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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. Estimating myocardial perfusion from dynamic contrast-enhanced CMR with a model-independent deconvolution method

    PubMed Central

    Pack, Nathan A; DiBella, Edward VR; Rust, Thomas C; Kadrmas, Dan J; McGann, Christopher J; Butterfield, Regan; Christian, Paul E; Hoffman, John M

    2008-01-01

    Background Model-independent analysis with B-spline regularization has been used to quantify myocardial blood flow (perfusion) in dynamic contrast-enhanced cardiovascular magnetic resonance (CMR) studies. However, the model-independent approach has not been extensively evaluated to determine how the contrast-to-noise ratio between blood and tissue enhancement affects estimates of myocardial perfusion and the degree to which the regularization is dependent on the noise in the measured enhancement data. We investigated these questions with a model-independent analysis method that uses iterative minimization and a temporal smoothness regularizer. Perfusion estimates using this method were compared to results from dynamic 13N-ammonia PET. Results An iterative model-independent analysis method was developed and tested to estimate regional and pixelwise myocardial perfusion in five normal subjects imaged with a saturation recovery turboFLASH sequence at 3 T CMR. Estimates of myocardial perfusion using model-independent analysis are dependent on the choice of the regularization weight parameter, which increases nonlinearly to handle large decreases in the contrast-to-noise ratio of the measured tissue enhancement data. Quantitative perfusion estimates in five subjects imaged with 3 T CMR were 1.1 ± 0.8 ml/min/g at rest and 3.1 ± 1.7 ml/min/g at adenosine stress. The perfusion estimates correlated with dynamic 13N-ammonia PET (y = 0.90x + 0.24, r = 0.85) and were similar to results from other validated CMR studies. Conclusion This work shows that a model-independent analysis method that uses iterative minimization and temporal regularization can be used to quantify myocardial perfusion with dynamic contrast-enhanced perfusion CMR. Results from this method are robust to choices in the regularization weight parameter over relatively large ranges in the contrast-to-noise ratio of the tissue enhancement data. PMID:19014509

  3. A linear mixed perfusion model for tissue partial volume correction of perfusion estimates in dynamic susceptibility contrast MRI: Impact on absolute quantification, repeatability, and agreement with pseudo-continuous arterial spin labeling.

    PubMed

    Ahlgren, André; Wirestam, Ronnie; Lind, Emelie; Ståhlberg, Freddy; Knutsson, Linda

    2017-06-01

    The partial volume effect (PVE) is an important source of bias in brain perfusion measurements. The impact of tissue PVEs in perfusion measurements with dynamic susceptibility contrast MRI (DSC-MRI) has not yet been well established. The purpose of this study was to suggest a partial volume correction (PVC) approach for DSC-MRI and to study how PVC affects DSC-MRI perfusion results. A linear mixed perfusion model for DSC-MRI was derived and evaluated by way of simulations. Twenty healthy volunteers were scanned twice, including DSC-MRI, arterial spin labeling (ASL), and partial volume measurements. Two different algorithms for PVC were employed and assessed. Simulations showed that the derived model had a tendency to overestimate perfusion values in voxels with high fractions of cerebrospinal fluid. PVC reduced the tissue volume dependence of DSC-MRI perfusion values from 44.4% to 4.2% in gray matter and from 55.3% to 14.2% in white matter. One PVC method significantly improved the voxel-wise repeatability, but PVC did not improve the spatial agreement between DSC-MRI and ASL perfusion maps. Significant PVEs were found for DSC-MRI perfusion estimates, and PVC successfully reduced those effects. The findings suggest that PVC might be an important consideration for DSC-MRI applications. Magn Reson Med 77:2203-2214, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  4. 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.

  5. 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

  6. Cerebral-Body Perfusion Model

    DTIC Science & Technology

    1990-07-01

    compared to the 0.5g curve) fall in flow. Fig. 9b, showing the 5g case, strongly suggests a possible, so-called, " luxury perfusion ", in which natural...as the luxury perfusion situation which bypasses the flow with the nutrients it carries (through newly opened collaterals) and result in a "blackout...89-0054 CEREBRAL-BODY PERFUSION MODEL S. Sorek’, J. Bear2, and M., Feinsod3 in Collaboration with K. Allen4, L. Bunt5 and S. Ben-IHaiM6 July 1990

  7. Distributed Perfusion Educational Model: A Shift in Perfusion Economic Realities

    PubMed Central

    Austin, Jon W.; Evans, Edward L.; Hoerr, Harry R.

    2005-01-01

    Abstract: In recent years, a steady decline in the number of perfusion education programs in the United States has been noted. At the same time, there has been a parallel decline in the number of students graduated from perfusion educational programs in the United States. Also, as noted by several authors, there has been an increase in demand for perfusion graduates. The decline in programs and graduates has also been noted in anesthesia and surgical residency programs. The shift is caused by a combination of economic and clinical factors. First, decreased reimbursement has led to reallocation of hospital resources. Second, the original enthusiasm for beating heart coronary artery bypass surgery was grossly overestimated and has led to further reallocation of hospital resources and denigration of cardiopulmonary bypass. This paper describes two models of perfusion education programs: serial perfusion education model (SPEM) and the distributed perfusion education model (DPEM). Arguments are presented that the SPEM has some serious limitations and challenges for long-term economic survival. The authors feel the DPEM along with dependence on tuition funding can survive the current clinical and economic conditions and allow the profession to adapt to changes in scope of practice. PMID:16524152

  8. Space-dependent perfusion coefficient estimation in a 2D bioheat transfer problem

    NASA Astrophysics Data System (ADS)

    Bazán, Fermín S. V.; Bedin, Luciano; Borges, Leonardo S.

    2017-05-01

    In this work, a method for estimating the space-dependent perfusion coefficient parameter in a 2D bioheat transfer model is presented. In the method, the bioheat transfer model is transformed into a time-dependent semidiscrete system of ordinary differential equations involving perfusion coefficient values as parameters, and the estimation problem is solved through a nonlinear least squares technique. In particular, the bioheat problem is solved by the method of lines based on a highly accurate pseudospectral approach, and perfusion coefficient values are estimated by the regularized Gauss-Newton method coupled with a proper regularization parameter. The performance of the method on several test problems is illustrated numerically.

  9. Parametric estimation of ventilation-perfusion ratio distributions.

    PubMed

    Stewart, W E; Mastenbrook, S M

    1983-07-01

    We present a model and rigorous statistical approach for recovery of ventilation-perfusion ratio (V/Q) distribution parameters from multiple inert gas elimination data. We model the lung as a parallel combination of shunt, dead space, and one to three log-normal distributions of gas exchange units. This model provides a natural set of parameters for characterizing V/Q distributions. The log-normal terms are adjustable to represent smooth or sharp peaks in the distribution. Since the peak locations and widths are explicit in the model, very few parameters are needed. We select and estimate the significant parameters of the model by use of standard statistical tests and constrained least squares. This method provides two major advances in V/Q distribution estimation: 1) it allows flexible pooling and statistical comparisons of multiple experiments, and 2) it simultaneously gives both point estimates and 95% probability intervals for the V/Q distribution parameters. We present results of our procedure for data from humans in health, stress, and pulmonary disease. A program package, VQPAR, in FORTRAN is available for implementing the procedure.

  10. Comparison of Myocardial Perfusion Estimates From Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Four Quantitative Analysis Methods

    PubMed Central

    Pack, Nathan A.; DiBella, Edward V. R.

    2012-01-01

    Dynamic contrast-enhanced MRI has been used to quantify myocardial perfusion in recent years. Published results have varied widely, possibly depending on the method used to analyze the dynamic perfusion data. Here, four quantitative analysis methods (two-compartment modeling, Fermi function modeling, model-independent analysis, and Patlak plot analysis) were implemented and compared for quantifying myocardial perfusion. Dynamic contrast-enhanced MRI data were acquired in 20 human subjects at rest with low-dose (0.019 ± 0.005 mmol/kg) bolus injections of gadolinium. Fourteen of these subjects were also imaged at adenosine stress (0.021 ± 0.005 mmol/kg). Aggregate rest perfusion estimates were not significantly different between all four analysis methods. At stress, perfusion estimates were not significantly different between two-compartment modeling, model-independent analysis, and Patlak plot analysis. Stress estimates from the Fermi model were significantly higher (~20%) than the other three methods. Myocardial perfusion reserve values were not significantly different between all four methods. Model-independent analysis resulted in the lowest model curve-fit errors. When more than just the first pass of data was analyzed, perfusion estimates from two-compartment modeling and model-independent analysis did not change significantly, unlike results from Fermi function modeling. PMID:20577976

  11. Bayesian optimization of perfusion and transit time estimation in PASL-MRI.

    PubMed

    Santos, Nuno; Sanches, João; Figueiredo, Patrícia

    2010-01-01

    Pulsed Arterial Spin Labeling (PASL) techniques potentially allow the absolute, non-invasive quantification of brain perfusion and arterial transit time. This can be achieved by fitting a kinetic model to the data acquired at a number of inversion time points (TI). The intrinsically low SNR of PASL data, together with the uncertainty in the model parameters, can hinder the estimation of the parameters of interest. Here, a two-compartment kinetic model is used to estimate perfusion and transit time, based on a Maximum a Posteriori (MAP) criterion. A priori information concerning the physiological variation of the multiple model parameters is used to guide the solution. Monte Carlo simulations are performed to compare the accuracy of our proposed Bayesian estimation method with a conventional Least Squares (LS) approach, using four different sets of TI points. Each set is obtained either with a uniform distribution or an optimal sampling strategy designed based on the same MAP criterion. We show that the estimation errors are minimized when our proposed Bayesian estimation method is employed in combination with an optimal set of sampling points. In conclusion, our results indicate that PASL perfusion and transit time measurements would benefit from a Bayesian approach for the optimization of both the sampling strategy and the estimation algorithm, whereby prior information on the parameters is used.

  12. Transport of benzo[alpha]pyrene in the dually perfused human placenta perfusion model: effect of albumin in the perfusion medium.

    PubMed

    Mathiesen, Line; Rytting, Erik; Mose, Tina; Knudsen, Lisbeth E

    2009-09-01

    Transport of benzo[alpha]pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)]. The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 +/- 0.10 after 3 hr and 0.78 +/- 0.11 after 6 hr, whereas the FM ratio in perfusions without albumin was only 0.05 +/- 0.03 after 6 hr of perfusion. Less BaP accumulated in placental tissue in perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances.

  13. Error estimation for perfusion parameters obtained using the two-compartment exchange model in dynamic contrast-enhanced MRI: a simulation study

    NASA Astrophysics Data System (ADS)

    Luypaert, R.; Sourbron, S.; Makkat, S.; de Mey, J.

    2010-11-01

    In theory, the application of the two-compartment exchange model (2CXM) to data from a dynamic contrast-enhanced (DCE) MRI exam allows the estimation of the plasma flow, plasma volume, extraction flow and extravascular-extracellular volume. The aim of this paper was to explore whether simulations based on the 2CXM could provide useful information on the trustworthiness of the results. The deviations from the input values of the haemodynamic quantities were estimated for a 'reference tissue' with a clear bi-phasic response and four 'limit tissues' with more challenging 2CXM fitting properties. The impact of the instrumental factors sampling step (Ts), acquisition window (Tacq) and contrast-to-noise ratio (CNR) was investigated. Each factor was varied separately, while keeping the other ones at a value above concern. Measurement guidelines to ensure that all deviations fell within a predefined range (±20%) could not be derived, but simulations for fixed Ts and Tacq were found to provide a practical tool for studying the error behaviour to be expected from a given experimental set-up and for comparing measurement protocols. At the level of an individual DCE exam, a bootstrap version of the simulation approach was shown to lead to a useful estimate of the errors on the fitted parameters.

  14. NOTE: Estimating perfusion using microCT to locate microspheres

    NASA Astrophysics Data System (ADS)

    Marxen, M.; Paget, C.; Yu, L. X.; Henkelman, R. M.

    2006-01-01

    The injection of microspheres into the blood stream has been a common method to measure the spatial distribution of blood flow (perfusion). A technique to conduct this kind of measurement in small animal organs is presented using silver-coated microspheres with a diameter of 16 µm and high-resolution computed tomography (microCT) to detect individual microspheres. Phantom experiments demonstrate the detectability of individual spheres. The distribution of microspheres within a rat heart is given as an example. Using non-destructive, three-dimensional imaging for microsphere detection avoids the cumbersome dissection of the organ into samples or slices and their subsequent registration. The detection of individual spheres allows high-resolution measurements of perfusion and arbitrary definition of regions of interest. These, in turn, allow for accurate statistical analysis of perfusion such as relative dispersion curves.

  15. Estimation of pyruvate decarboxylation in perfused rat skeletal muscle.

    PubMed

    Schadewaldt, P; Münch, U; Prengel, M; Staib, W

    1983-10-31

    By the determination of pyruvate dehydrogenase activity in tissue homogenates only limited information is gained on the actual metabolic flux. We therefore determined pyruvate decarboxylation in isolated rat hindlimbs non recirculating perfused with physiological (1-14C)pyruvate levels. On the basis of perfusate pyruvate specific activity a 14CO2 production of 15.8 +/- 0.5 nmol/min per g muscle was measured. However, by this method the actual pyruvate flux through the enzyme complex is underestimated by a factor of 7 due to the intracellular dilution of label.

  16. Estimation of regional pulmonary perfusion parameters from microfocal angiograms

    SciTech Connect

    Clough, A.V.; Al-Tinawi, A.; Linehan, J.H.; Dawson, C.A. |

    1995-12-31

    An important application of functional imaging is the estimation of regional blood flow and volume using residue detection of vascular indicators. An indicator-dilution model applicable to tissue regions distal from the inlet site was developed. Theoretic methods for determining regional blood flow, volume and mean transit time parameters from time-absorbance curves arise from this model. The robustness of the parameter estimation methods was evaluated using a computer-simulated vessel network model. Flow through arterioles, networks of capillaries and venules was simulated. Parameter identification and practical implementation issues were addressed. The shape of the inlet concentration curve and moderate amounts of random noise did not effect the ability of the method to recover accurate parameter estimates. The parameter estimates degraded in the presence of significant dispersion of the measured inlet concentration curve as it traveled through arteries upstream from the microvascular region. The methods were applied to image data obtained using microfocal x-ray angiography to study the pulmonary microcirculation. Time-absorbance curves were acquired from a small feeding artery, the surrounding microvasculature and a draining vein of an isolated dog lung as contrast material passed through the field-of-view. Changes in regional microvascular volume were determined from these curves.

  17. Estimation of regional pulmonary perfusion parameters from microfocal angiograms

    NASA Astrophysics Data System (ADS)

    Clough, Anne V.; Al-Tinawi, Amir; Linehan, John H.; Dawson, Christopher A.

    1995-05-01

    An important application of functional imaging is the estimation of regional blood flow and volume using residue detection of vascular indicators. An indicator-dilution model applicable to tissue regions distal from the inlet site was developed. Theoretical methods for determining regional blood flow, volume, and mean transit time parameters from time-absorbance curves arise from this model. The robustness of the parameter estimation methods was evaluated using a computer-simulated vessel network model. Flow through arterioles, networks of capillaries, and venules was simulated. Parameter identification and practical implementation issues were addressed. The shape of the inlet concentration curve and moderate amounts of random noise did not effect the ability of the method to recover accurate parameter estimates. The parameter estimates degraded in the presence of significant dispersion of the measured inlet concentration curve as it traveled through arteries upstream from the microvascular region. The methods were applied to image data obtained using microfocal x-ray angiography to study the pulmonary microcirculation. Time- absorbance curves were acquired from a small feeding artery, the surrounding microvasculature and a draining vein of an isolated dog lung as contrast material passed through the field-of-view. Changes in regional microvascular volume were determined from these curves.

  18. Assessment of peripheral tissue perfusion by optical dynamic fluorescence imaging and nonlinear regression modeling

    NASA Astrophysics Data System (ADS)

    Kang, Yujung; Lee, Jungsul; Kwon, Kihwan; Choi, Chulhee

    2010-02-01

    The purpose of this study is to examine the peripheral tissue perfusion rates by time-series analysis of distribution and elimination kinetics of a clinically proven NIR fluorescence probe, indocyanine green (ICG). We developed a new method, dynamic ICG perfusion imaging technique to evaluate peripheral tissue perfusion that employs planar imaging with a CCD digital imaging system and time-series analysis of the spatiotemporal dynamics (150s) of intravenously injected ICG by using nonlinear regression and differential evolution methods. Six parameters (α, β, s, d, m; parameters which depend on an arterial input function (AIF) into a lower extremity and p; perfusion rates in the lower extremity) were estimated by the nonlinear regression modeling method. We have confirmed the validity of our new method by applying the method to a normal control and a patient with peripheral arterial occlusion disease (PAOD). PAOD patient showed a unique AIF curve pattern, which was caused by collateral blood flow bypassing the occluded major artery. The lower extremity tissue perfusion rate of the PAOD patient was estimated as about 35% of those of normal values. These results indicate that ICG perfusion imaging method is sensitive enough to diagnose PAOD and capable of diagnosing functional arterial diseases.

  19. Placental Perfusion In Uterine Ischemia Model as Evaluated by Dynamic Contrast Enhanced MRI

    PubMed Central

    Drobyshevsky, Alexander

    2017-01-01

    Background To validate DCE MRI method of placental perfusion estimation and to demonstrate application of the method in a rabbit model of fetal antenatal hypoxia-ischemia. Methods Placental perfusion was estimated by dynamic contrast imaging with bolus injection of Gd-DTPA in 3 Tesla GE magnet in a rabbit model of placental ischemia–reperfusion in rabbit dams at embryonic day 25 gestation age. Placental perfusion was measured using steepest slope method on DCE MRI before and after intermittent 40 min uterine ischemia. Antioxidants (n = 2 dams, 9 placentas imaged) or vehicle (n = 5 dams, 23 placenta imaged) were given systemically in a separate group of dams during reperfusion–reoxygenation. Placental perfusion was also measured in two dams from the antioxidant group (10 placentas) and two dams from the control group (12 placentas) by fluorescent microspheres method. Results While placental perfusion estimates between fluorescent microspheres and DCE MRI were significantly correlated (R2 = 0.85; P < 0.01), there was approximately 33% systematic underestimation by the latter technique. DCE MRI showed a significant decrease in maternal placental perfusion in reperfusion–reoxygenation phase in the saline, 0.44 ± 0.06 mL/min/g (P = 0.012, t-test), but not in the antioxidant group, 0.62 ± 0.06 mL/min/g, relative to preocclusion values (0.77 ± 0.07 and 0.84 ± 0.12 mL/min/g, correspondingly). Conclusion Underestimation of true perfusion in placenta by steepest slope DCE MRI is significant and the error appears to be systematic. PMID:25854322

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

    PubMed Central

    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. PMID:26741344

  1. 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.

  2. Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.

    PubMed

    Râdegran, G; Blomstrand, E; Saltin, B

    1999-12-01

    The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O(2) uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233-249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the (133)Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O(2) uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 +/- 0.17 (range 1. 31-3.27) liters, corresponding to 2.48 +/- 0.18 (range 1.37-3.43) kg. Anthropometry overestimated the muscle volume by approximately 21-46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 +/- 7 (range 55-100) W rendered peak values for leg blood flow (thermodilution) of 5.99 +/- 0.66 (range 4.15-9.52) l/min and leg O(2) uptake of 856 +/- 109 (range 590-1,521) ml/min. Muscle perfusion and O(2) uptake reached peak values of 246 +/- 24 (range 149-373) and 35.2 +/- 3.7 (range 22.6-59. 6) ml. min(-1). 100 g muscle(-1), respectively. These peak values are approximately 19-33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O(2) uptake in human skeletal muscle may be up to approximately 30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow

  3. Perfusion estimation using contrast enhanced three-dimensional subharmonic ultrasound imaging: an in vivo study

    PubMed Central

    Sridharan, Anush; Eisenbrey, John R.; Liu, Ji-Bin; Machado, Priscilla; Halldorsdottir, Valgerdur G.; Dave, Jaydev K.; Zhao, Hongjia; He, Yu; Park, Suhyun; Dianis, Scott; Wallace, Kirk; Thomenius, Kai E.; Forsberg, Flemming

    2013-01-01

    Objectives The ability to estimate tissue perfusion (in mL/min/g) in vivo using contrast-enhanced three-dimensional (3D) harmonic and subharmonic ultrasound imaging was investigated. Materials and Methods A Logiq 9 scanner (GE Healthcare, Milwaukee, WI) equipped with a 4D10L probe was modified to perform 3D harmonic imaging (HI; ftransmit = 5 MHz and freceive = 10 MHz) and subharmonic imaging (SHI; ftransmit= 5.8 MHz and freceive= 2.9 MHz). In vivo imaging was performed in the lower pole of both kidneys in five open-abdomen canines after injection of the ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, MA). The canines received a 5 μL/kg bolus injection of Definity for HI and a 20 μL/kg bolus for SHI in triplicate for each kidney. Ultrasound data acquisition was started just prior to injection of UCA (in order to capture the wash-in) and continued until washout. A microvascular staining technique based on stable (non-radioactive) isotope-labeled microspheres (Biophysics Assay Laboratory Inc, Worcester, MA) was used to quantify the degree of perfusion in each kidney (the reference standard). Ligating a surgically exposed branch of the renal arteries induced lower perfusion rates. This was followed by additional contrast-enhanced imaging and microsphere injections to measure post-ligation perfusion. Slice data were extracted from the 3D ultrasound volumes and used to generate time-intensity curves off-line in the regions corresponding to the tissue samples used for microvascular staining. The mid-line plane was also selected from the 3D volume (as a quasi-2D image) and compared to the 3D imaging modes. Perfusion was estimated from the initial slope of the fractional blood volume uptake (for both HI and SHI) and compared to the reference standard using linear regression analysis. Results Both 3D HI and SHI were able to provide visualization of flow and, thus, perfusion in the kidneys. However, SHI provided near complete tissue

  4. Modelling of temperature and perfusion during scalp cooling.

    PubMed

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

    2005-09-07

    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 degrees C to 18.3 degrees 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 degrees C to 21.8 degrees C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  5. 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.

  6. 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.

  7. A novel extracorporeal kidney perfusion system: a concept model.

    PubMed

    Szajer, Michael; Shah, Gaurang; Kittur, Dilip; Searles, Bruce; Li, Lu; Bruch, David; Darling, Edward

    2004-01-01

    The number of patients awaiting kidney transplantation has more than doubled in the past decade while the number of available donor organs has seen only a modest increase, leading to a critical shortage of organs. In response to this extreme shortage, the criteria for accepting organs have been modified to include marginal donors such as non-heart beating donors (NHBD). In these kidneys, determining viability is important for success of transplantation. Therefore, a study was undertaken to develop a system that would allow the extracorporeal assessment of function and compatibility of the donor organ before the patient is exposed to the risks associated with surgery. Following bilateral nephrectomy, the kidneys of 10 pigs (approximately 30 kg) were connected to a commercially available hypothermic pulsatile kidney perfusion apparatus. This system was modified to allow for normothermic pulsatile renal perfusion using the potential recipient's blood, via vascular access. These kidneys were perfused with the animal's blood for a minimum of two hours while various parameters were monitored. Perfusion pressures were kept between 60 and 90 mmHg, which correlated to flows between 70 and 150 mL/min. A decrease in perfusion pressure with a concomitant rise in flow over the two-hour period served as a good predictor of a viable and compatible graft. The modified kidney preservation system allows the normothermic, pulsatile extracorporeal perfusion of donor kidneys with the ability to monitor resistance to flow and urine production. This model also allows observation of the kidney for signs of hyperacute rejection. Further research needs to be conducted in order to determine if the system represents a methodology to increase the pool of available donor organs.

  8. 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.

  9. A Generic Bioheat Transfer Thermal Model for a Perfused Tissue

    PubMed Central

    Vaughan, J. Thomas

    2009-01-01

    A thermal model was needed to predict temperatures in a perfused tissue, which satisfied the following three criteria. One, the model satisfied conservation of energy. Two, the heat transfer rate from blood vessels to tissue was modeled without following a vessel path. Three, the model applied to any unheated and heated tissue. To meet these criteria, a generic bioheat transfer model (BHTM) was derived here by conserving thermal energy in a heated, vascularized, finite tissue and by making a few simplifying assumptions. Two linear, coupled differential equations were obtained with the following two variables: tissue volume averaged temperature and blood volume averaged temperature. The generic model was compared to the widely employed, empirical Pennes’ BHTM. The comparison showed that the Pennes’ perfusion term wCp(1−ε) should be interpreted as a local vasculature dependent heat transfer coefficient term. Suggestions are presented for further adaptations of the general BHTM for specific tissues using imaging techniques and numerical simulations. PMID:19640142

  10. A generic bioheat transfer thermal model for a perfused tissue.

    PubMed

    Shrivastava, Devashish; Vaughan, J Thomas

    2009-07-01

    A thermal model was needed to predict temperatures in a perfused tissue, which satisfied the following three criteria. One, the model satisfied conservation of energy. Two, the heat transfer rate from blood vessels to tissue was modeled without following a vessel path. Three, the model applied to any unheated and heated tissue. To meet these criteria, a generic bioheat transfer model (BHTM) was derived here by conserving thermal energy in a heated vascularized finite tissue and by making a few simplifying assumptions. Two linear coupled differential equations were obtained with the following two variables: tissue volume averaged temperature and blood volume averaged temperature. The generic model was compared with the widely employed empirical Pennes' BHTM. The comparison showed that the Pennes' perfusion term wC(p)(1-epsilon) should be interpreted as a local vasculature dependent heat transfer coefficient term. Suggestions are presented for further adaptations of the general BHTM for specific tissues using imaging techniques and numerical simulations.

  11. Modeling of nanotherapeutics delivery based on tumor perfusion

    PubMed Central

    van de Ven, Anne L.; Abdollahi, Behnaz; Martinez, Carlos J.; Burey, Lacey A.; Landis, Melissa D.; Chang, Jenny C.; Ferrari, Mauro; Frieboes, Hermann B.

    2013-01-01

    Heterogeneities in the perfusion of solid tumors prevent optimal delivery of nanotherapeutics. Clinical imaging protocols to obtain patient-specific data have proven difficult to implement. It is challenging to determine which perfusion features hold greater prognostic value and to relate measurements to vessel structure and function. With the advent of systemically administered nanotherapeutics, whose delivery is dependent on overcoming diffusive and convective barriers to transport, such knowledge is increasingly important. We describe a framework for the automated evaluation of vascular perfusion curves measured at the single vessel level. Primary tumor fragments, collected from triple-negative breast cancer patients and grown as xenografts in mice, were injected with fluorescence contrast and monitored using intravital microscopy. The time to arterial peak and venous delay, two features whose probability distributions were measured directly from time-series curves, were analyzed using a Fuzzy C-mean (FCM) supervised classifier in order to rank individual tumors according to their perfusion characteristics. The resulting rankings correlated inversely with experimental nanoparticle accumulation measurements, enabling modeling of nanotherapeutics delivery without requiring any underlying assumptions about tissue structure or function, or heterogeneities contained within. With additional calibration, these methodologies may enable the study of nanotherapeutics delivery strategies in a variety of tumor models. PMID:24039540

  12. Modeling of nanotherapeutics delivery based on tumor perfusion

    NASA Astrophysics Data System (ADS)

    van de Ven, Anne L.; Abdollahi, Behnaz; Martinez, Carlos J.; Burey, Lacey A.; Landis, Melissa D.; Chang, Jenny C.; Ferrari, Mauro; Frieboes, Hermann B.

    2013-05-01

    Heterogeneities in the perfusion of solid tumors prevent optimal delivery of nanotherapeutics. Clinical imaging protocols for obtaining patient-specific data have proven difficult to implement. It is challenging to determine which perfusion features hold greater prognostic value and to relate measurements to vessel structure and function. With the advent of systemically administered nanotherapeutics whose delivery is dependent on overcoming diffusive and convective barriers to transport, such knowledge is increasingly important. We describe a framework for the automated evaluation of vascular perfusion curves measured at the single vessel level. Primary tumor fragments, collected from triple-negative breast cancer patients and grown as xenografts in mice, were injected with fluorescence contrast and monitored using intravital microscopy. The time to arterial peak and venous delay, two features whose probability distributions were measured directly from time-series curves, were analyzed using a fuzzy c-mean supervised classifier in order to rank individual tumors according to their perfusion characteristics. The resulting rankings correlated inversely with experimental nanoparticle accumulation measurements, enabling the modeling of nanotherapeutics delivery without requiring any underlying assumptions about tissue structure or function, or heterogeneities contained therein. With additional calibration, these methodologies may enable the investigation of nanotherapeutics delivery strategies in a variety of tumor models.

  13. Hepatic Blood Perfusion Estimated by Dynamic Contrast-Enhanced Computed Tomography in Pigs Limitations of the Slope Method

    PubMed Central

    Winterdahl, Michael; Sørensen, Michael; Keiding, Susanne; Mortensen, Frank V.; Alstrup, Aage K. O.; Hansen, Søren B.; Munk, Ole L.

    2012-01-01

    Objective To determine whether dynamic contrast-enhanced computed tomography (DCE-CT) and the slope method can provide absolute measures of hepatic blood perfusion from hepatic artery (HA) and portal vein (PV) at experimentally varied blood flow rates. Materials and Methods Ten anesthetized 40-kg pigs underwent DCE-CT during periods of normocapnia (normal flow), hypocapnia (decreased flow), and hypercapnia (increased flow), which was induced by adjusting the ventilation. Reference blood flows in HA and PV were measured continuously by surgically-placed ultrasound transit-time flowmeters. For each capnic condition, the DCE-CT estimated absolute hepatic blood perfusion from HA and PV were calculated using the slope method and compared with flowmeter based absolute measurements of hepatic perfusions and relative errors were analyzed. Results The relative errors (mean±SEM) of the DCE-CT based perfusion estimates were −21±23% for HA and 81±31% for PV (normocapnia), 9±23% for HA and 92±42% for PV (hypocapnia), and 64±28% for HA and −2±20% for PV (hypercapnia). The mean relative errors for HA were not significantly different from zero during hypo- and normocapnia, and the DCE-CT slope method could detect relative changes in HA perfusion between scans. Infusion of contrast agent led to significantly increased hepatic blood perfusion, which biased the PV perfusion estimates. Conclusions Using the DCE-CT slope method, HA perfusion estimates were accurate at low and normal flow rates whereas PV perfusion estimates were inaccurate and imprecise. At high flow rate, both HA perfusion estimates were significantly biased. PMID:22836307

  14. The precision of DCE-MRI using the tissue homogeneity model with continuous formulation of the perfusion parameters.

    PubMed

    Bartoš, Michal; Jiřík, Radovan; Kratochvíla, Jiří; Standara, Michal; Starčuk, Zenon; Taxt, Torfinn

    2014-06-01

    The present trend in dynamic contrast-enhanced MRI is to increase the number of estimated perfusion parameters using complex pharmacokinetic models. However, less attention is given to the precision analysis of the parameter estimates. In this paper, the distributed capillary adiabatic tissue homogeneity pharmacokinetic model is extended by the bolus arrival time formulated as a free continuous parameter. With the continuous formulation of all perfusion parameters, it is possible to use standard gradient-based optimization algorithms in the approximation of the tissue concentration time sequences. This new six-parameter model is investigated by comparing Monte-Carlo simulations with theoretically derived covariance matrices. The covariance-matrix approach is extended from the usual analysis of the primary perfusion parameters of the pharmacokinetic model to the analysis of the perfusion parameters derived from the primary ones. The results indicate that the precision of the estimated perfusion parameters can be described by the covariance matrix for signal-to-noise ratio higher than~20dB. The application of the new analysis model on a real DCE-MRI data set is also presented. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Perfusion-diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep.

    PubMed

    Doolette, David J; Upton, Richard N; Grant, Cliff

    2005-03-01

    This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain.

  16. Quantification of tumor perfusion using dynamic contrast-enhanced ultrasound: impact of mathematical modeling

    NASA Astrophysics Data System (ADS)

    Doury, Maxime; Dizeux, Alexandre; de Cesare, Alain; Lucidarme, Olivier; Pellot-Barakat, Claire; Bridal, S. Lori; Frouin, Frédérique

    2017-02-01

    Dynamic contrast-enhanced ultrasound has been proposed to monitor tumor therapy, as a complement to volume measurements. To assess the variability of perfusion parameters in ideal conditions, four consecutive test-retest studies were acquired in a mouse tumor model, using controlled injections. The impact of mathematical modeling on parameter variability was then investigated. Coefficients of variation (CV) of tissue blood volume (BV) and tissue blood flow (BF) based-parameters were estimated inside 32 sub-regions of the tumors, comparing the log-normal (LN) model with a one-compartment model fed by an arterial input function (AIF) and improved by the introduction of a time delay parameter. Relative perfusion parameters were also estimated by normalization of the LN parameters and normalization of the one-compartment parameters estimated with the AIF, using a reference tissue (RT) region. A direct estimation (rRTd) of relative parameters, based on the one-compartment model without using the AIF, was also obtained by using the kinetics inside the RT region. Results of test-retest studies show that absolute regional parameters have high CV, whatever the approach, with median values of about 30% for BV, and 40% for BF. The positive impact of normalization was established, showing a coherent estimation of relative parameters, with reduced CV (about 20% for BV and 30% for BF using the rRTd approach). These values were significantly lower (p  <  0.05) than the CV of absolute parameters. The rRTd approach provided the smallest CV and should be preferred for estimating relative perfusion parameters.

  17. Isolated perfused liver model: the rat and guinea pig compared.

    PubMed

    Chaïb, Samira; Charrueau, Christine; Neveux, Nathalie; Coudray-Lucas, Colette; Cynober, Luc; De Bandt, Jean-Pascal

    2004-05-01

    Although the rat is the most commonly used species for the study of hepatic metabolism, the physiology of the guinea pig is closer to human physiology. We compared the model of isolated perfused guinea pig liver with the classic model of isolated perfused rat liver, especially with respect to amino acid metabolism. After validation of an anesthetic mixture of ketamine, diazepam, and xylazine for the guinea pig, isolated perfused livers were harvested for both species. Three groups of animals were compared for the study of liver metabolic fluxes: 6-wk-old male Sprague-Dawley rats (R; 230 +/- 10 g, n = 5), young male Hartley guinea pigs (YG; 223 +/- 8 g, n = 6) matched to rats by liver weight, and adult male Hartley guinea pigs (AG; 389 +/- 5 g, n = 6) matched to rats by age. Results (mean +/- standard error of the mean) were compared by analysis of variance and Newman-Keuls tests. Both models displayed a satisfactory hepatic viability, but differences were noted, with higher portal flows (R: 3.1 +/- 0.3 versus YG: 4.5 +/- 0.3 and AG: 4.2 +/- 0.3 mL. min(-1). g(-1); P < 0.05, YG and AG versus R) and bile flows (R: 0.34 +/- 0.01 versus YG: 2.38 +/- 0.22 versus AG: 3.17 +/- 0.28 microL. min(-1). g(-1); P < 0.05, YG and AG versus R, and YG versus AG) and higher amino acid fluxes (P < 0.05) leading to greater nitrogen uptake (P < 0.05) in guinea pigs. We performed a second set of experiments to evaluate the influence of anesthesia and portal flow on this last parameter. In these experiments, rats were anesthetized with ketamine, diazepam, and xylazine and guinea pig livers were perfused at rat blood flow. Apart from a 50% anesthesia-related mortality for rats, bile flow and metabolic parameters were only slightly modified. However, some amino acid fluxes were statistically different (aspartate, serine, and histidine; P < 0.05), as confirmed by a higher transfer constant. Our results indicate that the isolated perfused guinea pig liver is a suitable model for the study of

  18. A poroelastic model valid in large strains with applications to perfusion in cardiac modeling

    NASA Astrophysics Data System (ADS)

    Chapelle, D.; Gerbeau, J.-F.; Sainte-Marie, J.; Vignon-Clementel, I. E.

    2009-12-01

    This paper is motivated by the modeling of blood flows through the beating myocardium, namely cardiac perfusion. As in other works, perfusion is modeled here as a flow through a poroelastic medium. The main contribution of this study is the derivation of a general poroelastic model valid for a nearly incompressible medium which experiences finite deformations. A numerical procedure is proposed to iteratively solve the porous flow and the nonlinear poroviscoelastic problems. Three-dimensional numerical experiments are presented to illustrate the model. The first test cases consist of typical poroelastic configurations: swelling and complete drainage. Finally, a simulation of cardiac perfusion is presented in an idealized left ventricle embedded with active fibers. Results show the complex temporal and spatial interactions of the muscle and blood, reproducing several key phenomena observed in cardiac perfusion.

  19. Placental transfer of the HIV integrase inhibitor dolutegravir in an ex vivo human cotyledon perfusion model.

    PubMed

    Schalkwijk, Stein; Greupink, Rick; Colbers, Angela P; Wouterse, Alfons C; Verweij, Vivienne G M; van Drongelen, Joris; Teulen, Marga; van den Oetelaar, Daphne; Burger, David M; Russel, Frans G M

    2016-02-01

    Data on fetal exposure to antiretroviral agents during pregnancy are important to estimate their potential for prevention of mother-to-child transmission (PMTCT) and possible toxicity. For the recently developed HIV integrase inhibitor dolutegravir, clinical data on fetal disposition are not yet available. Dual perfusion of a single placental lobule (cotyledon) provides a useful ex vivo model to predict the in vivo maternal-to-fetal transfer of this drug. The aim of this study was to estimate the transfer of dolutegravir across the human term placenta, using a dual-perfusion cotyledon model. After cannulation of the cotyledons (n = 6), a fetal circulation of 6 mL/min and maternal circulation of 12 mL/min were initiated. The perfusion medium consisted of Krebs-Henseleit buffer (pH = 7.2-7.4) supplemented with 10.1 mM glucose, 30 g/L human serum albumin and 0.5 mL/L heparin 5000IE. Dolutegravir was administered to the maternal circulation (∼ 4.2 mg/L) and analysed by UPLC-MS/MS. After 3 h of perfusion, the mean ± SD fetal-to-maternal (FTM) concentration ratio of dolutegravir was 0.6 ± 0.2 and the mean ± SD concentrations in the maternal and fetal compartments were 2.3 ± 0.4 and 1.3 ± 0.3 mg/L, respectively. Dolutegravir crosses the blood-placental barrier with a mean FTM concentration ratio of 0.6. Compared with other antiretroviral agents, placental transfer of dolutegravir is moderate to high. These data suggest that dolutegravir holds clinical potential for pre-exposure prophylaxis and consequently PMTCT, but also risk of fetal toxicity. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. 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

  1. The isolated perfused human skin flap model: A missing link in skin penetration studies?

    PubMed

    Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

    2017-01-01

    Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Comparison of the Diagnostic Performance of Four Quantitative Myocardial Perfusion Estimation Methods Used in Cardiac MR Imaging: CE-MARC Substudy.

    PubMed

    Biglands, John D; Magee, Derek R; Sourbron, Steven P; Plein, Sven; Greenwood, John P; Radjenovic, Aleksandra

    2015-05-01

    To compare the diagnostic performance of four tracer kinetic analysis methods to quantify myocardial perfusion from magnetic resonance (MR) imaging cardiac perfusion data sets in terms of their ability to lead to the diagnosis of myocardial ischemia. The study was approved by the regional ethics committee, and all patients gave written consent. A representative sample of 50 patients with suspected ischemic heart disease was retrospectively selected from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease trial data set. Quantitative myocardial blood flow (MBF) was estimated from rest and adenosine stress MR imaging perfusion data sets by using four established methods. A matching diagnosis of both an inducible defect as assessed with single photon emission computed tomography and a luminal stenosis of 70% or more as assessed with quantitative x-ray angiography was used as the reference standard for the presence of myocardial ischemia. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis for each method, with stress MBF and myocardial perfusion reserve (MPR) serving as continuous measures. Area under the ROC curve with stress MBF and MPR as the outcome measures, respectively, was 0.86 and 0.92 for the Fermi model, 0.85 and 0.87 for the uptake model, 0.85 and 0.80 for the one-compartment model, and 0.87 and 0.87 for model-independent deconvolution. There was no significant difference between any of the models or between MBF and MPR, except that the Fermi model outperformed the one-compartment model if MPR was used as the outcome measure (P = .02). Diagnostic performance of quantitative myocardial perfusion estimates is not affected by the tracer kinetic analysis method used. (©) RSNA

  3. Modeling of Tracer Transport Delays for Improved Quantification of Regional Pulmonary 18F-FDG Kinetics, Vascular Transit Times, and Perfusion

    PubMed Central

    Wellman, Tyler J.; Winkler, Tilo; Vidal Melo, Marcos F.

    2015-01-01

    18F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary 18F-FDG kinetics do not account for delays in 18F-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of 18F-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic 18F-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n=6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. 13NN bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of 18F-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0–13.6s, averaging 6.4±2.9s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on 13NN-PET (R2=0.92, p<0.001). By incorporating local vascular transports delays, this model of pulmonary 18F-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation. PMID:25940652

  4. 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%.

  5. 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. Copyright © 2012 Wiley Periodicals, Inc.

  6. 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

  7. Acute myocardial infarction: estimation of at-risk and salvaged myocardium at myocardial perfusion SPECT 1 month after infarction.

    PubMed

    Romero-Farina, Guillermo; Aguadé-Bruix, Santiago; Candell-Riera, Jaume; Pizzi, M Nazarena; Pineda, Victor; Figueras, Jaume; Cuberas, Gemma; de León, Gustavo; Castell-Conesa, Joan; García-Dorado, David

    2013-11-01

    To estimate at-risk and salvaged myocardium by using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging after acute myocardial infarction (AMI). The study was approved by the hospital's Ethical Committee on Clinical Trials (trial register number, PR(HG)36/2000), and all patients gave informed consent. Forty patients (mean age, 61.78 years; eight women) with a first AMI underwent two gated SPECT examinations--one before percutaneous coronary intervention (PCI) and one 4-5 weeks after PCI. Myocardium at risk was estimated by assessing the perfusion defect at the first gated SPECT examination, and salvaged myocardium was estimated by assessing the risk area minus necrosis at the second examination. Myocardium at risk was estimated by determining the discordance between the areas of left ventricular (LV) wall motion and perfusion at the second examination. Concordance between tests was analyzed by means of linear regression analysis, the Pearson correlation, the intraclass correlation coefficient, and Bland-Altman analysis. An improvement in perfusion, wall motion, wall thickening, and LV ejection fraction (P < .001) was observed at 1 month. At 1 month, the area with abnormal wall motion was greater than the area of altered perfusion (35.47 vs 23.1 cm(2); P = .007). The extent of myocardium at risk estimated from this discordance correlated well with myocardium at risk measured at the first gated SPECT examination and with salvaged myocardium between both studies (Pearson correlation: 0.78 and 0.6, respectively). Concordance for correct classification of patients with salvaged myocardium of 50% or greater was 83% (κ = 0.65). Myocardial perfusion gated SPECT performed 1 month after early PCI in a first AMI provides potentially useful information on at-risk and salvaged myocardium. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122324/-/DC1. RSNA, 2013

  8. Fuel Burn Estimation Model

    NASA Technical Reports Server (NTRS)

    Chatterji, Gano

    2011-01-01

    Conclusions: Validated the fuel estimation procedure using flight test data. A good fuel model can be created if weight and fuel data are available. Error in assumed takeoff weight results in similar amount of error in the fuel estimate. Fuel estimation error bounds can be determined.

  9. An educational training simulator for advanced perfusion techniques using a high-fidelity virtual patient model.

    PubMed

    Tokaji, Megumi; Ninomiya, Shinji; Kurosaki, Tatsuya; Orihashi, Kazumasa; Sueda, Taijiro

    2012-12-01

    The operation of cardiopulmonary bypass procedure requires an advanced skill in both physiological and mechanical knowledge. We developed a virtual patient simulator system using a numerical cardiovascular regulation model to manage perfusion crisis. This article evaluates the ability of the new simulator to prevent perfusion crisis. It combined short-term baroreflex regulation of venous capacity, vascular resistance, heart rate, time-varying elastance of the heart, and plasma-refilling with a simple lumped parameter model of the cardiovascular system. The combination of parameters related to baroreflex regulation was calculated using clinical hemodynamic data. We examined the effect of differences in autonomous-nerve control parameter settings on changes in blood volume and hemodynamic parameters and determined the influence of the model on operation of the control arterial line flow and blood volume during the initiation and weaning from cardiopulmonary bypass. Typical blood pressure (BP) changes (hypertension, stable, and hypotension) were reproducible using a combination of four control parameters that can be estimated from changes in patient physiology, BP, and blood volume. This simulation model is a useful educational tool to learn the recognition and management skills of extracorporeal circulation. Identification method for control parameter can be applied for diagnosis of heart failure.

  10. Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion.

    PubMed

    Gowrishankar, T R; Stewart, Donald A; Martin, Gregory T; Weaver, James C

    2004-11-17

    Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1) surface contact heating and (2) spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42 degrees C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45 degrees C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. The heat transport system model of the skin was solved by exploiting the mathematical

  11. Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion

    PubMed Central

    Gowrishankar, TR; Stewart, Donald A; Martin, Gregory T; Weaver, James C

    2004-01-01

    Background Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. Methods We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1) surface contact heating and (2) spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42°C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. Results The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45°C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. Conclusions The heat transport system model of the skin was solved by

  12. Infrared face recognition based on modified blood perfusion model and 2DLDA in DWT domain

    NASA Astrophysics Data System (ADS)

    Wu, Shiqian; Liang, Wei; Fang, Zhijun; Yang, Jucheng; Yuan, Jiasheng

    2009-10-01

    A efficient method for infrared face recognition by modified blood perfusion model of human face and 2DLDA in DWT domain is proposed. Then we demonstrate from the theoretical that the 2DLDA subspace projection result remains the same with the original data are transformed using the wavelet transformation. The experiments conducted illustrate that the method proposed in this paper has better performance. While the recognition rate wasn't decrease based on modified blood perfusion model compared to blood perfusion model obviously and have even lightly improved in some cases.

  13. Evaluation of the maternal-fetal transfer of granisetron in an ex vivo placenta perfusion model.

    PubMed

    Julius, Justin M; Tindall, Andrew; Moise, Kenneth J; Refuerzo, Jerrie S; Berens, Pamela D; Smith, Judith A

    2014-11-01

    The objective of this study was to estimate maternal-fetal transplacental passage of granisetron in an ex vivo placental perfusion model. Term human placentas (N=8) were collected immediately after delivery. A single cotyledon from each placenta was perfused granisetron concentration to mimic systemic maternal peak plasma concentrations following either IV (50ng/mL) or transdermal administration (5ng/mL). To assess drug transfer and accumulation, samples were collected from maternal and fetal compartments. In the 50ng/mL open model, the mean transport fraction was 0.21±0.08 with clearance index of 0.53±0.66. Fetal peak concentrations achieved was 5.6±6.6ng/mL with mean accumulation of 5.35±6.4ng/mL. No drug was detected in the fetal compartment with the 5ng/mL models. Transplacental passage of granisetron was inconsistent at the 50ng/mL concentration that achieved with IV dosing. However, there consistently was no detectable passage in all the placentas evaluated of the granisetron at 5ng/mL concentration that would be achieved after transdermal patch administration. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The lognormal perfusion model for disruption replenishment measurements of blood flow: in vivo validation.

    PubMed

    Hudson, John M; Leung, Kogee; Burns, Peter N

    2011-10-01

    Dynamic contrast enhanced ultrasound (DCE-US) is evolving as a promising tool to noninvasively quantify relative tissue perfusion in organs and solid tumours. Quantification using the method of disruption replenishment is best performed using a model that accurately describes the replenishment of microbubble contrast agents through the ultrasound imaging plane. In this study, the lognormal perfusion model was validated using an exposed in vivo rabbit kidney model. Compared against an implanted transit time flow meter, longitudinal relative flow measurement was (×3) less variable and correlated better when quantification was performed with the lognormal perfusion model (Spearman r = 0.90, 95% confidence interval [CI] = 0.05) vs. the prevailing mono-exponential model (Spearman r = 0.54, 95% CI = 0.18). Disruption-replenishment measurements using the lognormal perfusion model were reproducible in vivo to within 12%.

  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. Understanding and modeling alternating tangential flow filtration for perfusion cell culture.

    PubMed

    Kelly, William; Scully, Jennifer; Zhang, Di; Feng, Gang; Lavengood, Mathew; Condon, Jason; Knighton, John; Bhatia, Ravinder

    2014-01-01

    Alternating tangential flow (ATF) filtration has been used with success in the Biopharmaceutical industry as a lower shear technology for cell retention with perfusion cultures. The ATF system is different than tangential flow filtration; however, in that reverse flow is used once per cycle as a means to minimize fouling. Few studies have been reported in the literature that evaluates ATF and how key system variables affect the rate at which ATF filters foul. In this study, an experimental setup was devised that allowed for determination of the time it took for fouling to occur for given mammalian (PER.C6) cell culture cell densities and viabilities as permeate flow rate and antifoam concentration was varied. The experimental results indicate, in accordance with D'Arcy's law, that the average resistance to permeate flow (across a cycle of operation) increases as biological material deposits on the membrane. Scanning electron microscope images of the post-run filtration surface indicated that both cells and antifoam micelles deposit on the membrane. A unique mathematical model, based on the assumption that fouling was due to pore blockage from the cells and micelles in combination, was devised that allowed for estimation of sticking factors for the cells and the micelles on the membrane. This model was then used to accurately predict the increase in transmembane pressure during constant flux operation for an ATF cartridge used for perfusion cell culture.

  17. 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 ≈ 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 territory. This ratio was 1.00 ± 0.08 at 70 ke

  18. 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

  19. Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

    PubMed

    Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

    2015-08-28

    To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and

  20. Continuously perfused microbubble array for 3D tumor spheroid model

    PubMed Central

    Agastin, Sivaprakash; Giang, Ut-Binh T.; Geng, Yue; DeLouise, Lisa A.; King, Michael R.

    2011-01-01

    Multi-cellular tumor spheroids (MCTSs) have been established as a 3D physiologically relevant tumor model for drug testing in cancer research. However, it is difficult to control the MCTS testing parameters and the entire process is time-consuming and expensive. To overcome these limitations, we developed a simple microfluidic system using polydimethylsiloxane (PDMS) microbubbles to culture tumor spheroids under physiological flow. The flow characteristics such as streamline directions, shear stress profile, and velocity profile inside the microfluidic system were first examined computationally using a COMSOL simulation. Colo205 tumor spheroids were created by a modified hanging drop method and maintained inside PDMS microbubble cavities in perfusion culture. Cell viability inside the microbubbles was examined by live cell staining and confocal imaging. E-selectin mediated cell sorting of Colo205 and MDA-MB-231 cell lines on functionalized microbubble and PDMS surfaces was achieved. Finally, to validate this microfluidic system for drug screening purposes, the toxicity of the anti-cancer drug, doxorubicin, on Colo205 cells in spheroids was tested and compared to cells in 2D culture. Colo205 spheroids cultured in flow showed a threefold increase in resistance to doxorubicin compared to Colo205 monolayer cells cultured under static conditions, consistent with the resistance observed previously in other MCTS models. The advantages presented by our microfluidic system, such as the ability to control the size uniformity of the spheroids and to perform real-time imaging on cells in the growth platform, show potential for high throughput drug screening development. PMID:21716809

  1. Optimization of an isolated perfused rainbow trout liver model: Clearance studies with 7-ethoxycoumarin.

    PubMed

    Nichols, John W; Hoffman, Alex D; Fitzsimmons, Patrick N

    2009-11-27

    To date, research with isolated perfused fish livers has been limited by the relatively short time period during which stable performance can be achieved. In the present study, modifications to existing methods were employed with the goal of extending the usable life of an isolated perfused trout liver preparation. Liver performance was evaluated by measuring O(2) consumption (VO(2)), vascular resistance, K(+) leakage, glucose flux, lactate flux, and clearance of a model metabolic substrate, 7-ethoxycoumarin (CL(H,7-EC)). Livers perfused with solutions containing 15, 38, or 150microM bovine serum albumin (BSA) exhibited relatively stable physiological performance for up to 10h. CL(H,7-EC) decreased rapidly between 1 and 2h in all livers tested, possibly due in part to accumulation of 7-EC within the tissue. CL(H,7-EC) declined slowly thereafter, decreasing by 30-40% between 2 and 10h. A linear equation was subsequently developed to correct measured levels of clearance for this decrease in metabolic activity over time. To illustrate the value of this preparation, experiments were conducted to examine the effects of protein binding on 7-EC clearance. Clearance rates corrected for declining activity (CL(H,7-EC,CORR)) changed in nearly direct proportion to changes in the free concentration of 7-EC efferent to the liver, as predicted by theoretical models of liver function. Additional studies were performed to characterize the concentration-dependence of 7-EC clearance. The rate of substrate disappearance from the perfusate increased in proportion to the total concentration of 7-EC afferent to the liver resulting in constant levels of CL(H,7-EC,CORR). CL(H,7-EC,CORR) values for four livers averaged 12.1+/-2.5mL/h/g-liver (mean+/-SD, n=57 individual determinations) and were in good agreement with an estimate of hepatic clearance obtained by extrapolating published in vitro data from isolated trout hepatocytes. The extended viability of isolated trout livers achieved in

  2. Estimating nonlinear models

    NASA Astrophysics Data System (ADS)

    Billings, S. A.

    1988-03-01

    Time and frequency domain identification methods for nonlinear systems are reviewed. Parametric methods, prediction error methods, structure detection, model validation, and experiment design are discussed. Identification of a liquid level system, a heat exchanger, and a turbocharge automotive diesel engine are illustrated. Rational models are introduced. Spectral analysis for nonlinear systems is treated. Recursive estimation is mentioned.

  3. Perfusion quantification by model-free arterial spin labeling using nonlinear stochastic regularization deconvolution.

    PubMed

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

    2013-11-01

    Quantification of cerebral blood flow can be accomplished by model-free arterial spin labeling using the quantitative STAR labeling of arterial regions (QUASAR) sequence. The required deconvolution is normally based on block-circulant singular value decomposition (cSVD)/oscillation SVD (oSVD), an algorithm associated with nonphysiological residue functions and potential effects of arterial dispersion. The aim of this work was to amend this by implementing nonlinear stochastic regularization (NSR) deconvolution, previously used to retrieve realistic residue functions in dynamic susceptibility contrast MRI. To characterize the residue function in model-free arterial spin labeling, and possibly to improve absolute cerebral blood flow quantification, NSR was applied to deconvolution of QUASAR data. For comparison, SVD-based deconvolution was also employed. Residue function characteristics and cerebral blood flow values from 10 volunteers were obtained. Simulations were performed to support the in vivo results. NSR was able to resolve realistic residue functions in contrast to the SVD-based methods. Mean cerebral blood flow estimates in gray matter were 36.6 ± 2.6, 28.6 ± 3.3, 40.9 ± 3.6, and 42.9 ± 3.9 mL/100 g/min for cSVD, oSVD, NSR, and NSR with correction for arterial dispersion, respectively. In simulations, the NSR-based perfusion estimates showed better accuracy than the SVD-based approaches. Perfusion quantification by model-free arterial spin labeling is evidently dependent on the selected deconvolution method, and NSR is a feasible alternative to SVD-based methods. Copyright © 2012 Wiley Periodicals, Inc.

  4. The effect of initial and dynamic liver conditions on RF ablation size: a study in perfused and non-perfused animal models

    NASA Astrophysics Data System (ADS)

    Belous, Anna; Podhajsky, Ronald J.

    2009-02-01

    Investigators reporting RF ablation (RFA) studies often use different initial and dynamic conditions, often in porcine or bovine liver models. This study examines the effects of initial temperature, prior freezing, and perfusion in these models. Understanding how these variables affect RFA size provides some basis for comparing data from different studies. We obtained porcine and bovine livers from a slaughterhouse and divided them into experimental groups each with discrete initial temperatures set in the range of 12 to 37°C. The livers were used either the day of harvest or frozen within 1-3 days prior to RFA treatment. A perfused liver model was developed to simulate human blood flow rates and allowed accurate control of the temperature and flow rate. Saline (0.9%) was substituted for blood. The non-perfused liver model group included bovine and porcine tissue; whereas the perfused liver model group included only porcine tissue. One experiment included porcine livers that were perfused at different flow rates and with different saline concentrations. Harvested tissue from this group was examined under a light microscope and the level of edema was assessed using image processing software. The results demonstrate no significant difference in RF lesion sizes between porcine and bovine livers. Freezing the tissue prior to treatment has no significant effect but the initial temperature does significantly affect the size of ablation. The ablation size in perfused liver is similar to in vivo results (earlier study) but is significantly smaller then non-perfused liver. Morphological analysis indicates that perfusion, freezing, and saline concentration cause significant tissue edema.

  5. Volume of myocardium perfused by coronary artery branches as estimated from 3D micro-CT images of rat hearts

    NASA Astrophysics Data System (ADS)

    Lund, Patricia E.; Naessens, Lauren C.; Seaman, Catherine A.; Reyes, Denise A.; Ritman, Erik L.

    2000-04-01

    Average myocardial perfusion is remarkably consistent throughout the heart wall under resting conditions and the velocity of blood flow is fairly reproducible from artery to artery. Based on these observations, and the fact that flow through an artery is the product of arterial cross-sectional area and blood flow velocity, we would expect the volume of myocardium perfused to be proportional to the cross-sectional area of the coronary artery perfusing that volume of myocardium. This relationship has been confirmed by others in pigs, dogs and humans. To test the body size-dependence of this relationship we used the hearts from rats, 3 through 25 weeks of age. The coronary arteries were infused with radiopaque microfil polymer and the hearts scanned in a micro- CT scanner. Using these 3D images we measured the volume of myocardium and the arterial cross-sectional area of the artery that perfused that volume of myocardium. The average constant of proportionality was found to be 0.15 +/- 0.08 cm3/mm2. Our data showed no statistically different estimates of the constant of proportionality in the rat hearts of different ages nor between the left and right coronary arteries. This constant is smaller than that observed in large animals and humans, but this difference is consistent with the body mass-dependence on metabolic rate.

  6. Discrepancy between microsphere and diffusible tracer estimates of perfusion to ischemic myocardium

    SciTech Connect

    Yoshida, S.; Akizuki, S.; Gowski, D.; Downey, J.M.

    1985-08-01

    This study critically tests the ability of microspheres to accurately measure perfusion to ischemic myocardium. The left anterior descending coronary artery was cannulated and perfused with arterial blood. The perfusion line was clamped, and a sidearm between the clamp and the cannula was opened to the atmosphere, allowing blood to flow retrograde from the distal segment of the artery. Measurement of regional blood flow during retrograde flow diversion with 15-micron microspheres revealed essentially zero flow to the perfused segment (0.005 ml X min-1 X g-1). Measurements under the same conditions by either /sup 86/Rb uptake or /sup 133/Xe washout revealed that an appreciable perfusion of the tissue persisted during retrograde flow diversion (0.043 and 0.11 ml X min-1 X g-1, respectively, for the 2 methods). Thus, the authors have identified a condition during which microspheres indicate zero flow to the tissue but diffusible tracers can both be washed in and washed out at a brisk rate. They conclude that with simple occlusion there is a hidden component of perfusion to an ischemic zone that cannot be measured by microspheres, causing them to underestimate flow by about 25% in that condition.

  7. Modeling of Tracer Transport Delays for Improved Quantification of Regional Pulmonary ¹⁸F-FDG Kinetics, Vascular Transit Times, and Perfusion.

    PubMed

    Wellman, Tyler J; Winkler, Tilo; Vidal Melo, Marcos F

    2015-11-01

    ¹⁸F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary ¹⁸F-FDG kinetics do not account for delays in ¹⁸F-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of ¹⁸F-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic ¹⁸F-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n = 6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. ¹³NN bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of ¹⁸F-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0 to 13.6 s, averaging 6.4 ± 2.9 s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on ¹³NN-PET (R² = 0.92, p < 0.001). By incorporating local vascular transports delays, this model of pulmonary ¹⁸F-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation.

  8. 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.

  9. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Aortic reservoir function, estimated myocardial demand and coronary perfusion pressure following steady-state and interval exercise.

    PubMed

    Lane, A D; Heffernan, K S; Rossow, L M; Fahs, C A; Ranadive, S M; Yan, H; Baynard, T; Wilund, K; Fernhall, B

    2012-09-01

    Aortic reservoir function is a measure of the aorta's ability to distribute blood during diastole, attenuating the pulsatility of blood flow, and is important in balancing cardiac flow. Effects of acute high versus moderate exercise intensity on reservoir function and cardiac energetics is unknown. Eighteen athletes completed a interval (INT) and steady-state (SS) cycling bout at 60% of VO(2) peak. Reservoir function was calculated as the ratio of diastolic run-off to stroke volume and expressed as a percentage. Coronary perfusion pressure was derived from tissue Doppler imaging and echocardiography. Systolic tension-time integral (TTI) from the aortic pressure waveform served as a measure of myocardial oxygen consumption. All measures were made at rest, 30-min postexercise and 60-min postexercise. Average reservoir function before SS was 76%, which was reduced to 62% 30-min post-SS and 67% 60-min post-SS (P<0.05). Significantly greater reductions in reservoir function were seen following INT (from 71% pre-INT to 45% 30-min post-INT and 53% 60-min INT, P<0.05). Estimated coronary perfusion pressure was reduced 30 min following INT but not SS; both bouts reduced coronary perfusion pressure at 60-min postexercise (P<0.05). TTI increased following both INT and SS at 30- and 60-min postexercise with greater increases following INT (P<0.05). Following exercise, reservoir function was associated with TTI (P<0.05), but not coronary perfusion pressure (P>0.05). We conclude that reservoir function is attenuated following acute SS and INT, but these reductions were greater post-INT, suggesting that exercise intensity affects reservoir function. Reduction of reservoir function following exercise is related to TTI, a reflection of myocardial oxygen consumption but apparently not associated with coronary perfusion pressure.

  11. [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.

  12. 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.

  13. Reference values and physiological characterization of a specific isolated pig kidney perfusion model

    PubMed Central

    Unger, Volker; Grosse-Siestrup, Christian; Fehrenberg, Claudia; Fischer, Axel; Meissler, Michael; Groneberg, David A

    2007-01-01

    Background Models of isolated and perfused kidneys are used to study the effects of drugs, hazardous or toxic substances on renal functions. Since physiological and morphological parameters of small laboratory animal kidneys are difficult to compare to human renal parameters, porcine kidney perfusion models have been developed to simulate closer conditions to the human situation, but exact values of renal parameters for different collection and perfusion conditions have not been reported so far. If the organs could be used out of regular slaughtering processes animal experiments may be avoided. Methods To assess renal perfusion quality, we analyzed different perfusion settings in a standardized model of porcine kidney hemoperfusion with organs collected in the operating theatre (OP: groups A-D) or in a public abattoir (SLA: group E) and compared the data to in vivo measurements in living animals (CON). Experimental groups had defined preservation periods (0, 2 and 24 hrs), one with additional albumin in the perfusate (C) for edema reduction. Results Varying perfusion settings resulted in different functional values (mean ± SD): blood flow (RBF [ml/min*100 g]: (A) 339.9 ± 61.1; (C) 244.5 ± 53.5; (D) 92.8 ± 25.8; (E) 153.8 ± 41.5); glomerular fitration (GFR [ml/min*100 g]: (CON) 76.1 ± 6.2; (A) 59.2 ± 13.9; (C) 25.0 ± 10.6; (D) 1.6 ± 1.3; (E) 16.3 ± 8.2); fractional sodium reabsorption (RFNa [%] (CON) 99.8 ± 0.1; (A) 82.3 ± 8.1; (C) 86.8 ± 10.3; (D) 38.4 ± 24.5; (E) 88.7 ± 5.8). Additionally the tubular coupling-ratio of Na-reabsorption/O2-consumption was determined (TNa/O2-cons [mmol-Na/mmol- O2] (CON) 30.1; (A) 42.0, (C) 80.6; (D) 17.4; (E) 23.8), exhibiting OP and SLA organs with comparable results. Conclusion In the present study functional values for isolated kidneys with different perfusion settings were determined to assess organ perfusion quality. It can be summarized that the hemoperfused porcine kidney can serve as a biological model with

  14. Dynamic Chest Image Analysis: Evaluation of Model-Based Pulmonary Perfusion Analysis With Pyramid Images

    DTIC Science & Technology

    2007-11-02

    Image Analysis 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 18,5,17,6. We have proposed and evaluated a multiresolutional method with an explicit ventilation model based on pyramid images for ventilation analysis. We have further extended the method for ventilation analysis to pulmonary perfusion. This paper focuses on the clinical evaluation of our method for

  15. 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

  16. Mathematical Models of Diffusion-Limited Gas Bubble Evolution in Perfused Tissue

    DTIC Science & Technology

    Mathematical models of gas and bubble dynamics in tissue are used in various algorithms to mitigate the incidence and severity of decompression ... sickness (DCS) in man. These are simple models that describe the diffusion and perfusion processes that underlie gas bubble growth and resolution in terms

  17. Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol

    PubMed Central

    Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

    2015-01-01

    AIM: To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. METHODS: Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. RESULTS: In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. CONCLUSION: It is feasible to establish an

  18. 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. Copyright © 2016 the American Physiological Society.

  19. 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.

  20. Iloprost donor treatment reduces ischemia-reperfusion injury in an isolated extracorporeal pig liver perfusion model.

    PubMed

    Schoening, Wenzel N; Feige, Ines; Schubert, Thomas; Olschewski, Peter; Buescher, Niklas; Helbig, Michael; Schmitz, Volker; Neuhaus, Peter; Pratschke, Johann; Puhl, Gero

    2015-02-01

    Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model. German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2 L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 μg/kg body weight), (3) addition of iloprost to Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 μg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4). Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens. Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls. Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage.

  1. A proposed study on the transplacental transport of parabens in the human placental perfusion model.

    PubMed

    Mathiesen, Line; Zuri, Giuseppina; Andersen, Maria H; Knudsen, Lisbeth E

    2013-12-01

    Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy. 2013 FRAME.

  2. Selective renal blood perfusion induces renal tubules injury in a porcine model.

    PubMed

    Kalder, Johannes; Kokozidou, Maria; Keschenau, Paula; Tamm, Miriam; Greiner, Andreas; Koeppel, Thomas A; Tolba, Rene; Jacobs, Michael J

    2016-03-01

    Extracorporeal circulation is routinely used in thoracoabdominal aortic aneurysm repair to preserve blood perfusion. Despite this protective measure, acute and chronic kidney disorders can develop. Therefore, the aim of this study was to establish a new large-animal model to assess the efficacy of selective renal perfusion (SRP) with extracorporeal circulation in a setting of thoracoabdominal aortic aneurysm repair. Eighteen pigs underwent a thoracolaparotomy, during with the aorta and renal arteries were exposed. The animals were divided into three cohorts of six pigs each: cohort I--control; cohort II--thoracic aortic clamping with distal aortic perfusion (DAP) using a roller pump; and cohort III--thoracic aortic clamping with DAP plus SRP. Kidney metabolism, kidney injury, and red blood cell damage were measured by oxygen extraction ratio (O2ER), neutrophil gelatinase-associated lipocalin, a marker for acute kidney damage, and serum free hemoglobin. With normal mean arterial blood pressures, flow rates in the renal arteries during perfusion decreased to 75% (group II) with DAP and to 50% (group III) with SRP compared with the control animals (group I; P = .0279 for I vs II; P = .0002 for I vs III). Microcirculation, measured by microspheres, did not differ significantly among the groups. In contrast, O2ER (P = .0021 for I vs III) and neutrophil gelatinase-associated lipocalin (P = .0083 for I vs III) levels were significantly increased in group III, whereas free hemoglobin was increased in groups II and III (P = .0406 for I vs II; P = .0018 for I vs III). SRP with a roller pump induces kidney tubule injury. Thus, distal aortic and SRP in our model does not provide adequate kidney protection. Furthermore, the perfusion system provokes red blood cell damage with increased free hemoglobin. Hence, the SRP perfusion technique should be revised and tested. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  3. Flat-panel volumetric computed tomography in cerebral perfusion: evaluation of three rat stroke models.

    PubMed

    Juenemann, Martin; Goegel, Sinja; Obert, Martin; Schleicher, Nadine; Ritschel, Nouha; Doenges, Simone; Eitenmueller, Inka; Schwarz, Niko; Kastaun, Sabrina; Yeniguen, Mesut; Tschernatsch, Marlene; Gerriets, Tibo

    2013-09-30

    Flat-panel volumetric computed tomography (fpVCT) is a non-invasive approach to three-dimensional small animal imaging. The capability of volumetric scanning and a high resolution in time and space enables whole organ perfusion studies. We aimed to assess feasibility and validity of fpVCT in cerebral perfusion measurement with impaired hemodynamics by evaluation of three well-established rat stroke models for temporary and permanent middle cerebral artery occlusion (MCAO). Male Wistar rats were randomly assigned to temporary (group I: suture model) and permanent (group II: suture model; III: macrosphere model) MCAO and to a control group. Perfusion scans with respect to cerebral blood flow (CBF) and volume (CBV) were performed 24h post intervention by fpVCT, using a Gantry rotation time of 1s and a total scanning time of 30s. Postmortem analysis included infarct-size calculation by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Infarct volumes did not differ significantly throughout intervention groups. After permanent MCAO, CBF significantly decreased in subcortical regions to 78.2% (group II, p=0.005) and 79.9% (group III, p=0.012) and in total hemisphere to 77.4% (group II, p=0.010) and 82.0% (group III, p=0.049). CBF was less impaired with temporary vessel occlusion. CBV measurement revealed no significant differences. Results demonstrate feasibility of cerebral perfusion quantification in rats with the fpVCT, which can be a useful tool for non-invasive dynamic imaging of cerebral perfusion in rodent stroke models. In addition to methodological advantages, CBF data confirm the macrosphere model as a useful alternative to the suture model for permanent experimental MCAO.

  4. Modulation and modeling of monoclonal antibody N-linked glycosylation in mammalian cell perfusion reactors.

    PubMed

    Karst, Daniel J; Scibona, Ernesto; Serra, Elisa; Bielser, Jean-Marc; Souquet, Jonathan; Stettler, Matthieu; Broly, Hervé; Soos, Miroslav; Morbidelli, Massimo; Villiger, Thomas K

    2017-09-01

    Mammalian cell perfusion cultures are gaining renewed interest as an alternative to traditional fed-batch processes for the production of therapeutic proteins, such as monoclonal antibodies (mAb). The steady state operation at high viable cell density allows the continuous delivery of antibody product with increased space-time yield and reduced in-process variability of critical product quality attributes (CQA). In particular, the production of a confined mAb N-linked glycosylation pattern has the potential to increase therapeutic efficacy and bioactivity. In this study, we show that accurate control of flow rates, media composition and cell density of a Chinese hamster ovary (CHO) cell perfusion bioreactor allowed the production of a constant glycosylation profile for over 20 days. Steady state was reached after an initial transition phase of 6 days required for the stabilization of extra- and intracellular processes. The possibility to modulate the glycosylation profile was further investigated in a Design of Experiment (DoE), at different viable cell density and media supplement concentrations. This strategy was implemented in a sequential screening approach, where various steady states were achieved sequentially during one culture. It was found that, whereas high ammonia levels reached at high viable cell densities (VCD) values inhibited the processing to complex glycan structures, the supplementation of either galactose, or manganese as well as their synergy significantly increased the proportion of complex forms. The obtained experimental data set was used to compare the reliability of a statistical response surface model (RSM) to a mechanistic model of N-linked glycosylation. The latter outperformed the response surface predictions with respect to its capability and reliability in predicting the system behavior (i.e., glycosylation pattern) outside the experimental space covered by the DoE design used for the model parameter estimation. Therefore, we can

  5. 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.

  6. Tmax Determined Using a Bayesian Estimation Deconvolution Algorithm Applied to Bolus Tracking Perfusion Imaging: A Digital Phantom Validation Study.

    PubMed

    Uwano, Ikuko; Sasaki, Makoto; Kudo, Kohsuke; Boutelier, Timothé; Kameda, Hiroyuki; Mori, Futoshi; Yamashita, Fumio

    2017-01-10

    The Bayesian estimation algorithm improves the precision of bolus tracking perfusion imaging. However, this algorithm cannot directly calculate Tmax, the time scale widely used to identify ischemic penumbra, because Tmax is a non-physiological, artificial index that reflects the tracer arrival delay (TD) and other parameters. We calculated Tmax from the TD and mean transit time (MTT) obtained by the Bayesian algorithm and determined its accuracy in comparison with Tmax obtained by singular value decomposition (SVD) algorithms. The TD and MTT maps were generated by the Bayesian algorithm applied to digital phantoms with time-concentration curves that reflected a range of values for various perfusion metrics using a global arterial input function. Tmax was calculated from the TD and MTT using constants obtained by a linear least-squares fit to Tmax obtained from the two SVD algorithms that showed the best benchmarks in a previous study. Correlations between the Tmax values obtained by the Bayesian and SVD methods were examined. The Bayesian algorithm yielded accurate TD and MTT values relative to the true values of the digital phantom. Tmax calculated from the TD and MTT values with the least-squares fit constants showed excellent correlation (Pearson's correlation coefficient = 0.99) and agreement (intraclass correlation coefficient = 0.99) with Tmax obtained from SVD algorithms. Quantitative analyses of Tmax values calculated from Bayesian-estimation algorithm-derived TD and MTT from a digital phantom correlated and agreed well with Tmax values determined using SVD algorithms.

  7. Improving Embryonic Stem Cell Expansion through the Combination of Perfusion and Bioprocess Model Design

    PubMed Central

    Yeo, David; Kiparissides, Alexandros; Cha, Jae Min; Aguilar-Gallardo, Cristobal; Polak, Julia M.; Tsiridis, Elefterios; Pistikopoulos, Efstratios N.; Mantalaris, Athanasios

    2013-01-01

    Background High proliferative and differentiation capacity renders embryonic stem cells (ESCs) a promising cell source for tissue engineering and cell-based therapies. Harnessing their potential, however, requires well-designed, efficient and reproducible expansion and differentiation protocols as well as avoiding hazardous by-products, such as teratoma formation. Traditional, standard culture methodologies are fragmented and limited in their fed-batch feeding strategies that afford a sub-optimal environment for cellular metabolism. Herein, we investigate the impact of metabolic stress as a result of inefficient feeding utilizing a novel perfusion bioreactor and a mathematical model to achieve bioprocess improvement. Methodology/Principal Findings To characterize nutritional requirements, the expansion of undifferentiated murine ESCs (mESCs) encapsulated in hydrogels was performed in batch and perfusion cultures using bioreactors. Despite sufficient nutrient and growth factor provision, the accumulation of inhibitory metabolites resulted in the unscheduled differentiation of mESCs and a decline in their cell numbers in the batch cultures. In contrast, perfusion cultures maintained metabolite concentration below toxic levels, resulting in the robust expansion (>16-fold) of high quality ‘naïve’ mESCs within 4 days. A multi-scale mathematical model describing population segregated growth kinetics, metabolism and the expression of selected pluripotency (‘stemness’) genes was implemented to maximize information from available experimental data. A global sensitivity analysis (GSA) was employed that identified significant (6/29) model parameters and enabled model validation. Predicting the preferential propagation of undifferentiated ESCs in perfusion culture conditions demonstrates synchrony between theory and experiment. Conclusions/Significance The limitations of batch culture highlight the importance of cellular metabolism in maintaining pluripotency, which

  8. Deconvolution-Based CT and MR Brain Perfusion Measurement: Theoretical Model Revisited and Practical Implementation Details.

    PubMed

    Fieselmann, Andreas; Kowarschik, Markus; Ganguly, Arundhuti; Hornegger, Joachim; Fahrig, Rebecca

    2011-01-01

    Deconvolution-based analysis of CT and MR brain perfusion data is widely used in clinical practice and it is still a topic of ongoing research activities. In this paper, we present a comprehensive derivation and explanation of the underlying physiological model for intravascular tracer systems. We also discuss practical details that are needed to properly implement algorithms for perfusion analysis. Our description of the practical computer implementation is focused on the most frequently employed algebraic deconvolution methods based on the singular value decomposition. In particular, we further discuss the need for regularization in order to obtain physiologically reasonable results. We include an overview of relevant preprocessing steps and provide numerous references to the literature. We cover both CT and MR brain perfusion imaging in this paper because they share many common aspects. The combination of both the theoretical as well as the practical aspects of perfusion analysis explicitly emphasizes the simplifications to the underlying physiological model that are necessary in order to apply it to measured data acquired with current CT and MR scanners.

  9. Application of the steepest slope model reveals different perfusion territories within the mouse placenta.

    PubMed

    Remus, C C; Sedlacik, J; Wedegaertner, U; Arck, P; Hecher, K; Adam, G; Forkert, N D

    2013-10-01

    The steepest slope model is a numerically robust and fast method for perfusion quantification. The purpose of this study was to evaluate if the steepest slope model can be used for quantifying placental perfusion in mice based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) datasets. T1-weighted DCE MRI was performed in 5 pregnant BALB/c mice on gestation day (gd) 14.5 and in 5 mice on gd 16.5 using a 7T small animal MRI scanner. The placentas were manually delineated in the DCE datasets and the arterial input function (AIF) was selected from the kidney hilus. Placental perfusion was determined on a voxel-by-voxel basis using the steepest slope model. Perfusion was averaged over the entire placenta as well as separately calculated for the high-flow compartment within the central labyrinth zone and for the remaining low-flow placenta tissue. The AIF selection was independently performed by two observers for assessment of inter-observer differences. Mean perfusion on gd 14.5 was 135 ml/min/100 ml (standard deviation SD: 29 ml/min/100 ml placenta) and 112 ml/min/100 ml on gd 16.5 for the whole placenta (SD: 32 ml/min/100 ml). Perfusion in the high flow compartment in the central labyrinth was significantly higher (p ≤ 0.002) than in the low-flow compartment including the remaining placenta tissue: 184 ml/min/100 ml (SD: 39 ml/min/100 ml) vs. 119 ml/min/100 ml (SD 28 ml/min/100 ml) on gd 14.5 and 158 ml/min/100 ml (SD: 58 ml/min/100 ml) vs. 114 ml/min/100 ml (SD: 52 ml/min/100 ml of placenta) on gd 16.5. The mean relative inter-rater observer difference was 6%. The steepest slope model is a computationally simple method, which allows perfusion quantification in the mouse placenta. Furthermore, the results of this work indicate that the different placental compartments should be analyzed separately to prevent biased results due to averaging. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Model-based estimation with boundary side information or boundary regularization

    SciTech Connect

    Chiao, P.C.; Rogers, W.L.; Fessler, J.A.; Clinthorne, N.H.; Hero, A.O. . Div. of Nuclear Medicine)

    1994-06-01

    The authors have previously developed a model-based strategy for joint estimation of myocardial perfusion and boundaries using ECT (Emission Computed Tomography). The authors have also reported difficulties with boundary estimation in low contrast and low count rate situations. In this paper, the authors propose using boundary side information (obtainable from high resolution MRI and CT images) or boundary regularization to improve both perfusion and boundary estimation in these situations. To fuse boundary side information into the emission measurements, the authors formulate a joint log-likelihood function to include auxiliary boundary measurements as well as ECT projection measurements. In addition, the authors introduce registration parameters to align auxiliary boundary measurements with ECT measurements and jointly estimate these parameters with other parameters of interest from the composite measurements. In simulated PET O-15 water myocardial perfusion studies using a simplified model, the authors show that the joint estimation improves perfusion estimation performance and gives boundary alignment accuracy of <0.5 mm even at 0.2 million counts. The authors implement boundary regularization through formulating a penalized log-likelihood function. The authors also demonstrate in simulations that simultaneous regularization of the epicardial boundary and myocardial thickness gives comparable perfusion estimation accuracy with the use of boundary side information.

  11. 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

  12. Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

    PubMed

    Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Chen, Bailiang; De Verbizier, Jacques; Beaumont, Marine; Badr, Sammy; Cotten, Anne; Blum, Alain

    2017-06-14

    To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

  13. Protective effect of active perfusion in porcine models of acute myocardial ischemia.

    PubMed

    Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

    2016-10-01

    Mortality rates associated with off‑pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor‑α (TNF‑α), cardiac troponin (cTnI), creatine kinase‑myocardial band (CK‑MB), interleukin (IL)‑6, IL‑10, B‑cell lymphoma 2 (Bcl‑2), and caspase‑3 were detected using enzyme‑linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, an increased rate of myocardial apoptosis, and a decreased expression level of anti‑apoptotic protein, Bcl‑2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl‑2. Furthermore, the current study indicated that active perfusion was more efficacious

  14. Probabilistic pharmacokinetic models of decompression sickness in humans, part 1: Coupled perfusion-limited compartments.

    PubMed

    Murphy, F Gregory; Hada, Ethan A; Doolette, David J; Howle, Laurens E

    2017-07-01

    Decompression sickness (DCS) is a disease caused by gas bubbles forming in body tissues following a reduction in ambient pressure, such as occurs in scuba diving. Probabilistic models for quantifying the risk of DCS are typically composed of a collection of independent, perfusion-limited theoretical tissue compartments which describe gas content or bubble volume within these compartments. It has been previously shown that 'pharmacokinetic' gas content models, with compartments coupled in series, show promise as predictors of the incidence of DCS. The mechanism of coupling can be through perfusion or diffusion. This work examines the application of five novel pharmacokinetic structures with compartments coupled by perfusion to the prediction of the probability and time of onset of DCS in humans. We optimize these models against a training set of human dive trial data consisting of 4335 exposures with 223 DCS cases. Further, we examine the extrapolation quality of the models on an additional set of human dive trial data consisting of 3140 exposures with 147 DCS cases. We find that pharmacokinetic models describe the incidence of DCS for single air bounce dives better than a single-compartment, perfusion-limited model. We further find the U.S. Navy LEM-NMRI98 is a better predictor of DCS risk for the entire training set than any of our pharmacokinetic models. However, one of the pharmacokinetic models we consider, the CS2T3 model, is a better predictor of DCS risk for single air bounce dives and oxygen decompression dives. Additionally, we find that LEM-NMRI98 outperforms CS2T3 on the extrapolation data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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.

  17. [Estimation of cardiac output by first-pass data with technetium-99m-labeled myocardial perfusion imaging agent].

    PubMed

    Muramori, A; Taki, J; Kinuya, S; Miyazaki, Y; Nakajima, K; Matsunari, I; Tonami, N

    1998-06-01

    Technetium-99m-tetrofosmin, a myocardial perfusion imaging agent was used for estimation of cardiac output by means of first-pass radionuclide angiography performed in the anterior projection. Region of interests (ROIs) were assigned over right ventricle, left ventricle and whole chest, and time activity curves (TACs) were obtained. Cardiac output indices (COIs) were calculated by the following equation; COI = p3/2. Qc/[symbol: see text] A(s)ds, where p = number of pixels of the ventricular ROI, Qc = the peak count rate of the TAC obtained from the whole chest's ROI and [symbol: see text] A(s)ds = the area under ventricular TAC. The COI (y) determined by ROI over the left ventricle yield the best correlation with the cardiac output by conventional radionuclide method (x) (y = 0.0381x + 6.22, r = 0.828, n = 48, p < 0.001). In conclusion, cardiac output can be easily measured with first pass data using myocardial perfusion imaging agent.

  18. Quantitative myocardial perfusion measurement using CT perfusion: a validation study in a porcine model of reperfused acute myocardial infarction.

    PubMed

    So, Aaron; Hsieh, Jiang; Li, Jian-Ying; Hadway, Jennifer; Kong, Hua-Fu; Lee, Ting-Yim

    2012-06-01

    We validated a CT perfusion technique with beam hardening (BH) correction for quantitative measurement of myocardial blood flow (MBF). Acute myocardial infarction (AMI) was created in four pigs by occluding the distal LAD for 1 h followed by reperfusion. MBF was measured from dynamic contrast enhanced CT (DCE-CT) scanning of the heart, with correction of cardiac motion and BH, before ischemic insult and on day 7, 10 and 14 post. On day 14 post, radiolabeled microspheres were injected to measure MBF and the results were compared with those measured by CT perfusion. Excised hearts were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine the relationship between MBF measured by CT Perfusion and myocardial viability. MBF measured by CT perfusion was strongly correlated with that by microspheres over a wide range of MBF values (R = 0.81, from 25 to 225 ml min(-1) 100 g(-1)). While MBF in the LAD territory decreased significantly from 98.4 ± 2.5 ml min(-1) 100 g(-1) at baseline to 32.2 ± 9.1 ml min(-1) 100 g(-1), P < 0.05 at day 7 and to 49.4 ± 9.3 ml min(-1) 100 g(-1), P < 0.05 at day 14, the decrease in remote myocardium (LCx territory) from baseline (103.9 ± 1.9 ml min(-1) 100 g(-1)) was minimal throughout the study (90.6 ± 5.1 ml min(-1) 100 g(-1) on day 14 post, P > 0.05). TTC staining confirmed incomplete infarction in the LAD territory and no infarction in the LCx territory. Microvascular obstruction in infarcted tissue resulted in no-reflow and hence persistently low MBF in the reperfused LAD territory which contained a mixture of viable and non-viable tissue. CT perfusion measurement of MBF was accurate and correlated well with histology and microspheres measurements.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. TU-G-204-03: Dynamic CT Myocardial Perfusion Measurement Using First Pass Analysis and Maximum Slope Models

    SciTech Connect

    Hubbard, L; Ziemer, B; Sadeghi, B; Javan, H; Lipinski, J; Molloi, S

    2015-06-15

    Purpose: To evaluate the accuracy of dynamic CT myocardial perfusion measurement using first pass analysis (FPA) and maximum slope models. Methods: A swine animal model was prepared by percutaneous advancement of an angioplasty balloon into the proximal left anterior descending (LAD) coronary artery to induce varying degrees of stenosis. Maximal hyperaemia was achieved in the LAD with an intracoronary adenosine drip (240 µg/min). Serial microsphere and contrast (370 mg/mL iodine, 30 mL, 5mL/s) injections were made over a range of induced stenoses, and dynamic imaging was performed using a 320-row CT scanner at 100 kVp and 200 mA. The FPA CT perfusion technique was used to make vessel-specific myocardial perfusion measurements. CT perfusion measurements using the FPA and maximum slope models were validated using colored microspheres as the reference gold standard. Results: Perfusion measurements using the FPA technique (P-FPA) showed good correlation with minimal offset when compared to perfusion measurements using microspheres (P- Micro) as the reference standard (P -FPA = 0.96 P-Micro + 0.05, R{sup 2} = 0.97, RMSE = 0.19 mL/min/g). In contrast, the maximum slope model technique (P-MS) was shown to underestimate perfusion when compared to microsphere perfusion measurements (P-MS = 0.42 P -Micro −0.48, R{sup 2} = 0.94, RMSE = 3.3 mL/min/g). Conclusion: The results indicate the potential for significant improvements in accuracy of dynamic CT myocardial perfusion measurement using the first pass analysis technique as compared with the standard maximum slope model.

  4. 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.

  5. Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.

    PubMed

    Oh, Jin Sun; Kwon, Yong Seok; Lee, Kyung Ho; Jeong, Woowon; Chung, Sang Kug; Rhee, Kyehan

    2014-01-01

    Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue.

  6. 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.

  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. (18)F-Fluoromisonidazole Kinetic Modeling for Characterization of Tumor Perfusion and Hypoxia in Response to Antiangiogenic Therapy.

    PubMed

    Grkovski, Milan; Emmas, Sally-Ann; Carlin, Sean D

    2017-10-01

    Multiparametric imaging of tumor perfusion and hypoxia with dynamic (18)F-fluoromisonidazole ((18)F-FMISO) PET may allow for an improved response assessment to antiangiogenic therapies. Cediranib (AZD2171) is a potent inhibitor of tyrosine kinase activity associated with vascular endothelial growth factor receptors 1, 2, and 3, currently in phase II/III clinical trials. Serial dynamic (18)F-FMISO PET was performed to investigate changes in tumor biomarkers of perfusion and hypoxia after cediranib treatment. Methods: Twenty-one rats bearing HT29 colorectal xenograft tumors were randomized into a vehicle-treated control group (0.5% methylcellulose daily for 2 d [5 rats] or 7 d [4 rats]) and a cediranib-treated test group (3 mg/kg daily for 2 or 7 d; 6 rats in both groups). All rats were imaged before and after treatment, using a 90-min dynamic PET acquisition after administration of 42.1 ± 3.9 MBq of (18)F-FMISO by tail vein injection. Tumor volumes were delineated manually, and the input function was image-derived (abdominal aorta). Kinetic modeling was performed using an irreversible 1-plasma 2-tissue compartmental model to estimate the kinetic rate constants K1, K1/k2, and k3-surrogates for perfusion, (18)F-FMISO distribution volume, and hypoxia-mediated entrapment, respectively. Tumor-to-blood ratios (TBRs) were calculated on the last dynamic frame (80-90 min). Tumors were assessed ex vivo by digital autoradiography and immunofluorescence for microscopic visualization of perfusion (pimonidazole) and hypoxia (Hoechst 33342). Results: Cediranib treatment resulted in significant reduction of mean voxelwise (18)F-FMISO TBR, K1, and K1/k2 in both the 2-d and the 7-d groups (P < 0.05). The k3 parameter was increased in both groups but reached significance only in the 2-d group. In the vehicle-treated groups, no significant change in TBR, K1, K1/k2, or k3 was observed (P > 0.2). Ex vivo tumor analysis confirmed the presence of hypoxic tumor regions that nevertheless

  9. Estimation in Latent Trait Models.

    ERIC Educational Resources Information Center

    Rigdon, Steven E.; Tsutakawa, Robert K.

    Estimation of ability and item parameters in latent trait models is discussed. When both ability and item parameters are considered fixed but unknown, the method of maximum likelihood for the logistic or probit models is well known. Discussed are techniques for estimating ability and item parameters when the ability parameters or item parameters…

  10. Myocardial contrast echocardiography to assess perfusion in a mouse model of ischemia/reperfusion injury

    NASA Astrophysics Data System (ADS)

    Hossack, John A.; Li, Yinbo; Christensen, Jonathan P.; Yang, Zequan; French, Brent A.

    2004-04-01

    Noninvasive approaches for measuring anatomical and physiological changes resulting from myocardial ischemia / reperfusion injury in the mouse heart have significant value since the mouse provides a practical, low-cost model for modeling human heart disease. In this work, perfusion was assessed before, during and after an induced closed- chest, coronary ischemic event. Ultrasound contrast agent, similar to MP1950, in a saline suspension, was injected via cannulated carotid artery as a bolus and imaged using a Siemens Sequoia 512 scanner and a 15L8 intraoperative transducer operating in second harmonic imaging mode. Image sequences were transferred from the scanner to a PC for analysis. Regions of interest were defined in septal and anterior segments of the myocardium. During the ischemic event, when perfusion was diminished in the anterior segment, mean video intensity in the affected segment was reduced by one half. Furthermore, following reperfusion, hyperemia (enhanced blood flow) was observed in the anterior segment. Specifically, the mean video intensity in the affected segment was increased by approximately 50% over the original baseline level prior to ischemia. Following the approach of Kaul et al., [1], gamma variate curves were fitted to the time varying level of mean video intensity. This foundation suggests the possibility of quantifying myocardial blood flow in ischemic regions of a mouse heart using automated analysis of contrast image data sets. An improved approach to perfusion assessment using the destruction-reperfusion approach [2] is also presented.

  11. Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model.

    PubMed

    Nassar, Ahmed; Liu, Qiang; Farias, Kevin; D'Amico, Giuseppe; Tom, Cynthia; Grady, Patrick; Bennett, Ana; Diago Uso, Teresa; Eghtesad, Bijan; Kelly, Dympna; Fung, John; Abu-Elmagd, Kareem; Miller, Charles; Quintini, Cristiano

    2015-02-01

    Normothermic machine perfusion (NMP) is an emerging preservation modality that holds the potential to prevent the injury associated with low temperature and to promote organ repair that follows ischemic cell damage. While several animal studies have showed its superiority over cold storage (CS), minimal studies in the literature have focused on safety, feasibility, and reliability of this technology, which represent key factors in its implementation into clinical practice. The aim of the present study is to report safety and performance data on NMP of DCD porcine livers. After 60 minutes of warm ischemia time, 20 pig livers were preserved using either NMP (n = 15; physiologic perfusion temperature) or CS group (n = 5) for a preservation time of 10 hours. Livers were then tested on a transplant simulation model for 24 hours. Machine safety was assessed by measuring system failure events, the ability to monitor perfusion parameters, sterility, and vessel integrity. The ability of the machine to preserve injured organs was assessed by liver function tests, hemodynamic parameters, and histology. No system failures were recorded. Target hemodynamic parameters were easily achieved and vascular complications were not encountered. Liver function parameters as well as histology showed significant differences between the 2 groups, with NMP livers showing preserved liver function and histological architecture, while CS livers presenting postreperfusion parameters consistent with unrecoverable cell injury. Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model. © The Author(s) 2014.

  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.

  13. Mathematical modeling of local perfusion in large distensible microvascular networks

    NASA Astrophysics Data System (ADS)

    Causin, Paola; Malgaroli, Francesca

    2017-08-01

    Microvessels -blood vessels with diameter less than 200 microns- form large, intricate networks organized into arterioles, capillaries and venules. In these networks, the distribution of flow and pressure drop is a highly interlaced function of single vessel resistances and mutual vessel interactions. In this paper we propose a mathematical and computational model to study the behavior of microcirculatory networks subjected to different conditions. The network geometry is composed of a graph of connected straight cylinders, each one representing a vessel. The blood flow and pressure drop across the single vessel, further split into smaller elements, are related through a generalized Ohm's law featuring a conductivity parameter, function of the vessel cross section area and geometry, which undergo deformations under pressure loads. The membrane theory is used to describe the deformation of vessel lumina, tailored to the structure of thick-walled arterioles and thin-walled venules. In addition, since venules can possibly experience negative transmural pressures, a buckling model is also included to represent vessel collapse. The complete model including arterioles, capillaries and venules represents a nonlinear system of PDEs, which is approached numerically by finite element discretization and linearization techniques. We use the model to simulate flow in the microcirculation of the human eye retina, a terminal system with a single inlet and outlet. After a phase of validation against experimental measurements, we simulate the network response to different interstitial pressure values. Such a study is carried out both for global and localized variations of the interstitial pressure. In both cases, significant redistributions of the blood flow in the network arise, highlighting the importance of considering the single vessel behavior along with its position and connectivity in the network.

  14. Assessment of the accuracy of a Bayesian estimation algorithm for perfusion CT by using a digital phantom.

    PubMed

    Sasaki, Makoto; Kudo, Kohsuke; Boutelier, Timothé; Pautot, Fabrice; Christensen, Soren; Uwano, Ikuko; Goodwin, Jonathan; Higuchi, Satomi; Ito, Kenji; Yamashita, Fumio

    2013-10-01

    A new deconvolution algorithm, the Bayesian estimation algorithm, was reported to improve the precision of parametric maps created using perfusion computed tomography. However, it remains unclear whether quantitative values generated by this method are more accurate than those generated using optimized deconvolution algorithms of other software packages. Hence, we compared the accuracy of the Bayesian and deconvolution algorithms by using a digital phantom. The digital phantom data, in which concentration-time curves reflecting various known values for cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and tracer delays were embedded, were analyzed using the Bayesian estimation algorithm as well as delay-insensitive singular value decomposition (SVD) algorithms of two software packages that were the best benchmarks in a previous cross-validation study. Correlation and agreement of quantitative values of these algorithms with true values were examined. CBF, CBV, and MTT values estimated by all the algorithms showed strong correlations with the true values (r = 0.91-0.92, 0.97-0.99, and 0.91-0.96, respectively). In addition, the values generated by the Bayesian estimation algorithm for all of these parameters showed good agreement with the true values [intraclass correlation coefficient (ICC) = 0.90, 0.99, and 0.96, respectively], while MTT values from the SVD algorithms were suboptimal (ICC = 0.81-0.82). Quantitative analysis using a digital phantom revealed that the Bayesian estimation algorithm yielded CBF, CBV, and MTT maps strongly correlated with the true values and MTT maps with better agreement than those produced by delay-insensitive SVD algorithms.

  15. Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model.

    PubMed

    Motoyama, Hideki; Chen, Fengshi; Ohsumi, Akihiro; Hijiya, Kyoko; Okita, Kenji; Nakajima, Daisuke; Sakamoto, Jin; Yamada, Tetsu; Sato, Masaaki; Aoyama, Akihiro; Bando, Toru; Date, Hiroshi

    2013-05-01

    Donor lung thrombi are considered an important etiology for primary graft dysfunction in lung transplantation. We hypothesized that thrombolysis before lung transplantation could alleviate ischemia-reperfusion injury. This study was designed to evaluate the effect of the fibrinolytic agent plasmin on lungs damaged by thrombi in an ex vivo lung perfusion (EVLP) system. Rats were divided into control, non-plasmin, and plasmin groups (n = 7 each). In the control and plasmin groups, cardiac arrest was induced by withdrawal of mechanical ventilation without heparinization. Ventilation was restarted 150 minutes after cardiac arrest. The lungs were flushed, and the heart and lungs were excised en bloc. The lungs were perfused in the EVLP system for 60 minutes, and plasmin or placebo was administered upon EVLP initiation. Fibrin/fibrinogen degradation products in the perfusate were significantly higher in the plasmin group than in the control and non-control groups (p < 0.001 for both). Plasmin administration significantly decreased pulmonary vascular resistance (plasmin vs non-plasmin, p = 0.011) and inhibited the exacerbation of dynamic compliance (plasmin vs non-plasmin, p = 0.003). Lung weight gain was less in the plasmin group than in the non-plasmin group (p = 0.04). Our results confirmed that plasmin administration in an EVLP model dissolved thrombi in the lungs, resulting in reconditioning of the lungs as assessed by various physiologic parameters. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  16. 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

  17. 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

  18. 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.

  19. Vertebral osteoporosis: perfused animal cadaver model for testing new vertebroplastic agents.

    PubMed

    Hoell, Thomas; Huschak, Gerald; Beier, Andre; Holzhausen, Hans-Juergen; Meisel, Hans-Joerg; Emmrich, Frank

    2010-12-01

    Experimental study. It was aimed to establish a cadaver model to imitate osteoporotic perfused vertebral bone and to allow for transpedicular transfer of bone cement and various new materials into vertebrae. The model was perfused to simulate vertebroplasty in the presence of transvertebral blood flow. The injection of bone cement into vertebrae bears the risk of irreversible discharge of material into the venous system of the spinal canal. The bovine cadaver model studied allows visual studies of material distribution in a vertebral bone, the potential spill-out of material, and quantification of washout and disintegration phenomena. Thoracic and lumbar vertebrae from 1-year-old calves were cut transversally into 5 mm slices, macerated, and decalcified. The softened bone slices were compressed between 2 transparent plastic discs. A standard vertebroplasty cannula (outer diameter 3.5 mm, inner diameter 2.5 mm) was inserted into the vertebral body via the pedicle to transfer the different vertebroplasty materials. Arterial blood flow was simulated by means of liquid irrigation via 2 needles in the ventral part of the vertebral body slice. Metal powder was mixed with the solution to indicate the blood flow in the bone. The model was evaluated with the vertebroplasty cement polymethylmethacrylate. The model permitted visualization of the insertion and distribution of vertebroplasty materials. Liquid bone cement was effused into the spinal canal as in the clinical situation. Higher modulus cement acted in the same way as in clinical vertebroplasty. Rigid vertebroplasty agents led to trabecular fractures and stable mechanical interactions with the bone and eventually moved dorsal bone fragments into the spinal canal. Sedimentation of the metal powder indicated regions of perfusion. The model simulated the clinical behavior of liquid and higher modulus vertebroplasty agents in the presence of blood flow. It enabled safe ex vivo testing of the mechanical and physical

  20. 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.

  1. NASA Software Cost Estimation Model: An Analogy Based Estimation Model

    NASA Technical Reports Server (NTRS)

    Hihn, Jairus; Juster, Leora; Menzies, Tim; Mathew, George; Johnson, James

    2015-01-01

    The cost estimation of software development activities is increasingly critical for large scale integrated projects such as those at DOD and NASA especially as the software systems become larger and more complex. As an example MSL (Mars Scientific Laboratory) developed at the Jet Propulsion Laboratory launched with over 2 million lines of code making it the largest robotic spacecraft ever flown (Based on the size of the software). Software development activities are also notorious for their cost growth, with NASA flight software averaging over 50% cost growth. All across the agency, estimators and analysts are increasingly being tasked to develop reliable cost estimates in support of program planning and execution. While there has been extensive work on improving parametric methods there is very little focus on the use of models based on analogy and clustering algorithms. In this paper we summarize our findings on effort/cost model estimation and model development based on ten years of software effort estimation research using data mining and machine learning methods to develop estimation models based on analogy and clustering. The NASA Software Cost Model performance is evaluated by comparing it to COCOMO II, linear regression, and K-­ nearest neighbor prediction model performance on the same data set.

  2. Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

    PubMed

    Bezinover, Dmitri; Ramamoorthy, Saravanan; Postula, Marek; Weller, Gregory; Mahmoud, Saifeldin; Mani, Haresh; Kadry, Zakiyah; Uemura, Tadahiro; Mets, Berend; Spiess, Bruce; Brucklacher, Robert; Freeman, Willard; Janicki, Piotr K

    2014-05-15

    Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. How influential is the duration of contrast material bolus injection in perfusion CT? evaluation in a swine model.

    PubMed

    Kandel, Sonja M; Meyer, Henning; Boehnert, Markus; Hoppel, Bernice; Paul, Narinder Singh; Rogalla, Patrik

    2014-01-01

    To analyze the effect of the duration of contrast material bolus injection on perfusion values in a swine model by using the maximum slope method. This study was approved by the institutional animal care committee. Twenty pigs (weight range, 63-77 kg) underwent dynamic volume computed tomography (CT) of the kidneys during suspended respiration. Before the CT examination, a miniature cuff-shaped ultrasonographic flow probe encircling the right renal artery was surgically implanted in each pig to obtain true perfusion values. Two sequential perfusion CT series were performed in 30 seconds, each comprising 30 volumes with identical parameters (100 kV, 200 mAs, 0.5 sec rotation time). The duration of contrast material bolus (0.5 mL/kg of body weight) was 3.8 seconds in the first series (short bolus series) and 11.5 seconds in the second series (long bolus series), and the injection flow rate was adapted accordingly. In each pig, cortical kidney volume was determined by using the volume with the highest cortical enhancement. CT perfusion values were calculated for both series by using the maximum slope method and were statistically compared and correlated with the true perfusion values from the flow probe by using linear regression analysis. Mean true perfusion and CT perfusion values (in minutes(-1)) for the short bolus series were 1.95 and 2.03, respectively (P = .22), and for the long bolus series, they were 2.02 and 1.92, respectively (P = .12). CT perfusion showed very good correlation with true perfusion in both the short (slope, 1.01; 95% confidence interval: 0.91, 1.11) and long (slope, 0.92; 95% confidence interval: 0.78, 1.04) series. On the basis of the regression analysis, CT perfusion values in the short bolus series were overestimated by 1% and those in the long bolus series were underestimated by 8%. Duration of contrast material bolus injection does not influence CT perfusion values substantially. The longer, clinically preferred intravenous injection

  4. Software Cost-Estimation Model

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1985-01-01

    Software Cost Estimation Model SOFTCOST provides automated resource and schedule model for software development. Combines several cost models found in open literature into one comprehensive set of algorithms. Compensates for nearly fifty implementation factors relative to size of task, inherited baseline, organizational and system environment and difficulty of task.

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

    PubMed

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

    2012-09-01

    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. 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. 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 H20 in Group 1 and 49.3 ml/cm H20 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). 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.

  6. A rabbit model of antegrade selective cerebral perfusion with cardioplegic arrest.

    PubMed

    Zou, L; Liu, J; Zhang, H; Wu, S; Long, C; Ji, B; Yu, Z; Tang, Y; Meng, L; Wu, A

    2016-05-01

    Due to the weak ascending aorta, it is extremely challenging to establish an anterograde selective cerebral perfusion (ASCP) model in rabbits, especially when cardioplegic arrest is required. Herein, the aim of this study was to establish a rabbit ASCP model with cardiac arrest being easily performed and being similar to the clinical scenario. Twenty-two adult New Zealand white rabbits were selected for ASCP model establishment and another 22 rabbits were utilized for blood donation. The cardiopulmonary bypass (CPB) circuit consisted of a roller pump, a membrane oxygenator, a heat-cooler system and a blood reservoir, which were connected by silicone tubing. The total priming volume of the circuit was 70 ml. Cannulations on the right and left subclavian arteries were used for arterial inflow and cardioplegia perfusion, respectively. Venous drainage was conducted through the right atrial appendage. ASCP was initiated by clamping the innominate artery; the flow rate was maintained 10 ml/kg/minute and sustained for 60 minutes. After 120 minutes of reperfusion, the rabbits were sacrificed. The mean arterial pressure, heart rate, electrocardiogram and urine output were monitored. Arterial blood samples were analyzed at the following time points: after anesthesia, immediately after CPB, after aorta cross-clamping and cardioplegia perfusion, 5 min after the re-opening of the aorta and at CPB termination. ASCP modeling was performed successfully on 18 rabbits and 4 rabbits unsuccessfully. Vital signs and blood gas indictors changed in an acceptable range throughout the experiments. One rabbit had ventricular fibrillation after re-opening of the ascending aorta. Obvious hemodilution occurred after the perfusion of cardioplegia, but the hematocrit improved after CPB termination. By using cannulation of the subclavian artery rather than the aorta and with a low priming volume, we established a modified rabbit model of ASCP with cardioplegic arrest. The model has excellent

  7. Electrocardiogram frequency change by extracorporeal blood perfusion in a swine ventricular fibrillation model

    PubMed Central

    2013-01-01

    Background Extracorporeal cardiopulmonary resuscitation (ECPR) refers to the application of extracorporeal blood circulation with oxygenation as a resuscitation tool. The objective of this study is to observe the frequency component changes in the electrocardiogram (ECG) by ECPR during prolonged ventricular fibrillation (VF). Methods Six swine were prepared as a VF model. Extracorporeal blood circulation with a pulsatile blood pump and oxygenator was set up for the model. ECG signals were measured for 13 min during VF and analyzed using frequency analysis methods. The median frequency (MF), dominant frequency (DF), and amplitude spectrum area (AMSA) were calculated from a spectrogram obtained using short-time Fourier transform (STFT). Results MF decreased from 11 Hz at the start to 9 Hz at 2 min after VF and then increased to 11 Hz at 4.5 min after VF. DF started at 7 Hz and increased to 11 Hz within the first min and decreased to 9 Hz at 2 min, then increased to 12 Hz at 4.5 min after VF. Both frequency components decreased gradually from 4.5 min until 10 min after VF. After the oxygenated blood perfusion was initiated, both MF and DF increased remarkably and exceeded 12 and 14 Hz, respectively. Similarly, AMSA decreased gradually for the first 10 min, but increased remarkably and varied beyond 13 mV∙Hz after the oxygenated blood supply started. Remarkable frequency increases in ECG due to the oxygenated blood perfusion during ECPR were observed in the swine VF model. Conclusions The ECG frequency analysis during ECPR can give the resuscitation provider important information about the cardiac perfusion status and the appropriateness of the ECPR setup as well as the prediction of defibrillation success. PMID:24274395

  8. Validation and evaluation of model-based crosstalk compensation method in simultaneous /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT

    NASA Astrophysics Data System (ADS)

    Song, X.; Frey, E. C.; Wang, W. T.; Du, Y.; Tsui, B. M. W.

    2004-02-01

    Simultaneous acquisition of /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT has several potential advantages, but the image quality is degraded by crosstalk between the Tc and Tl data. We have previously developed a crosstalk model that includes estimates of the downscatter and Pb X-ray for use in crosstalk compensation. In this work, we validated the model by comparing the crosstalk from /sup 99m/Tc to the Tl window calculated using a combination of the SimSET-MCNP Monte Carlo simulation codes. We also evaluated the model-based crosstalk compensation method using both simulated data from the 3-D MCAT phantom and experimental data from a physical phantom with a myocardial defect. In these studies, the Tl distributions were reconstructed from crosstalk contaminated data without crosstalk compensation, with compensation using the model-based crosstalk estimate, and with compensation using the known true crosstalk, and were compared with the Tl distribution reconstructed from uncontaminated Tl data. Results show that the model gave good estimates of both the downscatter photons and Pb X-rays in the simultaneous dual-isotopes myocardial perfusion SPECT. The model-based compensation method provided image quality that was significantly improved as compared to no compensation and was very close to that from the separate acquisition.

  9. Human Mesenchymal Stromal Cells Improve Cardiac Perfusion in an Ovine Immunocompetent Animal Model.

    PubMed

    Dayan, Victor; Sotelo, Veronica; Delfina, Valentina; Delgado, Natalia; Rodriguez, Carlos; Suanes, Carol; Langhain, María; Ferrando, Rodolfo; Keating, Armand; Benech, Alejandro; Touriño, Cristina

    2016-08-01

    Mesenchymal stromal cells (MSCs) hold considerable promise in the treatment of ischemic heart disease. Most preclinical studies of MSCs for acute myocardial infarction (AMI) have been performed either in syngeneic animal models or with human cells in xenogeneic immunodeficient animals. A preferable pre-clinical model, however, would involve human MSCs in an immunocompetent animal. AMI was generated in adult sheep by inducing ischemia reperfusion of the second diagonal branch. Sheep (n = 10) were randomized to receive an intravenous injection of human MSCs (1 × 10(6) cells/kg) or phosphate buffered saline. Cardiac function and remodeling were evaluated with echocardiography. Perfusion scintigraphy was used to identify sustained myocardial ischemia. Interaction between human MSCs and ovine lymphocytes was assessed by a mixed lymphocyte response (MLR). Sheep receiving human MSCs showed significant improvement in myocardial perfusion at 1 month compared with baseline measurements. There was no change in ventricular dimensions in either group after 1 month of AMI. No adverse events or symptoms were observed in the sheep receiving human MSCs. The MLR was negative. The immunocompetent ovine AMI model demonstrates the clinical safety and efficacy of human MSCs. The human cells do not appear to be immunogenic, further suggesting that immunocompetent sheep may serve as a suitable pre-clinical large animal model for testing human MSCs.

  10. 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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Use of perfusion bioreactors and large animal models for long bone tissue engineering.

    PubMed

    Gardel, Leandro S; Serra, Luís A; Reis, Rui L; Gomes, Manuela E

    2014-04-01

    Tissue engineering and regenerative medicine (TERM) strategies for generation of new bone tissue includes the combined use of autologous or heterologous mesenchymal stem cells (MSC) and three-dimensional (3D) scaffold materials serving as structural support for the cells, that develop into tissue-like substitutes under appropriate in vitro culture conditions. This approach is very important due to the limitations and risks associated with autologous, as well as allogenic bone grafiting procedures currently used. However, the cultivation of osteoprogenitor cells in 3D scaffolds presents several challenges, such as the efficient transport of nutrient and oxygen and removal of waste products from the cells in the interior of the scaffold. In this context, perfusion bioreactor systems are key components for bone TERM, as many recent studies have shown that such systems can provide dynamic environments with enhanced diffusion of nutrients and therefore, perfusion can be used to generate grafts of clinically relevant sizes and shapes. Nevertheless, to determine whether a developed tissue-like substitute conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation, and for this reason, the use of animal models is often an essential step in the testing of orthopedic implants before clinical use in humans. This review provides an overview of the concepts, advantages, and challenges associated with different types of perfusion bioreactor systems, particularly focusing on systems that may enable the generation of critical size tissue engineered constructs. Furthermore, this review discusses some of the most frequently used animal models, such as sheep and goats, to study the in vivo functionality of bone implant materials, in critical size defects.

  12. Chelidonium majus and its effects on uterine contractility in a perfusion model.

    PubMed

    Kuenzel, Julian; Geisler, Klaudija; Strahl, Olga; Grundtner, Philipp; Beckmann, Matthias W; Dittrich, Ralf

    2013-07-01

    The herbal agent celandine is thought to have mainly spasmolytic effects, but in the uterus it is regarded as promoting contractions, which can offer promising and innovative options for optimizing artificial reproduction. The aim of the present study was to investigate the effect of celandine on the uterine muscle, using a perfusion model of swine uteri. Sixteen swine uteri were perfused with Krebs-Ringer solution. Celandine (Chelidonium, Paverysat; Johannes Bürger Ysatfabrik Ltd., Bad Harzburg, Germany) was administered at increasing dosages. Intrauterine pressure (IUP) was recorded using an intrauterine double-chip microcatheter (Urobar 8 DS-F, Raumedic, Rehau AG & Co., Rehau, Germany). Differences in pressure (ΔP) and area under the curve (ΔAUC) after drug administration in the uterine body and uterine horn in the various dilution series were noted. A paired Student's t-test was used to evaluate differences between groups, with significance set at P<0.05. A significant initial increase in uterine activity was visible at each dosage. Inhibition of uterine activity was seen over longer periods of 5 and 10 min, particularly for a medium-dose range of 1-2mg/ml. At a dosage of 2mg/ml in particular, celandine almost always led to significant values. Following intra-arterial administration in a swine uterus perfusion model, celandine initially causes a significant increase in contractility, which is followed over time by a relaxation phase. This suggests interesting hypotheses on whether Chelidonium majus might be used to promote targeted sperm transport. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. HMGB1/TLR4 signaling induces an inflammatory response following high-pressure renal pelvic perfusion in a porcine model.

    PubMed

    Shao, Yi; Sha, Minglei; Chen, Lei; Li, Deng; Lu, Jun; Xia, Shujie

    2016-11-01

    Percutaneous nephrolithotomy (PCNL) causes a rapid increase in renal pelvic pressure in the kidney, which induces an inflammatory response. High-mobility group box-1 (HMGB1) is known to trigger the recruitment of inflammatory cells and the release of proinflammatory cytokines following ischemia reperfusion injury in the kidney, but the contribution of HMGB1 to the inflammatory response following high-pressure renal pelvic perfusion has not been investigated. In this study, high-pressure renal pelvic perfusion was induced in anesthetized pigs to examine the effect of HMGB1 on the inflammatory response. HMGB1 levels in the kidney increased following high-pressure renal pelvic perfusion, together with elevated levels of inflammatory cytokines in the plasma and kidney and an accumulation of neutrophils and macrophages. Inhibition of HMGB1 alleviated this inflammatory response while perfusion with recombinant HMGB1 had an augmentative effect, confirming the involvement of HMGB1 in the inflammatory response to high-pressure renal pelvic perfusion. HMGB1 regulated the inflammatory response by activating Toll-like receptor 4 (TLR4) signaling. In conclusion, this study has demonstrated that HMGB1/TLR4 signaling contributes to the inflammatory response following high-pressure renal pelvic perfusion in a porcine model and has implications for the management of inflammation after PCNL. Copyright © 2016 the American Physiological Society.

  14. Improving Temporal Resolution of Pulmonary Perfusion Imaging in Rats using the Partially Separable Function Model

    PubMed Central

    Brinegar, Cornelius; Schmitter, Sarah S.; Mistry, Nilesh N.; Johnson, G. Allan; Liang, Zhi-Pei

    2010-01-01

    Dynamic contrast-enhanced MRI (or DCE-MRI) is a useful tool for measuring blood flow and perfusion, and it has found use in the study of pulmonary perfusion in animal models. However, DCE-MRI experiments are difficult in small animals such as rats. A recently developed method known as Interleaved Radial Imaging and Sliding window-keyhole (IRIS) addresses this problem by using a data acquisition scheme that covers (k, t)-space with data acquired from multiple bolus injections of a contrast agent. However, the temporal resolution of IRIS is limited by the effects of temporal averaging inherent in the sliding window and keyhole operations. This paper describes a new method to cover (k, t)-space based on the theory of partially separable functions (PSF). Specifically, a sparse sampling of (k, t)-space is performed to acquire two data sets, one with high temporal resolution and the other with extended k-space coverage. The high temporal resolution training data are used to determine the temporal basis functions of the PSF model, while the other data set is used to determine the spatial variations of the model. The proposed method was validated by simulations and demonstrated by an experimental study. In this particular study, the proposed method achieved a temporal resolution of 32 ms. PMID:20564601

  15. 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.

  16. 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

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

    2015-01-01

    To test the hypothesis that taking translamina pressure difference into consideration changes associations between ocular perfusion pressure and glaucomatous optic neuropathy. 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/m(2)) + 0.16 diastolic blood pressure (mm Hg) - 0.18 × age (years) - 1.91. Translamina pressure difference was IOP minus cerebrospinal fluid pressure. 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). 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 support of the idea that ocular perfusion pressure plays a

  17. DCE-MRI of hepatocellular carcinoma: perfusion quantification with Tofts model versus shutter-speed model—initial experience

    PubMed Central

    Jajamovich, Guido H.; Huang, Wei; Besa, Cecilia; Li, Xin; Afzal, Aneela; Dyvorne, Hadrien A.; Taouli, Bachir

    2016-01-01

    Objective To quantify hepatocellular carcinoma (HCC) perfusion and flow with the fast exchange regime-allowed Shutter-Speed model (SSM) compared to the Tofts model (TM). Materials and methods In this prospective study, 25 patients with HCC underwent DCE-MRI. ROIs were placed in liver parenchyma, portal vein, aorta and HCC lesions. Signal intensities were analyzed employing dual-input TM and SSM models. ART (arterial fraction), Ktrans (contrast agent transfer rate constant from plasma to extravascular extracellular space), ve (extravascular extracellular volume fraction), kep (contrast agent intravasation rate constant), and τi (mean intracellular water molecule lifetime) were compared between liver parenchyma and HCC, and ART, Ktrans, ve and kep were compared between models using Wilcoxon tests and limits of agreement. Test–retest reproducibility was assessed in 10 patients. Results ART and ve obtained with TM; ART, ve, ke and τi obtained with SSM were significantly different between liver parenchyma and HCC (p < 0.04). Parameters showed variable reproducibility (CV range 14.7–66.5 % for both models). Liver Ktrans and ve; HCC ve and kep were significantly different when estimated with the two models (p < 0.03). Conclusion Our results show differences when computed between the TM and the SSM. However, these differences are smaller than parameter reproducibilities and may be of limited clinical significance. PMID:26646522

  18. 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

  19. Estimation of the percentage of transgenic Bt maize in maize flour mixtures using perfusion and monolithic reversed-phase high-performance liquid chromatography and chemometric tools.

    PubMed

    Rodríguez-Nogales, J M; Cifuentes, A; García, M C; Marina, M L

    2008-11-15

    The estimation of the percentage of transgenic Bt maize in maize flour mixtures has been achieved in this work by high-performance liquid chromatography using perfusion and monolithic columns and chemometric analysis. Principal component analysis allowed a preliminary study of the data structure. Then, linear discriminant analysis was used to develop decision rules to classify samples in the established categories (percentages of transgenic Bt maize). Finally, linear regression (LR) and multivariate regression models (namely, principal component analysis regression (PCR), partial least squares regression (PLS-1), and multiple linear regression (MLR)) were assayed for the prediction of the percentages of transgenic Bt maize present in a maize flour mixture. Using the relative areas of the protein peaks, MLR provided the best models and was able to predict the percentage of transgenic Bt maize in flour mixtures with an error of ±5.3%, ±2.3%, and ±3.8% in the predictions of Aristis Bt, DKC6575, and PR33P67, respectively.

  20. Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.

    PubMed

    Yumoto, Masato; Nishida, Osamu; Nakamura, Fujio; Katsuya, Hirotada

    2005-01-01

    Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values. Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.

  1. Calpain Inhibition Improves Collateral Dependent Perfusion in a Hypercholesterolemic Swine Model of Chronic Myocardial Ischemia

    PubMed Central

    Sabe, Ashraf A.; Potz, Brittany A.; Elmadhun, Nassrene Y.; Liu, Yuhong; Feng, Jun; Abid, M. Ruhul; Abbott, Jinnette D; Senger, Donald R; Sellke, Frank W.

    2015-01-01

    Background Calpain over-expression is implicated in aberrant angiogenesis. We hypothesized that calpain inhibition (CI, MDL28170) would improve collateral perfusion in a swine model with hypercholesterolemia and chronic myocardial ischemia. Methods and Results Yorkshire swine fed a high cholesterol diet for 4 weeks underwent surgical placement of an ameroid constrictor to their left circumflex coronary artery. Three weeks later, animals received either: no drug, high cholesterol control group (HCC; n= 8); low dose CI (0.12 mg/kg; LCI, n= 9); or high dose CI (0.25 mg/kg; HCI, n= 8). The heart was harvested after 5 weeks. There was a trend toward increased right to left collateral vessels on angiography with HCI. Myocardial perfusion in ischemic myocardium significantly improved with HCI at rest and with demand pacing (p = 0.016 and 0.011). Endothelium-dependent microvessel relaxation was significantly improved with LCI (p = 0.001). There was a significant increase in capillary density, with LCI and HCI (p= 0.01 and 0.01), and arteriolar density with LCI (p= 0.001). CI significantly increased several proangiogenic proteins including VEGF (p= 0.02), VEGFR1 (p= 0.003), VEGFR2 (p= 0.003) and talin, a microvascular structural protein (p= 0.0002). There was a slight increase in proteins implicated in endothelial-dependent (NO Mediated) relaxation including ERK, p-ERK and iNOS with CI. Conclusions In the setting of hypercholesterolemia, CI improved perfusion, with a trend toward increased collateralization on angiography and increased capillary and arteriolar densities in ischemic myocardium. CI also improved endothelium-dependent microvessel relaxation and increased expression of proteins implicated in angiogenesis and vasodilatation. PMID:26478238

  2. 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

  3. 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.

  4. 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.

  5. Theoretical considerations in measurement of time discrepancies between input and myocardial time-signal intensity curves in estimates of regional myocardial perfusion with first-pass contrast-enhanced MRI.

    PubMed

    Natsume, Takahiro; Ishida, Masaki; Kitagawa, Kakuya; Nagata, Motonori; Sakuma, Hajime; Ichihara, Takashi

    2015-11-01

    The purpose of this study was to develop a method to determine time discrepancies between input and myocardial time-signal intensity (TSI) curves for accurate estimation of myocardial perfusion with first-pass contrast-enhanced MRI. Estimation of myocardial perfusion with contrast-enhanced MRI using kinetic models requires faithful recording of contrast content in the blood and myocardium. Typically, the arterial input function (AIF) is obtained by setting a region of interest in the left ventricular cavity. However, there is a small delay between the AIF and the myocardial curves, and such time discrepancies can lead to errors in flow estimation using Patlak plot analysis. In this study, the time discrepancies between the arterial TSI curve and the myocardial tissue TSI curve were estimated based on the compartment model. In the early phase after the arrival of the contrast agent in the myocardium, the relationship between rate constant K1 and the concentrations of Gd-DTPA contrast agent in the myocardium and arterial blood (LV blood) can be described by the equation K1={dCmyo(tpeak)/dt}/Ca(tpeak), where Cmyo(t) and Ca(t) are the relative concentrations of Gd-DTPA contrast agent in the myocardium and in the LV blood, respectively, and tpeak is the time corresponding to the peak of Ca(t). In the ideal case, the time corresponding to the maximum upslope of Cmyo(t), tmax, is equal to tpeak. In practice, however, there is a small difference in the arrival times of the contrast agent into the LV and into the myocardium. This difference was estimated to correspond to the difference between tpeak and tmax. The magnitudes of such time discrepancies and the effectiveness of the correction for these time discrepancies were measured in 18 subjects who underwent myocardial perfusion MRI under rest and stress conditions. The effects of the time discrepancies could be corrected effectively in the myocardial perfusion estimates. Copyright © 2015 Elsevier Inc. All rights

  6. Estimating the sample size required to detect an arterial spin labelling magnetic resonance imaging perfusion abnormality in voxel-wise group analyses.

    PubMed

    Mersov, Anna M; Crane, David E; Chappell, Michael A; Black, Sandra E; MacIntosh, Bradley J

    2015-04-30

    Voxel-based analyses are pervasive across the range of neuroimaging techniques. In the case of perfusion imaging using arterial spin labelling (ASL), a low signal-to-noise technique, there is a tradeoff between the contrast-to-noise required to detect a perfusion abnormality and its spatial localisation. In exploratory studies, the use of an a priori region of interest (ROI), which has the benefit of averaging multiple voxels, may not be justified. Thus the question considered in this study pertains to the sample size that is required to detect a voxel-level perfusion difference between groups and two algorithms are considered. Empirical 3T ASL data were acquired from 25 older adults and simulations were performed based on the group template cerebral blood flow (CBF) images. General linear model (GLM) and permutation-based algorithms were tested for their ability to detect a predefined hypoperfused ROI. Simulation parameters included: inter and intra-subject variability, degree of hypoperfusion and sample size. The true positive rate was used as a measure of sensitivity. For a modest group perfusion difference, i.e., 10%, 37 participants per group were required when using the permutation-based algorithm, whereas 20 participants were required for the GLM-based algorithm. This study advances the perfusion power calculation literature by considering a voxel-wise analysis with correction for multiple comparison. The sample size requirement to detect group differences decreased exponentially in proportion to increased degree of hypoperfusion. In addition, sensitivity to detect a perfusion abnormality was influenced by the choice of algorithm. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Bayesian Estimation of Intrinsic Tissue Oxygenation and Perfusion from RGB Images.

    PubMed

    Jones, Geoffrey; Clancy, Neil; Helo, Yusuf; Arridge, Simon; Elson, Dan; Stoyanov, Danail

    2017-02-20

    Multispectral imaging (MSI) can potentially assist the intra-operative assessment of tissue structure, function and viability, by providing information about oxygenation. In this paper, we present a novel technique for recovering intrinsic MSI measurements from endoscopic RGB images without custom hardware adaptations. The advantage of this approach is that it requires no modification to existing surgical and diagnostic endoscopic imaging systems. Our method uses a radiometric colour calibration of the endoscopic camera's sensor in conjunction with a Bayesian framework to recover a per-pixel measurement of the total blood volume (THb) and oxygen saturation (SO2) in the observed tissue. The sensor's pixel measurements are modelled as weighted sums over a mixture of Poisson distributions and we optimise the variables SO2 and THb to maximise the likelihood of the observations. To validate our technique, we use synthetic images generated from Monte Carlo (MC) physics simulation of light transport through soft tissue containing sub-surface blood vessels. We also validate our method on in vivo data by comparing it to a MSI dataset acquired with a hardware system that sequentially images multiple spectral bands without overlap. Our results are promising and show that we are able to provide surgeons with additional relevant information by processing endoscopic images with our modelling and inference framework.

  8. Protease inhibitor nafamostat mesilate attenuates complement activation and improves function of xenografts in a discordant lung perfusion model.

    PubMed

    Tagawa, Tsutomu

    2011-01-01

    Anti-complement activity of nafamostat mesilate (FUT-175) is strong including its variety of pharmacological effects. The effect of FUT-175 for xenografts in an ex vivo guinea pig-to-rat lung perfusion model was evaluated. Heparinized Lewis rat blood was used to perfuse the lungs in three groups (n = 6 each). Group I used Lewis rat left lung for donor, Group X used guinea pig left lung for donor, and Group XF used guinea pig left lung for donor, which was perfused with Lewis rat blood with 0.2 mg/ml of FUT-175. Complement activity causing 50% hemolysis (CH50) in the perfusion blood and pulmonary function either before or during perfusion were serially measured. Pathological assessments of the lungs were also carried out after perfusion. The duration of satisfactory pulmonary function was significantly increased in Group XF. Complement activity causing 50% hemolysis in Group XF decreased more significantly compared to Group X. FUT-175 suppressed both the increase in pulmonary arterial pressure and airway resistance, and the decrease in dynamic lung compliance. In Group X, pathology showed intra-alveolar hemorrhage, perivascular edema, and medial thickening with endothelial swelling of the pulmonary arteries. In Group XF, less changes were observed compared to Group X. Group X showed deposition of IgM, IgG, and C3 at the endothelium of arteries, which was fewer in Group XF, and even fewer in Group I. This study suggests that FUT-175 inhibited complement activation and improved lung xenograft function. FUT-175 ameliorates hyperacute rejection in a guinea pig-to-rat ex vivo xenogeneic lung perfusion model. © 2011 John Wiley & Sons A/S.

  9. Perfusion computed tomography imaging of abdominal aortic aneurysms may be of value for patient specific rupture risk estimation.

    PubMed

    Kontopodis, Nikolaos; Galanakis, Nikolaos; Tsetis, Dimitrios; Ioannou, Christos V

    2017-04-01

    Abdominal aortic aneurysm (AAA) continues to pose a significant cause of unexpected mortality in the developed countries with its incidence constantly rising. The indication of elective surgical repair is currently based on the maximum diameter and growth rate criteria which represent an oversimplification of the Law of Laplace stating that the stress exerted in a cylinder or sphere is proportional to its radius. These criteria fail to capture the complex pathophysiology of the aneurismal disease thus often leading to therapeutic inaccuracies (treating large AAAs with a very low actual rupture risk while observing smaller ones with a much greater risk). Aneurysmal disease is mainly a degenerative process leading to loss of structural integrity of the diseased aortic wall which cannot withhold the stresses due to systemic pressurization. Moreover aortic wall degeneration has been shown to be a localized phenomenon and rupture depends on the pointwise comparison of strength and stress rather than a global aortic wall weakening. Ex-vivo mechanical studies have related vessel wall hypoxia to loss of structural endurance and reduced wall strength. Therefore a module to capture in vivo variation of aortic wall blood supply and oxygenation would be of value for the evaluation of AAA rupture risk. Perfusion computed tomography (PCT) imaging represents a novel technique which has been already used to estimate tissue vascularity in several clinical conditions but not aneurismal disease. We hypothesize that PCT could be used as an adjunct tool during AAA diagnostics in order to evaluate aortic wall oxygenation in vivo, therefore providing a possible means to identify weak spots making the lesion amenable to rupture.

  10. 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

  11. Accurate bolus arrival time estimation using piecewise linear model fitting

    NASA Astrophysics Data System (ADS)

    Abdou, Elhassan; de Mey, Johan; De Ridder, Mark; Vandemeulebroucke, Jef

    2017-02-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is an emerging radiological technique, which consists in acquiring a rapid sequence of CT images, shortly after the injection of an intravenous contrast agent. The passage of the contrast agent in a tissue results in a varying CT intensity over time, recorded in time-attenuation curves (TACs), which can be related to the contrast supplied to that tissue via the supplying artery to estimate the local perfusion and permeability characteristics. The time delay between the arrival of the contrast bolus in the feeding artery and the tissue of interest, called the bolus arrival time (BAT), needs to be determined accurately to enable reliable perfusion analysis. Its automated identification is however highly sensitive to noise. We propose an accurate and efficient method for estimating the BAT from DCE-CT images. The method relies on a piecewise linear TAC model with four segments and suitable parameter constraints for limiting the range of possible values. The model is fitted to the acquired TACs in a multiresolution fashion using an iterative optimization approach. The performance of the method was evaluated on simulated and real perfusion data of lung and rectum tumours. In both cases, the method was found to be stable, leading to average accuracies in the order of the temporal resolution of the dynamic sequence. For reasonable levels of noise, the results were found to be comparable to those obtained using a previously proposed method, employing a full search algorithm, but requiring an order of magnitude more computation time.

  12. 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.

  13. An approximate nonlinear model for time gain compensation of amplitude modulated images of ultrasound contrast agent perfusion.

    PubMed

    Mari, Jean; Hibbs, Kathryn; Stride, Eleanor; Eckersley, Robert; Tang, Meng

    2010-04-01

    Microbubble ultrasound contrast agents allow blood perfusion to be imaged at the cost of an increased attenuation that is not properly handled by existing time gain compensation methods. An automatic TGC has been developed that is able to account for different microbubble concentrations. The technique is an extension of a previously tested approach for modeling the nonlinear dependence of microbubble backscattering upon insonating pressure. The proposed method involves modeling in amplitude of the nonlinear attenuation for both forward and backward propagation, and the solution is achieved through an approximation set to overestimate the attenuation. The resulting equations are used to model and compensate amplitude modulation (AM) images; they are tested on radiofrequency data acquired using a clinical scanner from a gelatin tissue-mimicking phantom submerged in a contrast agent solution in the 0.08 MI to 0.51 MI range at 2 MHz. The nonlinear estimation equation presented here provides a significantly improved amplification profile compared with standard TGC algorithms, resulting in more accurate attenuation correction of the AM image.

  14. 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.

  15. Motion models in attitude estimation

    NASA Technical Reports Server (NTRS)

    Chu, D.; Wheeler, Z.; Sedlak, J.

    1994-01-01

    Attitude estimator use observations from different times to reduce the effects of noise. If the vehicle is rotating, the attitude at one time needs to be propagated to that at another time. If the vehicle measures its angular velocity, attitude propagating entails integrating a rotational kinematics equation only. If a measured angular velocity is not available, torques can be computed and an additional rotational dynamics equation integrated to give the angular velocity. Initial conditions for either of these integrations come from the estimation process. Sometimes additional quantities, such as gyro and torque parameters, are also solved for. Although the partial derivatives of attitude with respect to initial attitude and gyro parameters are well known, the corresponding partial derivatives with respect to initial angular velocity and torque parameters are less familiar. They can be derived and computed numerically in a way that is analogous to that used for the initial attitude and gyro parameters. Previous papers have demonstrated the feasibility of using dynamics models for attitude estimation but have not provided details of how each angular velocity and torque parameters can be estimated. This tutorial paper provides some of that detail, notably how to compute the state transition matrix when closed form expressions are not available. It also attempts to put dynamics estimation in perspective by showing the progression from constant to gyro-propagated to dynamics-propagated attitude motion models. Readers not already familiar with attitude estimation will find this paper an introduction to the subject, and attitude specialists may appreciate the collection of heretofore scattered results brought together in a single place.

  16. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease

    PubMed Central

    Kostrzewski, Tomasz; Cornforth, Terri; Snow, Sophie A; Ouro-Gnao, Larissa; Rowe, Cliff; Large, Emma M; Hughes, David J

    2017-01-01

    AIM To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factor-binding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantly reduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known anti-steatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium. CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. PMID:28127194

  17. 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

  18. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Myocardial perfusion distribution and coronary arterial pressure and flow signals: clinical relevance in relation to multiscale modeling, a review.

    PubMed

    Nolte, Froukje; Hyde, Eoin R; Rolandi, Cristina; Lee, Jack; van Horssen, Pepijn; Asrress, Kal; van den Wijngaard, Jeroen P H M; Cookson, Andrew N; van de Hoef, Tim; Chabiniok, Radomir; Razavi, Reza; Michler, Christian; Hautvast, Gilion L T F; Piek, Jan J; Breeuwer, Marcel; Siebes, Maria; Nagel, Eike; Smith, Nic P; Spaan, Jos A E

    2013-11-01

    Coronary artery disease, CAD, is associated with both narrowing of the epicardial coronary arteries and microvascular disease, thereby limiting coronary flow and myocardial perfusion. CAD accounts for almost 2 million deaths within the European Union on an annual basis. In this paper, we review the physiological and pathophysiological processes underlying clinical decision making in coronary disease as well as the models for interpretation of the underlying physiological mechanisms. Presently, clinical decision making is based on non-invasive magnetic resonance imaging, MRI, of myocardial perfusion and invasive coronary hemodynamic measurements of coronary pressure and Doppler flow velocity signals obtained during catheterization. Within the euHeart project, several innovations have been developed and applied to improve diagnosis-based understanding of the underlying biophysical processes. Specifically, MRI perfusion data interpretation has been advanced by the gradientogram, a novel graphical representation of the spatiotemporal myocardial perfusion gradient. For hemodynamic data, functional indices of coronary stenosis severity that do not depend on maximal vasodilation are proposed and the Valsalva maneuver for indicating the extravascular resistance component of the coronary circulation has been introduced. Complementary to these advances, model innovation has been directed to the porous elastic model coupled to a one-dimensional model of the epicardial arteries. The importance of model development is related to the integration of information from different modalities, which in isolation often result in conflicting treatment recommendations.

  20. Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model

    PubMed Central

    Dang, Yalong; Waxman, Susannah; Wang, Chao; Jensen, Adrianna; Loewen, Ralitsa T.; Bilonick, Richard A.

    2017-01-01

    Objective The trabecular meshwork (TM) is the primary substrate of outflow resistance in glaucomatous eyes. Repopulating diseased TM with fresh, functional TM cells might be a viable therapeutic approach. Decellularized TM scaffolds have previously been produced by ablating cells with suicide gene therapy or saponin, which risks incomplete cell removal or dissolution of the extracellular matrix, respectively. We hypothesized that improved trabecular meshwork cell ablation would result from freeze-thaw cycles compared to chemical treatment. Materials and Methods We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion within two hours of sacrifice. Intraocular pressure (IOP) was recorded continuously by a pressure transducer system. After 72 h of IOP stabilization, eight eyes were assigned to freeze-thaw (F) ablation (−80 °C × 2), to 0.02% saponin (S) treatment, or the control group (C), respectively. The TM was transduced with an eGFP expressing feline immunodeficiency viral (FIV) vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture media for 180 h. TM histology was assessed by hematoxylin and eosin staining. TM viability was evaluated by a calcein AM/propidium iodide (PI) assay. The TM extracellular matrix was stained with Picro Sirius Red. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with five degrees of freedom. Results F and S experienced a similar IOP reduction of 30% from baseline (P = 0.64). IOP reduction of about 30% occurred in F within 24 h and in S within 48 h. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis and Picro Sirius staining confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed very low

  1. The isolated perfused rat kidney model: a useful tool for drug discovery and development.

    PubMed

    Taft, David R

    2004-01-01

    Over the past three decades, the Isolated Perfused Rat Kidney (IPK) has been used to study numerous aspects of renal drug disposition. Among the available ex-vivo methods to study renal transport, the IPK allows for elucidation of the overall contributions of renal transport mechanisms on drug excretion. Therefore, IPK studies can provide a bridge between in vitro findings and in vivo disposition. This review paper begins with a detailed overview of IPK methodology (system components, surgical procedure, study design). Various applications of the IPK are then presented. These applications include characterizing renal excretion mechanisms, screening for clinically significant drug interactions, studying renal drug metabolism, and correlating renal drug disposition with drug-induced changes in kidney function. Lastly, the role of IPK studies in drug development is discussed. Demonstrated correlations between IPK data and clinical outcomes make the IPK model a potentially useful tool for drug discovery and evaluation.

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

    PubMed

    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; Lewis, R M

    2016-02-01

    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 [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]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 [(14)C]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 [(14)C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [(14)C]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.

  3. A continuum model of cell proliferation and nutrient transport in a perfusion bioreactor.

    PubMed

    Shakeel, Muhammad; Matthews, Paul C; Graham, Richard S; Waters, Sarah L

    2013-03-01

    Tissue engineering aims to regenerate, repair or replace organs or defective tissues. This tissue regeneration often occurs in a bioreactor. Important challenges in tissue engineering include ensuring adequate nutrient supply, maintaining the desired cell distribution and achieving sufficiently high cell yield. To put laboratory experiments into a theoretical framework, mathematical modelling of the physical and biochemical processes involved in tissue growth is a useful tool. In this work, we derive and solve a model for a cell-seeded porous scaffold placed in a perfusion bioreactor in which fluid delivers nutrients to the cells. The model describes the key features, including fluid flow, nutrient delivery, cell proliferation and consequent variation of scaffold porosity. Fluid flow through the porous scaffold is modelled by Darcy's law, and nutrient delivery is described by a reaction-advection-diffusion equation. A reaction-diffusion equation describes the evolution of cell density, in which cell proliferation is modelled via logistic growth and cell spreading via non-linear diffusion, which depends on cell density. The effect of shear stress on nutrient consumption and cell proliferation is also included in the model. COMSOL (a commercial finite element solver) is used to solve the model numerically. The results reveal the dependence of the cell distribution and total cell yield on the initial cell density and scaffold porosity. We suggest various seeding strategies and scaffold designs to improve the cell distribution and total cell yield in the engineered tissue construct.

  4. Safety and Effectiveness Evidence of SAM (registered trademark) Junctional Tourniquet to Control Inguinal Hemorrhage in a Perfused Cadaver Model

    DTIC Science & Technology

    2014-01-01

    The SJT was tested in a perfused cadaver experiment simulating inguinal or axillary wound hemorrhage. No safety problems or tissue damage occurred...to be safe and effective in hemorrhage control in a cadaver model for both the axillary and inguinal areas. The SJT’s Target Compression Devices

  5. 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

  6. 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

  7. Development of a Perfusion Platform for Dynamic Cultivation of in vitro Skin Models.

    PubMed

    Strüver, Kay; Friess, Wolfgang; Hedtrich, Sarah

    2017-01-01

    Reconstructed skin models are suitable test systems for toxicity testing and for basic investigations on (patho-)physiological aspects of human skin. Reconstructed human skin, however, has clear limitations such as the lack of immune cells and a significantly weaker skin barrier function compared to native human skin. Potential reasons for the latter might be the lack of mechanical forces during skin model cultivation which is performed classically in static well-plate setups. Mechanical forces and shear stress have a major impact on tissue formation and, hence, tissue engineering. In the present work, a perfusion platform was developed allowing dynamic cultivation of in vitro skin models. The platform was designed to cultivate reconstructed skin at the air-liquid interface with a laminar and continuous medium flow below the dermis equivalent. Histological investigations confirmed the formation of a significantly thicker stratum corneum compared to the control cultivated under static conditions. Moreover, the skin differentiation markers involucrin and filaggrin as well as the tight junction proteins claudin 1 and occludin showed increased expression in the dynamically cultured skin models. Unexpectedly, despite improved differentiation, the skin barrier function of the dynamically cultivated skin models was not enhanced compared with the skin models cultivated under static conditions. © 2017 S. Karger AG, Basel.

  8. Experimental evaluation and computational modeling of tissue damage from low-flow push-pull perfusion sampling in vivo.

    PubMed

    Cepeda, David E; Hains, Leah; Li, David; Bull, Joseph; Lentz, Stephen I; Kennedy, Robert T

    2015-03-15

    Neurochemical monitoring via sampling probes is valuable for deciphering neurotransmission in vivo. Microdialysis is commonly used; however, the spatial resolution is poor. Recently push-pull perfusion at low flow rates (50nL/min) has been proposed as a method for in vivo sampling from the central nervous system. Tissue damage from such probes has not been investigated in detail. In this work, we evaluated acute tissue response to low-flow push-pull perfusion by infusing the nuclear stains Sytox Orange and Hoechst 33342 through probes implanted in the striatum for 200min, to label damaged and total cells, respectively, in situ. Using the damaged/total labeled cell ratio as a measure of tissue damage, we found that 33±8% were damaged within the dye region around a microdialysis probe. We found that low-flow push-pull perfusion probes damaged 24±4% of cells in the sampling area. Flow had no effect on the number of damaged cells for low-flow push-pull perfusion. Modeling revealed that shear stress and pressure gradients generated by the flow were lower than thresholds expected to cause damage. Comparison with existing methods.Push-pull perfusion caused less tissue damage but yielded 1500-fold better spatial resolution. Push-pull perfusion at low flow rates is a viable method for sampling from the brain with potential for high temporal and spatial resolution. Tissue damage is mostly caused by probe insertion. Smaller probes may yield even lower damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Experimental Evaluation and Computational Modeling of Tissue Damage from Low-Flow Push-Pull Perfusion Sampling In Vivo

    PubMed Central

    Cepeda, David E.; Hains, Leah; Li, David; Bull, Joseph; Lentz, Stephen I.; Kennedy, Robert T.

    2015-01-01

    Background Neurochemical monitoring via sampling probes is valuable for deciphering neurotransmission in vivo. Microdialysis is commonly used; however, the spatial resolution is poor. New Method Recently push-pull perfusion at low flow rates (50 nL/min) has been proposed as a method for in vivo sampling from the central nervous system. Tissue damage from such probes has not been investigated in detail. In this work, we evaluated acute tissue response to low-flow push-pull perfusion by infusing the nuclear stains Sytox Orange and Hoechst 33342 through probes implanted in the striatum for 200 min, to label damaged and total cells, respectively, in situ. Results Using the damaged/total labeled cell ratio as a measure of tissue damage, we found that 33 ± 8% were damaged within the dye region around a microdialysis probe. We found that low-flow push-pull perfusion probes damaged 24 ± 4% of cells in the sampling area. Flow had no effect on the number of damaged cells for low-flow push-pull perfusion. Modeling revealed that shear stress and pressure gradients generated by the flow were lower than thresholds expected to cause damage. Comparison with existing methods Push-pull perfusion caused less tissue damage but yielded 1500-fold better spatial resolution. Conclusions Push-pull perfusion at low flow rates is a viable method for sampling from the brain with potential for high temporal and spatial resolution. Tissue damage is mostly caused by probe insertion. Smaller probes may yield even lower damage. PMID:25614385

  10. 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

  11. Postpartum Vascular Dysfunction in the Reduced Uteroplacental Perfusion Model of Preeclampsia

    PubMed Central

    Quon, Anita; Davidge, Sandra T.

    2016-01-01

    Preeclampsia is a disorder affecting 2–8% of all pregnancies, characterized by gestational hypertension (≥ 140/90 mmHg) and proteinuria (≥300 mg over 24 hours) diagnosed following the 20th week of pregnancy, and for which there is currently no available treatment. While the precise cause of preeclampsia is unknown, placental ischemia/hypoxia resulting from abnormal trophoblast invasion and maternal endothelial dysfunction are central characteristics. Preeclampsia is a major cause of both maternal and fetal morbidity and mortality in the perinatal period. In addition, women who have experienced preeclampsia are more likely to suffer cardiovascular disease later in life. The cause of this elevation in cardiovascular risk postpartum, however, is unknown. We hypothesize that there may be lasting vascular dysfunction following exposure to reduced uteroplacental perfusion during pregnancy that may contribute to increased cardiovascular risk postpartum. Using the rat reduced utero-placental perfusion pressure (RUPP) model of preeclampsia, blood pressure was assessed in dams at gestational day 20, one and three months postpartum. Mesenteric artery and aortic function were assessed using wire myography. We demonstrated hypertension and increased mesenteric artery responses to phenylephrine at gestational day 20, with the latter due to a decreased contribution of nitric oxide without any change in methylcholine-induced relaxation. At one month postpartum, we demonstrated a small but significant vasoconstrictive phenotype that was due to an underlying loss of basal nitric oxide contribution. At three months postpartum, endothelium-dependent relaxation of the aorta demonstrated sensitivity to oxLDL and mesenteric arteries demonstrated decreased nitric oxide bioavailability with impaired methylcholine-induced relaxation; indicative of an early development of endothelial dysfunction. In summary, we have demonstrated impaired vascular function following exposure to a RUPP

  12. GPU-accelerated voxelwise hepatic perfusion quantification

    NASA Astrophysics Data System (ADS)

    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.

  13. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-07

    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.

  14. GPU-Accelerated Voxelwise Hepatic Perfusion Quantification

    PubMed Central

    Wang, H; Cao, Y

    2012-01-01

    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 CUDA-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, non-linear 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 626400 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

  15. Tissue-specific sparse deconvolution for brain CT perfusion.

    PubMed

    Fang, Ruogu; Jiang, Haodi; Huang, Junzhou

    2015-12-01

    Enhancing perfusion maps in low-dose computed tomography perfusion (CTP) for cerebrovascular disease diagnosis is a challenging task, especially for low-contrast tissue categories where infarct core and ischemic penumbra usually occur. Sparse perfusion deconvolution has been recently proposed to effectively improve the image quality and diagnostic accuracy of low-dose perfusion CT by extracting the complementary information from the high-dose perfusion maps to restore the low-dose using a joint spatio-temporal model. However the low-contrast tissue classes where infarct core and ischemic penumbra are likely to occur in cerebral perfusion CT tend to be over-smoothed, leading to loss of essential biomarkers. In this paper, we propose a tissue-specific sparse deconvolution approach to preserve the subtle perfusion information in the low-contrast tissue classes. We first build tissue-specific dictionaries from segmentations of high-dose perfusion maps using online dictionary learning, and then perform deconvolution-based hemodynamic parameters estimation for block-wise tissue segments on the low-dose CTP data. Extensive validation on clinical datasets of patients with cerebrovascular disease demonstrates the superior performance of our proposed method compared to state-of-art, and potentially improve diagnostic accuracy by increasing the differentiation between normal and ischemic tissues in the brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Resuscitation of Ischemic Donor Livers with Normothermic Machine Perfusion: A Metabolic Flux Analysis of Treatment in Rats

    PubMed Central

    Izamis, Maria-Louisa; Tolboom, Herman; Uygun, Basak; Berthiaume, Francois; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    Normothermic machine perfusion has previously been demonstrated to restore damaged warm ischemic livers to transplantable condition in animal models. However, the mechanisms of recovery are unclear, preventing rational optimization of perfusion systems and slowing clinical translation of machine perfusion. In this study, organ recovery time and major perfusate shortcomings were evaluated using a comprehensive metabolic analysis of organ function in perfusion prior to successful transplantation. Two groups, Fresh livers and livers subjected to 1 hr of warm ischemia (WI) received perfusion for a total preservation time of 6 hrs, followed by successful transplantation. 24 metabolic fluxes were directly measured and 38 stoichiometrically-related fluxes were estimated via a mass balance model of the major pathways of energy metabolism. This analysis revealed stable metabolism in Fresh livers throughout perfusion while identifying two distinct metabolic states in WI livers, separated at t = 2 hrs, coinciding with recovery of oxygen uptake rates to Fresh liver values. This finding strongly suggests successful organ resuscitation within 2 hrs of perfusion. Overall perfused livers regulated metabolism of perfusate substrates according to their metabolic needs, despite supraphysiological levels of some metabolites. This study establishes the first integrative metabolic basis for the dynamics of recovery during perfusion treatment of marginal livers. Our initial findings support enhanced oxygen delivery for both timely recovery and long-term sustenance. These results are expected to lead the optimization of the treatment protocols and perfusion media from a metabolic perspective, facilitating translation to clinical use. PMID:23922793

  17. Perfusion kinetics in human brain tumor with DCE-MRI derived model and CFD analysis.

    PubMed

    Bhandari, A; Bansal, A; Singh, A; Sinha, N

    2017-07-05

    Cancer is one of the leading causes of death all over the world. Among the strategies that are used for cancer treatment, the effectiveness of chemotherapy is often hindered by factors such as irregular and non-uniform uptake of drugs inside tumor. Thus, accurate prediction of drug transport and deposition inside tumor is crucial for increasing the effectiveness of chemotherapeutic treatment. In this study, a computational model of human brain tumor is developed that incorporates dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data into a voxelized porous media model. The model takes into account realistic transport and perfusion kinetics parameters together with realistic heterogeneous tumor vasculature and accurate arterial input function (AIF), which makes it patient specific. The computational results for interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and tracer concentration show good agreement with the experimental results. The computational model can be extended further for predicting the deposition of chemotherapeutic drugs in tumor environment as well as selection of the best chemotherapeutic drug for a specific patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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

  19. Hepatic albumin and urea synthesis: The mathematical modelling of the dynamics of [14C]carbonate-derived guanidine-labelled arginine in the isolated perfused rat liver.

    PubMed Central

    Tavill, A S; Nadkarni, D; Metcalfe, J; Black, E; Hoffenberg, R; Carson, E R

    1975-01-01

    A mathematical model was constructed to define the dynamics of incorporation of radioactivity into urea carbon and the guanidine carbon of arginine in plasma albumin after the rapid intraportal-venous administration of Na214CO3 in the isolated perfused rat liver. 2. The model was formulated in terms of compartmental analysis and additional experiments were designed to provide further information on subsystem dynamics and to discriminate between alternative model structures. 3. Evidence for the rapid-time-constant of labelling of intracellular arginine was provided by precursor-product analysis of precursor [14C]carboante and product [14C]urea in the perfusate. 4. Compartmental analysis of the dynamics of newly synthesized urea was based on the fate of exogenous [13C]urea, endogenous [14C]urea and the accumulation of [12C]urea in perfusate water, confirming the early completion of urea carbon labelling, the absence of continuing synthesis of labelled urea, and the presence of a small intrahepatic urea-delay pool. 5. Analysis of the perfusate dynamics of endogenously synthesized and exogenously administered [6-14C]arginine indicated that although the capacity for extrahepatic formation of [14C]-urea exists, little or no arginine formed within the intrahepatic urea cycle was transported out of the liver. However, the presence of a rapidly turning-over intrahepatic arginine pool was confirmed. 6. On the basis of these subsystem analyses it was possible to offer feasible estimations for the parameters of the mathematical model. However, it was not possible to stimulate the form and magnitude of the dynamics of newly synthesized labelled urea and albumin which were simultaneously observed after administration of [14C]carbonate on the basis of a preliminary model which postulated that both products were derived from a single hepatic pool of [16-14C]arginine. On the other hand these observed dynamics could be satisfied to a two-compartment arginine model, which also

  20. Perfusion-weighted imaging and dynamic 4D angiograms for the estimation of collateral blood flow in lacunar infarction.

    PubMed

    Förster, Alex; Mürle, Bettina; Böhme, Johannes; Al-Zghloul, Mansour; Kerl, Hans U; Wenz, Holger; Groden, Christoph

    2016-10-01

    Although lacunar infarction accounts for approximately 25% of ischemic strokes, collateral blood flow through anastomoses is not well evaluated in lacunar infarction. In 111 lacunar infarction patients, we analyzed diffusion-weighted images, perfusion-weighted images, and blood flow on dynamic four-dimensional angiograms generated by use of Signal Processing In NMR-Software. Blood flow was classified as absent (type 1), from periphery to center (type 2), from center to periphery (type 3), and combination of type 2 and 3 (type 4). On diffusion-weighted images, lacunar infarction was found in the basal ganglia (11.7%), internal capsule (24.3%), corona radiata (30.6%), thalamus (24.3%), and brainstem (9.0%). In 58 (52.2%) patients, perfusion-weighted image showed a circumscribed hypoperfusion, in one (0.9%) a circumscribed hyperperfusion, whereas the remainder was normal. In 36 (62.1%) patients, a larger perfusion deficit (>7 mm) was observed. In these, blood flow was classified type 1 in four (11.1%), 2 in 17 (47.2%), 3 in 9 (25.0%), and 4 in six (16.7%) patients. Patients with lacunar infarction in the posterior circulation more often demonstrated blood flow type 2 and less often type 3 (p = 0.01). Detailed examination and graduation of blood flow in lacunar infarction by use of dynamic four-dimensional angiograms is feasible and may serve for a better characterization of this stroke subtype.

  1. Impact of Incremental Perfusion Loss on Oxygen Transport in a Capillary Network Mathematical Model.

    PubMed

    Fraser, Graham M; Sharpe, Michael D; Goldman, Daniel; Ellis, Christopher G

    2015-07-01

    To quantify how incremental capillary PL, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport. A computational model was applied to capillary networks with dimensions 84 × 168 × 342 (NI) and 70 × 157 × 268 (NII) μm, reconstructed in vivo from rat skeletal muscle. FCD loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis. A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under resting conditions. Increasing RBC SR to baseline levels returned tissue PO2 to within 5% of baseline. HC combined with a 40% FCD loss, resulted in tissue anoxia in both network volumes and median tissue PO2 of 11.5 and 8.9 mmHg in NI and NII respectively; median tissue PO2 was recovered to baseline levels by increasing total SR 3-4 fold. These results suggest a substantial increase in total SR is required in order to compensate for impaired oxygen delivery as a result of loss of capillary perfusion and increased oxygen consumption during sepsis. © 2015 John Wiley & Sons Ltd.

  2. Relaxin as a protective substance in preservation solutions for organ transplantation, as shown in an isolated perfused rat liver model.

    PubMed

    Boehnert, M U; Armbruster, F P; Hilbig, H

    2008-05-01

    Reperfusion injury, a well-known problem in organ transplantation, results from multiple pathologic mechanisms, including platelet/mast cell activation and peroxidation of cell membrane lipids. Relaxin was originally described as an insulin-like hormone produced in the ovaries during pregnancy. It causes vessel dilation and inhibition of platelet and mast cell activation. The present study investigated the protective effect of relaxin against reperfusion injury in liver tissue. We used a model of isolated perfused rat liver to simulate liver transplantation. Organ preservation was performed identical to human transplantation in 20 male Wistar rats. During preservation we applied 64 ng/mL relaxin. In contrast controls (n = 10) had no relaxin treatment. To quantify cell damage, we measured malonyldialdehyde (MDA; end product of lipid peroxidation) and myeloperoxidase activity (MPO; marker for accumulation of neutrophil granulocytes) in the perfusates. The livers were examined immunohistochemically for the same parameters. Relaxin as an additional substance in preservation solutions decreased perfusate MPO and MDA levels by up to 30%, as shown by immunohistochemistry. Our preliminary data suggested that relaxin is a promising agent to reduce hepatocyte damage caused by ischemia-reperfusion injury. Quantitative analysis of MDA and MPO levels in the perfusate is the subject of an ongoing study.

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

    PubMed Central

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

    2015-01-01

    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

  4. [Inotropic activity induced by carbamazepine-alkyne derivative in an isolated heart model and perfused to constant flow].

    PubMed

    Figueroa-Valverde, Lauro; Díaz-Cedillo, Francisco; López-Ramos, María; García-Cervera, Elodia; Quijano-Ascencio, Karen

    2011-06-01

    Inotropic activity induced by carbamazepine-alkyne derivative in an isolated heart model and perfused to constant flow Introduction. Few data exist with respect to the effects of carbamazepine and its derivatives at cardiovascular level; furthermore, the molecular mechanisms and cellular site of action are still unclear. Objective. The effects induced by carbamazepine-alquine derivative on perfusion pressure, vascular resistance and left ventricular pressure were evaluated. Materials and methods. The effects of carbamazepine and carbamazepine-alquine on the perfusion pressure, vascular resistance and left ventricular pressure were examined in isolated rat hearts (Langendorff model). Results. Four results were obtained: (1) The carbamazepine-alquine derivative 10-9 mM increased the perfusion pressure and vascular resistance in comparison with the carbamazepine 10-9 mM; (2) the effect of carbamazepine-alquine derivative 10-9-10-4 mM on left ventricular pressure not was inhibited by metoprolol or prazosin at a dose of 10-6 mM; (3) nifedipine 10-6 mM blocked the effects exerted by the carbamazepine-alquine derivative 10-9-10--4 mM on left ventricular pressure, and (4) the carbamazepine-alquine derivative at dose of 10-9 mM increased the concentration of intracellular calcium over a time period of 3-18 min; nevertheless, in presence of nifedipine 10-6 mM this effect was inhibited significantly (p=0.005). Conclusions. The activity exerted by carbamazepine-alquine derivative on perfusion pressure, vascular resistance and left ventricular pressure involved activation of calcium channel type-L, brought indirectly changes in the intracellular calcium levels and subsequently induced a positive inotropic effect.

  5. 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...

  6. 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...

  7. Ultrasound-enhanced drug delivery in a perfused ex vivo artery model

    NASA Astrophysics Data System (ADS)

    Hitchcock, Kathryn E.

    Acoustically driven stable cavitation may improve treatments of diseases in which passive penetration of drug into the target tissue is poor. Examples include atherosclerosis, in which the endothelium can prevent penetration of therapeutics into the plaque, and ischemic stroke, in which pathologically low flow of blood impedes the delivery of intravenous drugs to the clot. Understanding the way in which ultrasound cavitation agents nucleate cavitation in flowing blood-mimicking solutions is an important step in optimizing ultrasound-enhanced drug delivery. The use of a perfused, living ex vivo artery model permitted study of this phenomenon while still providing information on arterial bioeffects. Cavitation-enhanced delivery of anti-ICAM-1-targeted echogenic liposomes into and beyond the ex vivo murine aortic endothelium was demonstrated using 1-MHz continuous wave ultrasound. Acoustic cavitation had no apparent effect on the health of the murine arterial tissue. A method of maximizing the energy of stable cavitation through the use of intermittent 120-kHz ultrasound with quiescent periods to allow contrast agent inflow was developed. Using this insonificaiton method, sonothrombolysis was studied in ex vivo porcine carotid arteries using a 120-kHz center frequency and 0.44 MPa peak-to-peak pressure amplitude. Clot mass loss was used as a metric of thrombolytic efficacy. Clots exposed to recombinant tissue plasminogen activator and the ultrasound contrast agent, DefinityRTM in flowing porcine plasma without ultrasound experienced 34% mass loss. When robust stable cavitation was induced via 120-kHz insonation, the mean clot mass loss rose to 83%, which constituted a significant improvement (n = 6, p<0.0001). Without DefinityRTM there was no thrombolytic enhancement by ultrasound exposure alone at the same insonation pressure (n = 6, p<0.0001). Significant loss of endothelium occurred in 64% of the porcine carotid arteries, possibly due to poor oxygen delivery by the

  8. A numerical model suggests the interplay between nuclear plasticity and stiffness during a perfusion assay.

    PubMed

    Deveraux, Solenne; Allena, Rachele; Aubry, Denis

    2017-09-14

    Cell deformability is a necessary condition for a cell to be able to migrate, an ability that is vital both for healthy and diseased organisms. The nucleus being the largest and stiffest organelle, it often is a barrier to cell migration. It is thus essential to characterize its mechanical behaviour. First, we numerically investigate the visco-elasto-plastic properties of the isolated nucleus during a compression test. This simulation highlights the impact of the mechanical behaviour of the nuclear lamina and the nucleoplasm on the overall plasticity. Second, a whole cell model is developed to simulate a perfusion experiment to study the possible interactions between the cytoplasm and the nucleus. We analyze and discuss the role of the lamina for a wild-type cell model, and a lamin-deficient one, in which the Young's modulus of the lamina is set to 1% of its nominal value. This simulation suggests an interplay between the cytoplasm and the nucleoplasm, especially in the lamin-deficient cell, showing the need of a stiffer nucleoplasm to maintain nuclear plasticity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. A mathematical model of the metabolic and perfusion effects on cortical spreading depression.

    PubMed

    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.

  10. 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

  11. In vitro studies of ferric carboxymaltose on placental permeability using the dual perfusion model of human placenta.

    PubMed

    Malek, Antoine

    2010-01-01

    An in vitro perfusion model of human placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with 59Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ ml were also tested. The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of 59Fe-FCM. No transferred iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion. No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, with similar concentrations in placental tissue before and after perfusion. No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the

  12. The effects of triamcinolone crystals on retinal function in a model of isolated perfused vertebrate retina.

    PubMed

    Lüke, Matthias; Januschowski, Kai; Beutel, Julia; Warga, Max; Grisanti, Salvatore; Peters, Swaantje; Schneider, Toni; Lüke, Christoph; Bartz-Schmidt, Karl Ulrich; Szurman, Peter

    2008-07-01

    A good clinical experience of intravitreal triamcinolone acetonide (TA) has been reported in several studies, but there are growing indications that epiretinal crystals of TA exhibit retinal toxicity. To investigate the effects of TA on retinal function we used a model of an electrophysiological in vitro technique for testing retinal toxicity. Isolated bovine retinas were perfused with an oxygen saturated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. After reaching stable ERG-amplitudes TA at the maximum solubility equilibrium (36 microg/ml) was either applied to the nutrient solution for 45 min or TA was administered epiretinally at concentrations (1 mg/ml, 4 mg/ml, 8 mg/ml, 20 mg/ml and 40 mg/ml) above the maximum solubility equilibrium to assure direct contact of the TA crystals with the isolated perfused retinas. After that the retinas were reperfused for 75 min with the standard nutrient solution. The percentage of a- and b-wave reduction directly after the application and at the washout was calculated. To assess the effects of TA at the level of the ganglion cell layer a Viability/Cytotoxicity Kit for mammalian cells was used. No changes of the ERG-amplitudes were detected during the exposure to 36 microg/ml TA for 45 min (b-wave: 9.6 microV+/-2.1 vs. 8 microV+/-2.1 (p=0.135); a-wave: -11 microV+/-2.7 vs. -10.6 microV+/-2.3 (p=0.889)) and at the washout (b-wave: 8 microV+/-2.1 vs. 8.3 microV+/-2.4 (p=0.18); a-wave: -10.6 microV+/-2.3 vs. -12 microV+/-2.6 (p=0.225)). At concentrations higher than 1mg/ml TA induced a decrease of the a- and b-wave in a concentration dependent manner. These changes were reversible for concentrations of TA up to 20mg/ml (b-wave: 9 microV+/-2.4 vs. 6.6 microV+/-2.5 (p=0.08); a-wave: -11.4 microV+/-2.0 vs. -11.2 microV+/-2.2 (p=0.37)), but irreversible at 40 mg/ml even at the end of the washout (b-wave: 9.8 microV+/-1.9 vs. 3 microV+/-1.7 (p=0.009); a-wave: -9

  13. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

    PubMed Central

    Yamamoto, Tokihiro; Kent, Michael S.; Wisner, Erik R.; Johnson, Lynelle R.; Stern, Joshua A.; Qi, Lihong; Fujita, Yukio; Boone, John M.

    2016-01-01

    Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t

  14. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model.

    PubMed

    Yamamoto, Tokihiro; Kent, Michael S; Wisner, Erik R; Johnson, Lynelle R; Stern, Joshua A; Qi, Lihong; Fujita, Yukio; Boone, John M

    2016-07-01

    Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. The mean TRE

  15. Effects of norepinephrine on tissue perfusion in a sheep model of intra-abdominal hypertension.

    PubMed

    Ferrara, Gonzalo; Kanoore Edul, Vanina S; Caminos Eguillor, Juan F; Martins, Enrique; Canullán, Carlos; Canales, Héctor S; Ince, Can; Estenssoro, Elisa; Dubin, Arnaldo

    2015-12-01

    The aim of the study was to describe the effects of intra-abdominal hypertension (IAH) on regional and microcirculatory intestinal blood flow, renal blood flow, and urine output, as well as their response to increases in blood pressure induced by norepinephrine. This was a pilot, controlled study, performed in an animal research laboratory. Twenty-four anesthetized and mechanically ventilated sheep were studied. We measured systemic hemodynamics, superior mesenteric and renal blood flow, villi microcirculation, intramucosal-arterial PCO2, urine output, and intra-abdominal pressure. IAH (20 mm Hg) was generated by intraperitoneal instillation of warmed saline. After 1 h of IAH, sheep were randomized to IAH control (n = 8) or IAH norepinephrine (n = 8) groups, for 1 h. In this last group, mean arterial pressure was increased about 20 mm Hg with norepinephrine. A sham group (n = 8) was also studied. Fluids were administered to prevent decreases in cardiac output. Differences between groups were analyzed with two-way repeated measures of analysis of variance (ANOVA). After 2 h of IAH, abdominal perfusion pressure decreased in IAH control group compared to IAH norepinephrine and sham groups (49 ± 11, 73 ± 11, and 86 ± 15 mm Hg, P < 0.0001). There were no differences in superior mesenteric artery blood flow, intramucosal-arterial PCO2, and villi microcirculation among groups. Renal blood flow (49 ± 30, 32 ± 24, and 102 ± 45 mL.min(-1).kg(-1), P < 0.0001) and urinary output (0.3 ± 0.1, 0.2 ± 0.2, and 1.0 ± 0.6 mL.h(-1).kg(-1), P < 0.0001) were decreased in IAH control and IAH norepinephrine groups, compared to the sham group. In this experimental model of IAH, the gut and the kidney had contrasting responses: While intestinal blood flow and villi microcirculation remained unchanged, renal perfusion and urine output were severely compromised.

  16. Feasibility of quantitative lung perfusion by 4D CT imaging by a new dynamic-scanning protocol in an animal model

    NASA Astrophysics Data System (ADS)

    Wang, Yang; Goldin, Jonathan G.; Abtin, Fereidoun G.; Brown, Matt; McNitt-Gray, Mike

    2008-03-01

    The purpose of this study is to test a new dynamic Perfusion-CT imaging protocol in an animal model and investigate the feasibility of quantifying perfusion of lung parenchyma to perform functional analysis from 4D CT image data. A novel perfusion-CT protocol was designed with 25 scanning time points: the first at baseline and 24 scans after a bolus injection of contrast material. Post-contrast CT scanning images were acquired with a high sampling rate before the first blood recirculation and then a relatively low sampling rate until 10 minutes after administrating contrast agent. Lower radiation techniques were used to keep the radiation dose to an acceptable level. 2 Yorkshire swine with pulmonary emboli underwent this perfusion- CT protocol at suspended end inspiration. The software tools were designed to measure the quantitative perfusion parameters (perfusion, permeability, relative blood volume, blood flow, wash-in & wash-out enhancement) of voxel or interesting area of lung. The perfusion values were calculated for further lung functional analysis and presented visually as contrast enhancement maps for the volume being examined. The results show increased CT temporal sampling rate provides the feasibility of quantifying lung function and evaluating the pulmonary emboli. Differences between areas with known perfusion defects and those without perfusion defects were observed. In conclusion, the techniques to calculate the lung perfusion on animal model have potential application in human lung functional analysis such as evaluation of functional effects of pulmonary embolism. With further study, these techniques might be applicable in human lung parenchyma characterization and possibly for lung nodule characterization.

  17. Model optimization using statistical estimation

    NASA Technical Reports Server (NTRS)

    Collins, J. D.; Hart, G. C.; Hasselman, T. K.; Kennedy, B.; Pack, H., Jr.

    1974-01-01

    Program revises initial or prior estimate of stiffness and mass parameters to parameters yielding frequency and mode characteristics in agreement with test data. Variances are also calculated and consequently define uncertainties of final estimates.

  18. The interdependent contributions of gravitational and structural features to perfusion distribution in a multiscale model of the pulmonary circulation

    PubMed Central

    Tawhai, M. H.; Hoffman, E. A.; Burrowes, K. S.

    2011-01-01

    Recent experimental and imaging studies suggest that the influence of gravity on the measured distribution of blood flow in the lung is largely through deformation of the parenchymal tissue. To study the contribution of hydrostatic effects to regional perfusion in the presence of tissue deformation, we have developed an anatomically structured computational model of the pulmonary circulation (arteries, capillaries, veins), coupled to a continuum model of tissue deformation, and including scale-appropriate fluid dynamics for blood flow in each vessel type. The model demonstrates that both structural and the multiple effects of gravity on the pulmonary circulation make a distinct contribution to the distribution of blood. It shows that postural differences in perfusion gradients can be explained by the combined effect of tissue deformation and extra-acinar blood vessel resistance to flow in the dependent tissue. However, gravitational perfusion gradients persist when the effect of tissue deformation is eliminated, highlighting the importance of the hydrostatic effects of gravity on blood distribution in the pulmonary circulation. Coupling of large- and small-scale models reveals variation in microcirculatory driving pressures within isogravitational planes due to extra-acinar vessel resistance. Variation in driving pressures is due to heterogeneous large-vessel resistance as a consequence of geometric asymmetry in the vascular trees and is amplified by the complex balance of pressures, distension, and flow at the microcirculatory level. PMID:21292845

  19. Patterns of histological changes following hepatic electrolytic ablation in an ex-vivo perfused model.

    PubMed

    Gravante, Gianpiero; Ong, Seok Ling; West, Kevin; McGregor, Angus; Maddern, Guy J; Metcalfe, Matthew S; Lloyd, David M; Dennison, Ashley R

    2012-10-01

    Electrolytic ablation (EA) destroys the liver by releasing toxic radicles and producing modifications in the local pH without increasing the tissue temperature. We assessed the histological changes produced by EA using an ex-vivo perfused model. Five porcine livers were harvested, preserved in ice and reperfused for six hours in an extracorporeal circuit using autologous normothermic blood. One hour after reperfusion EA was performed and liver biopsies collected at the end of the experiments. The main necrotic zone consisted of coagulative necrosis, sinusoidal dilatation and haemorrhage with an unusual morphological pattern. The coagulative necrosis and haemorrhage affected mainly the peripheral area of the lobule with relative sparing of the area surrounding the centrilobular vein. Contrasting with this sinusoidal dilatation appeared to be more prominent in the centrilobular area. EA produces patterns of tissue destruction that have not been observed with the more commonly used thermal techniques. Further studies should obtain more information about the influence of adjacent biliary and vascular structures so that appropriate clinical trials can be designed.

  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.

  1. Establishment of an oral infection model resembling the periodontal pocket in a perfusion bioreactor system

    PubMed Central

    Bao, Kai; Papadimitropoulos, Adam; Akgül, Baki; Belibasakis, Georgios N; Bostanci, Nagihan

    2015-01-01

    Periodontal infection involves a complex interplay between oral biofilms, gingival tissues and cells of the immune system in a dynamic microenvironment. A humanized in vitro model that reduces the need for experimental animal models, while recapitulating key biological events in a periodontal pocket, would constitute a technical advancement in the study of periodontal disease. The aim of this study was to use a dynamic perfusion bioreactor in order to develop a gingival epithelial-fibroblast-monocyte organotypic co-culture on collagen sponges. An 11 species subgingival biofilm was used to challenge the generated tissue in the bioreactor for a period of 24 h. The histological and scanning electron microscopy analysis displayed an epithelial-like layer on the surface of the collagen sponge, supported by the underlying ingrowth of gingival fibroblasts, while monocytic cells were also found within the sponge mass. Bacterial quantification of the biofilm showed that in the presence of the organotypic tissue, the growth of selected biofilm species, especially Campylobacter rectus, Actinomyces oris, Streptococcus anginosus, Veillonella dispar, and Porphyromonas gingivalis, was suppressed, indicating a potential antimicrobial effect by the tissue. Multiplex immunoassay analysis of cytokine secretion showed that interleukin (IL)-1 β, IL-2, IL-4, and tumor necrosis factor (TNF)-α levels in cell culture supernatants were significantly up-regulated in presence of the biofilm, indicating a positive inflammatory response of the organotypic tissue to the biofilm challenge. In conclusion, this novel host-biofilm interaction organotypic model might resemble the periodontal pocket and have an important impact on the study of periodontal infections, by minimizing the need for the use of experimental animal models. PMID:25587671

  2. Establishment of an oral infection model resembling the periodontal pocket in a perfusion bioreactor system.

    PubMed

    Bao, Kai; Papadimitropoulos, Adam; Akgül, Baki; Belibasakis, Georgios N; Bostanci, Nagihan

    2015-01-01

    Periodontal infection involves a complex interplay between oral biofilms, gingival tissues and cells of the immune system in a dynamic microenvironment. A humanized in vitro model that reduces the need for experimental animal models, while recapitulating key biological events in a periodontal pocket, would constitute a technical advancement in the study of periodontal disease. The aim of this study was to use a dynamic perfusion bioreactor in order to develop a gingival epithelial-fibroblast-monocyte organotypic co-culture on collagen sponges. An 11 species subgingival biofilm was used to challenge the generated tissue in the bioreactor for a period of 24 h. The histological and scanning electron microscopy analysis displayed an epithelial-like layer on the surface of the collagen sponge, supported by the underlying ingrowth of gingival fibroblasts, while monocytic cells were also found within the sponge mass. Bacterial quantification of the biofilm showed that in the presence of the organotypic tissue, the growth of selected biofilm species, especially Campylobacter rectus, Actinomyces oris, Streptococcus anginosus, Veillonella dispar, and Porphyromonas gingivalis, was suppressed, indicating a potential antimicrobial effect by the tissue. Multiplex immunoassay analysis of cytokine secretion showed that interleukin (IL)-1 β, IL-2, IL-4, and tumor necrosis factor (TNF)-α levels in cell culture supernatants were significantly up-regulated in presence of the biofilm, indicating a positive inflammatory response of the organotypic tissue to the biofilm challenge. In conclusion, this novel host-biofilm interaction organotypic model might resemble the periodontal pocket and have an important impact on the study of periodontal infections, by minimizing the need for the use of experimental animal models.

  3. Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model

    PubMed Central

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F.; Wick, Peter; von Mandach, Ursula

    2013-01-01

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1. Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3, can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. PMID:23851364

  4. Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model.

    PubMed

    Grafmüller, Stefanie; Manser, Pius; Krug, Harald F; Wick, Peter; von Mandach, Ursula

    2013-06-18

    Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ (1). Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 (2) and continuously modified by Schneider et al. in 1972 (3), can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data.

  5. In silico multi-scale model of transport and dynamic seeding in a bone tissue engineering perfusion bioreactor.

    PubMed

    Spencer, T J; Hidalgo-Bastida, L A; Cartmell, S H; Halliday, I; Care, C M

    2013-04-01

    Computer simulations can potentially be used to design, predict, and inform properties for tissue engineering perfusion bioreactors. In this work, we investigate the flow properties that result from a particular poly-L-lactide porous scaffold and a particular choice of perfusion bioreactor vessel design used in bone tissue engineering. We also propose a model to investigate the dynamic seeding properties such as the homogeneity (or lack of) of the cellular distribution within the scaffold of the perfusion bioreactor: a pre-requisite for the subsequent successful uniform growth of a viable bone tissue engineered construct. Flows inside geometrically complex scaffolds have been investigated previously and results shown at these pore scales. Here, it is our aim to show accurately that through the use of modern high performance computers that the bioreactor device scale that encloses a scaffold can affect the flows and stresses within the pores throughout the scaffold which has implications for bioreactor design, control, and use. Central to this work is that the boundary conditions are derived from micro computed tomography scans of both a device chamber and scaffold in order to avoid generalizations and uncertainties. Dynamic seeding methods have also been shown to provide certain advantages over static seeding methods. We propose here a novel coupled model for dynamic seeding accounting for flow, species mass transport and cell advection-diffusion-attachment tuned for bone tissue engineering. The model highlights the timescale differences between different species suggesting that traditional homogeneous porous flow models of transport must be applied with caution to perfusion bioreactors. Our in silico data illustrate the extent to which these experiments have the potential to contribute to future design and development of large-scale bioreactors. Copyright © 2012 Wiley Periodicals, Inc.

  6. Usefulness of the novel risk estimation software, Heart Risk View, for the prediction of cardiac events in patients with normal myocardial perfusion SPECT.

    PubMed

    Sakatani, Tomohiko; Shimoo, Satoshi; Takamatsu, Kazuaki; Kyodo, Atsushi; Tsuji, Yumika; Mera, Kayoko; Koide, Masahiro; Isodono, Koji; Tsubakimoto, Yoshinori; Matsuo, Akiko; Inoue, Keiji; Fujita, Hiroshi

    2016-12-01

    Myocardial perfusion single-photon emission-computed tomography (SPECT) can predict cardiac events in patients with coronary artery disease with high accuracy; however, pseudo-negative cases sometimes occur. Heart Risk View, which is based on the prospective cohort study (J-ACCESS), is a software for evaluating cardiac event probability. We examined whether Heart Risk View was useful to evaluate the cardiac risk in patients with normal myocardial perfusion SPECT (MPS). We studied 3461 consecutive patients who underwent MPS to detect myocardial ischemia and those who had normal MPS were enrolled in this study (n = 698). We calculated cardiac event probability by Heart Risk View and followed-up for 3.8 ± 2.4 years. The cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization. During the follow-up period, 21 patients (3.0 %) had cardiac events. The event probability calculated by Heart Risk View was higher in the event group (5.5 ± 2.6 vs. 2.9 ± 2.6 %, p < 0.001). According to the receiver-operating characteristics curve, the cut-off point of the event probability for predicting cardiac events was 3.4 % (sensitivity 0.76, specificity 0.72, and AUC 0.85). Kaplan-Meier curves revealed that a higher event rate was observed in the high-event probability group by the log-rank test (p < 0.001). Although myocardial perfusion SPECT is useful for the prediction of cardiac events, risk estimation by Heart Risk View adds more prognostic information, especially in patients with normal MPS.

  7. A novel in vitro flat-bed perfusion biofilm model for determining the potential antimicrobial efficacy of topical wound treatments.

    PubMed

    Thorn, R M S; Greenman, J

    2009-12-01

    To develop an in vitro flat-bed perfusion biofilm model that could be used to determine the antimicrobial efficacy of topically applied treatments. Pseudomonas aeruginosa and Staphylococcus aureus biofilms were grown within continuously perfused cellulose matrices. Enumeration of the biofilm density and eluate was performed at various sampling times, enabling determination of the biofilm growth rate. Two antimicrobial wound dressings were applied to the surface of mature biofilms and periodically sampled. To enable real-time imaging of biofilm growth and potential antimicrobial kinetics, a bioluminescent Ps. aeruginosa biofilm was monitored using low-light photometry. Target species produced reproducible steady-state biofilms at a density of c. 10(7) per biofilm support matrix, after 24-h perfusion. Test dressings elicited significant antimicrobial effects, producing differing kill kinetic profiles. There was a good correlation between photon and viable count data. The model enables determination of the antimicrobial profile of topically applied treatments against target species biofilms, accurately differentiating bactericidal from bacteriostatic effects. Moreover, these effects could be monitored in real time using bioluminescence. This is the first in vitro biofilm model which can assess the antimicrobial potential of topical therapies in a dynamic growth environment.

  8. 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

  9. Diffusion model for iontophoresis measured by laser-Doppler perfusion flowmetry, applied to normal and preeclamptic pregnancies.

    PubMed

    de Mul, Frits F M; Blaauw, Judith; Aarnoudse, Jan G; Smit, Andries J; Rakhorst, Gerhard

    2007-01-01

    We present a physical model to describe iontophoresis time recordings. The model is a combination of monodimensional material diffusion and decay, probably due to transport by blood flow. It has four adjustable parameters, the diffusion coefficient, the decay constant, the height of the response, and the shot saturation constant, a parameter representing the relative importance of subsequent shots (in case of saturation). We test the model with measurements of blood perfusion in the capillary bed of the fingers of women who recently had preeclampsia and in women with a history of normal pregnancy. From the fits to the measurements, we conclude that the model provides a useful physical description of the iontophoresis process.

  10. Rasch model estimation: further topics.

    PubMed

    Linacre, John M

    2004-01-01

    Building on Wright and Masters (1982), several Rasch estimation methods are briefly described, including Marginal Maximum Likelihood Estimation (MMLE) and minimum chi-square methods. General attributes of Rasch estimation algorithms are discussed, including the handling of missing data, precision and accuracy, estimate consistency, bias and symmetry. Reasons for, and the implications of, measure misestimation are explained, including the effect of loose convergence criteria, and failure of Newton-Raphson iteration to converge. Alternative parameterizations of rating scales broaden the scope of Rasch measurement methodology.

  11. Kalman filter estimation model in flood forecasting

    NASA Astrophysics Data System (ADS)

    Husain, Tahir

    Elementary precipitation and runoff estimation problems associated with hydrologic data collection networks are formulated in conjunction with the Kalman Filter Estimation Model. Examples involve the estimation of runoff using data from a single precipitation station and also from a number of precipitation stations. The formulations demonstrate the role of state-space, measurement, and estimation equations of the Kalman Filter Model in flood forecasting. To facilitate the formulation, the unit hydrograph concept and antecedent precipitation index is adopted in the estimation model. The methodology is then applied to estimate various flood events in the Carnation Creek of British Columbia.

  12. Glutamate and Hypoxia as a Stress Model for the Isolated Perfused Vertebrate Retina

    PubMed Central

    Januschowski, Kai; Müller, Sebastian; Krupp, Carlo; Spitzer, Martin S.; Hurst, José; Schultheiss, Maximilian; Bartz-Schmidt, Karl-Ulrich; Szurman, Peter; Schnichels, Sven

    2015-01-01

    Neuroprotection has been a strong field of investigation in ophthalmological research in the past decades and affects diseases such as glaucoma, retinal vascular occlusion, retinal detachment, and diabetic retinopathy. It was the object of this study to introduce a standardized stress model for future preclinical therapeutic testing. Bovine retinas were prepared and perfused with an oxygen saturated standard solution, and the ERG was recorded. After recording stable b-waves, hypoxia (pure N2) or glutamate stress (250 µm glutamate) was exerted for 45 min. To investigate the effects on photoreceptor function alone, 1 mM aspartate was added to obtain a-waves. ERG-recovery was monitored for 75 min. For hypoxia, a decrease in a-wave amplitude of 87.0% was noted (p <0.01) after an exposition time of 45 min (decrease of 36.5% after the end of the washout p = 0.03). Additionally, an initial decrease in b-wave amplitudes of 87.23% was recorded, that reached statistical significance (p <0.01, decrease of 25.5% at the end of the washout, p = 0.03). For 250 µm glutamate, an initial 7.8% reduction of a-wave amplitudes (p >0.05) followed by a reduction of 1.9% (p >0.05). A reduction of 83.7% of b-wave amplitudes (p <0.01) was noted; after a washout of 75 min the reduction was 2.3% (p = 0.62). In this study, a standardized stress model is presented that may be useful to identify possible neuroprotective effects in the future. PMID:25868118

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

    PubMed

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

    2014-05-01

    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.

  14. 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.

  15. 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

  16. [Quantitative study of therapeutic efficacy on early intervention of hyperbaric oxygen to model of steroid-induced avascular osteonecrosis of femoral head by multi-slice perfusion imaging].

    PubMed

    Yang, Jin-cai; Pan, Zhen-yu; Gu, Hua; Li, Nan; Qian, Xiao-jun; Zhai, Ren-you; Wu, Lian-hua; Gao, Chun-jin

    2008-12-09

    To quantitatively evaluate the hemodynamic status in animal models of steroid-induced avascular osteonecrosis of femoral head (SANFH) by multislice CT (MSCT) perfusion imaging, and estimate the therapeutic efficacy on early intervention of hyperbaric oxygen (HBO) to improve the region blood flow (rBF) of ischemic femoral head. Forty-eight New Zealand male rabbits were injected with Escherichia coli endotoxin and methyl-prednisolone to establish SANFH models and then divided into 3 subgroups to undergo MSCT to measure the rBF, regional blood volume (rBV), and mean transit time (MTT) to obtain perfusion maps at the femoral head epiphysis, metaphysic, and neck of femur, and then were killed to undergo histological examination of the bilateral femoral heads 2, 4, and 6 weeks later respectively (Groups M(2), M(4), and M(6)). Twenty-four rabbits underwent HOB treatment after the second injection of E. c. endotoxin for 1-3 courses respectively (Groups H(1), H(2), and H(3)), and then underwent MSCT and pathological examination as described above. Eight rabbits were used as controls (Group N). (1) The rBF values of Groups M(2), M(4), and M(6) were all significantly lower than that of Group N (P < 0.001, < 0.001, and < 0.002). The rBF value of femoral head epiphysis of Group M(2) was remarkably lower than that of Group N, decreased to the lowest in Group M(4), and re-increased in Group M(6). The rBV value demonstrated similar change pattern in femoral head epiphysis. The MTT values of Groups M(2) and M(4) were longer than that of Group N, and then re-decreased in Group M(6). (2) It did differ significantly between the perfusion data of different femoral head anatomic regions in Groups M(2), M(4), M(6) and N (rBF: F = 52.190, P < 0.001; rBV: F = 42.677, P < 0.001; MTT: F = 3.09, P = 0.048). The changes of the perfusion data in femoral head epiphysis were more significant than those in other anatomic regions. (3) There were no statistically significant differences in the r

  17. Pseudolikelihood Estimation of the Rasch Model.

    ERIC Educational Resources Information Center

    Smit, Arnold; Kelderman, Henk

    2000-01-01

    Proposes an estimation method for the Rasch model that is based on the pseudolikelihood theory of B. Arnold and D. Strauss (1988). Simulation results show great similarity between estimates from this method with those from conditional maximum likelihood and unconditional maximum likelihood estimates for the item parameters of the Rasch model. (SLD)

  18. 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

  19. 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

  20. 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.

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

    PubMed

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

    2011-04-07

    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.

  2. 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.

  3. 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.

  4. Isolated swine heart ventricle perfusion model for implant assisted-magnetic drug targeting.

    PubMed

    Avilés, Misael O; Mangual, Jan O; Ebner, Armin D; Ritter, James A

    2008-09-01

    An isolated swine heart ventricle perfusion model was developed and used under physiologically relevant conditions to study implant assisted-magnetic drug targeting (IA-MDT). A stent coil was fabricated from a ferromagnetic SS 430 wire and used to capture 100-nm diameter magnetite particles that mimicked magnetic drug carrier particles (MDCPs). Four key cases were studied: (1) no stent and no magnet (control), (2) no magnet but with a stent, (3) no stent but with a magnet (traditional MDT), and (4) with a stent and a magnet (IA-MDT). When applied, the magnetic field was fixed at 0.125T. The performance of the system was based on the capture efficiency (CE) of the magnetite nanoparticles. The experiments done in the absence of the magnetic field showed minimal retention of any nanoparticles whether the stent was present or not. The experiments done in the presence of the magnetic field showed a statistically significant increase in the retention of the nanoparticles, with a marked difference between the traditional and IA-MDT cases. Compared to the control case, in one case there was nearly an 11-fold increase in CE for the IA-MDT case compared to only a threefold increase in CE for the traditional MDT case. This enhanced performance by the IA-MDT case was typical of all the experiments. Histology images of the cross-section of the coronary artery revealed that the nanoparticles were captured mainly in the vicinity of the stent. Overall, the IA-MDT results from this work with actual tissue were very encouraging and similar to those obtained from other non-tissue and theoretical studies; but, they did point to the need for further studies of IA-MDT.

  5. Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion.

    PubMed

    Brunner, Clément; Isabel, Clothilde; Martin, Abraham; Dussaux, Clara; Savoye, Anne; Emmrich, Julius; Montaldo, Gabriel; Mas, Jean-Louis; Baron, Jean-Claude; Urban, Alan

    2017-01-01

    Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject.

  6. Model-based cell number quantification using online single-oxygen sensor data for tissue engineering perfusion bioreactors.

    PubMed

    Lambrechts, T; Papantoniou, I; Sonnaert, M; Schrooten, J; Aerts, J-M

    2014-10-01

    Online and non-invasive quantification of critical tissue engineering (TE) construct quality attributes in TE bioreactors is indispensable for the cost-effective up-scaling and automation of cellular construct manufacturing. However, appropriate monitoring techniques for cellular constructs in bioreactors are still lacking. This study presents a generic and robust approach to determine cell number and metabolic activity of cell-based TE constructs in perfusion bioreactors based on single oxygen sensor data in dynamic perfusion conditions. A data-based mechanistic modeling technique was used that is able to correlate the number of cells within the scaffold (R(2)  = 0.80) and the metabolic activity of the cells (R(2)  = 0.82) to the dynamics of the oxygen response to step changes in the perfusion rate. This generic non-destructive measurement technique is effective for a large range of cells, from as low as 1.0 × 10(5) cells to potentially multiple millions of cells, and can open-up new possibilities for effective bioprocess monitoring.

  7. Ventilation-Perfusion Alterations after Inhalation Injury in an Ovine Model

    DTIC Science & Technology

    1996-05-01

    positioned prone and artificially ventilated. A gas samples for the natural occurrence of krypton (1.1 X 10-6 volume-limited ventilator (Bear 2, Bear...VA/Q devel- dead space, total peripheral resistance index, and pulmon - oped further and 42% of the cardiac output perfused the ary vascular index

  8. Computational modeling of combined cell population dynamics and oxygen transport in engineered tissue subject to interstitial perfusion.

    PubMed

    Galbusera, F; Cioffi, M; Raimondi, M T; Pietrabissa, R

    2007-08-01

    This work presents a computational model of tissue growth under interstitial perfusion inside a tissue engineering bioreactor. The model accounts both for the cell population dynamics, using a model based on cellular automata, and for the hydrodynamic microenvironment imposed by the bioreactor, using a model based on the Lattice-Boltzmann equation and the convection-diffusion equation. The conditions of static culture versus perfused culture were compared, by including the population dynamics along with oxygen diffusion, convective transport and consumption. The model is able to deal with arbitrary complex geometries of the spatial domain; in the present work, the domain modeled was the void space of a porous scaffold for tissue-engineered cartilage. The cell population dynamics algorithm provided results which qualitatively resembled population dynamics patterns observed in experimental studies, and these results were in good quantitative agreement with previous computational studies. Simulation of oxygen transport and consumption showed the fundamental contribution of convective transport in maintaining a high level of oxygen concentration in the whole spatial domain of the scaffold. The model was designed with the aim to be computationally efficient and easily expandable, i.e. to allow straightforward implementability of further models of complex biological phenomena of increasing scientific interest in tissue engineering, such as chemotaxis, extracellular matrix deposition and effect of mechanical stimulation.

  9. Estimating recharge rates with analytic element models and parameter estimation

    USGS Publications Warehouse

    Dripps, W.R.; Hunt, R.J.; Anderson, M.P.

    2006-01-01

    Quantifying the spatial and temporal distribution of recharge is usually a prerequisite for effective ground water flow modeling. In this study, an analytic element (AE) code (GFLOW) was used with a nonlinear parameter estimation code (UCODE) to quantify the spatial and temporal distribution of recharge using measured base flows as calibration targets. The ease and flexibility of AE model construction and evaluation make this approach well suited for recharge estimation. An AE flow model of an undeveloped watershed in northern Wisconsin was optimized to match median annual base flows at four stream gages for 1996 to 2000 to demonstrate the approach. Initial optimizations that assumed a constant distributed recharge rate provided good matches (within 5%) to most of the annual base flow estimates, but discrepancies of >12% at certain gages suggested that a single value of recharge for the entire watershed is inappropriate. Subsequent optimizations that allowed for spatially distributed recharge zones based on the distribution of vegetation types improved the fit and confirmed that vegetation can influence spatial recharge variability in this watershed. Temporally, the annual recharge values varied >2.5-fold between 1996 and 2000 during which there was an observed 1.7-fold difference in annual precipitation, underscoring the influence of nonclimatic factors on interannual recharge variability for regional flow modeling. The final recharge values compared favorably with more labor-intensive field measurements of recharge and results from studies, supporting the utility of using linked AE-parameter estimation codes for recharge estimation. Copyright ?? 2005 The Author(s).

  10. Lowering Perfusate Temperature From 37°C to 32°C Diminishes Function in a Porcine Model of Ex Vivo Kidney Perfusion

    PubMed Central

    Adams, Thomas D.; Patel, Meeta; Hosgood, Sarah A.; Nicholson, Michael L.

    2017-01-01

    Background Ex vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS). Methods Porcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C. After this, kidneys were reperfused with whole autologous blood at 37°C for 3 hours to assess renal function and injury. These were compared with a control group that underwent 24 hours CS. Results During EVP, kidneys perfused at 37°C had a higher level of renal blood flow and oxygen consumption compared with EVP at 32°C (P = 0.001, 0.002). During reperfusion, 32°C EVP kidneys had lower creatinine clearance and urine output than control (P = 0.023, 0.011) and a higher fractional excretion of sodium, serum potassium, and serum aspartate transaminase than 37°C EVP kidneys (P = 0.01, 0.023, 0.009). Conclusions Tubular and renal functions were better preserved by a near-physiological temperature of 37°C during 1 hour of EVP, when compared to EVP at 32°C or cold storage. PMID:28361124

  11. Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion.

    PubMed

    Ataç, Beren; Wagner, Ilka; Horland, Reyk; Lauster, Roland; Marx, Uwe; Tonevitsky, Alexander G; Azar, Reza P; Lindner, Gerd

    2013-09-21

    Substantial progress has been achieved over the last few decades in the development of skin equivalents to model the skin as an organ. However, their static culture still limits the emulation of essential physiological properties crucial for toxicity testing and compound screening. Here, we describe a dynamically perfused chip-based bioreactor platform capable of applying variable mechanical shear stress and extending culture periods. This leads to improvements of culture conditions for integrated in vitro skin models, ex vivo skin organ cultures and biopsies of single hair follicular units.

  12. 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.

  13. 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.

  14. SURE Estimates for a Heteroscedastic Hierarchical Model

    PubMed Central

    Xie, Xianchao; Kou, S. C.; Brown, Lawrence D.

    2014-01-01

    Hierarchical models are extensively studied and widely used in statistics and many other scientific areas. They provide an effective tool for combining information from similar resources and achieving partial pooling of inference. Since the seminal work by James and Stein (1961) and Stein (1962), shrinkage estimation has become one major focus for hierarchical models. For the homoscedastic normal model, it is well known that shrinkage estimators, especially the James-Stein estimator, have good risk properties. The heteroscedastic model, though more appropriate for practical applications, is less well studied, and it is unclear what types of shrinkage estimators are superior in terms of the risk. We propose in this paper a class of shrinkage estimators based on Stein’s unbiased estimate of risk (SURE). We study asymptotic properties of various common estimators as the number of means to be estimated grows (p → ∞). We establish the asymptotic optimality property for the SURE estimators. We then extend our construction to create a class of semi-parametric shrinkage estimators and establish corresponding asymptotic optimality results. We emphasize that though the form of our SURE estimators is partially obtained through a normal model at the sampling level, their optimality properties do not heavily depend on such distributional assumptions. We apply the methods to two real data sets and obtain encouraging results. PMID:25301976

  15. 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).

  16. Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits

    PubMed Central

    Nie, Maoxiao; Yan, Yunfeng

    2016-01-01

    Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5–146.8%, and 241.5–255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate. PMID:27965979

  17. 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.

  18. Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits.

    PubMed

    Nie, Maoxiao; Yan, Yunfeng; Li, Xinhe; Feng, Tingting; Zhao, Xin; Zhang, Mingduo; Zhao, Quanming

    2016-01-01

    Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5-146.8%, and 241.5-255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate.

  19. Bilinear modeling and nonlinear estimation

    NASA Technical Reports Server (NTRS)

    Dwyer, Thomas A. W., III; Karray, Fakhreddine; Bennett, William H.

    1989-01-01

    New methods are illustrated for online nonlinear estimation applied to the lateral deflection of an elastic beam on board measurements of angular rates and angular accelerations. The development of the filter equations, together with practical issues of their numerical solution as developed from global linearization by nonlinear output injection are contrasted with the usual method of the extended Kalman filter (EKF). It is shown how nonlinear estimation due to gyroscopic coupling can be implemented as an adaptive covariance filter using off-the-shelf Kalman filter algorithms. The effect of the global linearization by nonlinear output injection is to introduce a change of coordinates in which only the process noise covariance is to be updated in online implementation. This is in contrast to the computational approach which arises in EKF methods arising by local linearization with respect to the current conditional mean. Processing refinements for nonlinear estimation based on optimal, nonlinear interpolation between observations are also highlighted. In these methods the extrapolation of the process dynamics between measurement updates is obtained by replacing a transition matrix with an operator spline that is optimized off-line from responses to selected test inputs.

  20. Placental transfer of enfuvirtide in the ex vivo human placenta perfusion model.

    PubMed

    Ceccaldi, Pierre-Francois; Ferreira, Claudia; Gavard, Laurent; Gil, Sophie; Peytavin, Gilles; Mandelbrot, Laurent

    2008-04-01

    The objective of the study was to determine the placental transfer of the antiretroviral fusion inhibitor, enfuvirtide (Fuzeon). Human cotyledons were perfused for 90 minutes in an open dual circuit with enfuvirtide, and fetal venous samples were collected every 5 minutes. Three perfusion experiments were validated using antipyrine. Enfuvirtide was not detected in the fetal compartment in any of the 3 experiments. The mean concentration of the drug measured in the maternal compartment was 12,400 ng/mL (range, 6500-16,200 ng/mL), which is 2.5 times the maximum concentration recommended for patients treated with enfuvirtide. Even at maternal concentrations twice above therapeutic levels, no placental transfer of enfuvirtide was observed. The high molecular weight of the molecule (4492 kDa) and its ionized state may account for the lack of placental transfer. This result suggests that enfuvirtide could be used in HIV-infected pregnant women without causing fetal exposure.

  1. Estimation and Accuracy after Model Selection

    PubMed Central

    Efron, Bradley

    2013-01-01

    Classical statistical theory ignores model selection in assessing estimation accuracy. Here we consider bootstrap methods for computing standard errors and confidence intervals that take model selection into account. The methodology involves bagging, also known as bootstrap smoothing, to tame the erratic discontinuities of selection-based estimators. A useful new formula for the accuracy of bagging then provides standard errors for the smoothed estimators. Two examples, nonparametric and parametric, are carried through in detail: a regression model where the choice of degree (linear, quadratic, cubic, …) is determined by the Cp criterion, and a Lasso-based estimation problem. PMID:25346558

  2. Improved diagnostic model for estimating wind energy

    SciTech Connect

    Endlich, R.M.; Lee, J.D.

    1983-03-01

    Because wind data are available only at scattered locations, a quantitative method is needed to estimate the wind resource at specific sites where wind energy generation may be economically feasible. This report describes a computer model that makes such estimates. The model uses standard weather reports and terrain heights in deriving wind estimates; the method of computation has been changed from what has been used previously. The performance of the current model is compared with that of the earlier version at three sites; estimates of wind energy at four new sites are also presented.

  3. The suitability of an in situ perfusion model for permeability determinations: utility for BCS class I biowaiver requests.

    PubMed

    Kim, Jae-Seung; Mitchell, Stefanie; Kijek, Paul; Tsume, Yasuhiro; Hilfinger, John; Amidon, Gordon L

    2006-01-01

    The FDA has published recommendations for sponsors who wish to request a waiver of in vivo bioavailability (BA) or bioequivalence (BE) studies for immediate release (IR) solid oral dosage forms based on the Biopharmaceutics Classification System (BCS). Biowaivers can be requested for IR formulations in which the active ingredient is shown to be a BCS class I drug: that is, a drug showing high permeability and high solubility over a pH range of 1-7.5. For permeability determinations, a variety of experimental methods can be used, such as the rat in situ single pass perfusion or Caco-2 cell culture models, once the suitability of the particular method is established. Following the recommended procedure for assessing the suitability of permeability determinations, we determined the permeability of 20 test drugs using the in situ single pass perfusion model in rats. The test compounds were coperfused through jejunal intestinal segments with an internal permeability reference standard (metoprolol) over a 90 min time period. Sample analysis was performed by HPLC, and the ratio of the effective permeability, Peff (cm/s), of test compound to that of metoprolol was determined. To address the question of test drug permeabilities that approach that of the internal standard, we propose that a statistical analysis such as the "0.8-1.25 rule" used for in vivo or in vitro bioequivalence studies provide guidance for permeability classification using the in situ single pass perfusion model. We developed a method using the 90% confidence interval of the permeability ratio of the test to internal reference standard in order to differentiate between high and low permeability compounds. This analysis allowed for the proper permeability classification of all of the test compounds and suggests a robust means for assessing drug permeability classification.

  4. Comprehensive metabolic modeling of multiple 13C-isotopomer data sets to study metabolism in perfused working hearts.

    PubMed

    Crown, Scott B; Kelleher, Joanne K; Rouf, Rosanne; Muoio, Deborah M; Antoniewicz, Maciek R

    2016-10-01

    In many forms of cardiomyopathy, alterations in energy substrate metabolism play a key role in disease pathogenesis. Stable isotope tracing in rodent heart perfusion systems can be used to determine cardiac metabolic fluxes, namely those relative fluxes that contribute to pyruvate, the acetyl-CoA pool, and pyruvate anaplerosis, which are critical to cardiac homeostasis. Methods have previously been developed to interrogate these relative fluxes using isotopomer enrichments of measured metabolites and algebraic equations to determine a predefined metabolic flux model. However, this approach is exquisitely sensitive to measurement error, thus precluding accurate relative flux parameter determination. In this study, we applied a novel mathematical approach to determine relative cardiac metabolic fluxes using (13)C-metabolic flux analysis ((13)C-MFA) aided by multiple tracer experiments and integrated data analysis. Using (13)C-MFA, we validated a metabolic network model to explain myocardial energy substrate metabolism. Four different (13)C-labeled substrates were queried (i.e., glucose, lactate, pyruvate, and oleate) based on a previously published study. We integrated the analysis of the complete set of isotopomer data gathered from these mouse heart perfusion experiments into a single comprehensive network model that delineates substrate contributions to both pyruvate and acetyl-CoA pools at a greater resolution than that offered by traditional methods using algebraic equations. To our knowledge, this is the first rigorous application of (13)C-MFA to interrogate data from multiple tracer experiments in the perfused heart. We anticipate that this approach can be used widely to study energy substrate metabolism in this and other similar biological systems. Copyright © 2016 the American Physiological Society.

  5. Variance estimation for nucleotide substitution models.

    PubMed

    Chen, Weishan; Wang, Hsiuying

    2015-09-01

    The current variance estimators for most evolutionary models were derived when a nucleotide substitution number estimator was approximated with a simple first order Taylor expansion. In this study, we derive three variance estimators for the F81, F84, HKY85 and TN93 nucleotide substitution models, respectively. They are obtained using the second order Taylor expansion of the substitution number estimator, the first order Taylor expansion of a squared deviation and the second order Taylor expansion of a squared deviation, respectively. These variance estimators are compared with the existing variance estimator in terms of a simulation study. It shows that the variance estimator, which is derived using the second order Taylor expansion of a squared deviation, is more accurate than the other three estimators. In addition, we also compare these estimators with an estimator derived by the bootstrap method. The simulation shows that the performance of this bootstrap estimator is similar to the estimator derived by the second order Taylor expansion of a squared deviation. Since the latter one has an explicit form, it is more efficient than the bootstrap estimator.

  6. A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

    PubMed

    Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud

    2017-07-01

    Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (P<0.05). The decrease in the hepatic metabolism of tramadol and increase in the half-life of the elimination of tramadol in rats with BDL suggests that personalized treatment and the therapeutic drug monitoring (TDM) data examination are necessary for patients with bile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. 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.

  8. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model.

    PubMed

    Abarca, Eva M; Salmon, Jacklyn H; Gilger, Brian C

    2013-10-01

    To compare tissue distribution of dye-drug surrogates after intravitreal (IVT) and suprachoroidal (SCS) delivery to determine the influence of drug lipophilicity and choroidal circulation. Thirty-two pig eyes were collected immediately after euthanasia. Sixteen eyes were perfused for 30 min through one long posterior ciliary artery with nondye containing nutrient media. An IVT or SCS injection was performed with either a 100 μL balanced salt solution (BSS, n=8), 1% sodium fluorescein (NaF, n=12) or 0.12% lipophilic carbocyanine dye (DiI, n=12). Globes were maintained at 37°C for 15 min, and then snap-frozen and dissected. Aqueous extraction and measurement of NaF or DiI concentration was performed using spectrophotometry and spectrofluorometry, respectively. After SCS delivery of NaF scleral, iris-ciliary body, choroidal and vitreous dye levels were higher in nonperfused eyes compared to perfused eyes. After DiI SCS or IVT delivery, no significant differences were found in dye tissue concentrations in perfused eyes compared to nonperfused eyes. Following perfusion, a better and even drug distribution was found in the retinal pigmented epithelium (RPE)-choroid following IVT and SCS delivery of the hydrophilic drug and after IVT injection of the lipophilic drug compared to nonperfused eyes. Choroidal circulation reduces the tissue drug concentration of the hydrophilic drug suggesting an early clearance mechanism after SCS delivery. SCS injections of lipid and hydrophilic drugs allowed direct drug delivery to the retina and RPE-choroid with limited exposition to the anterior segment.

  9. Human Thiel-Embalmed Cadaveric Aortic Model with Perfusion for Endovascular Intervention Training and Medical Device Evaluation.

    PubMed

    McLeod, Helen; Cox, Ben F; Robertson, James; Duncan, Robyn; Matthew, Shona; Bhat, Raj; Barclay, Avril; Anwar, J; Wilkinson, Tracey; Melzer, Andreas; Houston, J Graeme

    2017-09-01

    The purpose of this investigation was to evaluate human Thiel-embalmed cadavers with the addition of extracorporeal driven ante-grade pulsatile flow in the aorta as a model for simulation training in interventional techniques and endovascular device testing. Three human cadavers embalmed according to the method of Thiel were selected. Extracorporeal pulsatile ante-grade flow of 2.5 L per min was delivered directly into the aorta of the cadavers via a surgically placed connection. During perfusion, aortic pressure and temperature were recorded and optimized for physiologically similar parameters. Pre- and post-procedure CT imaging was conducted to plan and follow up thoracic and abdominal endovascular aortic repair as it would be in a clinical scenario. Thoracic endovascular aortic repair (TEVAR) and endovascular abdominal repair (EVAR) procedures were conducted in simulation of a clinical case, under fluoroscopic guidance with a multidisciplinary team present. The Thiel cadaveric aortic perfusion model provided pulsatile ante-grade flow, with pressure and temperature, sufficient to conduct a realistic simulation of TEVAR and EVAR procedures. Fluoroscopic imaging provided guidance during the intervention. Pre- and post-procedure CT imaging facilitated planning and follow-up evaluation of the procedure. The human Thiel-embalmed cadavers with the addition of extracorporeal flow within the aorta offer an anatomically appropriate, physiologically similar robust model to simulate aortic endovascular procedures, with potential applications in interventional radiology training and medical device testing as a pre-clinical model.

  10. Perfusion of a cerebral protective solution enhances neuroprotection in a rabbit model of occlusion-reperfusion: prolonged cerebral dormancy time.

    PubMed

    Ye, Libin; Hua, Aiyuan; Dai, Bo; Lu, Tingting; Zhang, Zhaolin; Ye, Meilin; Weintraub, Michael; Li, Qingdi Quentin

    2014-01-01

    In the present study, we investigated the effect of a cerebral protective solution on prolongation of cerebral dormancy time in a rabbit model of occlusion-reperfusion. In a control group, rabbits were anesthetized and the four cerebral arteries (the left and right common carotid arteries and vertebral arteries) were occluded for 7.5 min followed by reperfusion. All six rabbits in the control group died. In contrast, a second group underwent perfusion of a cerebral protective solution for 15 min between artery occlusion and reperfusion. All six rabbits in this group survived. However, when the perfusion solution was changed to 5% glucose solution or rabbit plasma in two other groups, the rabbits in both the latter two groups also died. Neuroprotection was also observed when the protective solution was administered for 30-60 min after the onset of artery occlusion and before the return of blood flow (reperfusion). To understand the high rate of thrombotic stroke in the clinic, we assessed the influence of different organ tissue infusions on blood coagulation in vitro and found that blood clotting occurred faster in the presence of brain tissue infusion compared to liver, kidney, and heart tissue infusions. These results indicate a higher rate of thrombosis in brain tissue compared to any of the other tissues tested. The current study shows that perfusion of a cerebral protective solution produced a significant neuroprotective benefit in our rabbit model of occlusion-reperfusion, suggesting that administration of a cerebral protective solution may be an effective approach for the treatment of ischemic stroke.

  11. Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model

    PubMed Central

    Grafmueller, Stefanie; Manser, Pius; Diener, Liliane; Diener, Pierre-André; Maeder-Althaus, Xenia; Maurizi, Lionel; Jochum, Wolfram; Krug, Harald F.; Buerki-Thurnherr, Tina; von Mandach, Ursula

    2015-01-01

    Background Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown. Objectives In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles. Methods We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm. Results We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue. Conclusions Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers. Citation Grafmueller S, Manser P, Diener L, Diener PA, Maeder-Althaus X, Maurizi L, Jochum W, Krug HF, Buerki-Thurnherr T, von Mandach U, Wick P. 2015. Bidirectional transfer study of polystyrene nanoparticles across the placental barrier in an ex vivo human

  12. 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.

  13. Effects of model deficiencies on parameter estimation

    NASA Technical Reports Server (NTRS)

    Hasselman, T. K.

    1988-01-01

    Reliable structural dynamic models will be required as a basis for deriving the reduced-order plant models used in control systems for large space structures. Ground vibration testing and model verification will play an important role in the development of these models; however, fundamental differences between the space environment and earth environment, as well as variations in structural properties due to as-built conditions, will make on-orbit identification essential. The efficiency, and perhaps even the success, of on-orbit identification will depend on having a valid model of the structure. It is envisioned that the identification process will primarily involve parametric methods. Given a correct model, a variety of estimation algorithms may be used to estimate parameter values. This paper explores the effects of modeling errors and model deficiencies on parameter estimation by reviewing previous case histories. The effects depend at least to some extent on the estimation algorithm being used. Bayesian estimation was used in the case histories presented here. It is therefore conceivable that the behavior of an estimation algorithm might be useful in detecting and possibly even diagnosing deficiencies. In practice, the task is complicated by the presence of systematic errors in experimental procedures and data processing and in the use of the estimation procedures themselves.

  14. Recursive parameter estimation of hydrologic models

    NASA Astrophysics Data System (ADS)

    Rajaram, Harihar; Georgakakos, Konstantine P.

    1989-02-01

    Proposed is a nonlinear filtering approach to recursive parameter estimation of conceptual watershed response models in state-space form. The conceptual model state is augmented by the vector of free parameters which are to be estimated from input-output data, and the extended Kaiman filter is used to recursively estimate and predict the augmented state. The augmented model noise covariance is parameterized as the sum of two components: one due to errors in the augmented model input and another due to errors in the specification of augmented model constants that were estimated from other than input-output data (e.g., topographic and rating curve constants). These components depend on the sensitivity of the augmented model to input and uncertain constants. Such a novel parameterization allows for nonstationary model noise statistics that are consistent with the dynamics of watershed response as they are described by the conceptual watershed response model. Prior information regarding uncertainty in input and uncertain constants in the form of degree-of-belief estimates of hydrologists can be used directly within the proposed formulation. Even though model structure errors are not explicitly parameterized in the present formulation, such errors can be identified through the examination of the one-step ahead predicted normalized residuals and the parameter traces during convergence. The formulation is exemplified by the estimation of the parameters of a conceptual hydrologic model with data from the 2.1-km2 watershed of Woods Lake located in the Adirondack Mountains of New York.

  15. 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.

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

    PubMed

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

    2015-10-21

    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 TR ≈ 4500 ms, TE  =  74 ms, eight b-values of 0-1000 μs μm(-2), pixel size  =  1.98 × 1.98 mm(2), 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

  17. 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

  18. Quantitative measurement of tissue perfusion and diffusion in vivo.

    PubMed

    Chenevert, T L; Pipe, J G; Williams, D M; Brunberg, J A

    1991-01-01

    Magnetic resonance imaging techniques designed for sensitivity to microscopic motions of water diffusion and blood flow in the capillary network are also exceptionally sensitive to bulk motion properties of the tissue, which may lead to contrast artifact and large quantitative errors. The magnitude of bulk motion error that exists in human brain perfusion/diffusion imaging and the inability of cardiac gating to adequately control this motion are demonstrated by direct measurement of phase stability of voxels localized in the brain. Two methods are introduced to reduce bulk motion phase error. The first, a postprocessing phase correction algorithm, reduces coarse phase error but is inadequate by itself for quantitative perfusion/diffusion MRI. The second method employs orthogonal slice selection gradients to define a column of tissue in the object, from which echoes may be combined in a phase-insensitive manner to measure more reliably the targeted signal attenuation. Applying this acquisition technique and a simplistic model of perfusion and diffusion signal attenuations yields an estimated perfusion fraction of 3.4 +/- 1.1% and diffusion coefficient of 1.1 +/- 0.2 x 10(-5) cm2/s in the white matter of one normal volunteer. Successful separation of perfusion and diffusion effects by this technique is supported in a dynamic study of calf muscle. Periods of normal blood flow, low flow, and reactive hyperemia are clearly distinguished in the quantitative perfusion results, whereas measured diffusion remained nearly constant.

  19. Robust dynamic myocardial perfusion CT deconvolution for accurate residue function estimation via adaptive-weighted tensor total variation regularization: a preclinical study

    NASA Astrophysics Data System (ADS)

    Zeng, Dong; Gong, Changfei; Bian, Zhaoying; Huang, Jing; Zhang, Xinyu; Zhang, Hua; Lu, Lijun; Niu, Shanzhou; Zhang, Zhang; Liang, Zhengrong; Feng, Qianjin; Chen, Wufan; Ma, Jianhua

    2016-11-01

    Dynamic myocardial perfusion computed tomography (MPCT) is a promising technique for quick diagnosis and risk stratification of coronary artery disease. However, one major drawback of dynamic MPCT imaging is the heavy radiation dose to patients due to its dynamic image acquisition protocol. In this work, to address this issue, we present a robust dynamic MPCT deconvolution algorithm via adaptive-weighted tensor total variation (AwTTV) regularization for accurate residue function estimation with low-mA s data acquisitions. For simplicity, the presented method is termed ‘MPD-AwTTV’. More specifically, the gains of the AwTTV regularization over the original tensor total variation regularization are from the anisotropic edge property of the sequential MPCT images. To minimize the associative objective function we propose an efficient iterative optimization strategy with fast convergence rate in the framework of an iterative shrinkage/thresholding algorithm. We validate and evaluate the presented algorithm using both digital XCAT phantom and preclinical porcine data. The preliminary experimental results have demonstrated that the presented MPD-AwTTV deconvolution algorithm can achieve remarkable gains in noise-induced artifact suppression, edge detail preservation, and accurate flow-scaled residue function and MPHM estimation as compared with the other existing deconvolution algorithms in digital phantom studies, and similar gains can be obtained in the porcine data experiment.

  20. A PHARMACOKINETIC MODEL FOR ESTIMATING ...

    EPA Pesticide Factsheets

    Empirical evidence suggests that exposure of Americans to dioxin-like compounds was low during the early decades of the 20th century, then increased during the 1940s and 1950s reaching a peak in the 1960s and 1970s, and progressively decreased to lower levels in the 1980s and 1990s. Such evidence includes dioxin analysis of carbon-dated sediment cores of lakes and rivers, preserved meat samples from different decades of the 20th century, and limited body burden measurements of dioxin-like compounds. Pinsky and Lorber (1998) summarized studies measuring 2,3,7,8-TCDD in blood and adipose tissue finding a range of 10-20 pg/g (ppt) lipid during the 1970s, and 2-10 ppt lipid during the 1980s. This study reviews body burdens of dioxin toxic equivalents, TEQs, to find a range from about 50-80 ppt lipid during the 1970s, 30-50 ppt lipid during the 1980s, and 10-20 ppt lipid during the 1990s (TEQs comprised of the 17 dioxin and furan congeners only). Pinsky and Lorber (1998) investigated historical exposure trends for 2,3,7,8-TCDD by using a single-compartment, first-order pharmacokinetic model. The current study extends this prior effort by modeling dioxin TEQs instead of the single compound, 2,3,7,8-TCDD. TEQs are modeled as though they are a single compound, in contrast to an approach where the individual dioxin and furan congeners are modeled separately. It was found that body burdens of TEQs during the 1970s, 80s, and 90s could be modeled by assuming a histor

  1. 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.

  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. 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.

  4. MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis.

    PubMed

    Byk, Katarzyna; Jasinski, Krzysztof; Bartel, Zaneta; Jasztal, Agnieszka; Sitek, Barbara; Tomanek, Boguslaw; Chlopicki, Stefan; Skorka, Tomasz

    2016-12-01

    To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL). BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASH(TM) and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging. The average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min(-1) (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining. Both the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

  5. 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

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

    PubMed Central

    Duro, Dominique; Belissa, Emilie; Peytavin, Gilles

    2014-01-01

    Placental transfer of the HIV protease inhibitor darunavir was investigated in 5 term human cotyledons perfused with darunavir (1,000 ng/ml) in the maternal to fetal direction. The mean (± the standard deviation [SD]) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 15.0% ± 2.1%, and the mean (±SD) clearance index (darunavir FTR/antipyrine FTR) was 40.3% ± 5.8%. This shows that darunavir crosses the placenta at a relatively low rate, resulting in fetal exposure. PMID:24982090

  7. Placental transfer of darunavir in an ex vivo human cotyledon perfusion model.

    PubMed

    Mandelbrot, Laurent; Duro, Dominique; Belissa, Emilie; Peytavin, Gilles

    2014-09-01

    Placental transfer of the HIV protease inhibitor darunavir was investigated in 5 term human cotyledons perfused with darunavir (1,000 ng/ml) in the maternal to fetal direction. The mean (± the standard deviation [SD]) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 15.0%±2.1%, and the mean (±SD) clearance index (darunavir FTR/antipyrine FTR) was 40.3%±5.8%. This shows that darunavir crosses the placenta at a relatively low rate, resulting in fetal exposure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. Placental transfer of rilpivirine in an ex vivo human cotyledon perfusion model.

    PubMed

    Mandelbrot, Laurent; Duro, Dominique; Belissa, Emilie; Peytavin, Gilles

    2015-05-01

    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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. 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

  10. Amplitude Models for Discrimination and Yield Estimation

    SciTech Connect

    Phillips, William Scott

    2016-09-01

    This seminar presentation describes amplitude models and yield estimations that look at the data in order to inform legislation. The following points were brought forth in the summary: global models that will predict three-component amplitudes (R-T-Z) were produced; Q models match regional geology; corrected source spectra can be used for discrimination and yield estimation; three-component data increase coverage and reduce scatter in source spectral estimates; three-component efforts must include distance-dependent effects; a community effort on instrument calibration is needed.

  11. 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

  12. 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

  13. On parameter estimation in population models.

    PubMed

    Ross, J V; Taimre, T; Pollett, P K

    2006-12-01

    We describe methods for estimating the parameters of Markovian population processes in continuous time, thus increasing their utility in modelling real biological systems. A general approach, applicable to any finite-state continuous-time Markovian model, is presented, and this is specialised to a computationally more efficient method applicable to a class of models called density-dependent Markov population processes. We illustrate the versatility of both approaches by estimating the parameters of the stochastic SIS logistic model from simulated data. This model is also fitted to data from a population of Bay checkerspot butterfly (Euphydryas editha bayensis), allowing us to assess the viability of this population.

  14. 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.

  15. Roofed grooves: rapid layer engineering of perfusion channels in collagen tissue models.

    PubMed

    Tan, Noah S; Alekseeva, Tijna; Brown, Robert A

    2014-10-01

    Surface patterning (micro-moulding) of dense, biomimetic collagen is a simple tool to produce complex tissues using layer-by-layer assembly. The aim here was to channelise three-dimensional constructs for improved perfusion. Firstly, collagen fibril accumulation was measured by comparative image analysis to understand the mechanisms of structure formation in plastically compressed collagen during µ-moulding. This showed that shape (circular or rectangular) and dimensions of the template affected collagen distribution around moulded grooves and consequently their stability. In the second part, this was used for effective fabrication of multi-layered plastically compressed collagen constructs with internal channels by roofing the grooves with a second layer. Using rectangular templates of 25/50/100 µm widths and 75 µm depth, grooves were µ-moulded into the fluid-leaving surface of collagen layers with predictable width/depth fidelities. These grooves were then roofed by addition of a second plastically compressed collagen layer on top to produce µ-channels. Resulting µ-channels retained their dimensions and were stable over time in culture with fibroblasts and could be cell seeded with a lining layer by simple transfer of epithelial cells. The results of this study provide a valuable platform for rapid fabrication of complex collagen-based tissues in particular for provision of perfusing microchannels through the bulk material for improved core nutrient supply.

  16. Roofed grooves: Rapid layer engineering of perfusion channels in collagen tissue models

    PubMed Central

    Tan, Noah S; Alekseeva, Tijna

    2014-01-01

    Surface patterning (micro-moulding) of dense, biomimetic collagen is a simple tool to produce complex tissues using layer-by-layer assembly. The aim here was to channelise three-dimensional constructs for improved perfusion. Firstly, collagen fibril accumulation was measured by comparative image analysis to understand the mechanisms of structure formation in plastically compressed collagen during µ-moulding. This showed that shape (circular or rectangular) and dimensions of the template affected collagen distribution around moulded grooves and consequently their stability. In the second part, this was used for effective fabrication of multi-layered plastically compressed collagen constructs with internal channels by roofing the grooves with a second layer. Using rectangular templates of 25/50/100 µm widths and 75 µm depth, grooves were µ-moulded into the fluid-leaving surface of collagen layers with predictable width/depth fidelities. These grooves were then roofed by addition of a second plastically compressed collagen layer on top to produce µ-channels. Resulting µ-channels retained their dimensions and were stable over time in culture with fibroblasts and could be cell seeded with a lining layer by simple transfer of epithelial cells. The results of this study provide a valuable platform for rapid fabrication of complex collagen-based tissues in particular for provision of perfusing microchannels through the bulk material for improved core nutrient supply. PMID:24934499

  17. Maneuver Estimation Model for Geostationary Orbit Determination

    DTIC Science & Technology

    2006-06-01

    MODEL FOR GEOSTATIONARY ORBIT DETERMINATION THESIS Presented to the Faculty Department of Aeronautics and Astronautics Graduate...FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED. AFIT/GA/ENY/06-J01 MANEUVER ESTIMATION MODEL FOR GEOSTATIONARY ORBIT DETERMINATION...used to model the relative motion of a geostationary satellite about its intended location and a nonlinear least squares algorithm was developed to

  18. Intracranial pressure monitoring, cerebral perfusion pressure estimation, and ICP/CPP-guided therapy: a standard of care or optional extra after brain injury?

    PubMed

    Kirkman, M A; Smith, M

    2014-01-01

    Measurement of intracranial pressure (ICP) and mean arterial pressure (MAP) is used to derive cerebral perfusion pressure (CPP) and to guide targeted therapy of acute brain injury (ABI) during neurointensive care. Here we provide a narrative review of the evidence for ICP monitoring, CPP estimation, and ICP/CPP-guided therapy after ABI. Despite its widespread use, there is currently no class I evidence that ICP/CPP-guided therapy for any cerebral pathology improves outcomes; indeed some evidence suggests that it makes no difference, and some that it may worsen outcomes. Similarly, no class I evidence can currently advise the ideal CPP for any form of ABI. 'Optimal' CPP is likely patient-, time-, and pathology-specific. Further, CPP estimation requires correct referencing (at the level of the foramen of Monro as opposed to the level of the heart) for MAP measurement to avoid CPP over-estimation and adverse patient outcomes. Evidence is emerging for the role of other monitors of cerebral well-being that enable the clinician to employ an individualized multimodality monitoring approach in patients with ABI, and these are briefly reviewed. While acknowledging difficulties in conducting robust prospective randomized studies in this area, such high-quality evidence for the utility of ICP/CPP-directed therapy in ABI is urgently required. So, too, is the wider adoption of multimodality neuromonitoring to guide optimal management of ICP and CPP, and a greater understanding of the underlying pathophysiology of the different forms of ABI and what exactly the different monitoring tools used actually represent.

  19. 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. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. [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.

  1. Modeling and optimization of Look-Locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume.

    PubMed

    Francis, S T; Bowtell, R; Gowland, P A

    2008-02-01

    This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%. (c) 2008 Wiley-Liss, Inc.

  2. INTEGRATED SPEED ESTIMATION MODEL FOR MULTILANE EXPREESSWAYS

    NASA Astrophysics Data System (ADS)

    Hong, Sungjoon; Oguchi, Takashi

    In this paper, an integrated speed-estimation model is developed based on empirical analyses for the basic sections of intercity multilane expressway un der the uncongested condition. This model enables a speed estimation for each lane at any site under arb itrary highway-alignment, traffic (traffic flow and truck percentage), and rainfall conditions. By combin ing this model and a lane-use model which estimates traffic distribution on the lanes by each vehicle type, it is also possible to es timate an average speed across all the lanes of one direction from a traffic demand by vehicle type under specific highway-alignment and rainfall conditions. This model is exp ected to be a tool for the evaluation of traffic performance for expressways when the performance me asure is travel speed, which is necessary for Performance-Oriented Highway Planning and Design. Regarding the highway-alignment condition, two new estimators, called effective horizo ntal curvature and effective vertical grade, are proposed in this paper which take into account the influence of upstream and downstream alignment conditions. They are applied to the speed-estimation model, and it shows increased accuracy of the estimation.

  3. Two modeling strategies for empirical Bayes estimation.

    PubMed

    Efron, Bradley

    2014-05-01

    Empirical Bayes methods use the data from parallel experiments, for instance observations Xk ~ (Θ k , 1) for k = 1, 2, …, N, to estimate the conditional distributions Θ k |Xk . There are two main estimation strategies: modeling on the θ space, called "g-modeling" here, and modeling on the×space, called "f-modeling." The two approaches are de- scribed and compared. A series of computational formulas are developed to assess their frequentist accuracy. Several examples, both contrived and genuine, show the strengths and limitations of the two strategies.

  4. Reliability of parameter estimation in respirometric models.

    PubMed

    Checchi, Nicola; Marsili-Libelli, Stefano

    2005-09-01

    When modelling a biochemical system, the fact that model parameters cannot be estimated exactly stimulates the definition of tests for checking unreliable estimates and design better experiments. The method applied in this paper is a further development from Marsili-Libelli et al. [2003. Confidence regions of estimated parameters for ecological systems. Ecol. Model. 165, 127-146.] and is based on the confidence regions computed with the Fisher or the Hessian matrix. It detects the influence of the curvature, representing the distortion of the model response due to its nonlinear structure. If the test is passed then the estimation can be considered reliable, in the sense that the optimisation search has reached a point on the error surface where the effect of nonlinearities is negligible. The test is used here for an assessment of respirometric model calibration, i.e. checking the experimental design and estimation reliability, with an application to real-life data in the ASM context. Only dissolved oxygen measurements have been considered, because this is a very popular experimental set-up in wastewater modelling. The estimation of a two-step nitrification model using batch respirometric data is considered, showing that the initial amount of ammonium-N and the number of data play a crucial role in obtaining reliable estimates. From this basic application other results are derived, such as the estimation of the combined yield factor and of the second step parameters, based on a modified kinetics and a specific nitrite experiment. Finally, guidelines for designing reliable experiments are provided.

  5. USE OF A PROGRAMMABLE CALCULATOR IN CARDIOPULMONARY PERFUSION.

    PubMed

    Mills, J David; Tallent, Jerome H.

    1978-06-01

    This study describes a hand-held, battery-powered, programmable instrument (Calculator Model SR-52) that can be taken directly into the operating room by cardiopulmonary perfusionists. Three programs are described in detail: 1) Cardiopulmonary perfusion parameters and estimated blood volume; 2) blood gas parameters and saturations, with temperature corrections; and 3) cardiopulmonary oxygen transfer and oxygenator efficiency. This inexpensive calculator allows perfusion personnel to manipulate easily-derived data into values which heretofore have required elaborate nomograms or special slide rules-or were not available within a reasonable computational time.

  6. Regional fuzzy chain model for evapotranspiration estimation

    NASA Astrophysics Data System (ADS)

    Güçlü, Yavuz Selim; Subyani, Ali M.; Şen, Zekai

    2017-01-01

    Evapotranspiration (ET) is one of the main hydrological cycle components that has extreme importance for water resources management and agriculture especially in arid and semi-arid regions. In this study, regional ET estimation models based on the fuzzy logic (FL) principles are suggested, where the first stage includes the ET calculation via Penman-Monteith equation, which produces reliable results. In the second phase, ET estimations are produced according to the conventional FL inference system model. In this paper, regional fuzzy model (RFM) and regional fuzzy chain model (RFCM) are proposed through the use of adjacent stations' data in order to fill the missing ones. The application of the two models produces reliable and satisfactory results for mountainous and sea region locations in the Kingdom of Saudi Arabia, but comparatively RFCM estimations have more accuracy. In general, the mean absolute percentage error is less than 10%, which is acceptable in practical applications.

  7. Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

    PubMed

    Lee, Mi Ji; Son, Jeong Pyo; Kim, Suk Jae; Ryoo, Sookyung; Woo, Sook-Young; Cha, Jihoon; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Bang, Oh Young

    2015-10-01

    Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth. © 2015 American Heart Association, Inc.

  8. Adaptive Estimation with Partially Overlapping Models

    PubMed Central

    Shin, Sunyoung; Fine, Jason; Liu, Yufeng

    2015-01-01

    In many problems, one has several models of interest that capture key parameters describing the distribution of the data. Partially overlapping models are taken as models in which at least one covariate effect is common to the models. A priori knowledge of such structure enables efficient estimation of all model parameters. However, in practice, this structure may be unknown. We propose adaptive composite M-estimation (ACME) for partially overlapping models using a composite loss function, which is a linear combination of loss functions defining the individual models. Penalization is applied to pairwise differences of parameters across models, resulting in data driven identification of the overlap structure. Further penalization is imposed on the individual parameters, enabling sparse estimation in the regression setting. The recovery of the overlap structure enables more efficient parameter estimation. An oracle result is established. Simulation studies illustrate the advantages of ACME over existing methods that fit individual models separately or make strong a priori assumption about the overlap structure. PMID:26917931

  9. Computational fluid dynamics modeling of momentum transport in rotating wall perfused bioreactor for cartilage tissue engineering.

    PubMed

    Cinbiz, Mahmut N; Tığli, R Seda; Beşkardeş, Işil Gerçek; Gümüşderelioğlu, Menemşe; Colak, Uner

    2010-11-01

    In this study, computational fluid dynamics (CFD) analysis of a rotating-wall perfused-vessel (RWPV) bioreactor is performed to characterize the complex hydrodynamic environment for the simulation of cartilage development in RWPV bioreactor in the presence of tissue-engineered cartilage constructs, i.e., cell-chitosan scaffolds. Shear stress exerted on chitosan scaffolds in bioreactor was calculated for different rotational velocities in the range of 33-38 rpm. According to the calculations, the lateral and lower surfaces were exposed to 0.07926-0.11069 dyne/cm(2) and 0.05974-0.08345 dyne/cm(2), respectively, while upper surfaces of constructs were exposed to 0.09196-0.12847 dyne/cm(2). Results validate adequate hydrodynamic environment for scaffolds in RWPV bioreactor for cartilage tissue development which concludes the suitability of operational conditions of RWPV bioreactor.

  10. Does machine perfusion decrease ischemia reperfusion injury?

    PubMed

    Bon, D; Delpech, P-O; Chatauret, N; Hauet, T; Badet, L; Barrou, B

    2014-06-01

    In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival.

  11. Perfusion preservation maintains myocardial ATP levels and reduces apoptosis in an ex vivo rat heart transplantation model.

    PubMed

    Peltz, Matthias; He, Tian-Teng; Adams, Glenn A; Koshy, Seena; Burgess, Shawn C; Chao, Robert Y; Meyer, Dan M; Jessen, Michael E

    2005-10-01

    Machine perfusion preservation improves reperfusion function of many solid organs, compared with conventional storage, but has received limited clinical attention in preserving hearts for transplantation. We evaluated representative extracellular (Celsior) and intracellular (University of Wisconsion) storage solutions using static and perfusion protective strategies over a clinically relevant preservation period. Rat hearts were preserved for 200 minutes by either static storage or perfusion preservation in Celsior or University of Wisconsin solutions. Three conditions were studied: conventional static storage; static storage using either solution with 5.5 mmol/L glucose added; and perfusion preservation using either solution with 5.5 mmol/L glucose added. Glucose was provided as U-13C-labeled glucose, and glycolysis and oxidative metabolism during preservation were quantified from incorporation of (13)C into glycolytic and tricarboxylic acid cycle intermediates. Adenosine triphosphate levels after preservation, and apoptosis and cardiac function after reperfusion were measured. Both perfusion preservation groups had higher myocardial oxygen consumption during storage and better early graft function, compared with static preservation groups (P < .05). Adenosine triphosphate levels were higher after storage in the perfusion groups (P < .01). Apoptosis was reduced in the perfusion groups (P < .01). Comparing perfusion groups, hearts preserved with Celsior had higher myocardial oxygen consumption and glucose utilization during perfusion storage and exhibited decreased reperfusion coronary vascular resistance and myocardial water content, compared with the UW perfusion group (P < .05). Perfusion preservation results in greater metabolism during storage and superior cardiac function with improved myocyte survival, compared with static storage. Extracellular preservation solutions appear more effective for perfusion preservation, possibly by augmenting cellular

  12. 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.

  13. Estimating regional plant biodiversity with GIS modelling

    Treesearch

    Louis R. Iverson; Anantha M. Prasad; Anantha M. Prasad

    1998-01-01

    We analyzed a statewide species database together with a county-level geographic information system to build a model based on well-surveyed areas to estimate species richness in less surveyed counties. The model involved GIS (Arc/Info) and statistics (S-PLUS), including spatial statistics (S+SpatialStats).

  14. 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...

  15. 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...

  16. 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

  17. Systematic Error Modeling and Bias Estimation.

    PubMed

    Zhang, Feihu; Knoll, Alois

    2016-05-19

    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.

  18. 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.

  19. Two modeling strategies for empirical Bayes estimation

    PubMed Central

    Efron, Bradley

    2014-01-01

    Empirical Bayes methods use the data from parallel experiments, for instance observations Xk ~ 𝒩 (Θk, 1) for k = 1, 2, …, N, to estimate the conditional distributions Θk|Xk. There are two main estimation strategies: modeling on the θ space, called “g-modeling” here, and modeling on the×space, called “f-modeling.” The two approaches are de- scribed and compared. A series of computational formulas are developed to assess their frequentist accuracy. Several examples, both contrived and genuine, show the strengths and limitations of the two strategies. PMID:25324592

  20. 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.

  1. The free groin flap in the rat: a model for improving microsurgical skills and for microvascular perfusion studies.

    PubMed

    Wallmichrath, Jens; Baumeister, R G H; Gottschalk, O; Giunta, R E; Frick, A

    2014-06-01

    The goal of this study was to evaluate the free groin flap in the rat transplanted to the neck as a tool for extending microsurgical skills and to assess its suitability as a model for microvascular perfusion studies following secondary venous ischaemia. An analysis of 60 consecutive groin flap transplantations was performed in male Sprague Dawley rats with special regard to anatomy and operation times (Part I, animals No. 1-60). Following flap transplantation, the animals No. 10-30 (n = 21) were used for the determination of the critical time period of a complete venous stasis of the free groin flap resulting in a total flap loss (Part II). The flaps of animals No. 31-41 (n = 11) were used for assessing the feasibility and reproducibility of intra-vital video microscopy (IVM) of the flaps (Part III). The mean total operation time decreased from 166 (± 26) minutes ins the first 10 animals to 126 (± 21) minutes and 130 (± 12) minutes in the latter two groups of 10 animals, respectively. After a critical period of 35 minutes of a complete artificial venous stasis a complete flap necrosis occurred. IVM detected a higher functional capillary density of the skin of the transplanted groin flaps in the animals in which the flaps were rinsed with 1 ml of Ringer's lactated solution prior to I/R. In conclusion, this model is simple and reliable. The model may be a useful tool for evaluating and comparing the effects of various anticoagulants or vasomotor drugss on microvascular perfusion in critically compromised free flaps.

  2. The administration of argon during ex vivo normothermic perfusion in an experimental model of kidney ischemia-reperfusion injury.

    PubMed

    Smith, Stephanie F; Adams, Thomas; Hosgood, Sarah A; Nicholson, Michael L

    2017-10-01

    Argon has shown potential as an organoprotective agent in numerous models of ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. After a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide. After EVNP, kidneys were reperfused with whole blood under standard conditions for 3 h to assess renal function and injury. During 1-h EVNP, the mean renal blood flow was numerically higher in the argon group (49.2 ± 16.2 mL/min/100 g; P = 0.320) compared with the nitrogen and oxygen groups (42.9 ± 18.64 and 37.71 ± 7.0 mL/min/100 g, respectively). Other measures of renal function and hemodynamics were not significantly different between the argon and control groups during this period. During reperfusion, no significant differences were found in functional parameters or inflammatory markers (P < 0.05). Histologic analysis revealed no significant change in morphology or hypoxia-inducible factor-1 alpha staining between gaseous groups. Nuclear hypoxia-inducible factor-1 alpha staining was observed only after 3 h of reperfusion. Our findings suggest that using 70% argon during 1 h of EVNP does not mediate a measurable organoprotective effect in an experimental porcine model of IRI. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Simulation evaluation of quantitative myocardial perfusion assessment from cardiac CT

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    Contrast enhancement on cardiac CT provides valuable information about myocardial perfusion and methods have been proposed to assess perfusion with static and dynamic acquisitions. There is a lack of knowledge and consensus on the appropriate approach to ensure 1) sufficient diagnostic accuracy for clinical decisions and 2) low radiation doses for patient safety. This work developed a thorough dynamic CT simulation and several accepted blood flow estimation techniques to evaluate the performance of perfusion assessment across a range of acquisition and estimation scenarios. Cardiac CT acquisitions were simulated for a range of flow states (Flow = 0.5, 1, 2, 3 ml/g/min, cardiac output = 3,5,8 L/min). CT acquisitions were simulated with a validated CT simulator incorporating polyenergetic data acquisition and realistic x-ray flux levels for dynamic acquisitions with a range of scenarios including 1, 2, 3 sec sampling for 30 sec with 25, 70, 140 mAs. Images were generated using conventional image reconstruction with additional image-based beam hardening correction to account for iodine content. Time attenuation curves were extracted for multiple regions around the myocardium and used to estimate flow. In total, 2,700 independent realizations of dynamic sequences were generated and multiple MBF estimation methods were applied to each of these. Evaluation of quantitative kinetic modeling yielded blood flow estimates with an root mean square error (RMSE) of ~0.6 ml/g/min averaged across multiple scenarios. Semi-quantitative modeling and qualitative static imaging resulted in significantly more error (RMSE = ~1.2 and ~1.2 ml/min/g respectively). For quantitative methods, dose reduction through reduced temporal sampling or reduced tube current had comparable impact on the MBF estimate fidelity. On average, half dose acquisitions increased the RMSE of estimates by only 18% suggesting that substantial dose reductions can be employed in the context of quantitative myocardial

  4. Relaxin as an additional protective substance in preserving and reperfusion solution for liver transplantation, shown in a model of isolated perfused rat liver.

    PubMed

    Boehnert, Markus U; Hilbig, Heidegard; Armbruster, Franz P

    2005-05-01

    Reperfusion injury is a problem in organ transplantation. Relaxin causes vessel dilation and inhibition of platelet and mast cell activation. The study investigates the protective effect of relaxin on liver tissue against cell damage during organ preservation and reperfusion. Liver transplantation was simulated in a model of isolated perfused rat liver. Relaxin was applicated during reperfusion and/or preservation. To quantify cell damage, we examined the perfusate for malonyldialdehyde (MDA) and myeloperoxidase activity (MPO), and liver tissue underwent immunohistochemical study. Relaxin as an additional substance in preserving/reperfusion solution decreases MPO and MDA levels in the perfusate and immunohistochemical study. Relaxin seems to have a protective effect against cell damage in ischemia and reperfusion injury.

  5. Kernel bandwidth estimation for nonparametric modeling.

    PubMed

    Bors, Adrian G; Nasios, Nikolaos

    2009-12-01

    Kernel density estimation is a nonparametric procedure for probability density modeling, which has found several applications in various fields. The smoothness and modeling ability of the functional approximation are controlled by the kernel bandwidth. In this paper, we describe a Bayesian estimation method for finding the bandwidth from a given data set. The proposed bandwidth estimation method is applied in three different computational-intelligence methods that rely on kernel density estimation: 1) scale space; 2) mean shift; and 3) quantum clustering. The third method is a novel approach that relies on the principles of quantum mechanics. This method is based on the analogy between data samples and quantum particles and uses the SchrOdinger potential as a cost function. The proposed methodology is used for blind-source separation of modulated signals and for terrain segmentation based on topography information.

  6. Quantification of perfusion modes in terms of surplus hemodynamic energy levels in a simulated pediatric CPB model.

    PubMed

    Undar, Akif; Ji, Bingyang; Lukic, Branka; Zapanta, Conrad M; Kunselman, Allen R; Reibson, John D; Weiss, William J; Rosenberg, Gerson; Myers, John L

    2006-01-01

    The objective of this investigation was to compare pulsatile versus nonpulsatile perfusion modes in terms of surplus hemodynamic energy (SHE) levels during cardiopulmonary bypass (CPB) in a simulated neonatal model. The extracorporeal circuit consisted of a Jostra HL-20 heart-lung machine (for both pulsatile and nonpulsatile modes of perfusion), a Capiox Baby RX hollow-fiber membrane oxygenator, a Capiox pediatric arterial filter, 5 feet of arterial tubing and 6 feet of venous tubing with a quarter-inch diameter. The circuit was primed with a lactated Ringers solution. The systemic resistance of a pseudo-patient (mean weight, 3 kg) was simulated by placing a clamp at the end of the arterial line. The pseudo-patient was subjected to five pump flow rates in the 400 to 800 ml/min range. During pulsatile perfusion, the pump rate was kept constant at 120 bpm. Pressure waveforms were recorded at the preoxygenator, postoxygenator, and preaortic cannula sites. SHE was calculated by use of the following formula {SHE (ergs/cm) = 1,332 [((integral fpdt) / (integral fdt)) - Mean Arterial Pressure]} (f = pump flow and p = pressure). A total of 60 experiments were performed (n = 6 for nonpulsatile and n = 6 for pulsatile) at each of the five flow rates. A linear mixed-effects model, which accounts for the correlation among repeated measurements, was fit to the data to assess differences in SHE between flows, pumps, and sites. The Tukey multiple comparison procedure was used to adjust p values for post hoc pairwise comparisons. With a pump flow rate of 400 ml/min, pulsatile flow generated significantly higher surplus hemodynamic energy levels at the preoxygenator site (23,421 +/- 2,068 ergs/cm vs. 4,154 +/- 331 ergs/cm, p < 0.0001), the postoxygenator site (18,784 +/- 1,557 ergs/cm vs. 3,383 +/- 317 ergs/cm, p < 0.0001), and the precannula site (6,324 +/- 772 ergs/cm vs. 1,320 +/- 91 ergs/cm, p < 0.0001), compared with the nonpulsatile group. Pulsatile flow produced higher SHE

  7. 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

  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. 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.

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

    PubMed

    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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:27877820

  13. 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.

  14. Is the predicted postoperative FEV1 estimated by planar lung perfusion scintigraphy accurate in patients undergoing pulmonary resection? Comparison of two processing methods.

    PubMed

    Caglar, Meltem; Kara, Murat; Aksoy, Tamer; Kiratli, Pinar Ozgen; Karabulut, Erdem; Dogan, Riza

    2010-07-01

    Estimation of postoperative forced expiratory volume in 1 s (FEV1) with radionuclide lung scintigraphy is frequently used to define functional operability in patients undergoing lung resection. We conducted a study to outline the reliability of planar quantitative lung perfusion scintigraphy (QLPS) with two different processing methods to estimate the postoperative lung function in patients with resectable lung disease. Forty-one patients with a mean age of 57 +/- 12 years who underwent either a pneumonectomy (n = 14) or a lobectomy (n = 27) were included in the study. QLPS with Tc-99m macroaggregated albumin was performed. Both three equal zones were generated for each lung [zone method (ZM)] and more precise regions of interest were drawn according to their anatomical shape in the anterior and posterior projections [lobe mapping method (LMM)] for each patient. The predicted postoperative (ppo) FEV1 values were compared with actual FEV1 values measured on postoperative day 1 (pod1 FEV1) and day 7 (pod 7 FEV1). The mean of preoperative FEV1 and ppoFEV1 values was 2.10 +/- 0.57 and 1.57 +/- 0.44 L, respectively. The mean of Pod1FEV1 (1.04 +/- 0.30 L) was lower than ppoFEV1 (p < 0.0001) but increased on day 7 (1.31 +/- 0.32 L) (p < 0.0001); however, it never reached the predicted values. Zone and LMMs estimated mean ppoFEV1 as 1.56 +/- 0.45 and 1.57 +/- 0.44 L, respectively. Both methods overestimated the actual value by 50% (ZM), 51% (LMM) and 19% (ZM), 20% (LMM) for pod 1 and pod 7, respectively. This overestimation was more pronounced in patients with chronic lung disease and hilar tumors. No significant differences were observed between ppoFEV1 values estimated by ZM or by LMM (p > 0.05). PpoFEV1 values predicted by both the zone and LMMs overestimated the actual measured lung volumes in patients undergoing pulmonary resection in the early postoperative period. LMM is not superior to ZM.

  15. 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

    2015-04-07

    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

  16. 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

  17. Stoichiometric control of live cell mixing to enable fluidically-encoded co-culture models in perfused microbioreactor arrays.

    PubMed

    Occhetta, P; Glass, N; Otte, E; Rasponi, M; Cooper-White, J J

    2016-02-01

    In vivo, tissues are maintained and repaired through interactions between the present (different) cell types, which communicate with each other through both the secretion of paracrine factors and direct cell-cell contacts. In order to investigate and better understand this dynamic, complex interplay among diverse cell populations, we must develop new in vitro co-culture strategies that enable us to recapitulate such native tissue complexity. In this work, a microfluidic mixer based on a staggered herringbone design was computationally designed and experimentally validated that features the ability to mix large, non-diffusive particles (i.e. live cells) in a programmed manner. This is the first time that the herringbone mixer concept has been shown to effectively mix particles of the size range applicable to live cells. The cell mixer allowed for sequentially mixing of two cell types to generate reverse linear concentration co-culture patterns. Once validated, the mixer was integrated into a perfused microbioreactor array as an upstream module to deliver mixed cells to five downstream culture units, each consisting of ten serially-connected circular microculture chambers. This novel cell mixer microbioreactor array (CM-MBA) platform was validated through the establishment of spatio-temporally tunable osteogenic co-culture models, investigating the role of pre-osteoblastic cells (SAOS2) on human mesenchymal stem cells (hMSCs) commitment to an osteogenic endpoint. An increase on expression of alkaline phosphatase in sequential (downstream) chambers, consistent with the initial linear distribution of SAOS2, suggests not only osteoblastic cell-driven hMSCs induction towards the osteogenic phenotype, but also the importance of paracrine signaling. In conclusion, the cell mixer microbioreactor array combines the ability to rapidly establish cell co-culture models in a high-throughput, programmable fashion, with the additional advantage of maintaining cells in culture

  18. Resveratrol preserves myocardial function and perfusion in remote nonischemic myocardium in a swine model of metabolic syndrome.

    PubMed

    Robich, Michael P; Chu, Louis M; Burgess, Thomas A; Feng, Jun; Han, Yuchi; Nezafat, Reza; Leber, Michael P; Laham, Roger J; Manning, Warren J; Sellke, Frank W

    2012-11-01

    Resveratrol has been shown to reverse some of the detrimental effects of metabolic syndrome (MetS). We sought to define the impact of supplemental resveratrol on normal myocardium remote from an ischemic territory in a swine model of MetS and chronic myocardial ischemia. Yorkshire swine were fed a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with orally supplemented resveratrol (HCD-R; 100 mg/kg/day). Four weeks after diet modification, myocardial ischemia was induced by ameroid constrictor placement. Seven weeks later, myocardial tissue from a territory remote from the ischemia was harvested. Animals in the HCD and HCD-R groups underwent functional cardiac MRI before ischemia and before sacrifice. Tissue was harvested for protein expression analysis. After 7 weeks of ischemia, regional left ventricular systolic function was significantly increased in HCD-R as compared with HCD animals. During ventricular pacing the HCD group had significantly decreased flow (p = 0.03); perfusion in the HCD-R was preserved as compared with the control. There was no difference in microvascular relaxation. Expression of metabolic proteins Sirt-1 (p = 0.002), AMPkinase (p = 0.02), and carnitine palmitoyltransferase-I (p = 0.002) were upregulated in the HCD-R group. Levels of protein oxidative stress were significantly increased in the HCD and HCD-R groups, as compared with the controls (p = 0.003). Activated endothelial nitric oxide synthase (eNOS) was increased in the HCD-R group (p = 0.01). There was no difference in myocardial endothelial cell density between the groups; however, dividing endothelial cells were decreased in the HCD and HCD-R groups (p = 0.006). Resveratrol supplementation improves regional left ventricular function and preserves perfusion to myocardium remote from an area of ischemia in an animal model of metabolic syndrome and chronic myocardial ischemia. Copyright © 2012 American College of Surgeons. Published by Elsevier Inc

  19. 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.

  20. Developing Physician Migration Estimates for Workforce Models.

    PubMed

    Holmes, George M; Fraher, Erin P

    2017-02-01

    To understand factors affecting specialty heterogeneity in physician migration. Physicians in the 2009 American Medical Association Masterfile data were matched to those in the 2013 file. Office locations were geocoded in both years to one of 293 areas of the country. Estimated utilization, calculated for each specialty, was used as the primary predictor of migration. Physician characteristics (e.g., specialty, age, sex) were obtained from the 2009 file. Area characteristics and other factors influencing physician migration (e.g., rurality, presence of teaching hospital) were obtained from various sources. We modeled physician location decisions as a two-part process: First, the physician decides whether to move. Second, conditional on moving, a conditional logit model estimates the probability a physician moved to a particular area. Separate models were estimated by specialty and whether the physician was a resident. Results differed between specialties and according to whether the physician was a resident in 2009, indicating heterogeneity in responsiveness to policies. Physician migration was higher between geographically proximate states with higher utilization for that specialty. Models can be used to estimate specialty-specific migration patterns for more accurate workforce modeling, including simulations to model the effect of policy changes. © Health Research and Educational Trust.

  1. Automated detection of arterial input function in DSC perfusion MRI in a stroke rat model

    NASA Astrophysics Data System (ADS)

    Yeh, M.-Y.; Lee, T.-H.; Yang, S.-T.; Kuo, H.-H.; Chyi, T.-K.; Liu, H.-L.

    2009-05-01

    Quantitative cerebral blood flow (CBF) estimation requires deconvolution of the tissue concentration time curves with an arterial input function (AIF). However, image-based determination of AIF in rodent is challenged due to limited spatial resolution. We evaluated the feasibility of quantitative analysis using automated AIF detection and compared the results with commonly applied semi-quantitative analysis. Permanent occlusion of bilateral or unilateral common carotid artery was used to induce cerebral ischemia in rats. The image using dynamic susceptibility contrast method was performed on a 3-T magnetic resonance scanner with a spin-echo echo-planar-image sequence (TR/TE = 700/80 ms, FOV = 41 mm, matrix = 64, 3 slices, SW = 2 mm), starting from 7 s prior to contrast injection (1.2 ml/kg) at four different time points. For quantitative analysis, CBF was calculated by the AIF which was obtained from 10 voxels with greatest contrast enhancement after deconvolution. For semi-quantitative analysis, relative CBF was estimated by the integral divided by the first moment of the relaxivity time curves. We observed if the AIFs obtained in the three different ROIs (whole brain, hemisphere without lesion and hemisphere with lesion) were similar, the CBF ratios (lesion/normal) between quantitative and semi-quantitative analyses might have a similar trend at different operative time points. If the AIFs were different, the CBF ratios might be different. We concluded that using local maximum one can define proper AIF without knowing the anatomical location of arteries in a stroke rat model.

  2. A tourniquet assisted cardiopulmonary resuscitation augments myocardial perfusion in a porcine model of cardiac arrest.

    PubMed

    Yang, Zhengfei; Tang, David; Wu, Xiaobo; Hu, Xianwen; Xu, Jiefeng; Qian, Jie; Yang, Min; Tang, Wanchun

    2015-01-01

    During cardiopulmonary resuscitation (CPR), myocardial blood flow generated by chest compression rarely exceeds 35% of its normal level. Cardiac output generated by chest compression decreases gradually with the prolongation of cardiac arrest and resuscitation. Early studies have demonstrated that myocardial blood flow during CPR is largely dependent on peripheral vascular resistance. In this study, we investigated the effects of chest compression in combination with physical control of peripheral vascular resistance assisted by tourniquets on myocardial blood flow during CPR. Ventricular fibrillation was induced and untreated for 7 min in ten male domestic pigs weighing between 33 and 37 kg. The animals were then randomized to receive CPR alone or a tourniquet assisted CPR (T-CPR). In the CPR alone group, chest compression was performed by a miniaturized mechanical chest compressor. In the T-CPR group, coincident with the start of resuscitation, the thin elastic tourniquets were wrapped around the four limbs from the distal end to the proximal part. After 2 min of CPR, epinephrine (20 μg/kg) was administered via the femoral vein. After 5 min of CPR, defibrillation was attempted by a single 150 J shock. If resuscitation was not successful, CPR was resumed for 2 min before the next defibrillation. The protocol was continued until successful resuscitation or for a total of 15 min. Five minutes after resuscitation, the elastic tourniquets were removed. The resuscitated animals were observed for 2h. T-CPR generated significantly greater coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow. There was no difference in both intrathoracic positive and negative pressures between the two groups. All animals were successfully resuscitated with a single shock in both groups. There were no significant changes in hemodynamics observed in the animals treated in the T-CPR group before-and-after the release of tourniquets at post-resuscitation 5 min. T

  3. 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

  4. Bayesian inverse modeling for quantitative precipitation estimation

    NASA Astrophysics Data System (ADS)

    Schinagl, Katharina; Rieger, Christian; Simmer, Clemens; Xie, Xinxin; Friederichs, Petra

    2017-04-01

    Polarimetric radars provide us with a richness of precipitation related measurements. Especially the high spatial and temporal resolution make the data an important information, e.g. for hydrological modeling. However, uncertainties in the precipitation estimates are large. Their systematic assessment and quantification is thus of great importance. Polarimetric radar observables like horizontal and vertical reflectivity ZH and ZV , cross-correlation coefficient ρHV and specific differential phase KDP are related to the drop size distribution (DSD) in the scan. This relation is described by forward operators which are integrals over the DSD and scattering terms. Given the polarimetric observables, the respective forward operators and assumptions about the measurement errors, we investigate the uncertainty in the DSD parameter estimation and based on it the uncertainty of precipitation estimates. We assume that the DSD follows a Gamma model, N(D) = N0Dμ exp(-ΛD), where all three parameters are variable. This model allows us to account for the high variability of the DSD. We employ the framework of Bayesian inverse methods to derive the posterior distribution of the DSD parameters. The inverse problem is investigated in a simulated environment (SE) using the COSMO-DE numerical weather prediction model. The advantage of the SE is that - unlike in a real world application - we know the parameters we want to estimate. Thus, building the inverse model into the SE gives us the opportunity of verifying our results against the COSMO-simulated DSD-values.

  5. Placental transfer of lopinavir/ritonavir in the ex vivo human cotyledon perfusion model.

    PubMed

    Gavard, Laurent; Gil, Sophie; Peytavin, Gilles; Ceccaldi, Pierre-François; Ferreira, Claudia; Farinotti, Robert; Mandelbrot, Laurent

    2006-07-01

    This study was done to determine the placental transfer of the human immunodeficiency virus protease inhibitor lopinavir with ritonavir. Twenty-five human cotyledons that were obtained after uneventful pregnancies and deliveries were perfused in an open double circuit with lopinavir (1099-10,606 microg/L) and ritonavir (254-1147 microg/L) at various albumin concentrations (2, 10, and 40 g/L). The fetal transfer rate of lopinavir, when combined with ritonavir, was 23.6% +/- 6.9% at an albumin concentration of 2 g/L. The fetal transfer rate decreased to 20.7% +/- 10% at an albumin concentration of 10 g/L and to 3.3% +/- 0.5% at an albumin concentration of 40 g/L. The placental transfer of lopinavir, a highly protein-bound molecule, was compatible with passive diffusion of the unbound fraction. Even at physiologic maternal albumin concentrations, the amount of drug transferred into the fetal compartment was well above the 50% inhibitory concentration.

  6. Estimating Model Evidence Using Data Assimilation

    NASA Astrophysics Data System (ADS)

    Carrassi, Alberto; Bocquet, Marc; Hannart, Alexis; Ghil, Michael

    2017-04-01

    We review the field of data assimilation (DA) from a Bayesian perspective and show that, in addition to its by now common application to state estimation, DA may be used for model selection. An important special case of the latter is the discrimination between a factual model - which corresponds, to the best of the modeller's knowledge, to the situation in the actual world in which a sequence of events has occurred-and a counterfactual model, in which a particular forcing or process might be absent or just quantitatively different from the actual world. Three different ensemble-DA methods are reviewed for this purpose: the ensemble Kalman filter (EnKF), the ensemble four-dimensional variational smoother (En-4D-Var), and the iterative ensemble Kalman smoother (IEnKS). An original contextual formulation of model evidence (CME) is introduced. It is shown how to apply these three methods to compute CME, using the approximated time-dependent probability distribution functions (pdfs) each of them provide in the process of state estimation. The theoretical formulae so derived are applied to two simplified nonlinear and chaotic models: (i) the Lorenz three-variable convection model (L63), and (ii) the Lorenz 40- variable midlatitude atmospheric dynamics model (L95). The numerical results of these three DA-based methods and those of an integration based on importance sampling are compared. It is found that better CME estimates are obtained by using DA, and the IEnKS method appears to be best among the DA methods. Differences among the performance of the three DA-based methods are discussed as a function of model properties. Finally, the methodology is implemented for parameter estimation and for event attribution.

  7. Placental transfer of maraviroc in an ex vivo human cotyledon perfusion model and influence of ABC transporter expression.

    PubMed

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

    2013-03-01

    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.

  8. 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.

  9. 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.

  10. Monte Carlo estimation of scatter effects on quantitative myocardial blood flow and perfusable tissue fraction using 3D-PET and 15O-water

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Koshino, Kazuhiro; Watabe, Hiroshi; Fukushima, Kazuhito; Iida, Hidehiro

    2012-11-01

    In clinical cardiac positron emission tomography using 15O-water, significant tracer accumulation is observed not only in the heart but also in the liver and lung, which are partially outside the field-of-view. In this work, we investigated the effects of scatter on quantitative myocardium blood flow (MBF) and perfusable tissue fraction (PTF) by a precise Monte Carlo simulation (Geant4) and a numerical human model. We assigned activities to the heart, liver, and lung of the human model with varying ratios of organ activities according to an experimental time activity curve and created dynamic sinograms. The sinogram data were reconstructed by filtered backprojection. By comparing a scatter-corrected image (SC) with a true image (TRUE), we evaluated the accuracy of the scatter correction. TRUE was reconstructed using a scatter-eliminated sinogram, which can be obtained only in simulations. A scatter-uncorrected image (W/O SC) and an attenuation-uncorrected image (W/O AC) were also constructed. Finally, we calculated MBF and PTF with a single tissue-compartment model for four types of images. As a result, scatter was corrected accurately, and MBFs derived from all types of images were consistent with the MBF obtained from TRUE. Meanwhile, the PTF of only the SC was in agreement with the PTF of TRUE. From the simulation results, we concluded that quantitative MBF is less affected by scatter and absorption in 3D-PET using 15O-water. However, scatter correction is essential for accurate PTF.

  11. A Diagnostic Model for Estimating Orographic Precipitation.

    NASA Astrophysics Data System (ADS)

    Sinclair, Mark R.

    1994-10-01

    A simple model for estimating detailed orographic precipitation is presented. The model is initialized using coarse-resolution analyses from the European Centre for Medium-Range Weather Forecasts and is applied to the heavy rainfall over northern New Zealand from Tropical Cyclone Bola (March 1988). The model is based on the estimation of topographically forced vertical motion as V·zs, where zs is the height of the topography and V is the horizontal flow just upstream of the mountain. Model skill is evaluated by computing the correlation coefficient rg of the model results against 297 rain gauge measurements. Enhancement of the model by adding lee drying, wind drift effects, and modulation by larger-scale humidity and vertical-motion fields each led to a statistically significant increase in rg. Best results were obtained at a resolution near 10 km, for which an rg of 0.84 was obtained. However, ignoring drift effects at 25-km resolution resulted in model skill nearly equivalent to the full model at 10 km, highlighting the need to demonstrate that supposed model improvements do, in fact, lead to significant increases in skill.

  12. Testing the biocompatibility of a glutathione-containing intra-ocular irrigation solution by using an isolated perfused bovine retina organ culture model - an alternative to animal testing.

    PubMed

    Januschowski, Kai; Zhour, Ahmad; Lee, Albert; Maddani, Ramin; Mueller, Sebastien; Spitzer, Martin S; Schnichels, Sven; Schultheiss, Maximilian; Doycheva, Deshka; Bartz-Schmidt, Karl-Ulrich; Szurman, Peter

    2012-03-01

    The effects of a glutathione-containing intra-ocular irrigation solution, BSS Plus©, on retinal function and on the survival of ganglion cells in whole-mount retinal explants were studied. Evidence is provided that the perfused ex vivo bovine retina can serve as an alternative to in vivo animal testing. Isolated bovine retinas were prepared and perfused with an oxygen-saturated standard irrigation solution, and an electroretinogram was recorded to assess retinal function. After stable b-waves were detected, the isolated retinas were perfused with BSS Plus for 45 minutes. To investigate the effects of BSS Plus on photoreceptor function, 1mM aspartate was added to the irrigation solution in order to obtain a-waves, and the ERG trace was monitored for 75 minutes. For histological analysis, isolated whole retinal mounts were stored for 24 hours at 4°C, in the dark. The percentages of cell death in the retinal ganglion cell layer and in the outer and inner nuclear layers were estimated by using an ethidium homodimer-1 stain and the TUNEL assay. General swelling of the retina was examined with high-resolution optical coherence tomography. During perfusion with BSS Plus, no significant changes in a-wave and b-wave amplitudes were recorded. Retinas stored for 24 hours in BSS Plus showed a statistically significant smaller percentage (52.6%, standard deviation [SD] = 16.1%) of cell death in the retinal ganglion cell layer compared to the control group (69.6%, SD = 3.9, p = 0.0031). BSS Plus did not seem to affect short-term retinal function, and had a beneficial effect on the survival of retinal ganglion cells. This method for analysing the isolated perfused retina represents a valuable alternative for testing substances for their retinal biocompatibility and toxicity. 2012 FRAME.

  13. 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.

  14. 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

  15. [Use of SPECT-scanning of the heart in estimating of influence of drugs of the background therapy of ischemic heart disease on myocardial perfusion].

    PubMed

    Svistov, A S; Sukhov, V Iu; Makiev, R G; Alanichev, A E

    2012-10-01

    Some new facts about the influence of different groups of drugs on myocardial perfusion were educed during the research. Educed facts conduce representation extension by matching the optimal therapy of ischemic heart disease. With the help of SPECT-scanning were educed myocardial blood flow, areas of maximal hypoperfusion and its influence on time pattern and redistribution of myocardial blood flow in patients receiving disease-modifying agents and statins. Some regularities of change of myocardial blood flow depending on applied group of drugs and peculiarities of influence of myocardial perfusion in certain time interval were revealed. Criteria with prognostic significance in prospective individual effectiveness of anti-ischemic drugs were pointed out. New approach, based on choice of anti-ischemic therapy depending on extent of influence on myocardial perfusion and also individual clinical and functional traits of patients, was applied.

  16. Model diagnostics in reduced-rank estimation

    PubMed Central

    Chen, Kun

    2016-01-01

    Reduced-rank methods are very popular in high-dimensional multivariate analysis for conducting simultaneous dimension reduction and model estimation. However, the commonly-used reduced-rank methods are not robust, as the underlying reduced-rank structure can be easily distorted by only a few data outliers. Anomalies are bound to exist in big data problems, and in some applications they themselves could be of the primary interest. While naive residual analysis is often inadequate for outlier detection due to potential masking and swamping, robust reduced-rank estimation approaches could be computationally demanding. Under Stein's unbiased risk estimation framework, we propose a set of tools, including leverage score and generalized information score, to perform model diagnostics and outlier detection in large-scale reduced-rank estimation. The leverage scores give an exact decomposition of the so-called model degrees of freedom to the observation level, which lead to exact decomposition of many commonly-used information criteria; the resulting quantities are thus named information scores of the observations. The proposed information score approach provides a principled way of combining the residuals and leverage scores for anomaly detection. Simulation studies confirm that the proposed diagnostic tools work well. A pattern recognition example with hand-writing digital images and a time series analysis example with monthly U.S. macroeconomic data further demonstrate the efficacy of the proposed approaches. PMID:28003860

  17. Model-Based Estimation of Knee Stiffness

    PubMed Central

    Pfeifer, Serge; Vallery, Heike; Hardegger, Michael; Riener, Robert; Perreault, Eric J.

    2013-01-01

    During natural locomotion, the stiffness of the human knee is modulated continuously and subconsciously according to the demands of activity and terrain. Given modern actuator technology, powered transfemoral prostheses could theoretically provide a similar degree of sophistication and function. However, experimentally quantifying knee stiffness modulation during natural gait is challenging. Alternatively, joint stiffness could be estimated in a less disruptive manner using electromyography (EMG) combined with kinetic and kinematic measurements to estimate muscle force, together with models that relate muscle force to stiffness. Here we present the first step in that process, where we develop such an approach and evaluate it in isometric conditions, where experimental measurements are more feasible. Our EMG-guided modeling approach allows us to consider conditions with antagonistic muscle activation, a phenomenon commonly observed in physiological gait. Our validation shows that model-based estimates of knee joint stiffness coincide well with experimental data obtained using conventional perturbation techniques. We conclude that knee stiffness can be accurately estimated in isometric conditions without applying perturbations, which presents an important step towards our ultimate goal of quantifying knee stiffness during gait. PMID:22801482

  18. Improved Estimation Model of Lunar Surface Temperature

    NASA Astrophysics Data System (ADS)

    Zheng, Y.

    2015-12-01

    Lunar surface temperature (LST) is of great scientific interest both uncovering the thermal properties and designing the lunar robotic or manned landing missions. In this paper, we proposed the improved LST estimation model based on the one-dimensional partial differential equation (PDE). The shadow and surface tilts effects were combined into the model. Using the Chang'E (CE-1) DEM data from the Laser Altimeter (LA), the topographic effect can be estimated with an improved effective solar irradiance (ESI) model. In Fig. 1, the highest LST of the global Moon has been estimated with the spatial resolution of 1 degree /pixel, applying the solar albedo data derived from Clementine UV-750nm in solving the PDE function. The topographic effect is significant in the LST map. It can be identified clearly the maria, highland, and craters. The maximum daytime LST presents at the regions with low albedo, i.g. mare Procellarum, mare Serenitatis and mare Imbrium. The results are consistent with the Diviner's measurements of the LRO mission. Fig. 2 shows the temperature variations at the center of the disk in one year, assuming the Moon to be standard spherical. The seasonal variation of LST at the equator is about 10K. The highest LST occurs in early May. Fig.1. Estimated maximum surface temperatures of the global Moon in spatial resolution of 1 degree /pixel

  19. Multiscale modeling of the cardiovascular system: application to the study of pulmonary and coronary perfusions in the univentricular circulation.

    PubMed

    Laganà, Katia; Balossino, Rossella; Migliavacca, Francesco; Pennati, Giancarlo; Bove, Edward L; de Leval, Marc R; Dubini, Gabriele

    2005-05-01

    The objective of this study is to compare the coronary and pulmonary blood flow dynamics resulting from two configurations of systemic-to-pulmonary artery shunts currently utilized during the Norwood procedure: the central (CS) and modified Blalock Taussig (MBTS) shunts. A lumped parameter model of the neonatal cardiovascular circulation and detailed 3-D models of the shunt based on the finite volume method were constructed. Shunt sizes of 3, 3.5 and 4 mm were considered. A multiscale approach was adopted to prescribe appropriate and realistic boundary conditions for the 3-D models of the Norwood circulation. Results showed that the average shunt flow rate is higher for the CS option than for the MBTS and that pulmonary flow increases with shunt size for both options. Cardiac output is higher for the CS option for all shunt sizes. Flow distribution between the left and the right pulmonary arteries is not completely balanced, although for the CS option the discrepancy is low (50-51% of the pulmonary flow to the right lung) while for the MBTS it is more pronounced with larger shunt sizes (51-54% to the left lung). The CS option favors perfusion to the right lung while the MBTS favors the left. In the CS option, a smaller percentage of aortic flow is distributed to the coronary circulation, while that percentage rises for the MBTS. These findings may have important implications for coronary blood flow and ventricular function.

  20. Decimative Spectral Estimation with Unconstrained Model Order

    PubMed Central

    Fotinea, Stavroula-Evita; Dologlou, Ioannis; Bakamidis, Stylianos; Athanaselis, Theologos

    2012-01-01

    This paper presents a new state-space method for spectral estimation that performs decimation by any factor, it makes use of the full set of data and brings further apart the poles under consideration, while imposing almost no constraints to the size of the Hankel matrix (model order), as decimation increases. It is compared against two previously proposed techniques for spectral estimation (along with derived decimative versions), that lie among the most promising methods in the field of spectroscopy, where accuracy of parameter estimation is of utmost importance. Moreover, it is compared against a state-of-the-art purely decimative method proposed in literature. Experiments performed on simulated NMR signals prove the new method to be more robust, especially for low signal-to-noise ratio. PMID:22461845

  1. Ultrasound perfusion analysis combining bolus-tracking and burst-replenishment.

    PubMed

    Jirik, Radovan; Nylund, Kim; Gilja, Odd H; Mezl, Martin; Harabis, Vratislav; Kolar, Radim; Standara, Michal; Taxt, Torfinn

    2013-02-01

    A new signal model and processing method for quantitative ultrasound perfusion analysis is presented, called bolus-and-burst. The method has the potential to provide absolute values of blood flow, blood volume, and mean transit time. Furthermore, it provides an estimate of the local arterial input function which characterizes the arterial tree, allowing accurate estimation of the bolus arrival time. The method combines two approaches to ultrasound perfusion analysis: bolus-tracking and burst-replenishment. A pharmacokinetic model based on the concept of arterial input functions and tissue residue functions is used to model both the bolus and replenishment parts of the recording. The pharmacokinetic model is fitted to the data using blind deconvolution. A preliminary assessment of the new perfusion-analysis method is presented on clinical recordings.

  2. 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.

  3. Maximal perfusion of skeletal muscle in man.

    PubMed Central

    Andersen, P; Saltin, B

    1985-01-01

    Five subjects exercised with the knee extensor of one limb at work loads ranging from 10 to 60 W. Measurements of pulmonary oxygen uptake, heart rate, leg blood flow, blood pressure and femoral arterial-venous differences for oxygen and lactate were made between 5 and 10 min of the exercise. Flow in the femoral vein was measured using constant infusion of saline near 0 degrees C. Since a cuff was inflated just below the knee during the measurements and because the hamstrings were inactive, the measured flow represented primarily the perfusion of the knee extensors. Blood flow increased linearly with work load right up to an average value of 5.7 l min-1. Mean arterial pressure was unchanged up to a work load of 30 W, but increased thereafter from 100 to 130 mmHg. The femoral arterial-venous oxygen difference at maximum work averaged 14.6% (v/v), resulting in an oxygen uptake of 0.80 l min-1. With a mean estimated weight of the knee extensors of 2.30 kg the perfusion of maximally exercising skeletal muscle of man is thus in the order of 2.5 l kg-1 min-1, and the oxygen uptake 0.35 l kg-1 min-1. Limitations in the methods used previously to determine flow and/or the characteristics of the exercise model used may explain why earlier studies in man have failed to demonstrate the high perfusion of muscle reported here. It is concluded that muscle blood flow is closely related to the oxygen demand of the exercising muscles. The hyperaemia at low work intensities is due to vasodilatation, and an elevated mean arterial blood pressure only contributes to the linear increase in flow at high work rates. The magnitude of perfusion observed during intense exercise indicates that the vascular bed of skeletal muscle is not a limiting factor for oxygen transport. PMID:4057091

  4. An Evaluation of Software Cost Estimating Models.

    DTIC Science & Technology

    1981-06-01

    EVALUATION OF SOFTWARE COST ESTIMATING Sep 73- Oct 79 MODELS. R14- --. R IOTNME 7. AUTHOR (.) * ce.4 **CT OR GRANT NUMBER(C.’ * ~ Robert Thibodeau K 1 F30602...review of the draft DCP begins, the program can be terminated with the approval of the highest command level which authorized it. Once DSARC review begins...concert with many other elements. Initially, we might speak of the navigation subsystem and its functions. Later, we would describe the alignment element

  5. Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage in an isolated renal perfusion model

    PubMed Central

    Hüter, Lars; Simon, Tim-Philipp; Weinmann, Lenard; Schuerholz, Tobias; Reinhart, Konrad; Wolf, Gunter; Amann, Kerstin Ute; Marx, Gernot

    2009-01-01

    Introduction The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours. Methods Infusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed. Results Initially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 ± 23 U/L) compared with HES 130/0.42 (38 ± 12 U/L) and RL (21 ± 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 ± 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 ± 0.6; HES 130/0.42 = 2.0 ± 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 ± 1.0 vs. 0.2 ± 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 ± 6.9 vs. 6.5 ± 1.6; P = 0.006) with no significant difference in RL (13.5 ± 4.0). Conclusions We observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and

  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. 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.

  9. 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.

  10. 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.

  11. TU-CD-BRA-08: Single-Energy Computed Tomography-Based Pulmonary Perfusion Imaging: Proof-Of-Principle in a Canine Model

    SciTech Connect

    Yamamoto, T; Boone, J; Kent, M; Wisner, E; Fujita, Y

    2015-06-15

    Purpose: Pulmonary perfusion imaging has provided significant insights into pulmonary diseases, and can be useful in radiotherapy. The purpose of this study was to prospectively establish proof-of-principle in a canine model for single-energy CT-based perfusion imaging, which has the potential for widespread clinical implementation. Methods: Single-energy CT perfusion imaging is based on: (1) acquisition of inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast medium, (2) deformable image registration (DIR) of the two CT image data sets, and (3) subtraction of the pre-contrast image from post-contrast image, yielding a map of Hounsfield unit (HU) enhancement. These subtraction image data sets hypothetically represent perfused blood volume, a surrogate for perfusion. In an IACUC-approved clinical trial, we acquired pre- and post-contrast CT scans in the prone posture for six anesthetized, mechanically-ventilated dogs. The elastix algorithm was used for DIR. The registration accuracy was quantified using the target registration errors (TREs) for 50 pulmonary landmarks in each dog. The gradient of HU enhancement between gravity-dependent (ventral) and non-dependent (dorsal) regions was evaluated to quantify the known effect of gravity, i.e., greater perfusion in ventral regions. Results: The lung volume difference between the two scans was 4.3±3.5% on average (range 0.3%–10.1%). DIR demonstrated an average TRE of 0.7±1.0 mm. HU enhancement in lung parenchyma was 34±10 HU on average and varied considerably between individual dogs, indicating the need for improvement of the contrast injection protocol. HU enhancement in ventral (gravity-dependent) regions was found to be greater than in dorsal regions. A population average ventral-to-dorsal gradient of HU enhancement was strong (R{sup 2}=0.94) and statistically significant (p<0.01). Conclusion: This canine study demonstrated relatively accurate DIR and a strong ventral

  12. Function of the vascular endothelium after hypothermic storage at four degrees Celsius in a canine tibial perfusion model. The role of adrenomedullin in reperfusion injury.

    PubMed

    Kato, T; Bishop, A T; Tu, Y K; Wood, M B

    1998-09-01

    The function of the vascular endothelium after cold storage at 4 degrees Celsius for one, three, five, and seven days was investigated in a canine tibial perfusion model. Function was assessed in terms of changes in perfusion pressure, changes in the concentration of endothelin in the venous effluent from the perfused tibiae, adrenomedullin-induced vascular smooth-muscle relaxation, and norepinephrine-induced pressor responses in the presence of acetylcholine, N(G)-monomethyl-L-arginine acetate (an inhibitor of nitric oxide synthesis), or indomethacin (an inhibitor of prostaglandin synthesis) in phase 1 of the study. In phase 2 of the study, the effect of the infusion of tetraethylammonium (a potassium-channel blocker that inhibits the activity of endothelium-derived hyperpolarized factor) was analyzed. The baseline perfusion pressures increased in a time-dependent manner (p < 0.05). In tibiae that had been stored for one or three days, the production of endothelin-1 was less than one picogram per milliliter, but it markedly increased to a mean (and standard error of the mean) of 8.7 +/- 3.2 and 10.8 +/- 4.3 picograms per milliliter in tibiae that had been stored for five and seven days, respectively (p < 0.05). Acetylcholine attenuated the norepinephrine-induced pressor response in all groups (storage at 4 degrees Celsius for one, three, five, or seven days) compared with the response in the control tibiae (p < 0.05). Perfusion of acetylcholine in the tibiae that had been stored for three days significantly attenuated the pressor response to norepinephrine compared with that in the tibiae that had been stored for five days (p < 0.05). In the presence of N(G)-monomethyl-L-arginine acetate, the norepinephrine-induced pressor response significantly increased only in the tibiae that had been stored for one day (p < 0.05). In the presence of indomethacin, the norepinephrine-induced pressor response significantly decreased in the tibiae that had been stored at 4 degrees

  13. Multimodality imaging approach for serial assessment of regional changes in lower extremity arteriogenesis and tissue perfusion in a porcine model of peripheral arterial disease.

    PubMed

    Stacy, Mitchel R; Yu, Da Yu; Maxfield, Mark W; Jaba, Irina M; Jozwik, Bartosz P; Zhuang, Zhen W; Lin, Ben A; Hawley, Christi L; Caracciolo, Christopher M; Pal, Prasanta; Tirziu, Daniela; Sampath, Smita; Sinusas, Albert J

    2014-01-01

    A standard quantitative imaging approach to evaluate peripheral arterial disease does not exist. Quantitative tools for evaluating arteriogenesis in vivo are not readily available, and the feasibility of monitoring serial regional changes in lower extremity perfusion has not been examined. Serial changes in lower extremity arteriogenesis and muscle perfusion were evaluated after femoral artery occlusion in a porcine model using single photon emission tomography (SPECT)/CT imaging with postmortem validation of in vivo findings using gamma counting, postmortem imaging, and histological analysis. Hybrid 201Tl SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately postocclusion, and at 1 and 4 weeks postocclusion. CT imaging was used to identify muscle regions of interest in the ischemic and nonischemic hindlimbs for quantification of regional changes in CT-defined arteriogenesis and quantification of 201Tl perfusion. Four weeks postocclusion, postmortem tissue 201Tl activity was measured by gamma counting, and immunohistochemistry was performed to assess capillary density. Relative 201Tl retention (ischemic/nonischemic) was reduced immediately postocclusion in distal and proximal muscles and remained lower in calf and gluteus muscles 4 weeks later. Analysis of CT angiography revealed collateralization at 4 weeks within proximal muscles (P<0.05). SPECT perfusion correlated with tissue gamma counting at 4 weeks (P=0.01). Increased capillary density was seen within the ischemic calf at 4 weeks (P=0.004). 201Tl SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion after limb ischemia. This approach may be effective for detection of disease and monitoring therapy in peripheral arterial disease.

  14. Estimating standard errors in feature network models.

    PubMed

    Frank, Laurence E; Heiser, Willem J

    2007-05-01

    Feature network models are graphical structures that represent proximity data in a discrete space while using the same formalism that is the basis of least squares methods employed in multidimensional scaling. Existing methods to derive a network model from empirical data only give the best-fitting network and yield no standard errors for the parameter estimates. The additivity properties of networks make it possible to consider the model as a univariate (multiple) linear regression problem with positivity restrictions on the parameters. In the present study, both theoretical and empirical standard errors are obtained for the constrained regression parameters of a network model with known features. The performance of both types of standard error is evaluated using Monte Carlo techniques.

  15. 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.

  16. 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

  17. A new device for continuous assessment of gut perfusion: proof of concept on a porcine model of septic shock.

    PubMed

    Jacquet-Lagrèze, Matthias; Bonnet-Garin, Jeanne-Marie; Allaouchiche, Bernard; Vassal, Olivia; Restagno, Damien; Paquet, Christian; Ayoub, Jean-Yves; Etienne, Jérôme; Vandenesch, François; Daulwader, Olivier; Junot, Stéphane

    2014-07-16

    We evaluate an innovative device consisting of an enteral feeding tube equipped with a photoplethysmography (PPG) sensor in contact with the duodenal mucosa. This study aims to determine if the PPG signal, composed of a continuous (PDC) and a pulsatile part (PAC), is a reliable method to assess gut perfusion in a porcine model of septic shock. Fourteen piglets were anesthetized and mechanically ventilated. They were randomly assigned to two groups: the nonseptic (NS) group received an infusion of Ringer's lactate solution (RL) alone, the septic (S) group received in addition a suspension of live Pseudomonas aeruginosa. Heart rate (HR), pulse oximetry (SpO2), mean arterial pressure (MAP), cardiac index (CI) and serum lactates were recorded and gut microcirculation (GM) was monitored with a laser Doppler probe applied on the duodenal serosa. PDC and PAC were given by the PPG probe inserted in the duodenum. Data was collected every 15 minutes (t0, t15…) during 150 minutes (t150). After administration of the bacteria suspension (t0), resuscitation maneuvers were performed following a defined algorithm. GM PAC, and PDC were expressed as variation from baseline (GMvar, PACvar, PDCvar). Analysis of variance (ANOVA) with repeated measures was performed to compare hemodynamic variables, with Bonferroni correction as post hoc analysis on t0, t60 and t150. One piglet was withdrawn from analysis due to a defective probe. S group (six piglets) received resuscitation therapy while NS group (seven piglets) did not. A significant group effect was found for the all parameters except HR. Post hoc analysis found a significant decrease for GM and PAC at t60. The correlation between PAC, PDC and microcirculatory parameters were as follows: rPACvar-GMvar = 0.496, P <0.001, rPDCvar-GMvar = 0.244; P = 0.002. In the septic group, correlations were as follows: rPAC-lactate = -0.772, P <0.001; rPDC-lactate = -0.681, P <0.01). At the onset of shock, a decrease of PAC

  18. 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.

  19. Pedestrian crash estimation models for signalized intersections.

    PubMed

    Pulugurtha, Srinivas S; Sambhara, Venkata R

    2011-01-01

    The focus of this paper is twofold: (1) to examine the non-linear relationship between pedestrian crashes and predictor variables such as demographic characteristics (population and household units), socio-economic characteristics (mean income and total employment), land use characteristics, road network characteristics (the number of lanes, speed limit, presence of median, and pedestrian and vehicular volume) and accessibility to public transit systems, and (2) to develop generalized linear pedestrian crash estimation models (based on negative binomial distribution to accommodate for over-dispersion of data) by the level of pedestrian activity and spatial proximity to extract site specific data at signalized intersections. Data for 176 randomly selected signalized intersections in the City of Charlotte, North Carolina were used to examine the non-linear relationships and develop pedestrian crash estimation models. The average number of pedestrian crashes per year within 200 feet of each intersection was considered as the dependent variable whereas the demographic characteristics, socio-economic characteristics, land use characteristics, road network characteristics and the number of transit stops were considered as the predictor variables. The Pearson correlation coefficient was used to eliminate predictor variables that were correlated to each other. Models were then developed separately for all signalized intersections, high pedestrian activity signalized intersections and low pedestrian activity signalized intersections. The use of 0.25mile, 0.5mile and 1mile buffer widths to extract data and develop models was also evaluated.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Hierarchical Boltzmann simulations and model error estimation

    NASA Astrophysics Data System (ADS)

    Torrilhon, Manuel; Sarna, Neeraj

    2017-08-01

    A hierarchical simulation approach for Boltzmann's equation should provide a single numerical framework in which a coarse representation can be used to compute gas flows as accurately and efficiently as in computational fluid dynamics, but a subsequent refinement allows to successively improve the result to the complete Boltzmann result. We use Hermite discretization, or moment equations, for the steady linearized Boltzmann equation for a proof-of-concept of such a framework. All representations of the hierarchy are rotationally invariant and the numerical method is formulated on fully unstructured triangular and quadrilateral meshes using a implicit discontinuous Galerkin formulation. We demonstrate the performance of the numerical method on model problems which in particular highlights the relevance of stability of boundary conditions on curved domains. The hierarchical nature of the method allows also to provide model error estimates by comparing subsequent representations. We present various model errors for a flow through a curved channel with obstacles.

  5. [Quantitatively evaluating the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment].

    PubMed

    Xiong, Zeng; Deng, Pengbo; Hu, Chengping; Liu, Jinkang; Yang, Huaping; Zhou, Jianhua; Wang, Ying; Zhou, Hui; Zhu, Zhiming

    2016-01-26

    To quantitatively evaluate the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. To establish the preclinical transplantation model of lung adenocarcinoma, 60 BALB/c nu/nu mice was inoculated with A549 cell lines via axilla. Sixty mice were randomly divided into 2 groups. The treatment group was treated with intravenous Bevacizumab (10 mg/kg weight, in a single injection), and the control group received saline only in the same dose. Five times of volume perfusion CT (VPCT) scan was performed before treatment, and on the second, forth, sixth and tenth days of treatment, respectively. The values of blood flow (BF) in the A549 tumors were measured after scanning. The microvessel density (MVD), vessel maturity index (VMI) in the tumors were determined using multiplexed QDs-based immunohistochemical staining. Comparing the values of BF, VMI and MVD between the two groups on the same day before treatment, the values of BF, VMI and MVD of the treatment group were (13.5±1.5) ml·(100 ml)(-1)·min(-1,) 0.14±0.04, (45.7±16.5)/HPF, respectively, and those in the control group were (13.4±1.6) ml·(100 ml)(-1)·min(-1) , 0.14±0.05, (48.0±7.0) /HPF , respectively. There was no significant difference between the two groups (all P>0.05). And on the second, forth, sixth, tenth days of treatment, the values of BF of the treatment group were (17.9±7.3), (32.2±6.9), (18.5±2.4) and (13.8±1.8) ml·(100 ml)(-1)·min(-1,) respectively, and those in the control group were (10.5±0.6), (9.6±0.8), (5.7±1.2) and (1.9±1.0) ml·(100 ml)(-1)·min(-1,) respectively. The values of VMI of the treatment group were 1.17±0.22, 3.25±0.23, 2.94±0.31 and 1.07±0.18, respectively, and those in the control group were 0.12±0.03, 0.13±0.03, 0.15±0.03, and 0.13±0.03, respectively. The values of MVD of the treatment group were (38.0±6.3), (24.3±5.4), (15.2±3.4) and (13.5±4.7)/HPF, respectively, and those in the

  6. 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.

  7. 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...

  8. 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...

  9. Long-Term Evaluation of a Selective Retrograde Coronary Venous Perfusion Model in Pigs (Sus Scrofa Domestica)

    PubMed Central

    Harig, Frank; Schmidt, Joachim; Hoyer, Evelyn; Eckl, Sebastian; Adamek, Edytha; Ertel, Dirk; Nooh, Ehab; Amann, Kerstin; Weyand, Michael; Ensminger, Stephan M

    2011-01-01

    The lack of suitable target vessels remains a challenge for aortocoronary bypass grafting in end-stage coronary heart disease. This study aimed to investigate the arterialization of cardiac veins as an alternative myocardial revascularization strategy in an experimental long-term model in pigs. Selective retrograde perfusion of a coronary vein (aorta to coronary vein bypass, retrobypass) before ligation of the ramus interventricularis paraconalis (equivalent to the left anterior descending artery in humans) was performed in 20 German Landrace pigs (Sus scrofa domestica). Retroperfusion of the left anterior descending vein was performed in 10 pigs (RP+) but not in the other 10 (RP–), and the vena cordis magna was ligated (L+) in 5 pigs in each of these groups but left open (L–) in the remaining animals. Hemodynamic performance (for example, cardiac output) was significantly better in the group that underwent selective retroperfusion with proximal ligation of vena cordis magna (RP+L+; 4.1 L/min) compared with the other groups (RP+L–, 2.5 L/min; RP–L+, 2.2 L/min; RP–L–, 1.9 L/min). Long-term survival was significantly better in RP+L+ pigs (112 ± 16 d) than in all other groups. Histologic follow-up studies showed significantly less necrosis in the RP+L+ group compared with all other groups. Venous retroperfusion is an effective technique to achieve long-term survival after acute occlusion of the left anterior descending artery in a pig model. In this model, proximal ligation of vena cordis magna is essential. PMID:21535926

  10. A Biomechanical Modeling Guided CBCT Estimation Technique.

    PubMed

    Zhang, You; Tehrani, Joubin Nasehi; Wang, Jing

    2017-02-01

    Two-dimensional-to-three-dimensional (2D-3D) deformation has emerged as a new technique to estimate cone-beam computed tomography (CBCT) images. The technique is based on deforming a prior high-quality 3D CT/CBCT image to form a new CBCT image, guided by limited-view 2D projections. The accuracy of this intensity-based technique, however, is often limited in low-contrast image regions with subtle intensity differences. The solved deformation vector fields (DVFs) can also be biomechanically unrealistic. To address these problems, we have developed a biomechanical modeling guided CBCT estimation technique (Bio-CBCT-est) by combining 2D-3D deformation with finite element analysis (FEA)-based biomechanical modeling of anatomical structures. Specifically, Bio-CBCT-est first extracts the 2D-3D deformation-generated displacement vectors at the high-contrast anatomical structure boundaries. The extracted surface deformation fields are subsequently used as the boundary conditions to drive structure-based FEA to correct and fine-tune the overall deformation fields, especially those at low-contrast regions within the structure. The resulting FEA-corrected deformation fields are then fed back into 2D-3D deformation to form an iterative loop, combining the benefits of intensity-based deformation and biomechanical modeling for CBCT estimation. Using eleven lung cancer patient cases, the accuracy of the Bio-CBCT-est technique has been compared to that of the 2D-3D deformation technique and the traditional CBCT reconstruction techniques. The accuracy was evaluated in the image domain, and also in the DVF domain through clinician-tracked lung landmarks.

  11. Simultaneous determination of nine model compounds in permeability samples using RP-HPLC: application to prove the cassette administration principle in single pass intestinal perfusion study in rats.

    PubMed

    Wahajuddin; Singh, Sheelendra Pratap; Raju, K S R; Nafis, Asad; Jain, Girish Kumar

    2012-01-01

    A simple, sensitive and specific reversed phase high performance liquid chromatographic (RP-HPLC) method for simultaneous determination of atenolol, paracetamol, hydrochlorothiazide, caffeine, cephalexin, metoprolol, propranolol, ketoprofen along with phenol red (a non-absorbable compound) in samples obtained from intestinal in situ single-pass perfusion studies, was developed and validated. Chromatography was carried out on RP18 column with mobile phase comprising of 10 mM phosphate buffer (pH 2.5) and methanol in gradient mode. The calibration curves were linear for all nine permeability model compounds (r² > 0.999) across the concentration range of 1.25-40 μg/ml. The coefficient of variation for intra and inter-day assay precision was between 0.04 and 3.08% and the accuracy was between 98.39 and 109.45%. Stability studies were carried out at different storage conditions and all the analytes were found to be stable. The method was successfully applied for analysing the permeability samples obtained from in situ single pass perfusion studies. The effective permeability (P(eff)) values obtained upon cassette administration were in close proximity to the permeability values obtained upon single administration of model compounds. In conclusion, the developed RP-HPLC method can be used for high throughput cassette validation of rat in situ perfusion model for intestinal permeability assessment.

  12. Estimation of Model Parameters for Steerable Needles

    PubMed Central

    Park, Wooram; Reed, Kyle B.; Okamura, Allison M.; Chirikjian, Gregory S.

    2010-01-01

    Flexible needles with bevel tips are being developed as useful tools for minimally invasive surgery and percutaneous therapy. When such a needle is inserted into soft tissue, it bends due to the asymmetric geometry of the bevel tip. This insertion with bending is not completely repeatable. We characterize the deviations in needle tip pose (position and orientation) by performing repeated needle insertions into artificial tissue. The base of the needle is pushed at a constant speed without rotating, and the covariance of the distribution of the needle tip pose is computed from experimental data. We develop the closed-form equations to describe how the covariance varies with different model parameters. We estimate the model parameters by matching the closed-form covariance and the experimentally obtained covariance. In this work, we use a needle model modified from a previously developed model with two noise parameters. The modified needle model uses three noise parameters to better capture the stochastic behavior of the needle insertion. The modified needle model provides an improvement of the covariance error from 26.1% to 6.55%. PMID:21643451

  13. 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.

  14. A novel adenoviral gutless vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model.

    PubMed

    Lee, Jae Ung; Shin, Jinho; Song, Woohyuk; Kim, Hyunjoong; Lee, Seunghwan; Jang, Se Jin; Wong, S Chiu; Edelberg, Jay E; Liau, Gene; Hong, Mun K

    2005-11-01

    We previously demonstrated that sphingosine kinase (SPK) increases the level of extracellular sphingosine-1-phosphate and promotes neovascularization in a mouse matrigel model. In this study, we tested the hypothesis that SPK gene transfer using a novel adenoviral 'gutless' vector (AGV) can enhance arteriogenesis in a rabbit hindlimb ischemia model. Thirty-five male New Zealand white rabbits were randomized to the AGV-SPK group (n=13), AGV-null group (n=13), and control group (n=9). On day 10, after the induction of unilateral hindlimb ischemia, gene vectors or buffer were introduced and the effect examined on day 30, using calf blood pressure, quantitative angiographic analysis, and histology. Calf systolic blood pressure ratios of the ischemic limb to the normal limb on day 30 were 0.77+/-0.13 in control groups, including the AGV-null group, and 0.91+/-0.14 in the AGV-SPK group (P<0.05). Angiographic vessel counts were significantly increased (8.0+/-2.1 at baseline and 11.8+/-3.2 on day 30, P<0.001) in the AGV-SPK group. Histologic analysis showed that microscopic total vessel counts on day 30 were 3.5+/-1.8/field in the control and AGV-null group and 5.4+/-1.0/field in the AGV-SPK group. Arterioles (AGV-SPK; 3.0+/-0.8 versus control and AGV-null; 2.1+/-1.1, P<0.05) were significantly increased in the AGV-SPK group. This study shows that SPK promotes arteriogenesis, as evidenced by the maximal improvement in the blood pressure restoration and collateral vessel counts. SPK may be an important angiogenic target to improve perfusion in ischemic tissues.

  15. Modelling and simulation of the chondrocyte cell growth, glucose consumption and lactate production within a porous tissue scaffold inside a perfusion bioreactor.

    PubMed

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

    2015-03-01

    Mathematical and numerical modelling of the tissue culture process in a perfusion bioreactor is able to provide insight into the fluid flow, nutrients and wastes transport, dynamics of the pH value, and the cell growth rate. Knowing the complicated interdependence of these processes is essential for optimizing the culture process for cell growth. This paper presents a resolved scale numerical simulation, which allows one not only to characterize the supply of glucose inside a porous tissue scaffold in a perfusion bioreactor, but also to assess the overall culture condition and predict the cell growth rate. The simulation uses a simplified scaffold that consists of a repeatable unit composed of multiple strands. The simulation results explore some problematic regions inside the simplified scaffold where the concentration of glucose becomes lower than the critical value for the chondrocyte cell viability and the cell growth rate becomes significantly reduced.

  16. Modeling, simulation, and estimation of optical turbulence

    NASA Astrophysics Data System (ADS)

    Formwalt, Byron Paul

    This dissertation documents three new contributions to simulation and modeling of optical turbulence. The first contribution is the formalization, optimization, and validation of a modeling technique called successively conditioned rendering (SCR). The SCR technique is empirically validated by comparing the statistical error of random phase screens generated with the technique. The second contribution is the derivation of the covariance delineation theorem, which provides theoretical bounds on the error associated with SCR. It is shown empirically that the theoretical bound may be used to predict relative algorithm performance. Therefore, the covariance delineation theorem is a powerful tool for optimizing SCR algorithms. For the third contribution, we introduce a new method for passively estimating optical turbulence parameters, and demonstrate the method using experimental data. The technique was demonstrated experimentally, using a 100 m horizontal path at 1.25 m above sun-heated tarmac on a clear afternoon. For this experiment, we estimated C2n ≈ 6.01 · 10-9 m-23 , l0 ≈ 17.9 mm, and L0 ≈ 15.5 m.

  17. Computed Tomography Perfusion, Magnetic Resonance Imaging, and Histopathological Findings After Laparoscopic Renal Cryoablation: An In Vivo Pig Model.

    PubMed

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Graumann, Ole; Pedersen, Bodil Ginnerup; Andersen, Gratien; Høyer, Søren; Borre, Michael

    2017-08-01

    The present study investigates how computed tomography perfusion scans and magnetic resonance imaging correlates with the histopathological alterations in renal tissue after cryoablation. A total of 15 pigs were subjected to laparoscopic-assisted cryoablation on both kidneys. After intervention, each animal was randomized to a postoperative follow-up period of 1, 2, or 4 weeks, after which computed tomography perfusion and magnetic resonance imaging scans were performed. Immediately after imaging, open bilateral nephrectomy was performed allowing for histopathological examination of the cryolesions. On computed tomography perfusion and magnetic resonance imaging examinations, rim enhancement was observed in the transition zone of the cryolesion 1week after laparoscopic-assisted cryoablation. This rim enhancement was found to subside after 2 and 4 weeks of follow-up, which was consistent with the microscopic examinations revealing of fibrotic scar tissue formation in the peripheral zone of the cryolesion. On T2 magnetic resonance imaging sequences, a thin hypointense rim surrounded the cryolesion, separating it from the adjacent renal parenchyma. Microscopic examinations revealed hemorrhage and later hemosiderin located in the peripheral zone. No nodular or diffuse contrast enhancement was found in the central zone of the cryolesions at any follow-up stage on neither computed tomography perfusion nor magnetic resonance imaging. On microscopic examinations, the central zone was found to consist of coagulative necrosis 1 week after laparoscopic-assisted cryoablation, which was partially replaced by fibrotic scar tissue 4 weeks following laparoscopic-assisted cryoablation. Both computed tomography perfusion and magnetic resonance imaging found the renal collecting system to be involved at all 3 stages of follow-up, but on microscopic examination, the urothelium was found to be intact in all cases. In conclusion, cryoablation effectively destroyed renal parenchyma

  18. Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion: a continuum model of matrix metabolism and transport.

    PubMed

    Klein, T J; Sah, R L

    2007-01-01

    The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57-73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue- engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

  19. Dynamic CT perfusion imaging of the myocardium using a wide-detector scanner: a semiquantitative analysis in an animal model.

    PubMed

    Muenzel, Daniela; Noël, Peter B; Gramer, Bettina M; Leber, Vivian; Schneider, Armin; Leber, Alexander; Vembar, Mani; Fingerle, Alexander A; Rummeny, Ernst J; Huber, Armin

    2014-01-01

    Functional assessment of myocardial perfusion in computed tomography (CT) is a challenge. To evaluate CT dynamic myocardial perfusion imaging (MPI) using a wide-detector scanner. Time to peak (TTP), peak enhancement (PE), upslope (US), and the area under the curve (AUC) were calculated in 12 pigs (256-slice multidetector CT scanner). The entire myocardium was covered by the scan volume. TTP was increased, and PE, US, and AUC were decreased in poststenotic myocardium. CT MPI with complete coverage of the myocardium is feasible, providing evaluation of the physiological significance of coronary artery stenosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. 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

  1. 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.

  2. Transplantation and Perfusion of Microvascular Fragments in a Rodent Model of Volumetric Muscle Loss Injury

    DTIC Science & Technology

    2014-07-01

    Microvascular transplantation after acute myocardial infarction . Tissue Eng 13: 2871-2879. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ...when grafts were implanted after murine myocardial infarction (Shepherd, 2007, text reference). However, caution should be made when extrapolating...these findings to the current study due to the differences between the models ( myocardial infarction vs. VML) and the time allowed for microvessel

  3. 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…

  4. 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…

  5. 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.

  6. 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. © 2015 Wiley Periodicals, Inc.

  7. A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers of Cardiac Viability During Ex Vivo Heart Perfusion.

    PubMed

    Kearns, Mark J; Miller, Sally D; Cheung, Anson; Bashir, Jamil; Wong, Stephanie; Seidman, Michael A; Boyd, John H

    2017-08-01

    Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifying high-risk hearts at the point of harvest (Hsp90). We demonstrate that our preclinical model recapitulates the cardio-respiratory decompensation observed in humans, and that EVHP appears necessary to unmask distinguishing features of severely injured DCD hearts. Furthermore, we outline a clinically relevant multimodal approach to assessing candidate DCD hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in severely injured hearts during EVHP, and may also detect injury at the point of harvest.

  8. 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.

  9. Immersed Boundary Models for Quantifying Flow-Induced Mechanical Stimuli on Stem Cells Seeded on 3D Scaffolds in Perfusion Bioreactors

    PubMed Central

    Smeets, Bart; Odenthal, Tim; Luyten, Frank P.; Ramon, Herman; Papantoniou, Ioannis; Geris, Liesbet

    2016-01-01

    Perfusion bioreactors regulate flow conditions in order to provide cells with oxygen, nutrients and flow-associated mechanical stimuli. Locally, these flow conditions can vary depending on the scaffold geometry, cellular confluency and amount of extra cellular matrix deposition. In this study, a novel application of the immersed boundary method was introduced in order to represent a detailed deformable cell attached to a 3D scaffold inside a perfusion bioreactor and exposed to microscopic flow. The immersed boundary model permits the prediction of mechanical effects of the local flow conditions on the cell. Incorporating stiffness values measured with atomic force microscopy and micro-flow boundary conditions obtained from computational fluid dynamics simulations on the entire scaffold, we compared cell deformation, cortical tension, normal and shear pressure between different cell shapes and locations. We observed a large effect of the precise cell location on the local shear stress and we predicted flow-induced cortical tensions in the order of 5 pN/μm, at the lower end of the range reported in literature. The proposed method provides an interesting tool to study perfusion bioreactors processes down to the level of the individual cell’s micro-environment, which can further aid in the achievement of robust bioprocess control for regenerative medicine applications. PMID:27658116

  10. Effect of taurocholic acid on fetoplacental arterial pressures in a dual perfusion placental cotyledon model: a novel approach to intrahepatic cholestasis of pregnancy.

    PubMed

    Dolinsky, Brad M; Zelig, Craig M; Paonessa, Damian J; Hoeldtke, Nathan J; Napolitano, Peter G

    2014-01-01

    To determine if continuous infusion of taurocholic acid into the fetoplacental and intervillous circulation of a placental cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP). We selected 5 placentas from normal, unlabored patients. Two cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoplacental and intervillous circulation of the test cotyledon. After 30 minutes U44619 was injected into both the test and control cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Student's t test. There was significant attenuation of the pressure excursion in the cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p = 0.009). The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoplacental arterial circulation of a placental cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.

  11. Understanding the interplay of drug transporters involved in the disposition of rosuvastatin in the isolated perfused rat liver using a physiologically-based pharmacokinetic model.

    PubMed

    Hobbs, Michael; Parker, Connie; Birch, Helen; Kenworthy, Kathryn

    2012-04-01

    The role of hepatic uptake (Oatp1a1 and Oatp1b4) and efflux (Bcrp and Mrp2) transporters in the disposition of rosuvastatin were investigated using the isolated perfused rat liver (IPRL). A simple physiologically-based pharmacokinetic model was developed to quantitatively determine the interplay between the individual transporters. Uptake and elimination of rosuvastatin in the IPRL was rapid and extensive. In the presence of rifamycin (an equipotent inhibitor of both Oatp1a1 and Oatp1a4) the perfusate clearance of rosuvastatin was reduced, but rifampicin (a potent inhibitor of Oatp1a4) had no effect upon the perfusate clearance. This might indicate a limited role for Oatp1a4, but it is possible that Oatp1a1 (or other uptake transporters) may have redundancy in their affinity for rosuvastatin. In the presence of GF120918 (a potent inhibitor of Bcrp) and in the Wistar TR- rat (a naturally occurring mutant not expressing Mrp2) the biliary clearance was reduced and virtually abolished in the TR- pre-incubated GF120918. Bcrp and Mrp2 appear to represent the primary efflux mechanisms for rosuvastatin in the rat. Rosuvastatin disposition in the IPRL is mediated in part by Oatp1a1 and efflux is almost entirely by Mrp2 and Bcrp. Other uptake processes may be involved.

  12. Immersed Boundary Models for Quantifying Flow-Induced Mechanical Stimuli on Stem Cells Seeded on 3D Scaffolds in Perfusion Bioreactors.

    PubMed

    Guyot, Yann; Smeets, Bart; Odenthal, Tim; Subramani, Ramesh; Luyten, Frank P; Ramon, Herman; Papantoniou, Ioannis; Geris, Liesbet

    2016-09-01

    Perfusion bioreactors regulate flow conditions in order to provide cells with oxygen, nutrients and flow-associated mechanical stimuli. Locally, these flow conditions can vary depending on the scaffold geometry, cellular confluency and amount of extra cellular matrix deposition. In this study, a novel application of the immersed boundary method was introduced in order to represent a detailed deformable cell attached to a 3D scaffold inside a perfusion bioreactor and exposed to microscopic flow. The immersed boundary model permits the prediction of mechanical effects of the local flow conditions on the cell. Incorporating stiffness values measured with atomic force microscopy and micro-flow boundary conditions obtained from computational fluid dynamics simulations on the entire scaffold, we compared cell deformation, cortical tension, normal and shear pressure between different cell shapes and locations. We observed a large effect of the precise cell location on the local shear stress and we predicted flow-induced cortical tensions in the order of 5 pN/μm, at the lower end of the range reported in literature. The proposed method provides an interesting tool to study perfusion bioreactors processes down to the level of the individual cell's micro-environment, which can further aid in the achievement of robust bioprocess control for regenerative medicine applications.

  13. Characterization of gadolinium-based dynamic susceptibility contrast perfusion measurements in permanent and transient MCAO models with volumetric based validation by CASL

    PubMed Central

    Bråtane, Bernt T; Walvick, Ronn P; Corot, Claire; Lancelot, Eric; Fisher, Marc

    2010-01-01

    Perfusion imaging is crucial in imaging of ischemic stroke to determine ‘tissue at risk' for infarction. In this study we compared the volumetric quantification of the perfusion deficit in two rat middle-cerebral-artery occlusion (MCAO) models using two gadolinium-based contrast agents (P1152 (Guerbet) and Magnevist (Bayer-Schering, Pittsburgh, PA, USA)) as compared with our well established continuous arterial spin labeling (CASL) perfusion imaging technique. Animals underwent either permanent MCAO or transient MCAO with 80-min reperfusion. Imaging was performed at four different time points after MCAO. A region-of-interest (ROI) analysis of the subregions of the ischemic zone (core, penumbra, transient reversal (TR), and sustained reversal (SR)) using P1152 showed significant reduction in blood flow in the core and TR subregions relative to the penumbral and SR subregions while occluded. After reperfusion, a significant increase in blood flow was recorded at all time points after reperfusion in all regions except TR. From the ROI analysis the threshold for the penumbra was determined to be −62±11% and this value was subsequently used for quantification of the volumetric deficit. The ischemic volume as defined by dynamic susceptibility contrast (DSC), was only statistically different from the CASL-derived ischemic volume when using Magnevist at post-reperfusion time points. PMID:19826434

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

    PubMed Central

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

    2016-01-01

    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

  15. Personality factors correlate with regional cerebral perfusion.

    PubMed

    O'Gorman, R L; Kumari, V; Williams, S C R; Zelaya, F O; Connor, S E J; Alsop, D C; Gray, J A

    2006-06-01

    There is an increasing body of evidence pointing to a neurobiological basis of personality. The purpose of this study was to investigate the biological bases of the major dimensions of Eysenck's and Cloninger's models of personality using a noninvasive magnetic resonance perfusion imaging technique in 30 young, healthy subjects. An unbiased voxel-based analysis was used to identify regions where the regional perfusion demonstrated significant correlation with any of the personality dimensions. Highly significant positive correlations emerged between extraversion and perfusion in the basal ganglia, thalamus, inferior frontal gyrus and cerebellum and between novelty seeking and perfusion in the cerebellum, cuneus and thalamus. Strong negative correlations emerged between psychoticism and perfusion in the basal ganglia and thalamus and between harm avoidance and perfusion in the cerebellar vermis, cuneus and inferior frontal gyrus. These observations suggest that personality traits are strongly associated with resting cerebral perfusion in a variety of cortical and subcortical regions and provide further evidence for the hypothesized neurobiological basis of personality. These results may also have important implications for functional neuroimaging studies, which typically rely on the modulation of cerebral hemodynamics for detection of task-induced activation since personality effects may influence the intersubject variability for both task-related activity and resting cerebral perfusion. This technique also offers a novel approach for the exploration of the neurobiological correlates of human personality.

  16. Absolute ultrasound perfusion parameter quantification of a tissue-mimicking phantom using bolus tracking [Correspondence].

    PubMed

    Mezl, Martin; Jirik, Radovan; Harabis, Vratislav; Kolar, Radim; Standara, Michal; Nylund, Kim; Gilja, Odd Helge; Taxt, Torfinn

    2015-05-01

    This study presents three methods for absolute quantification in ultrasound perfusion analysis based on bolus tracking. The first two methods deconvolve the perfusion time sequence with a measured AIF, using a nonparametric or a parametric model of the tissue residue function, respectively. The third method is a simplified approach avoiding deconvolution by assuming a narrow AIF. A phantom with a dialyzer filter as a tissue-mimicking model was used for evaluation. Estimated mean transit times and blood volumes were compared with the theoretical values. A match with a maximum error of 12% was achieved.

  17. 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.

  18. AMEM-ADL Polymer Migration Estimation Model User's Guide

    EPA Pesticide Factsheets

    The user's guide of the Arthur D. Little Polymer Migration Estimation Model (AMEM) provides the information on how the model estimates the fraction of a chemical additive that diffuses through polymeric matrices.

  19. Dynamic contrast-enhanced perfusion area detector CT for non-small cell lung cancer patients: Influence of mathematical models on early prediction capabilities for treatment response and recurrence after chemoradiotherapy.

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Fujisawa, Yasuko; Yoshikawa, Takeshi; Seki, Shinichiro; Sugihara, Naoki; Sugimura, Kazuro

    2016-01-01

    To determine the capability and influence of the mathematical method on dynamic contrast-enhanced (CE-) perfusion area detector CT (ADCT) for early prediction of treatment response as well as progression free and overall survival (PFS and OS) of non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Sixty-six consecutive stage III NSCLC patients underwent dynamic CE-perfusion ADCT examinations, chemoradiotherapy and follow-up examinations. Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to divide all patients into responders and non-responders. Differences in each of the indices for all targeted lesions between measurements obtained 2 weeks prior to the first and the third course of chemotherapy were determined for all patients. ROC analyses were employed to determine the capability of perfusion indices as markers for distinguishing RECIST responders from non-responders. To evaluate their capability for early prediction of therapeutic effect, OS of perfusion index-based responders and non-responders were compared by using the Kaplan-Meier method followed by log-rank test. Area under the curve (Az) for total perfusion by means of the dual-input maximum slope method was significantly larger than that of pulmonary arterial perfusion using the same method (p=0.007) and of perfusion with the single-input maximum slope method (p=0.007). Mean OS demonstrated significantly difference between responder- and non-responder groups for total perfusion (p=0.02). Mathematical models have significant influence on assessment for early prediction of treatment response, disease progression and overall survival using dynamic CE-perfusion ADCT for NSCLC patients treated with chemoradiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Adaptive Estimation and Parameter Identification Using Multiple Model Estimation Algorithm

    DTIC Science & Technology

    1976-06-23

    Point Continuous Linear Smoothing ," Proc. Joint Automatic Control Conf., June 1967, pp. 249-257. [26] J. S. Meditch , "On Optimal Linear Smoothing ...Theory," Infor- mation and Control, 10, 598-615 (1967). [27] J. S. Meditch , "A Successive Approximation Procedure for Nonlinear Data Smoothing ," Proc...algorithm Kalman filter algorithms multiple model smoothing algorithm 70. ABSTRACT (Coensnia• en rever.e side if eceossuy Adidonilty by block nu.wbe

  1. 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

  2. T2-prepared steady-state free precession blood oxygen level-dependent MR imaging of myocardial perfusion in a dog stenosis model.

    PubMed

    Shea, Steven M; Fieno, David S; Schirf, Brian E; Bi, Xiaoming; Huang, Jie; Omary, Reed A; Li, Debiao

    2005-08-01

    To assess the ability of a T2-prepared steady-state free precession blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging sequence to depict changes in myocardial perfusion during stress testing in a dog stenosis model. Study was approved by the institutional Animal Care and Use Committee. A hydraulic occluder was placed in the left circumflex coronary artery (LCX) in 10 dogs. Adenosine was administered intravenously to increase coronary blood flow, and stenosis was achieved in the LCX with the occluder. A T2-prepared two-dimensional steady-state free precession sequence was used for BOLD imaging at a spatial resolution of 1.5 x 1.2 x 5.0 mm3, and first-pass perfusion images were acquired for visual comparison. Microspheres were injected to provide regional perfusion information. Mixed-effect regression analysis was performed to assess normalized MR signal intensity ratios and microsphere-measured perfusion differences. For the same data, 95% prediction intervals were calculated to determine the smallest perfusion change detectable. Means +/- standard deviations were calculated for myocardial regional comparison data. A two-tailed Student t test was used to determine if significant differences (P < .01) existed between different myocardial regions. Under maximal adenosine stress, MR clearly depicted stenotic regions and showed regional signal differences between the left anterior descending coronary artery (LAD)-fed myocardium and the stenosed LCX-fed myocardium. Visual comparisons with first-pass images were also excellent. Regional MR signal intensity differences between LAD and LCX-fed myocardium (1.24 +/- 0.08) were significantly different (P < .01) from differences between LAD and septal-fed myocardium (1.02 +/- 0.07), which was in agreement with microsphere-measured flow differences (LAD/LCX, 3.38 +/- 0.83; LAD/septal, 1.26 +/- 0.49). The linear mixed-effect regression model showed good correlation (R = 0.79) between MR differences and

  3. Perfusion decellularization of whole organs.

    PubMed

    Guyette, Jacques P; Gilpin, Sarah E; Charest, Jonathan M; Tapias, Luis F; Ren, Xi; Ott, Harald C

    2014-01-01

    The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.

  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. 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)…

  6. 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)…

  7. 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.

  8. Computer modeling of the combined effects of perfusion, electrical conductivity, and thermal conductivity on tissue heating patterns in radiofrequency tumor ablation.

    PubMed

    Ahmed, Muneeb; Liu, Zhengjun; Humphries, Stanley; Goldberg, S Nahum

    2008-11-01

    To use an established computer simulation model of radiofrequency (RF) ablation to characterize the combined effects of varying perfusion, and electrical and thermal conductivity on RF heating. Two-compartment computer simulation of RF heating using 2-D and 3-D finite element analysis (ETherm) was performed in three phases (n = 88 matrices, 144 data points each). In each phase, RF application was systematically modeled on a clinically relevant template of application parameters (i.e., varying tumor and surrounding tissue perfusion: 0-5 kg/m(3)-s) for internally cooled 3 cm single and 2.5 cm cluster electrodes for tumor diameters ranging from 2-5 cm, and RF application times (6-20 min). In the first phase, outer thermal conductivity was changed to reflect three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and 0.7 W/m- degrees C, respectively). In the second phase, electrical conductivity was changed to reflect different tumor electrical conductivities (0.5 and 4.0 S/m, representing soft tissue and adjuvant saline injection, respectively) and background electrical conductivity representing soft tissue, lung, and kidney (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst combinations of electrical and thermal conductivity characteristics were modeled in combination. Tissue heating patterns and the time required to heat the entire tumor +/-a 5 mm margin to >50 degrees C were assessed. Increasing background tissue thermal conductivity increases the time required to achieve a 50 degrees C isotherm for all tumor sizes and electrode types, but enabled ablation of a given tumor size at higher tissue perfusions. An inner thermal conductivity equivalent to soft tissue (0.5 W/m- degrees C) surrounded by fat (0.23 W/m- degrees C) permitted the greatest degree of tumor heating in the shortest time, while soft tissue surrounded by ascites (0.7 W/m- degrees C) took longer to achieve the 50 degrees C isotherm, and complete ablation

  9. Studying Closed Hydrodynamic Models of "In Vivo" DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans.

    PubMed

    Sendra, Luis; Miguel, Antonio; Pérez-Enguix, Daniel; Herrero, María José; Montalvá, Eva; García-Gimeno, María Adelaida; Noguera, Inmaculada; Díaz, Ana; Pérez, Judith; Sanz, Pascual; López-Andújar, Rafael; Martí-Bonmatí, Luis; Aliño, Salvador F

    2016-01-01

    Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest. A solution of naked DNA bearing the hAAT gene was retrogradely injected in 7 pig livers using two different closed perfusion procedures: an endovascular catheterization-mediated procedure (n = 3) with infrahepatic inferior vena cava and portal vein blockage; and a surgery-mediated procedure (n = 4) with completely sealed liver. Gene transfer was performed through the suprahepatic inferior cava vein in the endovascular procedure and through the infrahepatic inferior vena cava in the surgical procedure. The efficiency of the procedures was evaluated 14 days after hydrofection by quantifying the hAAT protein copies per cell in tissue and in plasma. For comparison, samples from mice (n = 7) successfully hydrofected with hAAT and healthy human liver segments (n = 4) were evaluated. Gene decoding occurs efficiently using both procedures, with liver vascular arrest improving its efficiency. The surgically closed procedure (sealed organ) reached higher tissue protein levels (4x10^5- copies/cell) than the endovascular procedure, though the levels were lower than in human liver (5x10^6- copies/cell) and hydrofected mouse liver (10^6- copies/cell). However, protein levels in plasma were lower (p<0.001) than the reference standards in all cases. Hydrofection of hAAT DNA to "in vivo" isolated pig liver mediates highly efficient gene delivery and protein expression in tissue. Both endovascular and surgically closed models mediate high tissue protein expression

  10. Studying Closed Hydrodynamic Models of “In Vivo” DNA Perfusion in Pig Liver for Gene Therapy Translation to Humans

    PubMed Central

    Sendra, Luis; Miguel, Antonio; Pérez-Enguix, Daniel; Montalvá, Eva; García-Gimeno, María Adelaida; Noguera, Inmaculada; Díaz, Ana; Pérez, Judith; Sanz, Pascual; López-Andújar, Rafael; Martí-Bonmatí, Luis; Aliño, Salvador F.

    2016-01-01

    Introduction Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest. Material and Methods A solution of naked DNA bearing the hAAT gene was retrogradely injected in 7 pig livers using two different closed perfusion procedures: an endovascular catheterization-mediated procedure (n = 3) with infrahepatic inferior vena cava and portal vein blockage; and a surgery-mediated procedure (n = 4) with completely sealed liver. Gene transfer was performed through the suprahepatic inferior cava vein in the endovascular procedure and through the infrahepatic inferior vena cava in the surgical procedure. The efficiency of the procedures was evaluated 14 days after hydrofection by quantifying the hAAT protein copies per cell in tissue and in plasma. For comparison, samples from mice (n = 7) successfully hydrofected with hAAT and healthy human liver segments (n = 4) were evaluated. Results Gene decoding occurs efficiently using both procedures, with liver vascular arrest improving its efficiency. The surgically closed procedure (sealed organ) reached higher tissue protein levels (4x10^5- copies/cell) than the endovascular procedure, though the levels were lower than in human liver (5x10^6- copies/cell) and hydrofected mouse liver (10^6- copies/cell). However, protein levels in plasma were lower (p<0.001) than the reference standards in all cases. Conclusion Hydrofection of hAAT DNA to “in vivo” isolated pig liver mediates highly efficient gene delivery and protein expression in tissue. Both endovascular and

  11. Separating blood and water: Perfusion and free water elimination from diffusion MRI in the human brain.

    PubMed

    Rydhög, Anna S; Szczepankiewicz, Filip; Wirestam, Ronnie; Ahlgren, André; Westin, Carl-Fredrik; Knutsson, Linda; Pasternak, Ofer

    2017-08-01

    The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free-water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b-value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b-value used in the fitting, and (ii) using a three-compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b-values reduced the perfusion effect but was highly sensitive to noise. The three-compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three-compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density

  12. 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.

  13. Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

    PubMed

    Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

    2015-12-01

    The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

  14. Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus.

    PubMed

    Papanastasiou, Giorgos; Williams, Michelle C; Kershaw, Lucy E; Dweck, Marc R; Alam, Shirjel; Mirsadraee, Saeed; Connell, Martin; Gray, Calum; MacGillivray, Tom; Newby, David E; Semple, Scott Ik

    2015-02-17

    Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods. Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05. Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter

  15. Early Cerebral Perfusion Pressure Augmentation with Phenylephrine after Traumatic Brain Injury may be Neuroprotective in a Pediatric Swine Model

    PubMed Central

    Friess, Stuart H.; Smith, Colin; Kilbaugh, Todd J.; Frangos, Suzanne G.; Ralston, Jill; Helfaer, Mark A; Margulies, Susan S.

    2012-01-01

    Objective Cerebral perfusion pressure (CPP) less than 40 mm Hg following pediatric traumatic brain injury (TBI) has been associated with increased mortality independent of age, and current guidelines recommend maintaining CPP between 40–60 mm Hg. Although adult TBI studies have observed an increased risk of complications associated with targeting a CPP > 70, we hypothesize that targeting a CPP of 70 mm Hg with the use of phenylephrine early after injury in the immature brain will be neuroprotective. Design Animals were randomly assigned to injury with CPP = 70 mm Hg (CPP70) or CPP = 40 mm Hg (CPP40). Diffuse TBI was produced by a single rapid rotation of the head in the axial plane. Cerebral microdialysis, brain tissue oxygen, intracranial pressure, and cerebral blood flow (CBF) were measured 30 min – 6 h post-injury. One hour after injury, CPP was manipulated with the vasoconstrictor phenylephrine. Animals were euthanized 6 h post-TBI, brains fixed, and stained to assess regions of cell injury and axonal dysfunction. Setting University center. Subject 21 four week-old female swine. Measurements and Main Results Augmentation of CPP to 70 mm Hg resulted in no change in axonal dysfunction, but significantly smaller cell injury volumes at 6 hours post injury compared to CPP40 (1.1% vs. 7.4%, p < 0.05). Microdialysis lactate/pyruvate ratios were improved at CPP70 compared to CPP40. CBF was higher in the CPP70 group but did not reach statistical significance. Phenylephrine was well tolerated and there were no observed increases in serum lactate or intracranial pressure in either group. Conclusions Targeting a CPP of 70 mm Hg resulted in a greater reduction in metabolic crisis and cell injury volumes compared to a CPP of 40 mm Hg in an immature swine model. Early aggressive CPP augmentation to a CPP of 70 mm Hg in pediatric TBI before severe intracranial hypertension has the potential to be neuroprotective, and further investigations are needed. PMID:22809910

  16. 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.

  17. Robotic Transabdominal Control of the Suprahepatic, Infradiaphragmatic Vena Cava to Enable Level 3 Caval Tumor Thrombectomy: Pilot Study in a Perfused-Cadaver Model.

    PubMed

    de Castro Abreu, Andre Luis; Chopra, Sameer; Azhar, Raed A; Berger, Andre K; Metcalfe, Charles; Minetti, Michael; Carey, Joseph N; Ukimura, Osamu; Desai, Mihir; Gill, Inderbir S

    2015-10-01

    To develop a robotic technique for exclusively transabdominal control of the suprahepatic, infradiaphragmatic inferior vena cava (IVC) to enable level 3 IVC tumor thrombectomy. Robotic technique was developed in three fresh, perfused-model cadavers. Preoperatively, inflow (right jugular vein) and outflow (left femoral vein) cannulae were inserted and connected to a centrifugal pump to establish a 10 mmHg pressure in the IVC for the water-perfused cadaver model. Using a five-port transperitoneal robotic approach, the falciform ligament was detached from the anterior abdominal wall toward its junction with the diaphragm and tautly retracted caudally; this adequately retracted the liver caudally as well. Triangular and coronary ligaments were incised, allowing ready visualization of suprahepatic/infradiaphragmatic IVC and right/left main hepatic veins. Under direct robotic visualization, IVC was circumferentially mobilized, vessel-looped, and controlled. All three robotic procedures were successfully completed transabdominally. Average robotic time to control the suprahepatic IVC was 37 minutes; in each case, the suprahepatic IVC was circumferentially controlled with a vessel-loop. There were no intraoperative complications. Length of the mobilized suprahepatic IVC measured between 2 and 3 cm. Right and left suprahepatic veins were clearly visualized in each case. Necropsy revealed no intra-abdominal/intrathoracic visceral or vascular injuries to the suprahepatic IVC, bilateral hepatic veins, or tributaries. We developed a novel robotic technique for transabdominal control of the suprahepatic infradiaphragmatic IVC in a perfused human cadaver model. This approach may extend the application of advanced robotic techniques for the performance of major vena caval, hepatic, and level 3 IVC renal tumor thrombus surgery.

  18. Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction

    PubMed Central

    Song, Guixian; Gu, Weijuan; Chen, Minglong; Yang, Bing; Li, Dianfu; Wang, Daowu; Cao, Kejiang

    2013-01-01

    Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively). Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p = 0.04) but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p = 0.02). The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p = 0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model. PMID:23805264

  19. Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

    PubMed

    Li, Xiaorong; Zhang, Fengxiang; Song, Guixian; Gu, Weijuan; Chen, Minglong; Yang, Bing; Li, Dianfu; Wang, Daowu; Cao, Kejiang

    2013-01-01

    Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively). Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p = 0.04) but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p = 0.02). The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p = 0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model.

  20. Value or waste: Perfusion imaging following radiofrequency ablation - early experience.

    PubMed

    Thieme, Stefan F; Vahldiek, Janis L; Tummler, Katja; Poch, Franz; Gemeinhardt, Ole; Hiebl, Bernhard; Lehmann, Kai S; Hamm, B; Niehues, Stefan M

    2015-01-01

    Radiofrequency ablation (RFA) is an evolving technique in treatment of hepatic malignant tumors. By heating local tissue it leads to coagulative necrotic areas around the ablation probe. Temperature falls with increasing distance to the probe, risking incomplete necrosis at the margins of the RFA-induced lesion. Therefore, immediate non-invasive and precise detection of incomplete ablation is necessary for early enlargement of the ablation if needed. This in vivo pig study compares early experiences of immediate post-interventional computed tomography (CT) perfusion volume analysis to macroscopic and CT image evaluation in healthy pig liver. RFA was performed in vivo in healthy pig livers. Different CT perfusion algorithms (Maximum slope analysis and Patlak plot) were used to quantify three different perfusion parameters. Data points were acquired from rectangular grids. These grids were semiautomatically overlayed to macroscopic images documented after liver explantation. Each data point was visually assigned to zones defined as "inner" and "outer necrotic zone", "margin" or "vital tissue". Significant differences between necrotic zones and vital tissue are shown for equivalent blood volume (p <  0.0001), arterial flow (p <  0.01) and flow extraction product (p <  0.001). Looking at equivalent blood volume and flow extraction product, there were also significant differences (EquivBV: p <  0.0001, FE: p <  0.001) between margins, necrotic and vital areas. In a porcine model these early results could show that all of the used CT perfusion parameters allowed discrimination of necrosis from vital tissue after RFA at high levels of significance. In addition, the parameters EquivBV and FE that give an estimate of the tissue blood volume and the permeability, were able to precisely discern different zones also seen macroscopically. From this data CT perfusion analysis could be precise tool for measurement and visualization of ablated liver lesions and

  1. Relaxin as a protective substance in the preserving solution for liver transplantation: spectrophotometric in vivo imaging of local oxygen supply in an isolated perfused rat liver model.

    PubMed

    Boehnert, Markus U; Armbruster, Franz Paul; Hilbig, Heidegard

    2009-04-01

    Ischemia reperfusion injury (IRI) is a problem in organ transplantation. Relaxin is known to have a protective effect against liver injury caused by IRI. Using a model of isolated perfused rat liver, the local oxygen supply in liver tissue was investigated by spectrophotometric in vivo imaging and compared to the protective effect of relaxin shown by immunohistochemical measurement of myeloperoxidase and malonyldialdehyde activities as determinants of oxidative stress. In relaxin-treated liver tissue, spectrophotometry showed a better oxygen supply and decreased myeloperoxidase and malonyldialdehyde activities. Our data suggest that relaxin can influence the oxygen distribution in liver tissue and reduce cell damage caused by IRI.

  2. Optimization of energy window and evaluation of scatter compensation methods in myocardial perfusion SPECT using the ideal observer with and without model mismatch and an anthropomorphic model observer

    PubMed Central

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

    2015-01-01

    Abstract. We used the ideal observer (IO) and IO with model mismatch (IO-MM) applied in the projection domain and an anthropomorphic channelized Hotelling observer (CHO) applied to reconstructed images to optimize the acquisition energy window width and to evaluate various scatter compensation methods in the context of a myocardial perfusion single-photon emission computed tomography (SPECT) defect detection task. The IO has perfect knowledge of the image formation process and thus reflects the performance with perfect compensation for image-degrading factors. Thus, using the IO to optimize imaging systems could lead to suboptimal parameters compared with those optimized for humans interpreting SPECT images reconstructed with imperfect or no compensation. The IO-MM allows incorporating imperfect system models into the IO optimization process. We found that with near-perfect scatter compensation, the optimal energy window for the IO and CHO was similar; in its absence, the IO-MM gave a better prediction of the optimal energy window for the CHO using different scatter compensation methods. These data suggest that the IO-MM may be useful for projection-domain optimization when MM is significant and that the IO is useful when followed by reconstruction with good models of the image formation process. PMID:26029730

  3. A Note on Structural Equation Modeling Estimates of Reliability

    ERIC Educational Resources Information Center

    Yang, Yanyun; Green, Samuel B.

    2010-01-01

    Reliability can be estimated using structural equation modeling (SEM). Two potential problems with this approach are that estimates may be unstable with small sample sizes and biased with misspecified models. A Monte Carlo study was conducted to investigate the quality of SEM estimates of reliability by themselves and relative to coefficient…

  4. A Note on Structural Equation Modeling Estimates of Reliability

    ERIC Educational Resources Information Center

    Yang, Yanyun; Green, Samuel B.

    2010-01-01

    Reliability can be estimated using structural equation modeling (SEM). Two potential problems with this approach are that estimates may be unstable with small sample sizes and biased with misspecified models. A Monte Carlo study was conducted to investigate the quality of SEM estimates of reliability by themselves and relative to coefficient…

  5. The Mapping Model: A Cognitive Theory of Quantitative Estimation

    ERIC Educational Resources Information Center

    von Helversen, Bettina; Rieskamp, Jorg

    2008-01-01

    How do people make quantitative estimations, such as estimating a car's selling price? Traditionally, linear-regression-type models have been used to answer this question. These models assume that people weight and integrate all information available to estimate a criterion. The authors propose an alternative cognitive theory for quantitative…

  6. Parameter Estimates in Differential Equation Models for Chemical Kinetics

    ERIC Educational Resources Information Center

    Winkel, Brian

    2011-01-01

    We discuss the need for devoting time in differential equations courses to modelling and the completion of the modelling process with efforts to estimate the parameters in the models using data. We estimate the parameters present in several differential equation models of chemical reactions of order n, where n = 0, 1, 2, and apply more general…

  7. Parameter Estimates in Differential Equation Models for Chemical Kinetics

    ERIC Educational Resources Information Center

    Winkel, Brian

    2011-01-01

    We discuss the need for devoting time in differential equations courses to modelling and the completion of the modelling process with efforts to estimate the parameters in the models using data. We estimate the parameters present in several differential equation models of chemical reactions of order n, where n = 0, 1, 2, and apply more general…

  8. Radiation dose reduction in computed tomography perfusion using spatial-temporal Bayesian methods

    NASA Astrophysics Data System (ADS)

    Fang, Ruogu; Raj, Ashish; Chen, Tsuhan; Sanelli, Pina C.

    2012-03-01

    In current computed tomography (CT) examinations, the associated X-ray radiation dose is of significant concern to patients and operators, especially CT perfusion (CTP) imaging that has higher radiation dose due to its cine scanning technique. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) parameter as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and degrade CT perfusion maps greatly if no adequate noise control is applied during image reconstruction. To capture the essential dynamics of CT perfusion, a simple spatial-temporal Bayesian method that uses a piecewise parametric model of the residual function is used, and then the model parameters are estimated from a Bayesian formulation of prior smoothness constraints on perfusion parameters. From the fitted residual function, reliable CTP parameter maps are obtained from low dose CT data. The merit of this scheme exists in the combination of analytical piecewise residual function with Bayesian framework using a simpler prior spatial constrain for CT perfusion application. On a dataset of 22 patients, this dynamic spatial-temporal Bayesian model yielded an increase in signal-tonoise-ratio (SNR) of 78% and a decrease in mean-square-error (MSE) of 40% at low dose radiation of 43mA.

  9. Quantitative Perfusion Analysis of First-Pass Contrast Enhancement Kinetics: Application to MRI of Myocardial Perfusion in Coronary Artery Disease

    PubMed Central

    Shah, Binita; Storey, Pippa; Iqbal, Sohah; Slater, James; Axel, Leon

    2016-01-01

    Purpose Perfusion analysis from first-pass contrast enhancement kinetics requires modeling tissue contrast exchange. This study presents a new approach for numerical implementation of the tissue homogeneity model, incorporating flexible distance steps along the capillary (NTHf). Methods The proposed NTHf model considers contrast exchange in fluid packets flowing along the capillary, incorporating flexible distance steps, thus allowing more efficient and stable calculations of the transit of tracer through the tissue. We prospectively studied 8 patients (62 ± 13 years old) with suspected CAD, who underwent first-pass perfusion CMR imaging at rest and stress prior to angiography. Myocardial blood flow (MBF) and myocardial perfusion reserve index (MPRI) were estimated using both the NTHf and the conventional adiabatic approximation of the TH models. Coronary artery lesions detected at angiography were clinically assigned to one of three categories of stenosis severity (‘insignificant’, ‘mild to moderate’ and ‘severe’) and related to corresponding myocardial territories. Results The mean MBF (ml/g/min) at rest/stress and MPRI were 0.80 ± 0.33/1.25 ± 0.45 and 1.68 ± 0.54 in the insignificant regions, 0.74 ± 0.21/1.09 ± 0.28 and 1.54 ± 0.46 in the mild to moderate regions, and 0.79 ± 0.28/0.63 ± 0.34 and 0.85 ± 0.48 in the severe regions, respectively. The correlation coefficients of MBFs at rest/stress and MPRI between the NTHf and AATH models were r = 0.97/0.93 and r = 0.91, respectively. Conclusions The proposed NTHf model allows efficient quantitative analysis of the transit of tracer through tissue, particularly at higher flow. Results of initial application to MRI of myocardial perfusion in CAD are encouraging. PMID:27583385

  10. Approximately Integrable Linear Statistical Models in Non-Parametric Estimation

    DTIC Science & Technology

    1990-08-01

    OTIC I EL COPY Lfl 0n Cf) NAPPROXIMATELY INTEGRABLE LINEAR STATISTICAL MODELS IN NON- PARAMETRIC ESTIMATION by B. Ya. Levit University of Maryland...Integrable Linear Statistical Models in Non- Parametric Estimation B. Ya. Levit Sumnmary / The notion of approximately integrable linear statistical models...models related to the study of the "next" order optimality in non- parametric estimation . It appears consistent to keep the exposition at present at the

  11. Selective cerebral perfusion for cerebral protection: what we do know

    PubMed Central

    Tang, Gilbert H. L.

    2013-01-01

    Selective antegrade cerebral perfusion (SACP) for aortic arch surgery has evolved considerably since it was first reported. Various pressure rates have been investigated through animal models, as has the effect of warmer perfusate temperatures and hematocrit. Clinical research into pH management, the role of unilateral and bilateral perfusion, and core temperatures have further refined the procedure. We recommend the following protocol for SACP: perfusion pressure between 40-60 mmHg, flow rates between 6-10 mL/kg/min, and perfusate temperature of 20-28 °C; core cooling to 18-30 °C contingent on duration of arrest; alpha-stat pH management; hematocrit between 25-30%; near infrared spectroscopy to monitor cerebral perfusion; and bilateral perfusion when prolonged durations of SACP is anticipated. PMID:23977601

  12. Bounded Influence Propagation tau -Estimation: A New Robust Method for ARMA Model Estimation

    NASA Astrophysics Data System (ADS)

    Muma, Michael; Zoubir, Abdelhak M.

    2017-04-01

    A new robust and statistically efficient estimator for ARMA models called the bounded influence propagation (BIP) {\\tau}-estimator is proposed. The estimator incorporates an auxiliary model, which prevents the propagation of outliers. Strong consistency and asymptotic normality of the estimator for ARMA models that are driven by independently and identically distributed (iid) innovations with symmetric distributions are established. To analyze the infinitesimal effect of outliers on the estimator, the influence function is derived and computed explicitly for an AR(1) model with additive outliers. To obtain estimates for the AR(p) model, a robust Durbin-Levinson type and a forward-backward algorithm are proposed. An iterative algorithm to robustly obtain ARMA(p,q) parameter estimates is also presented. The problem of finding a robust initialization is addressed, which for orders p+q>2 is a non-trivial matter. Numerical experiments are conducted to compare the finite sample performance of the proposed estimator to existing robust methodologies for different types of outliers both in terms of average and of worst-case performance, as measured by the maximum bias curve. To