with gestation or between normal and compromised pregnancy were demonstrated using this technique. This is the first demonstration of placental magnetic resonance relaxation and perfusion measurements in normal pregnancy using echo-planar magnetic resonance imaging. In the future it may be possible to identify compromised pregnancies by differences in placental T1 and T2 relaxation times, using this novel non-invasive technique. PMID:9778128

  7. Estimation of pharmacokinetic model parameters.

    PubMed

    Timcenko, A; Reich, D L; Trunfio, G

    1995-01-01

    This paper addresses the problem of estimating the depth of anesthesia in clinical practice where many drugs are used in combination. The aim of the project is to use pharmacokinetically-derived data to predict episodes of light anesthesia. The weighted linear combination of anesthetic drug concentrations was computed using a stochastic pharmacokinetic model. The clinical definition of light anesthesia was based on the hemodynamic consequences of autonomic nervous system responses to surgical stimuli. A rule-based expert system was used to review anesthesia records to determine instances of light anesthesia using hemodynamic criteria. It was assumed that light anesthesia was a direct consequence of the weighted linear combination of drug concentrations in the patient's body that decreased below a certain threshold. We augmented traditional two-compartment models with a stochastic component of anesthetics' concentrations to compensate for interpatient pharmacokinetic and pharmacodynamic variability. A cohort of 532 clinical anesthesia cases was examined and parameters of two compartment pharmacokinetic models for 6 intravenously administered anesthetic drugs (fentanyl, thiopenthal, morphine, propofol, midazolam, ketamine) were estimated, as well as the parameters for 2 inhalational anesthetics (N2O and isoflurane). These parameters were then prospectively applied to 22 cases that were not used for parameter estimation, and the predictive ability of the pharmacokinetic model was determined. The goal of the study is the development of a pharmacokinetic model that will be useful in predicting light anesthesia in the clinically relevant circumstance where many drugs are used concurrently. PMID:8563327

  8. Estimating proportions of materials using mixture models

    NASA Technical Reports Server (NTRS)

    Heydorn, R. P.; Basu, R.

    1983-01-01

    An approach to proportion estimation based on the notion of a mixture model, appropriate parametric forms for a mixture model that appears to fit observed remotely sensed data, methods for estimating the parameters in these models, methods for labelling proportion determination from the mixture model, and methods which use the mixture model estimates as auxiliary variable values in some proportion estimation schemes are addressed.

  9. Drug dosage in isolated limb perfusion: evaluation of a limb volume model for extremity volume calculation

    PubMed Central

    2014-01-01

    Background Exact drug dosing in isolated limb perfusion (ILP) and infusion (ILI) is essential. We developed and evaluated a model for calculating the volume of extremities and compared this model with body weight- and height-dependent parameters. Methods The extremity was modeled by a row of coupled truncated cones. The sizes of the truncated cone bases were derived from the circumference measurements of the extremity at predefined levels (5 cm). The resulting volumes were added. This extremity volume model was correlated to the computed tomography (CT) volume data of the extremity (total limb volume). The extremity volume was also correlated with the patient’s body weight, body mass index (BMI) and ideal body weight (IBW). The no-fat CT limb volume was correlated with the circumference-measured limb volume corrected by the ideal-body-weight to actual-body-weight ratio (IBW corrected-limb-volume). Results The correlation between the CT volume and the volume measured by the circumference was high and significant. There was no correlation between the limb volume and the bare body weight, BMI or IBW. The correlation between the no-fat CT volume and IBW-corrected limb volume was high and significant. Conclusions An appropriate drug dosing in ILP can be achieved by combining the limb volume with the simple circumference measurements and the IBW to body-weight ratio. PMID:24684972

  10. Parameter estimation for transformer modeling

    NASA Astrophysics Data System (ADS)

    Cho, Sung Don

    Large Power transformers, an aging and vulnerable part of our energy infrastructure, are at choke points in the grid and are key to reliability and security. Damage or destruction due to vandalism, misoperation, or other unexpected events is of great concern, given replacement costs upward of $2M and lead time of 12 months. Transient overvoltages can cause great damage and there is much interest in improving computer simulation models to correctly predict and avoid the consequences. EMTP (the Electromagnetic Transients Program) has been developed for computer simulation of power system transients. Component models for most equipment have been developed and benchmarked. Power transformers would appear to be simple. However, due to their nonlinear and frequency-dependent behaviors, they can be one of the most complex system components to model. It is imperative that the applied models be appropriate for the range of frequencies and excitation levels that the system experiences. Thus, transformer modeling is not a mature field and newer improved models must be made available. In this work, improved topologically-correct duality-based models are developed for three-phase autotransformers having five-legged, three-legged, and shell-form cores. The main problem in the implementation of detailed models is the lack of complete and reliable data, as no international standard suggests how to measure and calculate parameters. Therefore, parameter estimation methods are developed here to determine the parameters of a given model in cases where available information is incomplete. The transformer nameplate data is required and relative physical dimensions of the core are estimated. The models include a separate representation of each segment of the core, including hysteresis of the core, lambda-i saturation characteristic, capacitive effects, and frequency dependency of winding resistance and core loss. Steady-state excitation, and de-energization and re-energization transients

  11. Use of 3D DCE-MRI for the estimation of renal perfusion and glomerular filtration rate: an intrasubject comparison of FLASH and KWIC with a comprehensive framework for evaluation.

    PubMed

    Eikefjord, Eli; Andersen, Erling; Hodneland, Erlend; Zöllner, Frank; Lundervold, Arvid; Svarstad, Einar; Rørvik, Jarle

    2015-03-01

    OBJECTIVE. The purpose of this article is to compare two 3D dynamic contrast-enhanced (DCE) MRI measurement techniques for MR renography, a radial k-space weighted image contrast (KWIC) sequence and a cartesian FLASH sequence, in terms of intrasubject differences in estimates of renal functional parameters and image quality characteristics. SUBJECTS AND METHODS. Ten healthy volunteers underwent repeated breath-hold KWIC and FLASH sequence examinations with temporal resolutions of 2.5 and 2.8 seconds, respectively. A two-compartment model was used to estimate MRI-derived perfusion parameters and glomerular filtration rate (GFR). The latter was compared with the iohexol GFR and the estimated GFR. Image quality was assessed using a visual grading characteristic analysis of relevant image quality criteria and signal-to-noise ratio calculations. RESULTS. Perfusion estimates from FLASH were closer to literature reference values than were the KWIC sequences. In relation to the iohexol GFR (mean [± SD], 103 ± 11 mL/min/1.73 m(2)), KWIC produced significant underestimations and larger bias in GFR values (mean, 70 ± 30 mL/min/1.73 m(2); bias = -33.2 mL/min/1.73 m(2)) compared with the FLASH GFR (110 ± 29 mL/min/1.73 m(2); bias = 6.4 mL/min/1.73 m(2)). KWIC was statistically significantly (p < 0.005) more impaired by artifacts than was FLASH (AUC = 0.18). The average signal-enhancement ratio (delta ratio) in the cortex was significantly lower for KWIC (delta ratio = 0.99) than for FLASH (delta ratio = 1.40). Other visually graded image quality characteristics and signal-to-noise ratio measurements were not statistically significantly different. CONCLUSION. Using the same postprocessing scheme and pharmacokinetic model, FLASH produced more accurate perfusion and filtration parameters than did KWIC compared with clinical reference methods. Our data suggest an apparent relationship between image quality characteristics and the degree of stability in the numeric model

  12. Perfusion single photon emission computed tomography in a mouse model of neurofibromatosis type 1: towards a biomarker of neurologic deficits.

    PubMed

    Apostolova, Ivayla; Niedzielska, Dagmara; Derlin, Thorsten; Koziolek, Eva J; Amthauer, Holger; Salmen, Benedikt; Pahnke, Jens; Brenner, Winfried; Mautner, Victor F; Buchert, Ralph

    2015-08-01

    Neurofibromatosis type 1 (NF1) is a single-gene disorder affecting neurologic function in humans. The NF1+/- mouse model with germline mutation of the NF1 gene presents with deficits in learning, attention, and motor coordination, very similar to NF1 patients. The present study performed brain perfusion single-photon emission computed tomography (SPECT) in NF1+/- mice to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1. Cerebral perfusion was measured with hexamethyl-propyleneamine oxime (HMPAO) SPECT in NF1+/- mice and their wild-type littermates longitudinally at juvenile age and at young adulthood. Histology and immunohistochemistry were performed to test for structural changes. There was increased HMPAO uptake in NF1 mice in the amygdala at juvenile age, which reduced to normal levels at young adulthood. There was no genotype effect on thalamic HMPAO uptake, which was confirmed by ex vivo measurements of F-18-fluorodeoxyglucose uptake in the thalamus. Morphologic analyses showed no major structural abnormalities. However, there was some evidence of increased density of microglial somata in the amygdala of NF1-deficient mice. In conclusion, there is evidence of increased perfusion and increased density of microglia in juvenile NF1 mice specifically in the amygdala, both of which might be associated with altered synaptic plasticity and, therefore, with cognitive deficits in NF1. PMID:25785829

  13. Optimization of an Isolated Perfused Rainbow Trout Liver Model: Clearance Studies with 7-Ethoxycoumarin

    EPA Science Inventory

    Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption (VO2), vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase (ALT) leakage, and meta...

  14. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model.

    PubMed

    Wang, Jian; Zhou, DA-Qing; He, Meng; Li, Wen-Gang; Pang, Xiang; Yu, Xiao-Xiang; Jiang, Bo

    2013-05-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  15. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model

    PubMed Central

    WANG, JIAN; ZHOU, DA-QING; HE, MENG; LI, WEN-GANG; PANG, XIANG; YU, XIAO-XIANG; JIANG, BO

    2013-01-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  16. A Mathematical Model of the Metabolic and Perfusion Effects on Cortical Spreading Depression

    PubMed Central

    Chang, Joshua C.; Brennan, Kevin C.; He, Dongdong; Huang, Huaxiong; Miura, Robert M.; Wilson, Phillip L.; Wylie, Jonathan J.

    2013-01-01

    Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarizations, CSD also involves significant changes in perfusion and metabolism—aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium–ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD—vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization—found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease. PMID:23967075

  17. Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.

    PubMed

    Boyle, Erin C; Dombrowsky, Heike; Sarau, Jürgen; Braun, Janin; Aepfelbacher, Martin; Lautenschläger, Ingmar; Grassl, Guntram A

    2016-01-15

    Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine. PMID:26564721

  18. Temperature-dependent versus constant-rate blood perfusion modelling in ferromagnetic thermoseed hyperthermia: results with a model of the human prostate.

    PubMed

    Tompkins, D T; Vanderby, R; Klein, S A; Beckman, W A; Steeves, R A; Frye, D M; Paliwal, B R

    1994-01-01

    Finite-element solutions to the Pennes bioheat equation are obtained with a model of a tumour-containing, human prostate and surrounding normal tissues. Simulations of ferromagnetic hyperthermia treatments are conducted on the tissue model in which the prostate is implanted with an irregularly spaced array of thermoseeds. Several combinations of thermoseed temperatures with different Curie points are investigated. Non-uniform, constant-rate blood perfusion models are studied and compared with temperature-dependent descriptions of blood perfusion. Blood perfusions in the temperature-dependent models initially increase with tissue temperature and then decrease at higher temperatures. Simulations with temperature-dependent versus constant-rate blood perfusion models reveal significant differences in temperature distributions in and surrounding the tumour-containing prostate. Results from the simulations include differences (between temperature-dependent and constant-rate models) in (1) the percentage of normal tissue volume and tumour volume at temperatures > 42 degrees C, and (2) temperature descriptors in the tumour (subscript t) and normal (subscript n) tissues including Tmax.t, Tmin.t and Tmax.n. Isotherms and grey-scale contours in the tumour and surrounding normal tissues are presented for four simulations that model a combination of high-temperature thermoseeds. Several simulations show that Tmin.t is between 1.7 and 2.6 degrees C higher and Tmax.n is between 2.1 and 3.3 degrees C higher with a temperature-dependent versus a comparable constant-rate blood perfusion model. The same simulations reveal that the percentages of tumour volume at temperatures > 42 degrees C are between 0 and 68% higher with the temperature-dependent versus the constant-rate perfusion model over all seed combinations studied. In summary, a numerical method is presented which makes it possible to investigate temperature-dependent, continuous functions of blood perfusion in simulations

  19. An integrated in vitro model of perfused tumor and cardiac tissue

    PubMed Central

    2013-01-01

    Cancer and cardiovascular disease remain the two leading causes of death in the United States. Progress in treatment to reduce morbidity and mortality will include the development of new drugs. Recent advances in induced pluripotent stem cell technology, tissue engineering, and microfabrication techniques have created a unique opportunity to develop three-dimensional (3D) microphysiological systems that more accurately reflect in vivo human biology when compared with two-dimensional flat systems or animal models. Our group is working to develop 3D microphysiological systems using induced pluripotent stem cell technology that simulates the microcirculation, the cardiac muscle, and the solid tumor, and then to combine these systems into an integrated microphysiological system that simulates perfused cardiac muscle and solid tumor on a single platform. The platform will be initially validated to predict anti-cancer efficacy while minimizing cardiac muscle toxicity. A critical feature will be blood flow through a human microcirculation (capillaries and larger microvessels), which is necessary to overcome diffusion limitations of nutrients and waste products in realistic 3D cultures, and serves to integrate multiple organ systems. This is a necessary and critical feature of any platform that seeks to simulate integrated human organ systems. The results of our project should produce a new paradigm for efficient and accurate drug and toxicity screening, initially for anti-cancer drugs with minimal cardiac side effects, and a platform technology that can be eventually used to integrate multiple major organ systems of the human body. PMID:24565445

  20. Femoral perfusion after pulsed electromagnetic field stimulation in a steroid-induced osteonecrosis model.

    PubMed

    Ikegami, Akira; Ueshima, Keiichiro; Saito, Masazumi; Ikoma, Kazuya; Fujioka, Mikihiro; Hayashi, Shigeki; Ishida, Masashi; Fujiwara, Hiroyoshi; Mazda, Osam; Kubo, Toshikazu

    2015-07-01

    This study was designed to evaluate femoral perfusion after pulsed electromagnetic field (PEMF) stimulation in a steroid-induced osteonecrosis rabbit model by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Steroid-induced osteonecrosis was produced by single intramuscular injection of methylprednisolone in 15 rabbits. Eight rabbits underwent PEMF stimulation (PEMF group) and seven did not (control group). DCE-MRI was performed before PEMF stimulation, immediately before steroid administration, and 1, 5, 10, and 14 days after steroid administration. Regions of interest were set in the bilateral proximal femora. Enhancement ratio (ER), initial slope (IS), and area under the curve (AUC) were analyzed. ER, IS, and AUC in the control group significantly decreased after steroid administration compared with before administration (P<0.05). In PEMF group, IS significantly decreased; however, ER and AUC showed no significant differences after steroid administration compared with before. ER and IS in PEMF group were higher than in control group until 10th day, and AUC was higher until 5th day after steroid administration (P<0.05). PEMF stimulation restrains the decrease in blood flow after steroid administration. PMID:25808585

  1. Perfusion parameters as potential imaging biomarkers for the early prediction of radiotherapy response in a rat tumor model

    PubMed Central

    Lee, Ho Yun; Kim, Namkug; Goo, Jin Mo; Chie, Eui Kyu; Song, Hye Jong

    2016-01-01

    PURPOSE We aimed to compare various tumor-related radiologic morphometric changes and computed tomography (CT) perfusion parameters before and after treatment, and to determine the optimal imaging assessment technique for the prediction of early response in a rat tumor model treated with radiotherapy. METHODS Among paired tumors of FN13762 murine breast cancer cells implanted bilaterally in the necks of eight Fischer rats, tumors on the right side were treated with a single 20 Gy dose of radiotherapy. Perfusion CT studies were performed on day 0 before radiotherapy, and on days 1 and 5 after radiotherapy. Variables based on the size, including the longest diameter, tumor area, and volume, were measured. Quantitative perfusion analysis was performed for the whole tumor volume and permeabilities and blood volumes (BVs) were obtained. The area under the curve (AUC) difference in the histograms of perfusion parameters and texture analyses of uniformity and entropy were quantified. Apoptotic cell density was measured on pathology specimens immediately after perfusion imaging on day 5. RESULTS On day 1 after radiotherapy, differences in size between the irradiated and nonirradiated tumors were not significant. In terms of percent changes in the uniformity of permeabilities between tumors before irradiation and on day 1 after radiotherapy, the changes were significantly higher in the irradiated tumors than in the nonirradiated tumors (0.085 [−0.417, 0.331] vs. −0.131 [−0.536, 0.261], respectively; P = 0.042). The differences in AUCs of the histogram of voxel-by-voxel vascular permeability and BV in tumors between day 0 and day 1 were significantly higher in treated tumors compared with the control group (permeability, 21.4 [−2.2, 37.5] vs. 9.5 [−8.9, 33.8], respectively, P = 0.030; BV, 52.9 [−6186.0, 419.2] vs. 11.9 [−198.3, 346.7], respectively, P = 0.049). Apoptotic cell density showed a significantly positive correlation with the AUC difference of BV, the

  2. Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

    SciTech Connect

    Cao Yue; Wang Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2013-01-01

    Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which

  3. Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

    PubMed Central

    Cao, Yue; Wang, Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2013-01-01

    Purpose To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which

  4. A Perfusion-based Human Cadaveric Model for Management of Carotid Artery Injury during Endoscopic Endonasal Skull Base Surgery

    PubMed Central

    Pham, Martin; Kale, Aydemir; Marquez, Yvette; Winer, Jesse; Lee, Brian; Harris, Brianna; Minnetti, Michael; Carey, Joseph; Giannotta, Steven; Zada, Gabriel

    2014-01-01

    Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm. PMID:25301092

  5. A Naive-Bayes model observer for detection and localization of perfusion defects in cardiac SPECT-MPI

    NASA Astrophysics Data System (ADS)

    Parages, Felipe M.; O'Connor, J. Michael; Pretorius, P. Hendrik; Brankov, Jovan G.

    2014-03-01

    Model observers (MO) are widely used in medical imaging to act as surrogates of human observers in task-based image quality evaluation, frequently towards optimization of reconstruction algorithms. In SPECT myocardial perfusion imaging (MPI), a realistic task-based approach involves detection and localization of perfusion defects, as well as a subsequent assessment of defect severity. In this paper we explore a machine-learning MO based on Naive- Bayes classification (NB-MO). NB-MO uses a set of polar-map image features to predict lesion detection, localization and severity scores given by five human readers for a set of simulated 3D SPECT-MPI patients. The simulated dataset included lesions with different sizes, perfusion-reduction ratios, and locations. Simulated projections were reconstructed using two readily used methods namely: FBP and OSEM. For validation, a multireader multi-case (MRMC) analysis of alternative free-response ROC (AFROC) curve was performed for NB-MO and human observers. For comparison, we also report performances of a statistical Hotelling Observer applied on polar-map images. Results show excellent agreement between NB-MO and humans, as well as model's good generalization between different reconstruction treatments.

  6. A Perfusion-based Human Cadaveric Model for Management of Carotid Artery Injury during Endoscopic Endonasal Skull Base Surgery.

    PubMed

    Pham, Martin; Kale, Aydemir; Marquez, Yvette; Winer, Jesse; Lee, Brian; Harris, Brianna; Minnetti, Michael; Carey, Joseph; Giannotta, Steven; Zada, Gabriel

    2014-10-01

    Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm. PMID:25301092

  7. Ventricular Fibrillation Waveform Changes during Controlled Coronary Perfusion Using Extracorporeal Circulation in a Swine Model

    PubMed Central

    Kaufman, Christopher L.; Baetiong, Alvin; Radhakrishnan, Jeejabai

    2016-01-01

    Background Several characteristics of the ventricular fibrillation (VF) waveform have been found predictive of successful defibrillation and hypothesized to reflect the myocardial energy state. In an open-chest swine model of VF, we modeled “average CPR” using extracorporeal circulation (ECC) and assessed the time course of coronary blood flow, myocardial metabolism, and myocardial structure in relation to the amplitude spectral area (AMSA) of the VF waveform without artifacts related to chest compression. Methods VF was induced and left untreated for 8 minutes in 16 swine. ECC was then started adjusting its flow to maintain a coronary perfusion pressure of 10 mmHg for 10 minutes. AMSA was calculated in the frequency domain and analyzed continuously with a 2.1 s timeframe and a Tukey window that moved ahead every 0.5 s. Results AMSA progressively declined during untreated VF. With ECC, AMSA increased from 7.0 ± 1.9 mV·Hz (at minute 8) to 12.8 ± 3.3 mV·Hz (at minute 14) (p < 0.05) without subsequent increase and showing a modest correlation with coronary blood flow of borderline statistical significance (r = 0.489, p = 0.0547). Myocardial energy measurements showed marked reduction in phosphocreatine and moderate reduction in ATP with increases in ADP, AMP, and adenosine along with myocardial lactate, all indicative of ischemia. Yet, ischemia did not resolve during ECC despite a coronary blood flow of ~ 30% of baseline. Conclusion AMSA increased upon return of coronary blood flow during ECC. However, the maximal level was reached after ~ 6 minutes without further change. The significance of the findings for determining the optimal timing for delivering an electrical shock during resuscitation from VF remains to be further explored. PMID:27536996

  8. Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion

    NASA Astrophysics Data System (ADS)

    Paltiel, H. J.; Padua, H. M.; Gargollo, P. C.; Cannon, G. M., Jr.; Alomari, A. I.; Yu, R.; Clement, G. T.

    2011-04-01

    Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.

  9. Hepatic perfusion in a tumor model using DCE-CT: an accuracy and precision study

    NASA Astrophysics Data System (ADS)

    Stewart, Errol E.; Chen, Xiaogang; Hadway, Jennifer; Lee, Ting-Yim

    2008-08-01

    In the current study we investigate the accuracy and precision of hepatic perfusion measurements based on the Johnson and Wilson model with the adiabatic approximation. VX2 carcinoma cells were implanted into the livers of New Zealand white rabbits. Simultaneous dynamic contrast-enhanced computed tomography (DCE-CT) and radiolabeled microsphere studies were performed under steady-state normo-, hyper- and hypo-capnia. The hepatic arterial blood flows (HABF) obtained using both techniques were compared with ANOVA. The precision was assessed by the coefficient of variation (CV). Under normo-capnia the microsphere HABF were 51.9 ± 4.2, 40.7 ± 4.9 and 99.7 ± 6.0 ml min-1 (100 g)-1 while DCE-CT HABF were 50.0 ± 5.7, 37.1 ± 4.5 and 99.8 ± 6.8 ml min-1 (100 g)-1 in normal tissue, tumor core and rim, respectively. There were no significant differences between HABF measurements obtained with both techniques (P > 0.05). Furthermore, a strong correlation was observed between HABF values from both techniques: slope of 0.92 ± 0.05, intercept of 4.62 ± 2.69 ml min-1 (100 g)-1 and R2 = 0.81 ± 0.05 (P < 0.05). The Bland-Altman plot comparing DCE-CT and microsphere HABF measurements gives a mean difference of -0.13 ml min-1 (100 g)-1, which is not significantly different from zero. DCE-CT HABF is precise, with CV of 5.7, 24.9 and 1.4% in the normal tissue, tumor core and rim, respectively. Non-invasive measurement of HABF with DCE-CT is accurate and precise. DCE-CT can be an important extension of CT to assess hepatic function besides morphology in liver diseases.

  10. Rapid decrease in tumor perfusion following VEGF blockade predicts long-term tumor growth inhibition in preclinical tumor models.

    PubMed

    Eichten, Alexandra; Adler, Alexander P; Cooper, Blerta; Griffith, Jennifer; Wei, Yi; Yancopoulos, George D; Lin, Hsin Chieh; Thurston, Gavin

    2013-04-01

    Vascular endothelial growth factor (VEGF) is a key upstream mediator of tumor angiogenesis, and blockade of VEGF can inhibit tumor angiogenesis and decrease tumor growth. However, not all tumors respond well to anti-VEGF therapy. Despite much effort, identification of early response biomarkers that correlate with long-term efficacy of anti-VEGF therapy has been difficult. These difficulties arise in part because the functional effects of VEGF inhibition on tumor vessels are still unclear. We therefore assessed rapid molecular, morphologic and functional vascular responses following treatment with aflibercept (also known as VEGF Trap or ziv-aflibercept in the United States) in preclinical tumor models with a range of responses to anti-VEGF therapy, including Colo205 human colorectal carcinoma (highly sensitive), C6 rat glioblastoma (moderately sensitive), and HT1080 human fibrosarcoma (resistant), and correlated these changes to long-term tumor growth inhibition. We found that an overall decrease in tumor vessel perfusion, assessed by dynamic contrast-enhanced ultrasound (DCE-US), and increases in tumor hypoxia correlated well with long-term tumor growth inhibition, whereas changes in vascular gene expression and microvessel density did not. Our findings support previous clinical studies showing that decreased tumor perfusion after anti-VEGF therapy (measured by DCE-US) correlated with response. Thus, measuring tumor perfusion changes shortly after treatment with VEGF inhibitors, or possibly other anti-angiogenic therapies, may be useful to predict treatment efficacy. PMID:23238831

  11. (Perfusion imaging: Instrumentation, modeling, and radiopharmaceuticals: Report of the scientific meeting: Final technical report)

    SciTech Connect

    Graham, M.M.

    1987-01-01

    This meeting provided an excellent overview of the state-of-the-art in perfusion imaging from the viewpoints of mathematical data analysis, radiochemical synthesis and evaluation, and instrumentation physics. The participants and audience had an opportunity to see how each of these aspects is essential for continued progress in this field.

  12. Estimation of brain perfusion using Va value as initial distribution volume in radionuclide angiography with technetium-99m HMPAO

    SciTech Connect

    Kawamoto, M.; Ikegami, T.

    1994-05-01

    Matsuda reported a non-invasive, simple method for the quantitative measurements of brain perfusion using radionuclide angiography with Tc-99m. HMPAO and showed graphical analysis of the ratio of brain activity to aortic arch activity gave two parameters, which are the slope of the fitted line (Ku:unidirectional influx constant) and its intercept with the yards (Vn:initial volume of distribution). Brain perfusion index (BPI),which is a connected Ku value, showed good correlation with cerebral blood flow determined with Xe-133 SPECT. The aim of our study is to elucidate the clinical significance of another parameter, Vn value, determined inpatients with cerebral vessel disease. Eighty-nine cases were studied and classified into three groups on the basis of clinical history and images of CT and/or MR: Group A, normal, 36 cases; Group B, infarction, 44 cases; Group C, subarachnoid hemorrhage, 9 cases. The average age of each group were not different statistically (63.3, 67.4 and 59.8, respectively). The average BPI values for group B and C were significantly lower than that of group A(7.7, 6. 8 and 9.5, respectively ). On the other hand, Vn for group C(0.23) was significantly lower than that for group A(0.45); however that for group B(0.49) was not. These findings indicate that cerebral blood flow in both infarction and subarachnoid hemorrhage decrease but their circumstances near vessels differ from the aspect of initial volume of tracer distribution. This might help to understand or diagnose cerebral vessel diseases.

  13. Effect of mouth-rinse formulations on oral malodour processes in tongue-derived perfusion biofilm model.

    PubMed

    Saad, S; Hewett, K; Greenman, J

    2012-03-01

    An in vitro matrix biofilm perfusion model of tongue-derived microcosms for studying volatile sulfur compound (VSC) biogenesis has been previously described. The model was modified in order to monitor H(2)S in situ by use of a specialized electrode assembly based on microbial fuel cell technology. This system was designed to give real-time measurements expressed as electrode power output, which were proportional to H(2)S levels, measured by other means. In addition to the model modifications, the aim of this study was to demonstrate the biofilm responses following single or multiple exposure to biocidal, biostatic or VSC-inhibiting active compounds used in products. Tongue-derived biofilms (n = 6 per experiment) were perfused with one-fifth strength BHI at 20 ml h(-1) pH 7.2 and pulsed with putative treatment agent, placebo and controls including Zn(2+) ions and chlorhexidine (CHX). Compared with their pre-treatment conditions, all biofilms responded to the treatments in terms of reductions in hydrogen sulfide generation (as detected by the biofilm-electrode response) and other microbial volatile organic compounds (VOCs) as detected using a selected ion flow tube mass spectrometry analyser. The microbiological analysis of the treated and control biofilms show that test products (formulations with active agents) all gave reduced cell populations compared to the control biofilm. An order of effects (magnitude and duration) suggests that both the test agent and CHX produced the strongest reductions, distinct from the responses obtained for the placebo and water controls, which were largely similar. It is concluded that the in vitro perfusion model may be used to replicate many of the activities and reactions believed to be occurring by the tongue biofilm microflora within a real mouth, including H(2)S and VOC biogenesis and their inhibition by exposure to active agents. PMID:22234955

  14. An in vivo autotransplant model of renal preservation: cold storage versus machine perfusion in the prevention of ischemia/reperfusion injury.

    PubMed

    La Manna, Gaetano; Conte, Diletta; Cappuccilli, Maria Laura; Nardo, Bruno; D'Addio, Francesca; Puviani, Lorenza; Comai, Giorgia; Bianchi, Francesca; Bertelli, Riccardo; Lanci, Nicole; Donati, Gabriele; Scolari, Maria Piera; Faenza, Alessandro; Stefoni, Sergio

    2009-07-01

    There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation. Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion (n = 6) or cold storage (n = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation. The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys. The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage. PMID:19566736

  15. Distributed estimation and joint probabilities estimation by entropy model

    NASA Astrophysics Data System (ADS)

    Fassinut-Mombot, B.; Zribi, M.; Choquel, J. B.

    2001-05-01

    This paper proposes the use of Entropy Model for distributed estimation system. Entropy Model is an entropic technique based on the minimization of conditional entropy and developed for Multi-Source/Sensor Information Fusion (MSIF) problem. We address the problem of distributed estimation from independent observations involving multiple sources, i.e., the problem of estimating or selecting one of several identity declaration, or hypothesis concerning an observed object. Two problems are considered in Entropy Model. In order to fuse observations using Entropy Model, it is necessary to know or estimate the conditional probabilities and by equivalent the joint probabilities. A common practice for estimating probability distributions from data when nothing is known (without a priori knowledge), one should prefer distributions that are as uniform as possible, that is, have maximal entropy. Next, the problem of combining (or ``fusing'') observations relating to identity hypotheses and selecting the most appropriate hypothesis about the object's identity is addressed. Much future work remains, but the results indicate that Entropy Model is a promising technique for distributed estimation. .

  16. Four-dimensional Transcatheter Intra-arterial Perfusion MR Imaging Before and After Uterine Artery Embolization in the Rabbit VX2 Tumor Model

    PubMed Central

    Chung, Johnathan C.; Wang, Dingxin; Lewandowski, Robert J.; Tang, Richard; Chrisman, Howard B.; Vogelzang, Robert L.; Woloschak, Gayle E.; Larson, Andrew C.; Omary, Reed A.; Ryu, Robert K.

    2010-01-01

    Purpose To test the hypothesis that four-dimensional (4D) transcatheter intra-arterial perfusion (TRIP) MR imaging can measure uterine fibroid perfusion changes immediately before and after uterine artery embolization (UAE) in the rabbit VX2 tumor model. Materials and Methods Eight VX2 uterine tumors were grown in 6 rabbits. After positioning a catheter within the uterine artery, we performed 4D TRIP-MRI measurements with 3 mL injections of 2.5% gadopentetate dimeglumine. We used a dynamic 3D spoiled-GRE sequence with in vivo B1-field correction for improved accuracy during perfusion quantification. We performed UAE using 1 mL of gelatin microspheres (2×106 particles; diameter 40-120 μm). Two regions-of-interest were drawn within each tumor upon perfusion maps. Functional embolic endpoints were reported as the mean percent reduction in fibroid tumor perfusion. Measurements before and after UAE were compared using paired t-tests (α = 0.05). Results VX2 uterine tumor perfusion decreased significantly from 27.1 at baseline to 7.09 after UAE (mL/min/100 mL tissue, p < 0.0001). Overall perfusion reduction was 76.3% (95% CI: 66.3%-86.3%). Conclusion 4D TRIP MRI can objectively quantify uterine fibroid perfusion reductions during UAE in VX2 rabbits. This technique could be used clinically to potentially determine an optimal embolic endpoint with the long-term goals of improving UAE success rates and minimizing procedure-related ischemic pain. PMID:20432349

  17. Numerical modeling of coupled nitrification-denitrification in sediment perfusion cores from the hyporheic zone of the Shingobee River, MN

    USGS Publications Warehouse

    Sheibley, R.W.; Jackman, A.P.; Duff, J.H.; Triska, F.J.

    2003-01-01

    Nitrification and denitrification kinetics in sediment perfusion cores were numerically modeled and compared to experiments on cores from the Shingobee River MN, USA. The experimental design incorporated mixing groundwater discharge with stream water penetration into the cores, which provided a well-defined, one-dimensional simulation of in situ hydrologic conditions. Ammonium (NH+4) and nitrate (NO-3) concentration gradients suggested the upper region of the cores supported coupled nitrification-denitrification, where groundwater-derived NH+4 was first oxidized to NO-3 then subsequently reduced via denitrification to N2. Nitrification and denitrification were modeled using a Crank-Nicolson finite difference approximation to a one-dimensional advection-dispersion equation. Both processes were modeled using first-order reaction kinetics because substrate concentrations (NH+4 and NO-3) were much smaller than published Michaelis constants. Rate coefficients for nitrification and denitrification ranged from 0.2 to 15.8 h-1 and 0.02 to 8.0 h-1, respectively. The rate constants followed an Arrhenius relationship between 7.5 and 22 ??C. Activation energies for nitrification and denitrification were 162 and 97.3 kJ/mol, respectively. Seasonal NH+4 concentration patterns in the Shingobee River were accurately simulated from the relationship between perfusion core temperature and NH+4 flux to the overlying water. The simulations suggest that NH+4 in groundwater discharge is controlled by sediment nitrification that, consistent with its activation energy, is strongly temperature dependent. ?? 2003 Elsevier Ltd. All rights reserved.

  18. Robust parameter estimation method for bilinear model

    NASA Astrophysics Data System (ADS)

    Ismail, Mohd Isfahani; Ali, Hazlina; Yahaya, Sharipah Soaad S.

    2015-12-01

    This paper proposed the method of parameter estimation for bilinear model, especially on BL(1,0,1,1) model without and with the presence of additive outlier (AO). In this study, the estimated parameters for BL(1,0,1,1) model are using nonlinear least squares (LS) method and also through robust approaches. The LS method employs the Newton-Raphson (NR) iterative procedure in estimating the parameters of bilinear model, but, using LS in estimating the parameters can be affected with the occurrence of outliers. As a solution, this study proposed robust approaches in dealing with the problem of outliers specifically on AO in BL(1,0,1,1) model. In robust estimation method, for improvement, we proposed to modify the NR procedure with robust scale estimators. We introduced two robust scale estimators namely median absolute deviation (MADn) and Tn in linear autoregressive model, AR(1) that be adequate and suitable for bilinear BL(1,0,1,1) model. We used the estimated parameter value in AR(1) model as an initial value in estimating the parameter values of BL(1,0,1,1) model. The investigation of the performance of LS and robust estimation methods in estimating the coefficients of BL(1,0,1,1) model is carried out through simulation study. The achievement of performance for both methods will be assessed in terms of bias values. Numerical results present that, the robust estimation method performs better than LS method in estimating the parameters without and with the presence of AO.

  19. Computed Tomography Perfusion Imaging Detection of Microcirculatory Dysfunction in Small Intestinal Ischemia-Reperfusion Injury in a Porcine Model

    PubMed Central

    Shi, Haifeng; Li, Ruokun; Qiang, Jinwei; Li, Ying; Wang, Li; Sun, Rongxun

    2016-01-01

    Objective To evaluate multi-slice computed tomography (CT) perfusion imaging (CTPI) for identifying microcirculatory dysfunction in small intestinal ischemia−reperfusion (IR) injury in a porcine model. Materials and Methods Fifty-two pigs were randomly divided into 4 groups: (1) the IR group (n = 24), where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA) for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively); (2) the sham-operated (SO) group (n = 20), where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively); (3) the ischemia group (n = 4), where the SMA was separated and clamped for 2 h, without reperfusion, and (4) baseline group (n = 4), an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) and for histopathological examination. Results The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia). The blood flow (BF), blood volume (BV), and permeability surface (PS) among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion. Conclusion CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury. PMID:27458696

  20. NIR fluorescent image-based evaluation of gastric tube perfusion after esophagectomy in preclinical model (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kim, Minji; Quan, Yuhua; Han, Kook Nam; Choi, Byeong Hyun; Choi, Yeonho; Kim, Hyun Koo; Kim, Beop-Min

    2016-03-01

    This study was to evaluate the feasibility of near infrared (NIR) fluorescent images as a tool for evaluating the perfusion of the gastric tube after esophagectomy. In addition, we investigated the time required to acquire enough signal to confirm the presence of ischemia in gastric tube after injection of indocyanine green (ICG) through peripheral versus and central venous route. 4 porcine underwent esophagogastrostomy and their right gastric arteries were ligated to mimic ischemic condition of gastric tube. ICG (0.6mg/kg) was intravenously injected and the fluorescence signal-to-background ratios (SBR) were measured by using the custom-built intraoperative color and fluorescence imaging system (ICFIS). We evaluated perfusion of gastric tubes by comparing their SBR with esophageal SBR. In ischemic models, SBR of esophagus was higher than that of gastric tube (2.8+/-0.54 vs. 1.7+/-0.37, p<0.05). It showed high esophagus-stomach signal to signal ratio. (SSR, 1.8+/-0.76). We also could observe recovery of blood perfusion in few minutes after releasing the ligation of right gastric artery. In addition, in comparison study according to the injection route of ICG, The time to acquire signal stabilization was faster in central than in peripheral route (119 +/- 65.1 seconds in central route vs. 295+/-130.4 in peripheral route, p<0.05). NIR fluorescent images could provide the real-time information if there was ischemia or not in gastric tube during operation. And, central injection of ICG might give that information faster than peripheral route.

  1. Deep space network software cost estimation model

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1981-01-01

    A parametric software cost estimation model prepared for Deep Space Network (DSN) Data Systems implementation tasks is presented. The resource estimation model incorporates principles and data from a number of existing models. The model calibrates task magnitude and difficulty, development environment, and software technology effects through prompted responses to a set of approximately 50 questions. Parameters in the model are adjusted to fit DSN software life cycle statistics. The estimation model output scales a standard DSN Work Breakdown Structure skeleton, which is then input into a PERT/CPM system, producing a detailed schedule and resource budget for the project being planned.

  2. Dynamic myocardial perfusion in a porcine balloon-induced ischemia model using a prototype spectral detector CT

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Fares, Anas; Levi, Jacob; Wu, Hao; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR < 0.7), and we found that flow

  3. Estimating Canopy Dark Respiration for Crop Models

    NASA Technical Reports Server (NTRS)

    Monje Mejia, Oscar Alberto

    2014-01-01

    Crop production is obtained from accurate estimates of daily carbon gain.Canopy gross photosynthesis (Pgross) can be estimated from biochemical models of photosynthesis using sun and shaded leaf portions and the amount of intercepted photosyntheticallyactive radiation (PAR).In turn, canopy daily net carbon gain can be estimated from canopy daily gross photosynthesis when canopy dark respiration (Rd) is known.

  4. Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Karki, Kishor; Hugo, Geoffrey D.; Ford, John C.; Olsen, Kathryn M.; Saraiya, Siddharth; Groves, Robert; Weiss, Elisabeth

    2015-10-01

    The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with \\text{TR}≈ 4500 ms, TE  =  74 ms, eight b-values of 0-1000 μs μm-2, pixel size  =  1.98× 1.98 mm2, slice thickness  =  6 mm, interslice gap  =  1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 μs μm-2 from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 μs μm-2 were not significantly different from ADCIVIM values (p>0.05 , paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets—0-1000 50-1000 100-1000 500-1000 and 250 and 800 μs μm-2 were significantly different from the ADCIVIM values. From Rician noise simulation

  5. The isolated perfused bovine udder as an in vitro model of percutaneous drug absorption. Skin viability and percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate.

    PubMed

    Kietzmann, M; Löscher, W; Arens, D; Maass, P; Lubach, D

    1993-10-01

    Using udders from slaughtered cows as a new in vitro model of percutaneous drug absorption, the tissue viability and the percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of glucose consumption, lactate production, lactate dehydrogenase activity, and pH in the perfusate, the tissue was viable over a 6-hr period. This was confirmed by a histological examination. Determination of the udder skin-fold thickness demonstrated that no edema developed within the perfusion period. A maximum skin penetration of dexamethasone was found after administration of dexamethasone dissolved in acetone with dimethyl sulfoxide, followed by ointment with salicylic acid, ointment without salicylic acid, and acetone solution. Experiments with benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was capable of metabolizing drugs in vitro. In conclusion, the isolated perfused bovine udder is a new in vitro model, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in vitro model, we note it is possible to compare the dermal penetration, metabolism, and absorption of substances after topical administration of different drug formulations. PMID:8298184

  6. Placental Transfer of Rilpivirine in an Ex Vivo Human Cotyledon Perfusion Model

    PubMed Central

    Duro, Dominique; Belissa, Emilie; Peytavin, Gilles

    2015-01-01

    Placental transfers of the HIV nonnucleoside reverse transcriptase inhibitor rilpivirine were investigated in 8 term human cotyledons perfused with rilpivirine (400 ng/ml) in the maternal-to-fetal direction. The mean fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 15 to 90 min) was 26% ± 8% (mean ± standard deviation), and the clearance index (rilpivirine FTR/antipyrine FTR) was 61% ± 20%. This shows that rilpivirine crosses the placenta at a relatively high rate, suggesting that the fetus is exposed to the compound during treatment of the mother. PMID:25691637

  7. Control by model error estimation

    NASA Technical Reports Server (NTRS)

    Likins, P. W.; Skelton, R. E.

    1976-01-01

    Modern control theory relies upon the fidelity of the mathematical model of the system. Truncated modes, external disturbances, and parameter errors in linear system models are corrected by augmenting to the original system of equations an 'error system' which is designed to approximate the effects of such model errors. A Chebyshev error system is developed for application to the Large Space Telescope (LST).

  8. Ecposure Related Dose Estimating Model

    EPA Science Inventory

    ERDEM is a physiologically based pharmacokinetic (PBPK) modeling system consisting of a general model and an associated front end. An actual model is defined when the user prepares an input command file. Such a command file defines the chemicals, compartments and processes that...

  9. Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse Model.

    PubMed

    Laemmel, Elisabeth; Segal, Nicolas; Mirshahi, Massoud; Azzazene, Dalel; Le Marchand, Sylvie; Wybier, Marc; Vicaut, Eric; Laredo, Jean-Denis

    2016-06-01

    Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the

  10. WE-G-18C-02: Estimation of Optimal B-Value Set for Obtaining Apparent Diffusion Coefficient Free From Perfusion in Non-Small Cell Lung Cancer

    SciTech Connect

    Karki, K; Hugo, G; Ford, J; Saraiya, S; Weiss, E; Olsen, K; Groves, R

    2014-06-15

    Purpose: Diffusion-weighted MRI (DW-MRI) is increasingly being investigated for radiotherapy planning and response assessment. Selection of a limited number of b-values in DW-MRI is important to keep geometrical variations low and imaging time short. We investigated various b-value sets to determine an optimal set for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in nonsmall cell lung cancer. Methods: Seven patients had 27 DW-MRI scans before and during radiotherapy in a 1.5T scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=4500ms approximately, TE=74ms, pixel size=1.98X1.98mm{sub 2}, slice thickness=4–6mm and 7 axial slices. Diffusion gradients were applied to all three axes producing traceweighted images with eight b-values of 0–1000μs/μm{sup 2}. Monoexponential model ADC values using various b-value sets were compared to ADCIVIM using all b-values. To compare the relative noise in ADC maps, intra-scan coefficient of variation (CV) of active tumor volumes was computed. Results: ADCIVIM, perfusion coefficient and perfusion fraction for tumor volumes were in the range of 880-1622 μm{sup 2}/s, 8119-33834 μm{sup 2}/s and 0.104–0.349, respectively. ADC values using sets of 250, 800 and 1000; 250, 650 and 1000; and 250–1000μs/μm{sup 2} only were not significantly different from ADCIVIM(p>0.05, paired t-test). Error in ADC values for 0–1000, 50–1000, 100–1000, 250–1000, 500–1000, and three b-value sets- 250, 500 and 1000; 250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2} were 15.0, 9.4, 5.6, 1.4, 11.7, 3.7, 2.0 and 0.2% relative to the reference-standard ADCIVIM, respectively. Mean intrascan CV was 20.2, 20.9, 21.9, 24.9, 32.6, 25.8, 25.4 and 24.8%, respectively, whereas that for ADCIVIM was 23.3%. Conclusion: ADC values of two 3 b-value sets

  11. Deep space network software cost estimation model

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1981-01-01

    A parametric software cost estimation model prepared for Jet PRopulsion Laboratory (JPL) Deep Space Network (DSN) Data System implementation tasks is described. The resource estimation mdel modifies and combines a number of existing models. The model calibrates the task magnitude and difficulty, development environment, and software technology effects through prompted responses to a set of approximately 50 questions. Parameters in the model are adjusted to fit JPL software life-cycle statistics.

  12. Maximum Likelihood Estimation in Generalized Rasch Models.

    ERIC Educational Resources Information Center

    de Leeuw, Jan; Verhelst, Norman

    1986-01-01

    Maximum likelihood procedures are presented for a general model to unify the various models and techniques that have been proposed for item analysis. Unconditional maximum likelihood estimation, proposed by Wright and Haberman, and conditional maximum likelihood estimation, proposed by Rasch and Andersen, are shown as important special cases. (JAZ)

  13. RECURSIVE PARAMETER ESTIMATION OF HYDROLOGIC MODELS

    EPA Science Inventory

    Proposed is a nonlinear filtering approach to recursive parameter estimation of conceptual watershed response models in state-space form. he conceptual model state is augmented by the vector of free parameters which are to be estimated from input-output data, and the extended Kal...

  14. [Model of intraluminal perfusion of the guinea pig ileum in vitro in the study of the antidiarrheal properties of the guava (Psidium guajava)].

    PubMed

    Lozoya, X; Becerril, G; Martínez, M

    1990-01-01

    An experimental in vitro model was developed for the study of plant extracts reported by traditional medicines in the treatment of diarrhea. The guinea-pig isolated ileum is perfused with the plant extract using an intraluminal approach. The peristaltic reflex is induced by electrical stimulation while the plant extract is perfused. The spasmolytic effects of Psidium guajava leaf methanol, hexane and water extracts were demonstrated suggesting the existence of two different types of active components. The results obtained allow to propose this in vitro method as a useful model to reproduce some of the characteristics of the oral way of administration of plant extracts. PMID:2103704

  15. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. PMID:25777770

  16. The effects of continuous and intermittent reduced speed modes on renal and intestinal perfusion in an ovine model.

    PubMed

    Tuzun, Egemen; Chorpenning, Katherine; Liu, Maxine Qun; Bonugli, Katherine; Tamez, Dan; Lenox, Mark; Miller, Matthew W; Fossum, Theresa W

    2014-01-01

    The effects of the continuous-flow output on renal and intestinal microcirculation have not been extensively studied. To address this, the Heartware HVAD pump loaded with continuous and intermittent reduced speed (IRS) modes was implanted in four sheep and then operated at low and high speeds to mimic partial and complete unloading of the left ventricle. Then microsphere and positron emission tomography/computed tomography (PET/CT) studies were used to assess renal and intestinal tissue perfusion at various pump speeds and flow modes as compared with baseline (pump off). Arterial and venous oxygen (T02) and carbon dioxide (TCO2) contents were measured to assess changes in intestinal metabolism. Renal and intestinal regional blood flows did not produce any significant changes compared with baseline values in either continuous or IRS modes and speeds. The venous TO2 and TCO2 significantly increased in continuous and IRS modes and speeds compared with baseline. Our data suggested that renal and intestinal tissue perfusions were not adversely affected by continuous and IRS modes either in partial or complete unloading. Intestinal venous hyperoxia and increased TCO2 may be the evidence of intestinal arteriovenous shunting along with increased intestinal tissue metabolism. Longer-term studies are warranted in chronic heart failure models. PMID:24299973

  17. Modeling [15O] oxygen tracer data for estimating oxygen consumption

    PubMed Central

    Deussen, Andreas; Bassingthwaighte, James B.

    2010-01-01

    The most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water via mitochondrial respiration. To calculate oxygen consumption from the analysis of tissue residue curves or outflow dilution curves after injection of labeled oxygen one needs realistic mathematical models that account for convection, diffusion, and transformation in the tissue. A linear, three-region, axially distributed model accounts for intravascular convection, penetration of capillary and parenchymal cell barriers (with the use of appropriate binding spaces to account for oxygen binding to hemoglobin and myoglobin), the metabolism to [15O]water in parenchymal cells, and [15O]water transport into the venous effluent. Model solutions fit residue and outflow dilution data obtained in an isolated, red blood cell-perfused rabbit heart preparation and give estimates of the rate of oxygen consumption similar to those obtained experimentally from the flow times the arteriovenous differences in oxygen contents. The proposed application is for the assessment of regional oxidative metabolism in vivo from tissue 15O-residue curves obtained by positron emission tomography. PMID:8780210

  18. On Estimation of Partially Linear Transformation Models

    PubMed Central

    Lu, Wenbin; Zhang, Hao Helen

    2010-01-01

    We study a general class of partially linear transformation models, which extend linear transformation models by incorporating nonlinear covariate effects in survival data analysis. A new martingale-based estimating equation approach, consisting of both global and kernel-weighted local estimation equations, is developed for estimating the parametric and nonparametric covariate effects in a unified manner. We show that with a proper choice of the kernel bandwidth parameter, one can obtain the consistent and asymptotically normal parameter estimates for the linear effects. Asymptotic properties of the estimated nonlinear effects are established as well. We further suggest a simple resampling method to estimate the asymptotic variance of the linear estimates and show its effectiveness. To facilitate the implementation of the new procedure, an iterative algorithm is developed. Numerical examples are given to illustrate the finite-sample performance of the procedure. PMID:20802823

  19. On Estimation of Partially Linear Transformation Models.

    PubMed

    Lu, Wenbin; Zhang, Hao Helen

    2010-06-01

    We study a general class of partially linear transformation models, which extend linear transformation models by incorporating nonlinear covariate effects in survival data analysis. A new martingale-based estimating equation approach, consisting of both global and kernel-weighted local estimation equations, is developed for estimating the parametric and nonparametric covariate effects in a unified manner. We show that with a proper choice of the kernel bandwidth parameter, one can obtain the consistent and asymptotically normal parameter estimates for the linear effects. Asymptotic properties of the estimated nonlinear effects are established as well. We further suggest a simple resampling method to estimate the asymptotic variance of the linear estimates and show its effectiveness. To facilitate the implementation of the new procedure, an iterative algorithm is developed. Numerical examples are given to illustrate the finite-sample performance of the procedure. PMID:20802823

  20. Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

    PubMed Central

    Zhou, Wei; Di, Liu-qing; Wang, Juan; Shan, Jin-jun; Liu, Shi-jia; Ju, Wen-zheng; Cai, Bao-chang

    2012-01-01

    Aim: To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus. Methods: An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used. Results: In the in vitro Caco-2 cell model, the mean apparent permeability value (Papp-value) was 4.15×10-7 cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6–10.4 μg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport, >96% of the apically loaded FTA was retained on the apical side, while >97% of the basolaterally loaded FTA was retained on the basolateral side. The Papp-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the Papp-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the Papp-values. In the in situ intestinal perfusion model, both the absorption rate constant (Ka) and the effective permeability (Peff-values) following perfusion of FTA 2.6, 5.2 and 10.4 μg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the Peff-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the Peff-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the

  1. Parameter Estimation of Partial Differential Equation Models

    PubMed Central

    Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J.; Maity, Arnab

    2013-01-01

    Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data. PMID:24363476

  2. Parameter Estimation of Partial Differential Equation Models.

    PubMed

    Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J; Maity, Arnab

    2013-01-01

    Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data. PMID:24363476

  3. Mineral resources estimation based on block modeling

    NASA Astrophysics Data System (ADS)

    Bargawa, Waterman Sulistyana; Amri, Nur Ali

    2016-02-01

    The estimation in this paper uses three kinds of block models of nearest neighbor polygon, inverse distance squared and ordinary kriging. The techniques are weighting scheme which is based on the principle that block content is a linear combination of the grade data or the sample around the block being estimated. The case study in Pongkor area, here is gold-silver resource modeling that allegedly shaped of quartz vein as a hydrothermal process of epithermal type. Resources modeling includes of data entry, statistical and variography analysis of topography and geological model, the block model construction, estimation parameter, presentation model and tabulation of mineral resources. Skewed distribution, here isolated by robust semivariogram. The mineral resources classification generated in this model based on an analysis of the kriging standard deviation and number of samples which are used in the estimation of each block. Research results are used to evaluate the performance of OK and IDS estimator. Based on the visual and statistical analysis, concluded that the model of OK gives the estimation closer to the data used for modeling.

  4. Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia

    PubMed Central

    Robich, Michael P.; Osipov, Robert M.; Nezafat, Reza; Feng, Jun; Clements, Richard T.; Bianchi, Cesario; Boodhwani, Munir; Coady, Michael A.; Laham, Roger J.; Sellke, Frank W.

    2010-01-01

    Introduction Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. Methods and Results Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac magnetic resonance imaging and coronary angiography 7 weeks later, prior to sacrifice and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (p<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (p=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (p=0.32). Tissue blood flow during stress was 2.8 fold greater in HCRV swine when compared to HCC swine (p=0.04). Endothelial dependent microvascular relaxation response to Substance P was diminished in HCC swine which was rescued by resveratrol treatment (p=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine v. control swine (p=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV v. HCC swine of the following markers of angiogenesis: VEGF (p=0.002), peNOS(ser1177)(p=0.04), NFkB (p=0.004), and pAkt(thr308)(p=0.001). Conclusion Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelial dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway. PMID:20837905

  5. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

    Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.

    2016-04-01

    Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.

  6. The direct incorporation of perfusion defect information to define ischemia and infarction in a finite element model of the left ventricle.

    PubMed

    Veress, Alexander I; Fung, George S K; Lee, Taek-Soo; Tsui, Benjamin M W; Kicska, Gregory A; Paul Segars, W; Gullberg, Grant T

    2015-05-01

    This paper describes the process in which complex lesion geometries (specified by computer generated perfusion defects) are incorporated in the description of nonlinear finite element (FE) mechanical models used for specifying the motion of the left ventricle (LV) in the 4D extended cardiac torso (XCAT) phantom to simulate gated cardiac image data. An image interrogation process was developed to define the elements in the LV mesh as ischemic or infarcted based upon the values of sampled intensity levels of the perfusion maps. The intensity values were determined for each of the interior integration points of every element of the FE mesh. The average element intensity levels were then determined. The elements with average intensity values below a user-controlled threshold were defined as ischemic or infarcted depending upon the model being defined. For the infarction model cases, the thresholding and interrogation process were repeated in order to define a border zone (BZ) surrounding the infarction. This methodology was evaluated using perfusion maps created by the perfusion cardiac-torso (PCAT) phantom an extension of the 4D XCAT phantom. The PCAT was used to create 3D perfusion maps representing 90% occlusions at four locations (left anterior descending (LAD) segments 6 and 9, left circumflex (LCX) segment 11, right coronary artery (RCA) segment 1) in the coronary tree. The volumes and shapes of the defects defined in the FE mechanical models were compared with perfusion maps produced by the PCAT. The models were incorporated into the XCAT phantom. The ischemia models had reduced stroke volume (SV) by 18-59 ml. and ejection fraction (EF) values by 14-50% points compared to the normal models. The infarction models, had less reductions in SV and EF, 17-54 ml. and 14-45% points, respectively. The volumes of the ischemic/infarcted regions of the models were nearly identical to those volumes obtained from the perfusion images and were highly correlated (R

  7. Hydroxyethyl Starch (HES 130/0.4) Impairs Intestinal Barrier Integrity and Metabolic Function: Findings from a Mouse Model of the Isolated Perfused Small Intestine

    PubMed Central

    Dombrowsky, Heike; Zitta, Karina; Bein, Berthold; Krause, Thorsten; Goldmann, Torsten; Frerichs, Inez; Steinfath, Markus; Weiler, Norbert; Albrecht, Martin

    2015-01-01

    Background The application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine. Methods An isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups. Results Compared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces. Conclusion A vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small

  8. Model feedback in Bayesian propensity score estimation.

    PubMed

    Zigler, Corwin M; Watts, Krista; Yeh, Robert W; Wang, Yun; Coull, Brent A; Dominici, Francesca

    2013-03-01

    Methods based on the propensity score comprise one set of valuable tools for comparative effectiveness research and for estimating causal effects more generally. These methods typically consist of two distinct stages: (1) a propensity score stage where a model is fit to predict the propensity to receive treatment (the propensity score), and (2) an outcome stage where responses are compared in treated and untreated units having similar values of the estimated propensity score. Traditional techniques conduct estimation in these two stages separately; estimates from the first stage are treated as fixed and known for use in the second stage. Bayesian methods have natural appeal in these settings because separate likelihoods for the two stages can be combined into a single joint likelihood, with estimation of the two stages carried out simultaneously. One key feature of joint estimation in this context is "feedback" between the outcome stage and the propensity score stage, meaning that quantities in a model for the outcome contribute information to posterior distributions of quantities in the model for the propensity score. We provide a rigorous assessment of Bayesian propensity score estimation to show that model feedback can produce poor estimates of causal effects absent strategies that augment propensity score adjustment with adjustment for individual covariates. We illustrate this phenomenon with a simulation study and with a comparative effectiveness investigation of carotid artery stenting versus carotid endarterectomy among 123,286 Medicare beneficiaries hospitlized for stroke in 2006 and 2007. PMID:23379793

  9. Challenges for non-invasive brain perfusion quantification using arterial spin labeling.

    PubMed

    Sousa, I; Santos, N; Sanches, J; Figueiredo, P

    2011-03-29

    Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed. PMID:24059574

  10. Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts

    NASA Astrophysics Data System (ADS)

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Maurizi, Lionel; Diener, Pierre-André; Hofmann, Heinrich; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula; Wick, Peter

    2015-08-01

    Nanotechnology is a rapidly expanding and highly promising new technology with many different fields of application. Consequently, the investigation of engineered nanoparticles in biological systems is steadily increasing. Questions about the safety of such engineered nanoparticles are very important and the most critical subject with regard to the penetration of biological barriers allowing particle distribution throughout the human body. Such translocation studies are technically challenging and many issues have to be considered to obtain meaningful and comparable results. Here we report on the transfer of polystyrene nanoparticles across the human placenta using an ex vivo human placenta perfusion model. We provide an overview of several challenges that can potentially occur in any translocation study in relation to particle size distribution, functionalization and stability of labels. In conclusion, a careful assessment of nanoparticle properties in a physiologically relevant milieu is as challenging and important as the actual study of nanoparticle-cell interactions itself.

  11. Development of 4D mathematical observer models for the task-based evaluation of gated myocardial perfusion SPECT

    NASA Astrophysics Data System (ADS)

    Lee, Taek-Soo; Frey, Eric C.; Tsui, Benjamin M. W.

    2015-04-01

    This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of 99mTc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman’s rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the

  12. Development of 4D mathematical observer models for the task-based evaluation of gated myocardial perfusion SPECT.

    PubMed

    Lee, Taek-Soo; Frey, Eric C; Tsui, Benjamin M W

    2015-04-01

    This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of (99m)Tc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman's rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the

  13. Myocardial Drug Distribution Generated from Local Epicardial Application: Potential Impact of Cardiac Capillary Perfusion in a Swine Model Using Epinephrine

    PubMed Central

    Maslov, Mikhail Y.; Edelman, Elazer R.; Pezone, Matthew J.; Wei, Abraham E.; Wakim, Matthew G.; Murray, Michael R.; Tsukada, Hisashi; Gerogiannis, Iraklis S.; Groothuis, Adam; Lovich, Mark A.

    2014-01-01

    the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue. PMID:25234821

  14. Joint estimation of multiple graphical models

    PubMed Central

    Guo, Jian; Levina, Elizaveta; Michailidis, George; Zhu, Ji

    2011-01-01

    Summary Gaussian graphical models explore dependence relationships between random variables, through the estimation of the corresponding inverse covariance matrices. In this paper we develop an estimator for such models appropriate for data from several graphical models that share the same variables and some of the dependence structure. In this setting, estimating a single graphical model would mask the underlying heterogeneity, while estimating separate models for each category does not take advantage of the common structure. We propose a method that jointly estimates the graphical models corresponding to the different categories present in the data, aiming to preserve the common structure, while allowing for differences between the categories. This is achieved through a hierarchical penalty that targets the removal of common zeros in the inverse covariance matrices across categories. We establish the asymptotic consistency and sparsity of the proposed estimator in the high-dimensional case, and illustrate its performance on a number of simulated networks. An application to learning semantic connections between terms from webpages collected from computer science departments is included. PMID:23049124

  15. Placental Transfer of Maraviroc in an Ex Vivo Human Cotyledon Perfusion Model and Influence of ABC Transporter Expression

    PubMed Central

    Vinot, C.; Gavard, L.; Tréluyer, J. M.; Manceau, S.; Courbon, E.; Scherrmann, J. M.; Declèves, X.; Duro, D.; Peytavin, G.; Mandelbrot, L.

    2013-01-01

    Nowadays, antiretroviral therapy is recommended during pregnancy to prevent mother-to-child transmission of HIV. However, for many antiretroviral drugs, including maraviroc, a CCR5 antagonist, very little data exist regarding placental transfer. Besides, various factors may modulate this transfer, including efflux transporters belonging to the ATP-binding cassette (ABC) transporter superfamily. We investigated maraviroc placental transfer and the influence of ABC transporter expression on this transfer using the human cotyledon perfusion model. Term placentas were perfused ex vivo for 90 min with maraviroc (600 ng/ml) either in the maternal-to-fetal (n = 10 placentas) or fetal-to-maternal (n = 6 placentas) direction. Plasma concentrations were determined by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fetal transfer rates (FTR) and clearance indexes (CLI) were calculated as ratios of fetal to maternal concentrations at steady state (mean values between 30 and 90 min) and ratios of FTR of maraviroc to that of antipyrine, respectively. ABC transporter gene expression levels were determined by quantitative reverse transcription (RT)-PCR and ABCB1 protein expression by Western blotting. For the maternal-to-fetal direction, the mean FTR and CLI were 8.0% ± 3.0 and 0.26 ± 0.07, respectively, whereas the mean CLI was 0.52 ± 0.23 for the fetal-to-maternal direction. We showed a significant inverse correlation between maraviroc CLI and ABCC2, ABCC10, and ABCC11 placental gene expression levels (P < 0.05). To conclude, we report a low maraviroc placental transfer probably involving ABC efflux transporters and thus in all likelihood associated with a limited fetal exposition. Nevertheless, these results would need to be supported by in vivo data obtained from paired maternal and cord blood samples. PMID:23295922

  16. Density Estimation Framework for Model Error Assessment

    NASA Astrophysics Data System (ADS)

    Sargsyan, K.; Liu, Z.; Najm, H. N.; Safta, C.; VanBloemenWaanders, B.; Michelsen, H. A.; Bambha, R.

    2014-12-01

    In this work we highlight the importance of model error assessment in physical model calibration studies. Conventional calibration methods often assume the model is perfect and account for data noise only. Consequently, the estimated parameters typically have biased values that implicitly compensate for model deficiencies. Moreover, improving the amount and the quality of data may not improve the parameter estimates since the model discrepancy is not accounted for. In state-of-the-art methods model discrepancy is explicitly accounted for by enhancing the physical model with a synthetic statistical additive term, which allows appropriate parameter estimates. However, these statistical additive terms do not increase the predictive capability of the model because they are tuned for particular output observables and may even violate physical constraints. We introduce a framework in which model errors are captured by allowing variability in specific model components and parameterizations for the purpose of achieving meaningful predictions that are both consistent with the data spread and appropriately disambiguate model and data errors. Here we cast model parameters as random variables, embedding the calibration problem within a density estimation framework. Further, we calibrate for the parameters of the joint input density. The likelihood function for the associated inverse problem is degenerate, therefore we use Approximate Bayesian Computation (ABC) to build prediction-constraining likelihoods and illustrate the strengths of the method on synthetic cases. We also apply the ABC-enhanced density estimation to the TransCom 3 CO2 intercomparison study (Gurney, K. R., et al., Tellus, 55B, pp. 555-579, 2003) and calibrate 15 transport models for regional carbon sources and sinks given atmospheric CO2 concentration measurements.

  17. Robust estimation for ordinary differential equation models.

    PubMed

    Cao, J; Wang, L; Xu, J

    2011-12-01

    Applied scientists often like to use ordinary differential equations (ODEs) to model complex dynamic processes that arise in biology, engineering, medicine, and many other areas. It is interesting but challenging to estimate ODE parameters from noisy data, especially when the data have some outliers. We propose a robust method to address this problem. The dynamic process is represented with a nonparametric function, which is a linear combination of basis functions. The nonparametric function is estimated by a robust penalized smoothing method. The penalty term is defined with the parametric ODE model, which controls the roughness of the nonparametric function and maintains the fidelity of the nonparametric function to the ODE model. The basis coefficients and ODE parameters are estimated in two nested levels of optimization. The coefficient estimates are treated as an implicit function of ODE parameters, which enables one to derive the analytic gradients for optimization using the implicit function theorem. Simulation studies show that the robust method gives satisfactory estimates for the ODE parameters from noisy data with outliers. The robust method is demonstrated by estimating a predator-prey ODE model from real ecological data. PMID:21401565

  18. Systematic Error Modeling and Bias Estimation

    PubMed Central

    Zhang, Feihu; Knoll, Alois

    2016-01-01

    This paper analyzes the statistic properties of the systematic error in terms of range and bearing during the transformation process. Furthermore, we rely on a weighted nonlinear least square method to calculate the biases based on the proposed models. The results show the high performance of the proposed approach for error modeling and bias estimation. PMID:27213386

  19. Systematic Error Modeling and Bias Estimation.

    PubMed

    Zhang, Feihu; Knoll, Alois

    2016-01-01

    This paper analyzes the statistic properties of the systematic error in terms of range and bearing during the transformation process. Furthermore, we rely on a weighted nonlinear least square method to calculate the biases based on the proposed models. The results show the high performance of the proposed approach for error modeling and bias estimation. PMID:27213386

  20. EXPOSURE RELATED DOSE ESTIMATING MODEL (ERDEM)

    EPA Science Inventory

    ERDEM is a physiologically-based pharmacokinetic (PBPK) model with a graphical user interface (GUI) front end. Such a mathematical model was needed to make reliable estimates of the chemical dose to organs of animals or humans because of uncertainties of making route-to route, lo...

  1. Estimating solar radiation for plant simulation models

    NASA Technical Reports Server (NTRS)

    Hodges, T.; French, V.; Leduc, S.

    1985-01-01

    Five algorithms producing daily solar radiation surrogates using daily temperatures and rainfall were evaluated using measured solar radiation data for seven U.S. locations. The algorithms were compared both in terms of accuracy of daily solar radiation estimates and terms of response when used in a plant growth simulation model (CERES-wheat). Requirements for accuracy of solar radiation for plant growth simulation models are discussed. One algorithm is recommended as being best suited for use in these models when neither measured nor satellite estimated solar radiation values are available.

  2. Hydrograph estimation with fuzzy chain model

    NASA Astrophysics Data System (ADS)

    Güçlü, Yavuz Selim; Şen, Zekai

    2016-07-01

    Hydrograph peak discharge estimation is gaining more significance with unprecedented urbanization developments. Most of the existing models do not yield reliable peak discharge estimations for small basins although they provide acceptable results for medium and large ones. In this study, fuzzy chain model (FCM) is suggested by considering the necessary adjustments based on some measurements over a small basin, Ayamama basin, within Istanbul City, Turkey. FCM is based on Mamdani and the Adaptive Neuro Fuzzy Inference Systems (ANFIS) methodologies, which yield peak discharge estimation. The suggested model is compared with two well-known approaches, namely, Soil Conservation Service (SCS)-Snyder and SCS-Clark methodologies. In all the methods, the hydrographs are obtained through the use of dimensionless unit hydrograph concept. After the necessary modeling, computation, verification and adaptation stages comparatively better hydrographs are obtained by FCM. The mean square error for the FCM is many folds smaller than the other methodologies, which proves outperformance of the suggested methodology.

  3. Modeling of a three-source perfusion and blood oxygenation sensor for transplant monitoring using multilayer Monte Carlo code

    NASA Astrophysics Data System (ADS)

    Ibey, Bennett L.; Lee, Seungjoon; Ericson, M. Nance; Wilson, Mark A.; Cote, Gerard L.

    2004-06-01

    A Multi-Layer Monte Carlo (MLMC) model was developed to predict the results of in vivo blood perfusion and oxygenation measurement of transplanted organs as measured by an indwelling optical sensor. A sensor has been developed which uses three-source excitation in the red and infrared ranges (660, 810, 940 nm). In vitro data was taken using this sensor by changing the oxygenation state of whole blood and passing it through a single-tube pump system wrapped in bovine liver tissue. The collected data showed that the red signal increased as blood oxygenation increased and infrared signal decreased. The center wavelength of 810 nanometers was shown to be quite indifferent to blood oxygenation change. A model was developed using MLMC code that sampled the wavelength range from 600-1000 nanometers every 6 nanometers. Using scattering and absorption data for blood and liver tissue within this wavelength range, a five-layer model was developed (tissue, clear tubing, blood, clear tubing, tissue). The theoretical data generated from this model was compared to the in vitro data and showed good correlation with changing blood oxygenation.

  4. Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

    PubMed Central

    Nelson, Kevin; Bobba, Christopher; Eren, Emre; Spata, Tyler; Tadres, Malak; Hayes,, Don; Black, Sylvester M.

    2015-01-01

    The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and “pearls of wisdom”/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible. PMID:25741794

  5. Method of isolated ex vivo lung perfusion in a rat model: lessons learned from developing a rat EVLP program.

    PubMed

    Nelson, Kevin; Bobba, Christopher; Eren, Emre; Spata, Tyler; Tadres, Malak; Hayes, Don; Black, Sylvester M; Ghadiali, Samir; Whitson, Bryan A

    2015-01-01

    The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and "pearls of wisdom"/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible. PMID:25741794

  6. Myocardial perfusion with rubidium-82. III. Theory relating severity of coronary stenosis to perfusion deficit

    SciTech Connect

    Mullani, N.A.

    1984-11-01

    The relation between the quantitative perfusion deficit, as measured by emission computerized tomography, and the severity of coronary artery stenosis is important for the noninvasive clinical evaluation of coronary artery disease in man. Positron emission tomography allows direct noninvasive measurement of myocardial perfusion and quantification of the size of the perfusion defect. Given this important imformation, a mathematical model has been derived to gauge the severity of a coronary stenosis from quantitative perfusion measurements in the normal and poststenotic regions of the heart. The theoretical basis is presented for relating regional myocardial perfusion and regional perfusion resistance to total, coronary blood flow and resistance at normal resting flow and during maximal coronary vasodilation. The concept of perfusion reserve is presented as a clinical measure of the severity of a stenosis.

  7. Feasibility Study of Myocardial Perfusion and Oxygenation by Non-Contrast MRI: Comparison with PET Study in a Canine Model

    PubMed Central

    McCommis, Kyle S.; Zhang, Haosen; Herrero, Pilar; Gropler, Robert J.; Zheng, Jie

    2008-01-01

    The purpose of this study was to examine the feasibility of quantifying myocardial blood flow (MBF) and rate of myocardial oxygen consumption (MVO2) during pharmacologically induced stress without using a contrast agent. The former was measured by the arterial spin labeling (ASL) method and the later was obtained by measuring the oxygen extraction fraction (OEF) with the magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) effect and Fick's law. The MRI results were compared with the established positron emission tomography (PET) methods. Six mongrel dogs with induced acute moderate left coronary artery stenosis were scanned using a clinical PET and a 1.5T MRI system, in the same day. Regional MBF, myocardial OEF, and MVO2 were measured with both imaging modalities. Correlation coefficients (R2) of the three myocardial indexes (MBF, OEF, and MVO2) between MRI and PET methods ranged from 0.70 to 0.93. Bland-Altman statistics demonstrated that the estimated precision of the limits of agreement between MRI and PET measurements varied from 18% (OEF), to 37% (MBF), and 45% (MVO2). The detected changes in these indexes, at rest and during dobutamine stress, were similar between two image modalities. The proposed non-contrast MRI technique is a promising method to quantitatively assess myocardial perfusion and oxygenation. PMID:17566684

  8. Optimal estimator model for human spatial orientation

    NASA Technical Reports Server (NTRS)

    Borah, J.; Young, L. R.; Curry, R. E.

    1979-01-01

    A model is being developed to predict pilot dynamic spatial orientation in response to multisensory stimuli. Motion stimuli are first processed by dynamic models of the visual, vestibular, tactile, and proprioceptive sensors. Central nervous system function is then modeled as a steady-state Kalman filter which blends information from the various sensors to form an estimate of spatial orientation. Where necessary, this linear central estimator has been augmented with nonlinear elements to reflect more accurately some highly nonlinear human response characteristics. Computer implementation of the model has shown agreement with several important qualitative characteristics of human spatial orientation, and it is felt that with further modification and additional experimental data the model can be improved and extended. Possible means are described for extending the model to better represent the active pilot with varying skill and work load levels.

  9. Cerebrospinal fluid reconstitution via a perfusion-based cadaveric model: feasibility study demonstrating surgical simulation of neuroendoscopic procedures.

    PubMed

    Winer, Jesse L; Kramer, Daniel R; Robison, Richard A; Ohiorhenuan, Ifije; Minneti, Michael; Giannotta, Steven; Zada, Gabriel

    2015-11-01

    Cadaveric surgical simulation carries the advantage of realistic anatomy and haptic feedback but has been historically difficult to model for intraventricular approaches given the need for active flow of CSF. This feasibility study was designed to simulate intraventricular neuroendoscopic approaches and techniques by reconstituting natural CSF flow in a cadaveric model. In 10 fresh human cadavers, a simple cervical laminectomy and dural opening were made, and a 12-gauge arterial catheter was introduced. Saline was continuously perfused at physiological CSF pressures to reconstitute the subarachnoid space and ventricles. A neuroendoscope was subsequently inserted via a standard right frontal bur hole. In 8 of the 10 cadavers, adequate reconstitution and endoscopic access of the lateral and third ventricles were achieved. In 2 cadavers, ventricular access was not feasible, perhaps because of a small ventricle size and/or deteriorated tissue quality. In all 8 cadavers with successful CSF flow reconstitution and endoscopic access, identifying the foramen of Monro was possible, as was performing septum pellucidotomy and endoscopic third ventriculostomy. Furthermore, navigation of the cerebral aqueduct, fourth ventricle, prepontine cistern, and suprasellar cistern via the lamina terminalis was possible, providing a complementary educational paradigm for resident education that cannot typically be performed in live surgery. Surgical simulation plays a critical and increasingly prominent role in surgical education, particularly for techniques with steep learning curves including intraventricular neuroendoscopic procedures. This novel model provides feasible and realistic surgical simulation of neuroendoscopic intraventricular procedures and approaches. PMID:25859805

  10. Estimation and uncertainty of reversible Markov models

    NASA Astrophysics Data System (ADS)

    Trendelkamp-Schroer, Benjamin; Wu, Hao; Paul, Fabian; Noé, Frank

    2015-11-01

    Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta-stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software — http://pyemma.org — as of version 2.0.

  11. Pulmonary ventilation/perfusion scan

    MedlinePlus

    V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health ...

  12. Long-term effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model

    PubMed Central

    Nishino, Asuka; Tajima, Yosuke; Takuwa, Hiroyuki; Masamoto, Kazuto; Taniguchi, Junko; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Urushihata, Takuya; Aoki, Ichio; Kanno, Iwao; Tomita, Yutaka; Suzuki, Norihiro; Ikoma, Yoko; Ito, Hiroshi

    2016-01-01

    We investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [11C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before, and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO. PMID:27116932

  13. Long-term effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model.

    PubMed

    Nishino, Asuka; Tajima, Yosuke; Takuwa, Hiroyuki; Masamoto, Kazuto; Taniguchi, Junko; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Urushihata, Takuya; Aoki, Ichio; Kanno, Iwao; Tomita, Yutaka; Suzuki, Norihiro; Ikoma, Yoko; Ito, Hiroshi

    2016-01-01

    We investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [(11)C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before, and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO. PMID:27116932

  14. Robust estimation procedure in panel data model

    SciTech Connect

    Shariff, Nurul Sima Mohamad; Hamzah, Nor Aishah

    2014-06-19

    The panel data modeling has received a great attention in econometric research recently. This is due to the availability of data sources and the interest to study cross sections of individuals observed over time. However, the problems may arise in modeling the panel in the presence of cross sectional dependence and outliers. Even though there are few methods that take into consideration the presence of cross sectional dependence in the panel, the methods may provide inconsistent parameter estimates and inferences when outliers occur in the panel. As such, an alternative method that is robust to outliers and cross sectional dependence is introduced in this paper. The properties and construction of the confidence interval for the parameter estimates are also considered in this paper. The robustness of the procedure is investigated and comparisons are made to the existing method via simulation studies. Our results have shown that robust approach is able to produce an accurate and reliable parameter estimates under the condition considered.

  15. Robust estimation procedure in panel data model

    NASA Astrophysics Data System (ADS)

    Shariff, Nurul Sima Mohamad; Hamzah, Nor Aishah

    2014-06-01

    The panel data modeling has received a great attention in econometric research recently. This is due to the availability of data sources and the interest to study cross sections of individuals observed over time. However, the problems may arise in modeling the panel in the presence of cross sectional dependence and outliers. Even though there are few methods that take into consideration the presence of cross sectional dependence in the panel, the methods may provide inconsistent parameter estimates and inferences when outliers occur in the panel. As such, an alternative method that is robust to outliers and cross sectional dependence is introduced in this paper. The properties and construction of the confidence interval for the parameter estimates are also considered in this paper. The robustness of the procedure is investigated and comparisons are made to the existing method via simulation studies. Our results have shown that robust approach is able to produce an accurate and reliable parameter estimates under the condition considered.

  16. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  17. Generalized Mixture Models for Molecular Phylogenetic Estimation

    PubMed Central

    Evans, Jason; Sullivan, Jack

    2012-01-01

    The rapidly growing availability of multigene sequence data during the past decade has enabled phylogeny estimation at phylogenomic scales. However, dealing with evolutionary process heterogeneity across the genome becomes increasingly challenging. Here we develop a mixture model approach that uses reversible jump Markov chain Monte Carlo (MCMC) estimation to permit as many distinct models as the data require. Each additional model considered may be a fully parametrized general time-reversible model or any of its special cases. Furthermore, we expand the usual proposal mechanisms for topology changes to permit hard polytomies (i.e., zero-length internal branches). This new approach is implemented in the Crux software toolkit. We demonstrate the feasibility of using reversible jump MCMC on mixture models by reexamining a well-known 44-taxon mammalian data set comprising 22 concatenated genes. We are able to reproduce the results of the original analysis (with respect to bipartition support) when we make identical assumptions, but when we allow for polytomies and/or use data-driven mixture model estimation, we infer much lower bipartition support values for several key bipartitions. PMID:21873377

  18. Modeling non-linear kinetics of hyperpolarized [1-(13)C] pyruvate in the crystalloid-perfused rat heart.

    PubMed

    Mariotti, E; Orton, M R; Eerbeek, O; Ashruf, J F; Zuurbier, C J; Southworth, R; Eykyn, T R

    2016-04-01

    Hyperpolarized (13)C MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-(13)C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-(13)C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. PMID:26777799

  19. Modeling non‐linear kinetics of hyperpolarized [1‐13C] pyruvate in the crystalloid‐perfused rat heart

    PubMed Central

    Mariotti, E.; Orton, M. R.; Eerbeek, O.; Ashruf, J. F.; Zuurbier, C. J.; Southworth, R.

    2016-01-01

    Hyperpolarized 13C MR measurements have the potential to display non‐linear kinetics. We have developed an approach to describe possible non‐first‐order kinetics of hyperpolarized [1‐13C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second‐order model for conversion of [1‐13C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second‐order modeling yielded significantly improved fits of pyruvate–bicarbonate kinetics compared with the more traditionally used first‐order model and suggested time‐dependent decreases in pyruvate–bicarbonate flux. Second‐order modeling gave time‐dependent changes in forward and reverse reaction kinetics of pyruvate–lactate exchange and pyruvate–alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first‐order model. The mechanism giving rise to second‐order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD+ (the cofactor for PDH), consistent with the non‐linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:26777799

  20. Differential expression of cytoprotective and apoptotic genes in an ischaemia-reperfusion isolated organ perfusion model of the transplanted kidney.

    PubMed

    Waller, Helen L; Harper, Simon J F; Hosgood, Sarah A; Bagul, Atul; Kay, Mark D; Kaushik, Monika; Yang, Bin; Bicknell, Gareth R; Nicholson, Michael L

    2007-07-01

    The optimal kidney preservation system and methods to ameliorate reperfusion injury are major factors in accomplishing successful graft function following transplantation. Ischaemia and reperfusion lead to cellular stress and the adaptive response may include the activation of genes involved in cellular protection and/or cell death by apoptosis. We investigated the expression of cytoprotective heme oxygenase-1 (HO-1), anti-apoptotic Bcl-2 and pro-apoptotic Bax after 6 h isolated organ perfusion in porcine kidneys that had been given 10 and 40 min warm ischaemic time. The level of HO-1 was shown to be significantly higher in the 10-min warm ischaemic group compared with 40-min group (0.90 +/- 0.03 vs. 0.83 +/- 0.03; P = 0.002). The levels of HO-1 showed a significant positive correlated with parameters of renal function, creatinine clearance, and renal blood flow and urine output (AUC; r = 0.8042, P = 0.03; r = 0.6028, P = 0.04; r = 0.6055, P = 0.04), demonstrating a possible protective role of this gene in this model of renal transplantation. PMID:17639610

  1. Extreme Earthquake Risk Estimation by Hybrid Modeling

    NASA Astrophysics Data System (ADS)

    Chavez, M.; Cabrera, E.; Ashworth, M.; Garcia, S.; Emerson, D.; Perea, N.; Salazar, A.; Moulinec, C.

    2012-12-01

    The estimation of the hazard and the economical consequences i.e. the risk associated to the occurrence of extreme magnitude earthquakes in the neighborhood of urban or lifeline infrastructure, such as the 11 March 2011 Mw 9, Tohoku, Japan, represents a complex challenge as it involves the propagation of seismic waves in large volumes of the earth crust, from unusually large seismic source ruptures up to the infrastructure location. The large number of casualties and huge economic losses observed for those earthquakes, some of which have a frequency of occurrence of hundreds or thousands of years, calls for the development of new paradigms and methodologies in order to generate better estimates, both of the seismic hazard, as well as of its consequences, and if possible, to estimate the probability distributions of their ground intensities and of their economical impacts (direct and indirect losses), this in order to implement technological and economical policies to mitigate and reduce, as much as possible, the mentioned consequences. Herewith, we propose a hybrid modeling which uses 3D seismic wave propagation (3DWP) and neural network (NN) modeling in order to estimate the seismic risk of extreme earthquakes. The 3DWP modeling is achieved by using a 3D finite difference code run in the ~100 thousands cores Blue Gene Q supercomputer of the STFC Daresbury Laboratory of UK, combined with empirical Green function (EGF) techniques and NN algorithms. In particular the 3DWP is used to generate broadband samples of the 3D wave propagation of extreme earthquakes (plausible) scenarios corresponding to synthetic seismic sources and to enlarge those samples by using feed-forward NN. We present the results of the validation of the proposed hybrid modeling for Mw 8 subduction events, and show examples of its application for the estimation of the hazard and the economical consequences, for extreme Mw 8.5 subduction earthquake scenarios with seismic sources in the Mexican

  2. An Evaluation of the Venous Equilibrium Model for Hepatic Clearance using Isolated Perfused Rainbow Trout Livers

    EPA Science Inventory

    The venous equilibrium model is widely used to describe hepatic clearance (CLH) of chemicals metabolized by the liver. If chemical delivery to the tissue does not limit CLH, this model predicts that CLH will approximately equal the product of intrinsic metabolic clearance and a t...

  3. Evaluation of tumour vascularisation in two rat sarcoma models for studying isolated lung perfusion. Injection route determines the origin of tumour vessels.

    PubMed

    Pan, Youmin; Krueger, T; Tran, Nam; Yan, Hua; Ris, H-B; McKee, T A

    2005-01-01

    Isolated cytostatic lung perfusion (ILP) is an attractive technique allowing delivery of a high-dose of cytostatic agents to the lungs while limiting systemic toxicity. In developing a rat model of ILP, we have analysed the effect of the route of tumour cell injection on the source of tumour vessels. Pulmonary sarcomas were established by injecting a sarcoma cell suspension either by the intravenous (i.v.) route or directly into the lung parenchyma. Ink perfusion through either pulmonary artery (PA) or bronchial arteries (BA) was performed and the characteristics of the tumour deposits defined. i.v. and direct injection methods induced pulmonary sarcoma nodules, with similar histological features. The intraparenchymal injection of tumour cells resulted in more reliable and reproducible tumour growth and was associated with a longer survival of the animals. i.v. injected tumours developed a PA-derived vascular tree whereas directly injected tumours developed a BA-derived vasculature. PMID:15905614

  4. Estimating population trends with a linear model

    USGS Publications Warehouse

    Bart, J.; Collins, B.; Morrison, R.I.G.

    2003-01-01

    We describe a simple and robust method for estimating trends in population size. The method may be used with Breeding Bird Survey data, aerial surveys, point counts, or any other program of repeated surveys at permanent locations. Surveys need not be made at each location during each survey period. The method differs from most existing methods in being design based, rather than model based. The only assumptions are that the nominal sampling plan is followed and that sample size is large enough for use of the t-distribution. Simulations based on two bird data sets from natural populations showed that the point estimate produced by the linear model was essentially unbiased even when counts varied substantially and 25% of the complete data set was missing. The estimating-equation approach, often used to analyze Breeding Bird Survey data, performed similarly on one data set but had substantial bias on the second data set, in which counts were highly variable. The advantages of the linear model are its simplicity, flexibility, and that it is self-weighting. A user-friendly computer program to carry out the calculations is available from the senior author.

  5. Entropy Based Modelling for Estimating Demographic Trends.

    PubMed

    Li, Guoqi; Zhao, Daxuan; Xu, Yi; Kuo, Shyh-Hao; Xu, Hai-Yan; Hu, Nan; Zhao, Guangshe; Monterola, Christopher

    2015-01-01

    In this paper, an entropy-based method is proposed to forecast the demographical changes of countries. We formulate the estimation of future demographical profiles as a constrained optimization problem, anchored on the empirically validated assumption that the entropy of age distribution is increasing in time. The procedure of the proposed method involves three stages, namely: 1) Prediction of the age distribution of a country's population based on an "age-structured population model"; 2) Estimation the age distribution of each individual household size with an entropy-based formulation based on an "individual household size model"; and 3) Estimation the number of each household size based on a "total household size model". The last stage is achieved by projecting the age distribution of the country's population (obtained in stage 1) onto the age distributions of individual household sizes (obtained in stage 2). The effectiveness of the proposed method is demonstrated by feeding real world data, and it is general and versatile enough to be extended to other time dependent demographic variables. PMID:26382594

  6. Model-based estimation of individual fitness

    USGS Publications Warehouse

    Link, W.A.; Cooch, E.G.; Cam, E.

    2002-01-01

    Fitness is the currency of natural selection, a measure of the propagation rate of genotypes into future generations. Its various definitions have the common feature that they are functions of survival and fertility rates. At the individual level, the operative level for natural selection, these rates must be understood as latent features, genetically determined propensities existing at birth. This conception of rates requires that individual fitness be defined and estimated by consideration of the individual in a modelled relation to a group of similar individuals; the only alternative is to consider a sample of size one, unless a clone of identical individuals is available. We present hierarchical models describing individual heterogeneity in survival and fertility rates and allowing for associations between these rates at the individual level. We apply these models to an analysis of life histories of Kittiwakes (Rissa tridactyla) observed at several colonies on the Brittany coast of France. We compare Bayesian estimation of the population distribution of individual fitness with estimation based on treating individual life histories in isolation, as samples of size one (e.g. McGraw and Caswell, 1996).

  7. Model-based estimation of individual fitness

    USGS Publications Warehouse

    Link, W.A.; Cooch, E.G.; Cam, E.

    2002-01-01

    Fitness is the currency of natural selection, a measure of the propagation rate of genotypes into future generations. Its various definitions have the common feature that they are functions of survival and fertility rates. At the individual level, the operative level for natural selection, these rates must be understood as latent features, genetically determined propensities existing at birth. This conception of rates requires that individual fitness be defined and estimated by consideration of the individual in a modelled relation to a group of similar individuals; the only alternative is to consider a sample of size one, unless a clone of identical individuals is available. We present hierarchical models describing individual heterogeneity in survival and fertility rates and allowing for associations between these rates at the individual level. We apply these models to an analysis of life histories of Kittiwakes (Rissa tridactyla ) observed at several colonies on the Brittany coast of France. We compare Bayesian estimation of the population distribution of individual fitness with estimation based on treating individual life histories in isolation, as samples of size one (e.g. McGraw & Caswell, 1996).

  8. Ischaemia-related cell damage in extracorporeal preserved tissue – new findings with a novel perfusion model

    PubMed Central

    Taeger, Christian D; Müller-Seubert, Wibke; Horch, Raymund E; Präbst, Konstantin; Münch, Frank; Geppert, Carol I; Birkholz, Torsten; Dragu, Adrian

    2014-01-01

    Tissue undergoing free transfer in transplant or reconstructive surgery always is at high risk of ischaemia-related cell damage. This study aims at assessing different procedures using an extracorporeal perfusion and oxygenation system to investigate the expression of hypoxia inducible factor (HIF)-1-α as marker for hypoxia and of the pro-apoptotic protein Caspase-3 in skeletal muscle to elucidate potential improvements in tissue conservation. Twenty-four porcine rectus abdominis muscles were assigned to five different groups and examined after they had been extracorporeally preserved for 60 min. time. Group I was left untreated (control), group II was perfused with a cardioplegic solution, group III was flushed with 10 ml of a cardioplegic solution and then left untreated. Group IV and V were perfused and oxygenated with either an isotone crystalloid solution or a cardioplegic solution. Among others, immunohistochemistry (Caspase-3 and HIF-1-α) of muscle samples was performed. Furthermore, oxygen partial pressure in the perfusate at the arterial and venous branch was measured. Expression of Caspase-3 after 60 min. was reduced in all groups compared to the control group. Furthermore, all groups (except group III) expressed less HIF-1-α than the control group. Oxygenation leads to higher oxygen levels at the venous branch compared to groups without oxygenation. Using an extracorporeal perfusion and oxygenation system cell damage could be reduced as indicated by stabilized expressions of Caspase-3 and HIF-1-α for 60 min. of tissue preservation. Complete depletion of oxygen at the venous branch can be prevented by oxygenation of the perfusate with ambient air. PMID:24636195

  9. Heritability Estimation using Regression Models for Correlation

    PubMed Central

    Lee, Hye-Seung; Paik, Myunghee Cho; Rundek, Tatjana; Sacco, Ralph L; Dong, Chuanhui; Krischer, Jeffrey P

    2012-01-01

    Heritability estimates a polygenic effect on a trait for a population. Reliable interpretation of heritability is critical in planning further genetic studies to locate a gene responsible for the trait. This study accommodates both single and multiple trait cases by employing regression models for correlation parameter to infer the heritability. Sharing the properties of regression approach, the proposed methods are exible to incorporate non-genetic and/or non-additive genetic information in the analysis. The performances of the proposed model are compared with those using the likelihood approach through simulations and carotid Intima Media Thickness analysis from Northern Manhattan family Study. PMID:22457844

  10. Uncertainty estimation in reconstructed deformable models

    SciTech Connect

    Hanson, K.M.; Cunningham, G.S.; McKee, R.

    1996-12-31

    One of the hallmarks of the Bayesian approach to modeling is the posterior probability, which summarizes all uncertainties regarding the analysis. Using a Markov Chain Monte Carlo (MCMC) technique, it is possible to generate a sequence of objects that represent random samples drawn from the posterior distribution. We demonstrate this technique for reconstructions of two-dimensional objects from noisy projections taken from two directions. The reconstructed object is modeled in terms of a deformable geometrically-defined boundary with a constant interior density yielding a nonlinear reconstruction problem. We show how an MCMC sequence can be used to estimate uncertainties in the location of the edge of the reconstructed object.

  11. A new estimator method for GARCH models

    NASA Astrophysics Data System (ADS)

    Onody, R. N.; Favaro, G. M.; Cazaroto, E. R.

    2007-06-01

    The GARCH (p, q) model is a very interesting stochastic process with widespread applications and a central role in empirical finance. The Markovian GARCH (1, 1) model has only 3 control parameters and a much discussed question is how to estimate them when a series of some financial asset is given. Besides the maximum likelihood estimator technique, there is another method which uses the variance, the kurtosis and the autocorrelation time to determine them. We propose here to use the standardized 6th moment. The set of parameters obtained in this way produces a very good probability density function and a much better time autocorrelation function. This is true for both studied indexes: NYSE Composite and FTSE 100. The probability of return to the origin is investigated at different time horizons for both Gaussian and Laplacian GARCH models. In spite of the fact that these models show almost identical performances with respect to the final probability density function and to the time autocorrelation function, their scaling properties are, however, very different. The Laplacian GARCH model gives a better scaling exponent for the NYSE time series, whereas the Gaussian dynamics fits better the FTSE scaling exponent.

  12. Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models

    NASA Astrophysics Data System (ADS)

    Shitzer, Avraham; Arens, Edward; Zhang, Hui

    2015-11-01

    The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.

  13. Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models.

    PubMed

    Shitzer, Avraham; Arens, Edward; Zhang, Hui

    2016-07-01

    The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and

  14. Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models

    NASA Astrophysics Data System (ADS)

    Shitzer, Avraham; Arens, Edward; Zhang, Hui

    2016-07-01

    The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.

  15. On Bayesian estimation of marginal structural models.

    PubMed

    Saarela, Olli; Stephens, David A; Moodie, Erica E M; Klein, Marina B

    2015-06-01

    The purpose of inverse probability of treatment (IPT) weighting in estimation of marginal treatment effects is to construct a pseudo-population without imbalances in measured covariates, thus removing the effects of confounding and informative censoring when performing inference. In this article, we formalize the notion of such a pseudo-population as a data generating mechanism with particular characteristics, and show that this leads to a natural Bayesian interpretation of IPT weighted estimation. Using this interpretation, we are able to propose the first fully Bayesian procedure for estimating parameters of marginal structural models using an IPT weighting. Our approach suggests that the weights should be derived from the posterior predictive treatment assignment and censoring probabilities, answering the question of whether and how the uncertainty in the estimation of the weights should be incorporated in Bayesian inference of marginal treatment effects. The proposed approach is compared to existing methods in simulated data, and applied to an analysis of the Canadian Co-infection Cohort. PMID:25677103

  16. Parameter Estimation of Spacecraft Fuel Slosh Model

    NASA Technical Reports Server (NTRS)

    Gangadharan, Sathya; Sudermann, James; Marlowe, Andrea; Njengam Charles

    2004-01-01

    Fuel slosh in the upper stages of a spinning spacecraft during launch has been a long standing concern for the success of a space mission. Energy loss through the movement of the liquid fuel in the fuel tank affects the gyroscopic stability of the spacecraft and leads to nutation (wobble) which can cause devastating control issues. The rate at which nutation develops (defined by Nutation Time Constant (NTC can be tedious to calculate and largely inaccurate if done during the early stages of spacecraft design. Pure analytical means of predicting the influence of onboard liquids have generally failed. A strong need exists to identify and model the conditions of resonance between nutation motion and liquid modes and to understand the general characteristics of the liquid motion that causes the problem in spinning spacecraft. A 3-D computerized model of the fuel slosh that accounts for any resonant modes found in the experimental testing will allow for increased accuracy in the overall modeling process. Development of a more accurate model of the fuel slosh currently lies in a more generalized 3-D computerized model incorporating masses, springs and dampers. Parameters describing the model include the inertia tensor of the fuel, spring constants, and damper coefficients. Refinement and understanding the effects of these parameters allow for a more accurate simulation of fuel slosh. The current research will focus on developing models of different complexity and estimating the model parameters that will ultimately provide a more realistic prediction of Nutation Time Constant obtained through simulation.

  17. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion.

    PubMed

    Bell, Robert M; Mocanu, Mihaela M; Yellon, Derek M

    2011-06-01

    In the late 19th century, a number of investigators were working on perfecting isolated heart model, but it was Oscar Langendorff who, in 1895, pioneered the isolated perfused mammalian heart. Since that time, the Langendorff preparation has evolved and provided a wealth of data underpinning our understanding of the fundamental physiology of the heart: its contractile function, coronary blood flow regulation and cardiac metabolism. In more recent times, the procedure has been used to probe pathophysiology of ischaemia/reperfusion and disease states, and with the dawn of molecular biology and genetic manipulation, the Langendorff perfused heart has remained a stalwart tool in the study of the impact upon the physiology of the heart by pharmacological inhibitors and targeted deletion or up-regulation of genes and their impact upon intracellular signalling and adaption to clinically relevant stressful stimuli. We present here the basic structure of the Langendorff system and the fundamental experimental rules which warrant a viable heart preparation. In addition, we discuss the use of the isolated retrograde perfused heart in the model of ischaemia-reperfusion injury ex-vivo, and its applicability to other areas of study. The Langendorff perfusion apparatus is highly adaptable and this is reflected not only in the procedure's longevity but also in the number of different applications to which it has been turned. PMID:21385587

  18. Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

  19. Cost-efficacy modeling of functional testing with perfusion imaging to detect asymptomatic restenosis following percutaneous transluminal coronary angioplasty.

    PubMed

    Mak, K H; Eisenberg, M J; Shaw, J

    1999-12-01

    The objective of this study was to perform a theoretical cost-efficacy analysis on the use of routine functional testing with perfusion imaging to identify patients with asymptomatic restenosis following percutaneous transluminal coronary angioplasty (PTCA) procedures. Approximately 50% of patients with restenosis following PTCA are asymptomatic. Routine functional testing is commonly performed at 3 to 6 months to identify these patients. The cost-efficacy associated with this strategy is unknown. Theoretical models were constructed based on assumed costs for functional testing (U.S. $1,300) and coronary angiography (U.S. $3,000). Restenosis rates were assumed to be 40%, and half of patients with restenosis were assumed to be asymptomatic. To provide a range of costs to identify a patient with asymptomatic restenosis, three scenarios were constructed based on the diagnostic test characteristics of functional testing. Sensitivity analyses were performed using a range of costs for functional testing, restenosis rates, and proportion of patients with restenosis who are asymptomatic. Depending on the diagnostic accuracy of functional testing, it costs $8,200 to $22,400 to identify an asymptomatic patient with restenosis following PTCA. The cost to identify a patient with asymptomatic restenosis varies inversely with the rates of restenosis. When restenosis rates are < 20%, the cost to identify a patient with asymptomatic restenosis exceeds $10,000. Similarly, the cost to identify a patient with asymptomatic restenosis increases when the proportion of patients with asymptomatic restenosis decreases. The cost, associated with the use of routine functional testing for the identification of asymptomatic patients with restenosis appears exorbitant. However, a formal study is warranted to determine the cost-efficacy of such a strategy. Cathet. Cardiovasc. Intervent. 48:352-356, 1999. PMID:10559811

  20. A three-dimensional computational fluid dynamics model of shear stress distribution during neotissue growth in a perfusion bioreactor.

    PubMed

    Guyot, Y; Luyten, F P; Schrooten, J; Papantoniou, I; Geris, L

    2015-12-01

    Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the scaffold pores leading a fully filled scaffold following the scaffold's geometric characteristics. Current computational fluid dynamic approaches for tissue engineering bioreactor systems have been mostly carried out for empty scaffolds. The effect of 3D cell growth and extracellular matrix formation (termed in this study as neotissue growth), on its surrounding fluid flow field is a challenge yet to be tackled. In this work a combined approach was followed linking curvature driven cell growth to fluid dynamics modeling. The level-set method (LSM) was employed to capture neotissue growth driven by curvature, while the Stokes and Darcy equations, combined in the Brinkman equation, provided information regarding the distribution of the shear stress profile at the neotissue/medium interface and within the neotissue itself during growth. The neotissue was assumed to be micro-porous allowing flow through its structure while at the same time allowing the simulation of complete scaffold filling without numerical convergence issues. The results show a significant difference in the amplitude of shear stress for cells located within the micro-porous neo-tissue or at the neotissue/medium interface, demonstrating the importance of taking along the neotissue in the calculation of the mechanical stimulation of cells during culture.The presented computational framework is used on different scaffold pore geometries demonstrating its potential to be used a design as tool for scaffold architecture taking into account the growing neotissue. Biotechnol. Bioeng. 2015;112: 2591-2600. © 2015 Wiley Periodicals, Inc. PMID:26059101

  1. Characterization of bone perfusion by dynamic contrast-enhanced magnetic resonance imaging and positron emission tomography in the Dunkin-Hartley guinea pig model of advanced osteoarthritis.

    PubMed

    Dyke, Jonathan P; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K

    2015-03-01

    This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523

  2. Characterization of Bone Perfusion by Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Positron Emission Tomography in the Dunkin-Hartley Guinea Pig Model of Advanced Osteoarthritis

    PubMed Central

    Dyke, Jonathan P.; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K.

    2014-01-01

    Purpose This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. Methods We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Results Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. Discussion MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523

  3. Assessing the repair of critical size bone defects performed in a goat tibia model using tissue-engineered constructs cultured in a bidirectional flow perfusion bioreactor.

    PubMed

    Gardel, Ls; Afonso, M; Frias, C; Gomes, Me; Reis, Rl

    2014-01-01

    This work evaluated in vivo performance of a tissue-engineered bone-like matrix obtained by culturing cell-scaffold constructs in a flow perfusion bioreactor, designed to enable culture of large constructs, envisioning the regeneration of critical-sized defects. A blend of starch with polycaprolactone scaffolds was seeded with goat bone marrow stromal cells (GBMSCs) cultured in the perfusion bioreactor for 14 days using osteogenic medium. Cell seeded scaffolds cultured in static conditions acted as controls. After 14 days, constructs (42 mm length and 16 mm in diameter) were implanted in critical size defects performed in the tibial bone of six adult goats from which the bone marrow had been collected previously. Explants were retrieved after six and 12 weeks of implantation and characterized using scanning electron microscopy, energy-dispersive spectroscopy, micro-computed tomography and radiographic analysis to assess tissue morphology and calcification. Explants were histologically analyzed, using Hematoxylin & Eosin and Masson Trichrome staining. Results provided relevant information about the performance and functionality of starch with polycaprolactone-goat bone marrow stromal cell constructs in a critical size orthotopic defect performed in a large animal model and demonstrated that culture of the starch with polycaprolactone scaffolds with the autologous cells in perfusion culture provide a good therapy for the healing and regenerative process of bone defects. PMID:24413026

  4. A weakly acidic solution containing deoxycholic acid induces esophageal epithelial apoptosis and impairs integrity in an in vivo perfusion rabbit model.

    PubMed

    Pardon, Nicolas A; Vicario, Maria; Vanheel, Hanne; Vanuytsel, Tim; Ceulemans, Laurens J; Vieth, Michael; Jimenez, Marcel; Tack, Jan; Farré, Ricard

    2016-04-01

    Impaired esophageal mucosal integrity may be an important contributor in the pathophysiology of gastroesophageal reflux disease (GERD). Nevertheless, the effect of potentially harmful agents on epithelial integrity is mainly evaluated in vitro for a short period of time and the possible induction of epithelial apoptosis has been neglected. Our objective was to assess the effect of an acidic and weakly acidic solution containing deoxycholic acid (DCA) on the esophageal epithelium in an in vivo rabbit model of esophageal perfusion and to evaluate the role of the epithelial apoptosis. The esophagus of 55 anesthetized rabbits was perfused for 30 min with different solutions at pH 7.2, pH 5.0, pH 1.0, and pH 5.0 containing 200 and 500 μM DCA. Thereafter, animals were euthanized immediately or at 24 or 48 h after the perfusion. Transepithelial electrical resistance, epithelial dilated intercellular spaces, and apoptosis were assessed in Ussing chambers, by transmission electron microscopy, and by TUNEL staining, respectively. No macroscopic or major microscopic alterations were observed after the esophageal perfusions. The acidic and weakly acidic solution containing DCA induced similar long-lasting functional impairment of the epithelial integrity but different ultrastructural morphological changes. Only the solution containing DCA induced epithelial apoptosis in vivo and in vitro in rabbit and human tissue. In contrast to acid, a weakly acidic solution containing DCA induces epithelial apoptosis and a long-lasting impaired mucosal integrity. The presence of apoptotic cells in the esophageal epithelium may be used as a marker of impaired integrity and/or bile reflux exposure. PMID:26797397

  5. Migration of bone marrow-derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction

    PubMed Central

    Brunner, Stefan; Huber, Bruno C; Weinberger, Tobias; Vallaster, Marcus; Wollenweber, Tim; Gerbitz, Armin; Hacker, Marcus; Franz, Wolfgang-Michael

    2012-01-01

    Abstract Erythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor-dependent mechanisms, mobilization and homing of bone marrow-derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO-treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c-kit, CXCR-4 and Sca-1) of EGFP+ cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single-photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO-treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO-treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR-4+ (4.3-fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively. PMID:21362129

  6. Model estimates hurricane wind speed probabilities

    NASA Astrophysics Data System (ADS)

    Mumane, Richard J.; Barton, Chris; Collins, Eric; Donnelly, Jeffrey; Eisner, James; Emanuel, Kerry; Ginis, Isaac; Howard, Susan; Landsea, Chris; Liu, Kam-biu; Malmquist, David; McKay, Megan; Michaels, Anthony; Nelson, Norm; O Brien, James; Scott, David; Webb, Thompson, III

    In the United States, intense hurricanes (category 3, 4, and 5 on the Saffir/Simpson scale) with winds greater than 50 m s -1 have caused more damage than any other natural disaster [Pielke and Pielke, 1997]. Accurate estimates of wind speed exceedance probabilities (WSEP) due to intense hurricanes are therefore of great interest to (re)insurers, emergency planners, government officials, and populations in vulnerable coastal areas.The historical record of U.S. hurricane landfall is relatively complete only from about 1900, and most model estimates of WSEP are derived from this record. During the 1899-1998 period, only two category-5 and 16 category-4 hurricanes made landfall in the United States. The historical record therefore provides only a limited sample of the most intense hurricanes.

  7. Selection and estimation for mixed graphical models

    PubMed Central

    Chen, Shizhe; Witten, Daniela M.; shojaie, Ali

    2016-01-01

    Summary We consider the problem of estimating the parameters in a pairwise graphical model in which the distribution of each node, conditioned on the others, may have a different exponential family form. We identify restrictions on the parameter space required for the existence of a well-defined joint density, and establish the consistency of the neighbourhood selection approach for graph reconstruction in high dimensions when the true underlying graph is sparse. Motivated by our theoretical results, we investigate the selection of edges between nodes whose conditional distributions take different parametric forms, and show that efficiency can be gained if edge estimates obtained from the regressions of particular nodes are used to reconstruct the graph. These results are illustrated with examples of Gaussian, Bernoulli, Poisson and exponential distributions. Our theoretical findings are corroborated by evidence from simulation studies.

  8. Validation of Kp Estimation and Prediction Models

    NASA Astrophysics Data System (ADS)

    McCollough, J. P., II; Young, S. L.; Frey, W.

    2014-12-01

    Specifification and forecast of geomagnetic indices is an important capability for space weather operations. The University Partnering for Operational Support (UPOS) effort at the Applied Physics Laboratory of Johns Hopkins University (JHU/APL) produced many space weather models, including the Kp Predictor and Kp Estimator. We perform a validation of index forecast products against definitive indices computed by the Deutches GeoForschungsZentstrum Potsdam (GFZ). We compute continuous predictant skill scores, as well as 2x2 contingency tables and associated scalar quantities for different index thresholds. We also compute a skill score against a nowcast persistence model. We discuss various sources of error for the models and how they may potentially be improved.

  9. Parameter Estimation for Viscoplastic Material Modeling

    NASA Technical Reports Server (NTRS)

    Saleeb, Atef F.; Gendy, Atef S.; Wilt, Thomas E.

    1997-01-01

    A key ingredient in the design of engineering components and structures under general thermomechanical loading is the use of mathematical constitutive models (e.g. in finite element analysis) capable of accurate representation of short and long term stress/deformation responses. In addition to the ever-increasing complexity of recent viscoplastic models of this type, they often also require a large number of material constants to describe a host of (anticipated) physical phenomena and complicated deformation mechanisms. In turn, the experimental characterization of these material parameters constitutes the major factor in the successful and effective utilization of any given constitutive model; i.e., the problem of constitutive parameter estimation from experimental measurements.

  10. 3D functional and perfusable microvascular networks for organotypic microfluidic models.

    PubMed

    Bersini, Simone; Moretti, Matteo

    2015-05-01

    The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases. PMID:25893395

  11. Quantitative Cardiac Perfusion: A Noninvasive Spin-labeling Method That Exploits Coronary Vessel Geometry1

    PubMed Central

    Reeder, Scott B.; Atalay, Michael K.; McVeigh, Elliot R.; Zerhouni, Elias A.; Forder, John R.

    2007-01-01

    PURPOSE: To quantitate myocardial arterial perfusion with a noninvasive magnetic resonance (MR) imaging technique that exploits the geometry of coronary vessel anatomy. MATERIALS AND METHODS: MR imaging was performed with a spinlabeling method in six arrested rabbit hearts at 4.7 T. Selective inversion of magnetization in the short-axis imaging section along with all myocardium apical to that section produces signal enhancement from arterial perfusion. A linescan protocol was used for validation of flow enhancement. Flow was quantitated from two images and validated with spin-echo (SE) imaging. Regional perfusion defects were created by means of coronary artery ligation and delineated with gadolinium-enhanced imaging. RESULTS: Linescan estimates of T1 obtained at physiologic flows agreed with model predictions. Flow-induced signal enhancement measured on SE images also agreed with expected values. Finally, perfusion abnormalities created by means of coronary artery ligation were detected. CONCLUSION: This spin-labeling method provides quantitative estimates of myocardial arterial perfusion in this model and may hold promise for clinical applications. PMID:8657907

  12. Solar sails: Modeling, estimation, and trajectory control

    NASA Astrophysics Data System (ADS)

    Rios-Reyes, Leonel

    There has been great interest in developing solar sail technology and missions by several international space agencies in recent years. However, at present there is no consensus on how one can mathematically model forces and moments acting on a solar sail. Traditional analytical models and finite element methods are not feasible for integration into a precise navigation system. This dissertation takes a step toward resolving this issue by developing tools and concepts that can be integrated into a precise solar sail navigation system. These steps are the derivation of a generalized sail model, a linear estimation method for estimating and predicting forces and moments acting on a solar sail, and a new trajectory control methodology for tracking a nominal trajectory when the sail performance exceeds the nominal design performance. The main contributions of this dissertation follow. First, the generalized sail model (GSM) is defined to analytically describe the forces and moments acting on a solar sail of arbitrary shape. The GSM is derived by performing an integration, of all the differential forces and moments acting on the sail, over the sail surface. Next, the GSM is applied to several examples to illustrate the use of the GSM's analytic equations. These examples allow comparisons of forces and moments generated by different solar sails, the computation of force derivatives, and the application of the model to orbital mechanics problems. Since it is difficult to model the sail geometry based on ground measurements; errors in the sail model are expected once the sail is deployed in space. Due to this difficulty; a least-squares estimation method for the force and moment coefficients of the GSM is derived. For realistic implementation of a sail trajectory, the deployed sail must have an excess thrust capacity. We develop and implement a control methodology for flying a nominal mission profile with such an excess capacity. Control laws for maintaining a flat, ideal

  13. Regression models for estimating coseismic landslide displacement

    USGS Publications Warehouse

    Jibson, R.W.

    2007-01-01

    Newmark's sliding-block model is widely used to estimate coseismic slope performance. Early efforts to develop simple regression models to estimate Newmark displacement were based on analysis of the small number of strong-motion records then available. The current availability of a much larger set of strong-motion records dictates that these regression equations be updated. Regression equations were generated using data derived from a collection of 2270 strong-motion records from 30 worldwide earthquakes. The regression equations predict Newmark displacement in terms of (1) critical acceleration ratio, (2) critical acceleration ratio and earthquake magnitude, (3) Arias intensity and critical acceleration, and (4) Arias intensity and critical acceleration ratio. These equations are well constrained and fit the data well (71% < R2 < 88%), but they have standard deviations of about 0.5 log units, such that the range defined by the mean ?? one standard deviation spans about an order of magnitude. These regression models, therefore, are not recommended for use in site-specific design, but rather for regional-scale seismic landslide hazard mapping or for rapid preliminary screening of sites. ?? 2007 Elsevier B.V. All rights reserved.

  14. Quantification of myocardial perfusion based on signal intensity of flow sensitized MRI

    NASA Astrophysics Data System (ADS)

    Abeykoon, Sumeda B.

    maximum percentage deviation is about 5%. Then the SI-method was used in comparison to a delayed enhanced method to qualitatively and quantitatively assess perfusion deficits in an ischemia-reperfusion (IR) mouse model. The infarcted region of the perfusion map is comparable to the hyper intense region of the delayed enhanced image of the IR mouse. The SI method also used to record a chronological comparison of perfusion on delta sarcoglycan null (DSG) mice. Perfusion of DSG and wild-type (WT) mice at ages of 12 weeks and 32 weeks were compared and percentage change of perfusion was estimated. The result shows that in DSG mice perfusion changes considerably. Finally, the SI method was implemented on a 3 Tesla Philip scanner by modifying to data acquisition method. The perfusion obtained in this is consistent with literature values but further adjustment of pulse sequence and modification of numerical solution is needed. The most important benefit of the SI method is that it reduces scan time 30%--40% and lessens motion artifacts of images compared to the T1 method. This study demonstrates that the signal intensity-based ASL method is a robust alternative to the conventional T1-method.

  15. Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling

    PubMed Central

    Chapman, Lloyd A. C.; Shipley, Rebecca J.; Whiteley, Jonathan P.; Ellis, Marianne J.; Byrne, Helen M.; Waters, Sarah L.

    2014-01-01

    The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges to (equivalent to to ) and to (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells. PMID:25157635

  16. Nonlinear models for estimating GSFC travel requirements

    NASA Technical Reports Server (NTRS)

    Buffalano, C.; Hagan, F. J.

    1974-01-01

    A methodology is presented for estimating travel requirements for a particular period of time. Travel models were generated using nonlinear regression analysis techniques on a data base of FY-72 and FY-73 information from 79 GSFC projects. Although the subject matter relates to GSFX activities, the type of analysis used and the manner of selecting the relevant variables would be of interest to other NASA centers, government agencies, private corporations and, in general, any organization with a significant travel budget. Models were developed for each of six types of activity: flight projects (in-house and out-of-house), experiments on non-GSFC projects, international projects, ART/SRT, data analysis, advanced studies, tracking and data, and indirects.

  17. A mathematical model and computational framework for three-dimensional chondrocyte cell growth in a porous tissue scaffold placed inside a bi-directional flow perfusion bioreactor.

    PubMed

    Shakhawath Hossain, Md; Bergstrom, D J; Chen, X B

    2015-12-01

    The in vitro chondrocyte cell culture for cartilage tissue regeneration in a perfusion bioreactor is a complex process. Mathematical modeling and computational simulation can provide important insights into the culture process, which would be helpful for selecting culture conditions to improve the quality of the developed tissue constructs. However, simulation of the cell culture process is a challenging task due to the complicated interaction between the cells and local fluid flow and nutrient transport inside the complex porous scaffolds. In this study, a mathematical model and computational framework has been developed to simulate the three-dimensional (3D) cell growth in a porous scaffold placed inside a bi-directional flow perfusion bioreactor. The model was developed by taking into account the two-way coupling between the cell growth and local flow field and associated glucose concentration, and then used to perform a resolved-scale simulation based on the lattice Boltzmann method (LBM). The simulation predicts the local shear stress, glucose concentration, and 3D cell growth inside the porous scaffold for a period of 30 days of cell culture. The predicted cell growth rate was in good overall agreement with the experimental results available in the literature. This study demonstrates that the bi-directional flow perfusion culture system can enhance the homogeneity of the cell growth inside the scaffold. The model and computational framework developed is capable of providing significant insight into the culture process, thus providing a powerful tool for the design and optimization of the cell culture process. PMID:26061385

  18. Comparisons of Four Methods for Estimating a Dynamic Factor Model

    ERIC Educational Resources Information Center

    Zhang, Zhiyong; Hamaker, Ellen L.; Nesselroade, John R.

    2008-01-01

    Four methods for estimating a dynamic factor model, the direct autoregressive factor score (DAFS) model, are evaluated and compared. The first method estimates the DAFS model using a Kalman filter algorithm based on its state space model representation. The second one employs the maximum likelihood estimation method based on the construction of a…

  19. Estimating Resolution Lengths of Hybrid Turbulence Models

    NASA Technical Reports Server (NTRS)

    Abdol-Hamid, Khaled S.; Girimaji, Sharath S.

    2006-01-01

    A two-stage procedure has been devised for estimating the spatial resolution achievable in the simulation of a given flow on a given computational grid by a computational fluid dynamics (CFD) code that incorporates a hybrid model of turbulence. The hybrid models to which this procedure is especially relevant are those of the Reynolds-averaged Navier-Stokes (RANS) and the partial-averaged Navier-Stokes (PANS) approaches. This procedure represents the first step toward adding variable-resolution turbulence-modeling capabilities to CFD codes as part of a continuing effort to increase the accuracy and robustness of CFD simulations of unsteady flows. Some background information is prerequisite to a meaningful summary of the procedure. Among experts in CFD, it is well known that combination of the Reynolds-averaged Navier-Stokes (RANS) approach and eddy-viscosity turbulence models offers limited capability for simulating unsteady and complex flows. The RANS approach includes an assumption that most of the energy in a given flow is modeled through turbulence-transport equations and is resolved in a computational grid used to simulate the flow. RANS also overpredicts eddy viscosity, thereby yielding excessive damping of unsteady motion. The eddy viscosity attains an unphysically large value because of unresolved scales, and suppresses most temporal and spatial fluctuations in the resolved flow field. One approach used to overcome this deficiency is to provide a mechanism for the RANS equations to resolve motion only on the largest scales and to use a hybrid model to represent effects at smaller scales. The RANS approach involves the use of a standard two-equation turbulence model in which the effect of turbulence is summarized by a viscosity that is a function of (1) the time-averaged kinetic- energy density (k) associated with the local fluctuating (turbulent) component of flow and (2) the time-averaged rate of dissipation of the turbulent-kinetic- energy density ( ). In

  20. Deformation simulation of cells seeded on a collagen-GAG scaffold in a flow perfusion bioreactor using a sequential 3D CFD-elastostatics model.

    PubMed

    Jungreuthmayer, C; Jaasma, M J; Al-Munajjed, A A; Zanghellini, J; Kelly, D J; O'Brien, F J

    2009-05-01

    Tissue-engineered bone shows promise in meeting the huge demand for bone grafts caused by up to 4 million bone replacement procedures per year, worldwide. State-of-the-art bone tissue engineering strategies use flow perfusion bioreactors to apply biophysical stimuli to cells seeded on scaffolds and to grow tissue suitable for implantation into the patient's body. The aim of this study was to quantify the deformation of cells seeded on a collagen-GAG scaffold which was perfused by culture medium inside a flow perfusion bioreactor. Using a microCT scan of an unseeded collagen-GAG scaffold, a sequential 3D CFD-deformation model was developed. The wall shear stress and the hydrostatic wall pressure acting on the cells were computed through the use of a CFD simulation and fed into a linear elastostatics model in order to calculate the deformation of the cells. The model used numerically seeded cells of two common morphologies where cells are either attached flatly on the scaffold wall or bridging two struts of the scaffold. Our study showed that the displacement of the cells is primarily determined by the cell morphology. Although cells of both attachment profiles were subjected to the same mechanical load, cells bridging two struts experienced a deformation up to 500 times higher than cells only attached to one strut. As the scaffold's pore size determines both the mechanical load and the type of attachment, the design of an optimal scaffold must take into account the interplay of these two features and requires a design process that optimizes both parameters at the same time. PMID:19109048

  1. The Mayfield method of estimating nesting success: A model, estimators and simulation results

    USGS Publications Warehouse

    Hensler, G.L.; Nichols, J.D.

    1981-01-01

    Using a nesting model proposed by Mayfield we show that the estimator he proposes is a maximum likelihood estimator (m.l.e.). M.l.e. theory allows us to calculate the asymptotic distribution of this estimator, and we propose an estimator of the asymptotic variance. Using these estimators we give approximate confidence intervals and tests of significance for daily survival. Monte Carlo simulation results show the performance of our estimators and tests under many sets of conditions. A traditional estimator of nesting success is shown to be quite inferior to the Mayfield estimator. We give sample sizes required for a given accuracy under several sets of conditions.

  2. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.

    PubMed

    Wang, Kai; Zhou, Xiaorong; Huang, Yanming; Khalil, Mazen; Wiktor, Dominik; van Giezen, J J J; Penn, Marc S

    2010-09-01

    Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. PMID:20694285

  3. Estimation Methods for One-Parameter Testlet Models

    ERIC Educational Resources Information Center

    Jiao, Hong; Wang, Shudong; He, Wei

    2013-01-01

    This study demonstrated the equivalence between the Rasch testlet model and the three-level one-parameter testlet model and explored the Markov Chain Monte Carlo (MCMC) method for model parameter estimation in WINBUGS. The estimation accuracy from the MCMC method was compared with those from the marginalized maximum likelihood estimation (MMLE)…

  4. Benefit Estimation Model for Tourist Spaceflights

    NASA Astrophysics Data System (ADS)

    Goehlich, Robert A.

    2003-01-01

    It is believed that the only potential means for significant reduction of the recurrent launch cost, which results in a stimulation of human space colonization, is to make the launcher reusable, to increase its reliability, and to make it suitable for new markets such as mass space tourism. But such space projects, that have long range aspects are very difficult to finance, because even politicians would like to see a reasonable benefit during their term in office, because they want to be able to explain this investment to the taxpayer. This forces planners to use benefit models instead of intuitive judgement to convince sceptical decision-makers to support new investments in space. Benefit models provide insights into complex relationships and force a better definition of goals. A new approach is introduced in the paper that allows to estimate the benefits to be expected from a new space venture. The main objective why humans should explore space is determined in this study to ``improve the quality of life''. This main objective is broken down in sub objectives, which can be analysed with respect to different interest groups. Such interest groups are the operator of a space transportation system, the passenger, and the government. For example, the operator is strongly interested in profit, while the passenger is mainly interested in amusement, while the government is primarily interested in self-esteem and prestige. This leads to different individual satisfactory levels, which are usable for the optimisation process of reusable launch vehicles.

  5. ARM Climate Modeling Best Estimate Data

    SciTech Connect

    Xie, S.; Jensen, M.; McCoy, R. B.; Klein, S. A.; Cederwall, R. T.; Wiscombe, W. J.; Clothiaux, E. E.; Gaustad, K. L.; Golaz, J.-C.; Hall, S.; Johnson, K. L.; Lin, Y.; Long, C. N.; Mather, J. H.; McCord, R. A.; McFarlane, S. A.; Palanisamy, G.; Shi, Y.; Turner, D. D.

    2010-01-01

    can hamper the use of ACRF data by the climate community. To make ACRF data better serve the needs of climate studies and model development, ARM has developed a data product specifically tailored for use by the climate community. The new data product, named the Climate Modeling Best Estimate (CMBE) dataset, assembles those quantities that are both well observed by ACRF over many years and are often used in model evaluation into one single dataset. The CMBE product consists of hourly averages and thus has temporal resolution comparable to a typical resolution used in climate model output. It also includes standard deviations within the averaged hour and quality control flags for the selected quantities to indicate the temporal variability and data quality. Since its initial release in February 2008, the new data product has quickly drawn the attention of the climate modeling community. It is being used for model evaluation by two major U.S. climate modeling centers, the National Center for Atmospheric Research (NCAR) and the Geophysical Fluid Dynamics Laboratory (GFDL). The purpose of this paper is to provide an overview of CMBE data and a few examples that demonstrate the potential value of CMBE data for climate modeling and in studies of cloud processes and climate variability and change.

  6. A novel technique for simultaneous whole-body and multi-organ decellularization: umbilical artery catheterization as a perfusion-based method in a sheep foetus model.

    PubMed

    Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Akbarzadeh, Aram; Sabetkish, Shabnam; Sabetkish, Nastaran; Saadat, Paria; Tehrani, Mona

    2015-04-01

    The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body. PMID:26031202

  7. Development of a dynamic model for real-time determination of membrane-bound acetylcholinesterase activity upon perfusion with inhibitors and reactivators.

    PubMed

    Eckert, Saskia; Eyer, Peter; Mückter, Harald; Worek, Franz

    2006-07-28

    Quantitative predictions of the course of acetylcholinesterase (AChE) activity, following interference of inhibitors and reactivators, are usually obscured by the time-dependent changes of all reaction partners. To mimic these dynamics we developed an in vitro model. Immobilized human erythrocyte ghosts in a bioreactor were continuously perfused while AChE activity was monitored by a modified Ellman method. The perfusion system consisted of two HPLC pumps with integrated quaternary low-pressure gradient formers that were programmed by a computer using commercial HPLC software. The combined eluates passed a particle filter (Millex-GS, 0.22 microm) containing a thin layer of erythrocytes that was immersed in a temperature-controlled water bath. The effluent passed a flow cell in a UV-vis detector, the signal of which was digitized, written to disc and calculated with curve fitting programs. AChE activity decreased by 3.4% within 2.5 h. The day-to-day variation of the freshly prepared bioreactor using the same enzyme source was +/-3.3%. Residual activity of 0.2% marked the limit of quantification. Following perfusion with paraoxon, pseudo first-order rate constants of inhibition were established that did not differ from results obtained in conventional assays. The same holds true for reactivation with obidoxime. The set-up presented allows freely programmable time-dependent changes of up to eight solvents to mimic pharmacokinetic profiles without accumulation of products. Due to some hysteresis in the system, reaction half-lives should be >3 min and concentration changes in critical compounds should exceed half-lives of 5 min. Otherwise, the system offers much flexibility and operates with high precision. PMID:16725113

  8. A novel technique for simultaneous whole-body and multi-organ decellularization: umbilical artery catheterization as a perfusion-based method in a sheep foetus model

    PubMed Central

    Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Akbarzadeh, Aram; Sabetkish, Shabnam; Sabetkish, Nastaran; Saadat, Paria; Tehrani, Mona

    2015-01-01

    The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body. PMID:26031202

  9. Optimising Golgi–Cox staining for use with perfusion-fixed brain tissue validated in the zQ175 mouse model of Huntington's disease

    PubMed Central

    Bayram-Weston, Zubeyde; Olsen, Elliott; Harrison, David J.; Dunnett, Stephen B.; Brooks, Simon P.

    2016-01-01

    Background The Golgi–Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured. New methods Conventional rapid Golgi and Golgi–Cox methods all require fresh impregnation in unfixed brain blocks. Here, we describe a modified method that gives high quality staining on brain tissue blocks perfusion-fixed with 4% paraformaldehyde (PFA) and post-fixed by immersion for 24 h. Results Tissue perfused with 4% PFA and post fixed for 24 h remained viable for the modified Golgi–Cox silver impregnation staining of mouse striatum from perfused wild type and zQ175. It was not found necessary to impregnate tissue blocks with Golgi solutions prior to sectioning, as post-sectioned tissues yielded equally good impregnation. Impregnation for 14 days resulted in optimal visualisation of striatal neuron and dendritic morphology. Although no modifications applied to the rapid Golgi method were reliable, the modified Golgi–Cox method yielded consistently reliable high-quality staining. Comparison with existing methods The current method used fixed tissues to reduce damage and preserve cell morphology. The revised method was found to be fast, reliable and cost effective without the need for expensive staining kits and could be performed in any neuroscience lab with limited specialist equipment. Conclusions The present study introduces a robust reproducible and inexpensive staining method for identifying neuronal morphological changes in the post fixed mouse brain, and is suitable for assessing changes in cell morphology in models of neurodegeneration and in response to experimental treatment. PMID:26459195

  10. Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

    SciTech Connect

    Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank

    2010-08-01

    Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.