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.
Borges, João Batista; Suarez-Sipmann, Fernando; Bohm, Stephan H; Tusman, Gerardo; Melo, Alexandre; Maripuu, Enn; Sandström, Mattias; Park, Marcelo; Costa, Eduardo L V; Hedenstierna, Göran; Amato, Marcelo
2012-01-01
The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.
Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R; La Riviere, Patrick J; Alessio, Adam M
2014-04-01
Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This
NASA Astrophysics Data System (ADS)
Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R.; La Riviere, Patrick J.; Alessio, Adam M.
2014-04-01
Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)-1, cardiac output = 3, 5, 8 L min-1). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that
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
Tomographic digital subtraction angiography for lung perfusion estimation in rodents
Badea, Cristian T.; Hedlund, Laurence W.; De Lin, Ming; Boslego Mackel, Julie S.; Samei, Ehsan; Allan Johnson, G.
2007-05-15
In vivo measurements of perfusion present a challenge to existing small animal imaging techniques such as magnetic resonance microscopy, micro computed tomography, micro positron emission tomography, and microSPECT, due to combined requirements for high spatial and temporal resolution. We demonstrate the use of tomographic digital subtraction angiography (TDSA) for estimation of perfusion in small animals. TDSA augments conventional digital subtraction angiography (DSA) by providing three-dimensional spatial information using tomosynthesis algorithms. TDSA is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of {mu}L volumes of contrast at a series of different angles of rotation. The capabilities of TDSA are established in studies on lung perfusion in rats. Using an imaging system developed in-house, we acquired data for four-dimensional (4D) imaging with temporal resolution of 140 ms, in-plane spatial resolution of 100 {mu}m, and slice thickness on the order of millimeters. Based on a structured experimental approach, we optimized TDSA imaging providing a good trade-off between slice thickness, the number of injections, contrast to noise, and immunity to artifacts. Both DSA and TDSA images were used to create parametric maps of perfusion. TDSA imaging has potential application in a number of areas where functional perfusion measurements in 4D can provide valuable insight into animal models of disease and response to therapeutics.
Distributed perfusion educational model: a shift in perfusion economic realities.
Austin, Jon W; Evans, Edward L; Hoerr, Harry R
2005-12-01
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
Bayesian hemodynamic parameter estimation by bolus tracking perfusion weighted imaging.
Boutelier, Timothé; Kudo, Koshuke; Pautot, Fabrice; Sasaki, Makoto
2012-07-01
A delay-insensitive probabilistic method for estimating hemodynamic parameters, delays, theoretical residue functions, and concentration time curves by computed tomography (CT) and magnetic resonance (MR) perfusion weighted imaging is presented. Only a mild stationarity hypothesis is made beyond the standard perfusion model. New microvascular parameters with simple hemodynamic interpretation are naturally introduced. Simulations on standard digital phantoms show that the method outperforms the oscillating singular value decomposition (oSVD) method in terms of goodness-of-fit, linearity, statistical and systematic errors on all parameters, especially at low signal-to-noise ratios (SNRs). Delay is always estimated sharply with user-supplied resolution and is purely arterial, by contrast to oSVD time-to-maximum TMAX that is very noisy and biased by mean transit time (MTT), blood volume, and SNR. Residue functions and signals estimates do not suffer overfitting anymore. One CT acute stroke case confirms simulation results and highlights the ability of the method to reliably estimate MTT when SNR is low. Delays look promising for delineating the arterial occlusion territory and collateral circulation. PMID:22410325
Efficiency of U.S. Tissue Perfusion Estimators.
Kim, MinWoo; Abbey, Craig K; Insana, Michael F
2016-08-01
We measure the detection and discrimination efficiencies of conventional power-Doppler estimation of perfusion without contrast enhancement. The measurements are made in a phantom with known blood-mimicking fluid flow rates in the presence of clutter and noise. Efficiency is measured by comparing functions of the areas under the receiver operating characteristic curve for Doppler estimators with those of the ideal discriminator, for which we estimate the temporal covariance matrix from echo data. Principal-component analysis is examined as a technique for increasing the accuracy of covariance matrices estimated from echo data. We find that Doppler estimators are <50% efficient at directed perfusion detection between 0.1 and 2.0 mL/min per 2 cm(2) flow area. The efficiency was 20%-40% for the task of discriminating between two perfusion rates in the same range. We conclude that there are reasons to search for more efficient perfusion estimators, one that incorporates covariance matrix information that could significantly enhance the utility of Doppler ultrasound without contrast enhancement. PMID:27244733
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
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.
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.
Dillon, C R; Borasi, G; Payne, A
2016-01-21
For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one. PMID:26741344
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.
A fast nonlinear regression method for estimating permeability in CT perfusion imaging
Bennink, Edwin; Riordan, Alan J; Horsch, Alexander D; Dankbaar, Jan Willem; Velthuis, Birgitta K; de Jong, Hugo W
2013-01-01
Blood–brain barrier damage, which can be quantified by measuring vascular permeability, is a potential predictor for hemorrhagic transformation in acute ischemic stroke. Permeability is commonly estimated by applying Patlak analysis to computed tomography (CT) perfusion data, but this method lacks precision. Applying more elaborate kinetic models by means of nonlinear regression (NLR) may improve precision, but is more time consuming and therefore less appropriate in an acute stroke setting. We propose a simplified NLR method that may be faster and still precise enough for clinical use. The aim of this study is to evaluate the reliability of in total 12 variations of Patlak analysis and NLR methods, including the simplified NLR method. Confidence intervals for the permeability estimates were evaluated using simulated CT attenuation–time curves with realistic noise, and clinical data from 20 patients. Although fixating the blood volume improved Patlak analysis, the NLR methods yielded significantly more reliable estimates, but took up to 12 × longer to calculate. The simplified NLR method was ∼4 × faster than other NLR methods, while maintaining the same confidence intervals (CIs). In conclusion, the simplified NLR method is a new, reliable way to estimate permeability in stroke, fast enough for clinical application in an acute stroke setting. PMID:23881247
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.
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.
Estimation of bone perfusion as a function of intramedullary pressure in sheep
Rosenthal, M.S.; Lehner, C.E.; Pearson, D.W.; Kanikula, T.M.; Adler, G.G.; Venci, R.; Lanphier, E.H.; De Luca, P.M.
1985-05-01
It has been reported previously that following decompression (i.e. diving ascents) the intramedullary pressure (IMP) in bone can rise dramatically and possibly by the mechanism which can induce dysbaric osteonecrosis or the ''silent bends''. If the blood supply for the bone transverses the marrow compartment, than an increase in IMP could cause a temporary decrease in perfusion or hemostasis and hence ischemia leading to bone necrosis. To test this hypothesis, the authors measured the perfusion of bone in sheep as a function of IMP. The bone perfusion was estimated by measuring the perfusion-limited clearance of Ar-41 (E..gamma..=1293 keV, T/sub 1/2/=1.83 h) from the bone mineral matrix of sheep's tibia. The argon gas was formed in vivo by the fast neutron activation of Ca-44 to Ar-41 following the Ca-44(n,..cap alpha..) reaction. Clearance of Ar-41 was measured by time gated gamma-ray spectroscopy. These results indicate that an elevation of intramedullary pressure can decrease perfusion in bone and may cause bone necrosis.
Modeling of nanotherapeutics delivery based on tumor perfusion
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
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.
Simulation model for contrast agent dynamics in brain perfusion scans.
Bredno, Jörg; Olszewski, Mark E; Wintermark, Max
2010-07-01
Standardization efforts are currently under way to reduce the heterogeneity of quantitative brain perfusion methods. A brain perfusion simulation model is proposed to generate test data for an unbiased comparison of these methods. This model provides realistic simulated patient data and is independent of and different from any computational method. The flow of contrast agent solute and blood through cerebral vasculature with disease-specific configurations is simulated. Blood and contrast agent dynamics are modeled as a combination of convection and diffusion in tubular networks. A combination of a cerebral arterial model and a microvascular model provides arterial-input and time-concentration curves for a wide range of flow and perfusion statuses. The model is configured to represent an embolic stroke in one middle cerebral artery territory and provides physiologically plausible vascular dispersion operators for major arteries and tissue contrast agent retention functions. These curves are fit to simpler template curves to allow the use of the simulation results in multiple validation studies. A gamma-variate function with fit parameters is proposed as the vascular dispersion operator, and a combination of a boxcar and exponential decay function is proposed as the retention function. Such physiologically plausible operators should be used to create test data that better assess the strengths and the weaknesses of various analysis methods.
Cao Yue; Platt, Joel F.; Francis, Isaac R; Balter, James M.; Pan, Charlie; Normolle, Daniel; Ben-Josef, Edgar; Haken, Randall K. ten; Lawrence, Theodore S.
2007-02-15
We have shown that high dose conformal radiation combined with chemotherapy appears to prolong the survival of patients with unresectable intrahepatic cancers. The ability to safely deliver higher doses is primarily limited by the development of radiation-induced liver disease, characterized by venous occlusion. In this study, we investigated whether portal venous perfusion measured prior to the end of radiation therapy (RT) together with dose could predict liver venous perfusion dysfunction after treatment. Ten patients with unresectable intrahepatic cancer participated in an IRB-approved computer tomography (CT) perfusion study. Hepatic arterial and portal vein perfusion distributions were estimated by using dynamic contrast enhanced CT and the single compartmental model. Scans were obtained at four time points: prior to treatment, after 15 and 30 fractions of 1.5 Gy treatments, and one month following the completion of RT. Multivariant linear regression was used to determine covariances among the first three time point measurements plus dose for prediction of the post RT measurement. The reduction in the regional venous perfusion one month following RT was predicted by the local accumulated dose and the change in the regional venous perfusion after {approx}30 fractions (F=90.6,p<0.000 01). Each Gy produced an approximately 1.2% of reduction in the venous perfusion. This local dose and venous perfusion model has the potential to predict individual sensitivity to radiation. This is the first step toward developing a method to deliver higher and potentially more curative radiation doses to the patients who can safely receive these higher doses.
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.
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
Breakthroughs in computational modeling of cartilage regeneration in perfused bioreactors.
Raimondi, Manuela T; Causin, Paola; Mara, Andrea; Nava, Michele; Laganà, Matteo; Sacco, Riccardo
2011-12-01
We report about two specific breakthroughs, relevant to the mathematical modeling and numerical simulation of tissue growth in the context of cartilage tissue engineering in vitro. The proposed models are intended to form the building blocks of a bottom-up multiscale analysis of tissue growth, the idea being that a full microscale analysis of the construct, a 3-D partial differential equation (PDE) problem with internal moving boundaries, is computationally unaffordable. We propose to couple a PDE microscale model of a single functional tissue subunit with the information computed at the macroscale by 2-D-0-D models of reduced computational cost. Preliminary results demonstrate the effectiveness of the proposed models in describing the interplay among interstitial perfusion flow, nutrient delivery, and consumption and tissue growth in realistic scaffold geometries.
Uterine perfusion model for analyzing barriers to transport in fibroids.
Stirland, Darren L; Nichols, Joseph W; Jarboe, Elke; Adelman, Marisa; Dassel, Mark; Janát-Amsbury, Margit-Maria; Bae, You Han
2015-09-28
This project uses an ex vivo human perfusion model for studying transport in benign, fibrous tumors. The uterine arteries were cannulated to perfuse the organ with a buffer solution containing blood vessel stain and methylene blue to analyze intratumoral transport. Gross examination revealed tissue expansion effects and a visual lack of methylene blue in the fibroids. Some fibroids exhibited regions with partial methylene blue penetration into the tumor environment. Histological analysis comparing representative sections of fibroids and normal myometrium showed a smaller number of vessels with decreased diameters within the fibroid. Imaging of fluorescently stained vessels exposed a stark contrast between fluorescence within the myometrium and relatively little within the fibroid tissues. Imaging at higher magnification revealed that fibroid blood vessels were indeed perfused and stained with the lipophilic membrane dye; however, the vessels were only the size of small capillaries and the blood vessel coverage was only 12% that of the normal myometrium. The majority of sampled fibroids had a strong negative correlation (Pearson's r=-0.68 or beyond) between collagen and methylene blue staining. As methylene blue was able to passively diffuse into fibroid tissue, the true barrier to transport in these fibroids is likely high interstitial fluid pressure, correlating with high collagen content and solid stress observed in the fibroid tissue. Fibroids had an average elevated interstitial fluid pressure of 4mmHg compared to -1mmHg in normal myometrium. Our findings signify relationships between drug distribution in fibroids and between vasculature characteristics, collagen levels, and interstitial fluid pressure. Understanding these barriers to transport can lead to developments in drug delivery for the treatment of uterine fibroids and tumors of similar composition. PMID:26184049
Uterine perfusion model for analyzing barriers to transport in fibroids.
Stirland, Darren L; Nichols, Joseph W; Jarboe, Elke; Adelman, Marisa; Dassel, Mark; Janát-Amsbury, Margit-Maria; Bae, You Han
2015-09-28
This project uses an ex vivo human perfusion model for studying transport in benign, fibrous tumors. The uterine arteries were cannulated to perfuse the organ with a buffer solution containing blood vessel stain and methylene blue to analyze intratumoral transport. Gross examination revealed tissue expansion effects and a visual lack of methylene blue in the fibroids. Some fibroids exhibited regions with partial methylene blue penetration into the tumor environment. Histological analysis comparing representative sections of fibroids and normal myometrium showed a smaller number of vessels with decreased diameters within the fibroid. Imaging of fluorescently stained vessels exposed a stark contrast between fluorescence within the myometrium and relatively little within the fibroid tissues. Imaging at higher magnification revealed that fibroid blood vessels were indeed perfused and stained with the lipophilic membrane dye; however, the vessels were only the size of small capillaries and the blood vessel coverage was only 12% that of the normal myometrium. The majority of sampled fibroids had a strong negative correlation (Pearson's r=-0.68 or beyond) between collagen and methylene blue staining. As methylene blue was able to passively diffuse into fibroid tissue, the true barrier to transport in these fibroids is likely high interstitial fluid pressure, correlating with high collagen content and solid stress observed in the fibroid tissue. Fibroids had an average elevated interstitial fluid pressure of 4mmHg compared to -1mmHg in normal myometrium. Our findings signify relationships between drug distribution in fibroids and between vasculature characteristics, collagen levels, and interstitial fluid pressure. Understanding these barriers to transport can lead to developments in drug delivery for the treatment of uterine fibroids and tumors of similar composition.
Dynamic chest image analysis: model-based pulmonary perfusion analysis with pyramid images
NASA Astrophysics Data System (ADS)
Liang, Jianming; Haapanen, Arto; Jaervi, Timo; Kiuru, Aaro J.; Kormano, Martti; Svedstrom, Erkki; Virkki, Raimo
1998-07-01
The aim of the study 'Dynamic Chest Image Analysis' is to develop computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected at different phases of the respiratory/cardiac cycles in a short period of time. We have proposed a framework for ventilation study with an explicit ventilation model based on pyramid images. In this paper, we extend the framework to pulmonary perfusion study. A perfusion model and the truncated pyramid are introduced. The perfusion model aims at extracting accurate, geographic perfusion parameters, and the truncated pyramid helps in understanding perfusion at multiple resolutions and speeding up the convergence process in optimization. Three cases are included to illustrate the experimental results.
Development of an Ex Vivo, Beating Heart Model for CT Myocardial Perfusion
Pelgrim, Gert Jan; Das, Marco; Haberland, Ulrike; Slump, Cees; Handayani, Astri; van Tuijl, Sjoerd; Stijnen, Marco; Klotz, Ernst; Oudkerk, Matthijs; Wildberger, Joachim E.; Vliegenthart, Rozemarijn
2015-01-01
Objective. To test the feasibility of a CT-compatible, ex vivo, perfused porcine heart model for myocardial perfusion CT imaging. Methods. One porcine heart was perfused according to Langendorff. Dynamic perfusion scanning was performed with a second-generation dual source CT scanner. Circulatory parameters like blood flow, aortic pressure, and heart rate were monitored throughout the experiment. Stenosis was induced in the circumflex artery, controlled by a fractional flow reserve (FFR) pressure wire. CT-derived myocardial perfusion parameters were analysed at FFR of 1 to 0.10/0.0. Results. CT images did not show major artefacts due to interference of the model setup. The pacemaker-induced heart rhythm was generally stable at 70 beats per minute. During most of the experiment, blood flow was 0.9–1.0 L/min, and arterial pressure varied between 80 and 95 mm/Hg. Blood flow decreased and arterial pressure increased by approximately 10% after inducing a stenosis with FFR ≤ 0.50. Dynamic perfusion scanning was possible across the range of stenosis grades. Perfusion parameters of circumflex-perfused myocardial segments were affected at increasing stenosis grades. Conclusion. An adapted Langendorff porcine heart model is feasible in a CT environment. This model provides control over physiological parameters and may allow in-depth validation of quantitative CT perfusion techniques. PMID:26185756
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%.
Liu, J; Xu, L X
1999-09-01
A closed form analytical solution of the Pennes' bio-heat equation was obtained for temperature distributions in the skin tissue subject to the sinusoidal heat flux. Phase shifts in the surface temperature response were revealed to be related to local blood perfusion rate and heating frequency. The influence of the thermal contact resistance on the perfusion estimation was investigated. It has been proved that this influence is relatively small because of the phase shift based estimation and can be effectively eliminated by application of highly conductive grease. This analysis provides the theoretical foundation for a new noninvasive modality of blood perfusion estimation based on the surface temperature measurement which can have significant applications in future clinical practices.
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.
Whole Ovine Ovaries as a Model for Human: Perfusion with Cryoprotectants In Vivo and In Vitro
Isachenko, Vladimir; Rahimi, Gohar; Dattena, Maria; Mallmann, Peter; Baikoshkarova, Saltanat; Kellerwessel, Elisabeth; Otarbaev, Marat; Shalakhmetova, Tamara; Isachenko, Evgenia
2014-01-01
These experiments were performed to test the perfusion of ovine as a model for human ovaries by cryoprotectants in vivo at high temperature when the permeability of capillaries is high and when blood is insensibly replaced by the solution of cryoprotectants. By our hypothetical supposition, ovaries could be saturated by cryoprotectants before their surgical removal. The objective was to examine the effectiveness of perfusion of ovine ovaries with vascular pedicle in vivo and in vitro. Arteria ovarica was cannuled and ovaries were perfused by Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink in vivo and in vitro. In the first and second cycle of experiments, ovaries (n = 13 and n = 23) were perfused in vivo and in vitro, respectively, during 60 min with the rate of perfusion 50 mL/h (0.8 mL/min). It was established with in vivo perfusion that only about 10% of ovarian tissues were perfused due to an appearance of multiple anastomoses when the perfusion medium goes from arteria ovarica to arteria uterina without inflow into the ovaries. It was concluded that in vitro perfusion of ovine intact ovaries with vascular pedicle by freezing medium is more effective than this manipulation performed in vivo. PMID:24701576
Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice
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
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.
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
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
Volentine, G.D.; Ogden, K.A.; Tuma, D.J.; Sorrell, M.F.
1987-05-01
The authors have previously shown that acute administration of ethanol inhibits hepatic glycoprotein secretion in vivo. This ethanol-induced effect appears to be mediated by its reactive metabolite, acetaldehyde. Since hormonal influences and vascular changes can not be controlled in vivo during ethanol administration, they investigated the effect of ethanol in the isolated perfused liver model. Rat liver from fed animals was perfused with oxygenated KRB at 3 ml/min/g liver for 4 hrs. Since ethanol inhibits proteins synthesis in vitro, protein acceptor pool size was equalized in both ethanol and control perfused livers with 1 mM cycloheximide. /sup 3/H-glucosamine was used to label hepatic secretory glycoproteins in the perfusate. Colchicine, a known inhibitor of protein secretion, impaired the secretion of labeled glycoproteins with a concomitant retention of these export proteins in the liver; therefore, confirming the authors secretory model. Ethanol (50 mM) inhibited the appearance of glucosamine-labeled glycoproteins by 60% into the perfusate as compared to control livers. Pretreatment of animals with cyanamide (an aldehyde dehydrogenase inhibitor) further potentiated this effect of ethanol in the isolated perfused liver. These data suggest that ethanol inhibits hepatic glycoprotein secretion in the isolated liver perfusion model, and this ethanol-induced impairment appears to be mediated by acetaldehyde.
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
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
Marval, Paul D; Perrin, Mandy E; Hancock, Sally M; Mahajan, Ravi P
2005-03-01
The zero flow pressure (ZFP) is the pressure at which blood flow ceases through a vascular bed. Using transcranial Doppler ultrasonography, we investigated the effects of propofol or sevoflurane on the estimated cerebral perfusion pressure (eCPP) and ZFP in the cerebral circulation. Twenty-three healthy patients undergoing nonneurosurgical procedures under general anesthesia were studied. After induction of anesthesia using propofol, the anesthesia was maintained with either propofol infusion (n = 13) or sevoflurane (n = 10). Middle cerebral artery flow velocity, noninvasive arterial blood pressure, and end-tidal carbon dioxide partial pressure were recorded awake as a baseline, and during steady-state anesthesia at normocapnia (baseline end-tidal carbon dioxide partial pressure) and hypocapnia (1 kPa below baseline). The eCPP and ZFP were calculated using an established formula. The mean arterial blood pressure decreased in both groups. The eCPP decreased significantly in the propofol group (median, from 58 to 41 mm Hg) but not in the sevoflurane group (from 60 to 62 mm Hg). Correspondingly, ZFP increased significantly in the propofol group (from 25 to 33 mm Hg) and it decreased significantly in the sevoflurane group (from 27 to 7 mm Hg). Hypocapnia did not change eCPP or ZFP in the propofol group, but it significantly decreased eCPP and increased ZFP in the sevoflurane group. PMID:15728076
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.
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.
A microfluidically perfused three dimensional human liver model.
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.
Nakanishi, Wataru; Imura, Takehiro; Inagaki, Akiko; Nakamura, Yasuhiro; Sekiguchi, Satoshi; Fujimori, Keisei; Satomi, Susumu; Goto, Masafumi
2012-01-01
Several studies have reported that pancreatic ductal preservation greatly improved the islet yield and function after cold storage. However, these studies were devoid of appropriate controls, such as vascular perfusion, which is routinely performed to preserve organs in the clinical setting. In this study, we created a vascular perfusion model using inbred rats, and investigated the effect of ductal injection on the islet yield and function after cold storage. Rat pancreases after 10 h cold ischemia were classified as follows: without ductal/vascular perfusion; with ductal injection; with vascular perfusion; and with ductal/vascular perfusion. The islet yield, function, viability, release of inflammatory mediators, and pathological changes in the exocrine tissues were assessed in the Hanks' Balanced Salt Solution (HBSS) model. The islet yield was also assesed by introducing University of Wisconsin Solution (UWS) and Histidine-Tryptophan-Ketoglutarate solution (HTK), which are the standard clinical preservation solutions. In the HBSS model, ductal injection and vascular perfusion significantly improved the islet yield compared with the control group. However, ductal injection showed no additional effects on the islet yield, function, viability and suppressing the release of inflammatory mediators when vascular perfusion was performed. Although ductal injection significantly decreased the apoptosis of exocrine cells, no beneficial effect on vacuolation was observed. In contrast, vascular perfusion significantly suppressed vacuolation in the exocrine tissues. Likewise, in the UWS and HTK model, ductal injection and vascular perfusion improved the islet yield compared with the control group. Nevertheless, the combination group showed no additional effects. These data suggest that ductal injection has no additional effect on islet yield and function after cold storage in a vascular perfusion model. We propose that ductal injection can be an effective and simple
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
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
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.
Preliminary Study of Open Quotient in an Ex-Vivo Perfused Human Larynx Model
Mendelsohn, Abie H.; Zhang, Zhaoyan; Luegmair, Georg; Orestes, Michael; Berke, Gerald S.
2016-01-01
Importance Scientific understanding human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. Due to its invasive nature, direct experimentation of human voice production has previously not been possible. The feasibility of an ex-vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. Objective In this study, the relationship between adductor muscle group stimulation and the open quotient (OQ) of vocal fold vibration was investigated using an ex-vivo perfused human larynx. Design Human perfused tissue study. Setting Physiology Laboratory. Participants Human larynx is recovered from research-consented organ donors within two hours of cardiac death. Interventions, Main Outcomes and Measures Perfusion with donated human blood is re-established shortly after cardiac death. Human perfused phonation is achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. The phonation resulting from the graded states of neuromuscular stimulations are evaluated through high-speed vibratory imaging. OQ is derived through digital kymography and glottal area waveform analysis. Results Under constant glottal flow, step-wise increase in adductor muscle group stimulation decreased OQ. Quantitatively, OQ values reached a lower limit of 0.42. Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. Conclusions and Relevance For the first time in a neuromuscularly activated human larynx, a negative relationship between adductor muscle group stimulation and phonatory OQ was demonstrated. Further experience with the ex-vivo perfused human phonatory model will work to systematically define this causal relationship. PMID:26181642
A Phantom Tissue System for the Calibration of Perfusion Measurements
Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Scott, Elaine P.; Diller, Thomas E.
2008-01-01
A convenient method for testing and calibrating surface perfusion sensors has been developed. A phantom tissue model is used to simulate the nondirectional blood flow of tissue perfusion. A computational fluid dynamics (CFD) model was constructed in Fluent® to design the phantom tissue and validate the experimental results. The phantom perfusion system was used with a perfusion sensor based on clearance of thermal energy. A heat flux gage measures the heat flux response of tissue when a thermal event (convective cooling) is applied. The blood perfusion and contact resistance are estimated by a parameter estimation code. From the experimental and analytical results, it was concluded that the probe displayed good measurement repeatability and sensitivity. The experimental perfusion measurements in the tissue were in good agreement with those of the CFD models and demonstrated the value of the phantom tissue system. PMID:19045509
Optical modeling toward optimizing monitoring of intestinal perfusion in trauma patients
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.
A proposed study on the transplacental transport of parabens in the human placental perfusion model.
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.
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.
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.
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
Cookson, A.N.; Lee, J.; Michler, C.; Chabiniok, R.; Hyde, E.; Nordsletten, D.; Smith, N.P.
2014-01-01
Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters
Model-based estimation with boundary side information or boundary regularization
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.
Model-based estimation for dynamic cardiac studies using ECT
Chiao, P.C.; Rogers, W.L.; Clinthorne, N.H.; Fessler, J.A.; Hero, A.O. . Div. of Nuclear Medicine)
1994-06-01
In this paper, the authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (Emission Computed Tomography). The authors construct an observation model to relate parameters of interest to the projection data and to account for limited ECT system resolution and measurement noise. The authors then use a maximum likelihood (ML) estimator to jointly estimate all the parameters directly from the projection data without reconstruction of intermediate images. The authors also simulate myocardial perfusion studies based on a simplified heart model to evaluate the performance of the model-based joint ML estimator and compare this performance to the Cramer-Rao lower bound. Finally, model assumptions and potential uses of the joint estimation strategy are discussed.
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.
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
Protective effect of active perfusion in porcine models of acute myocardial ischemia.
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
Protective effect of active perfusion in porcine models of acute myocardial ischemia
Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui
2016-01-01
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 in maintaining myocardial perfusion and alleviating
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.
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.
Chung, Wen Yuan; Gravante, Gianpiero; Al-Leswas, Dhya; Arshad, Ali; Sorge, Roberto; Watson, Chris C; Pollard, Cristina; Metcalfe, Matthew S; Dennison, Ashley R
2013-05-01
We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments. PMID:23489088
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.
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
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
Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.
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.
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.
Chung, Wen Yuan; Gravante, Gianpiero; Eltweri, Amar; Sorge, Roberto; Ong, Seok Ling; Pollard, Cristina; Metcalfe, Mathew; Dennison, Ashley
2015-06-01
The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu.
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
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.
Noninvasive Blood Perfusion Measurements of an Isolated Rat Liver and an Anesthetized Rat Kidney
Mudaliar, Ashvinikumar V.; Ellis, Brent E.; Ricketts, Patricia L.; Lanz, Otto I.; Lee, Charles Y.; Diller, Thomas E.; Scott, Elaine P.
2008-01-01
A simple, cost effective, and noninvasive blood perfusion system is tested in animal models. The system uses a small sensor to measure the heat transfer response to a thermal event (convective cooling) imposed on the tissue surface. Heat flux data are compared with a mathematical model of the tissue to estimate both blood perfusion and thermal contact resistance between the tissue and the probe. The perfusion system was evaluated for repeatability and sensitivity using isolated rat liver and exposed rat kidney tests. Perfusion in the isolated liver tests was varied by controlling the flow of the perfusate into the liver, and the perfusion in the exposed kidney tests was varied by temporarily occluding blood flow through the renal artery and vein. The perfusion estimated by the convective perfusion probe was in good agreement with that of the metered flow of the perfusate into the liver model. The liver tests indicated that the probe can be used to detect small changes in perfusion (0.005 ml/ml/s). The probe qualitatively tracked the changes in the perfusion in the kidney model due to occlusion of the renal artery and vein. PMID:19045542
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
Noninvasive methods of measuring bone blood perfusion
Dyke, J.P.; Aaron, R.K.
2010-01-01
Measurement of bone blood flow and perfusion characteristics in a noninvasive and serial manner would be advantageous in assessing revascularization after trauma and the possible risk of avascular necrosis. Many disease states, including osteoporosis, osteoarthritis, and bone neoplasms, result in disturbed bone perfusion. A causal link between bone perfusion and remodeling has shown its importance in sustained healing and regrowth following injury. Measurement of perfusion and permeability within the bone was performed with small and macromolecular contrast media, using dynamic contrast-enhanced magnetic resonance imaging in models of osteoarthritis and the femoral head. Bone blood flow and remodeling was estimated using 18F-Fluoride positron emission tomography in fracture healing and osteoarthritis. Multimodality assessment of bone blood flow, permeability, and remodeling by using noninvasive imaging techniques may provide information essential in monitoring subsequent rates of healing and response to treatment as well as identifying candidates for additional therapeutic or surgical interventions. PMID:20392223
NASA Astrophysics Data System (ADS)
Miyazaki, Shohei; Yamazaki, Youichi; Murase, Kenya
2008-11-01
We performed an error analysis of the quantification of liver perfusion from dynamic contrast-enhanced computed tomography (DCE-CT) data using a dual-input single-compartment model for various disease severities, based on computer simulations. In the simulations, the time-density curves (TDCs) in the liver were generated from an actually measured arterial input function using a theoretical equation describing the kinetic behavior of the contrast agent (CA) in the liver. The rate constants for the transfer of CA from the hepatic artery to the liver (K1a), from the portal vein to the liver (K1p), and from the liver to the plasma (k2) were estimated from simulated TDCs with various plasma volumes (V0s). To investigate the effect of the shapes of input functions, the original arterial and portal-venous input functions were stretched in the time direction by factors of 2, 3 and 4 (stretching factors). The above parameters were estimated with the linear least-squares (LLSQ) and nonlinear least-squares (NLSQ) methods, and the root mean square errors (RMSEs) between the true and estimated values were calculated. Sensitivity and identifiability analyses were also performed. The RMSE of V0 was the smallest, followed by those of K1a, k2 and K1p in an increasing order. The RMSEs of K1a, K1p and k2 increased with increasing V0, while that of V0 tended to decrease. The stretching factor also affected parameter estimation in both methods. The LLSQ method estimated the above parameters faster and with smaller variations than the NLSQ method. Sensitivity analysis showed that the magnitude of the sensitivity function of V0 was the greatest, followed by those of K1a, K1p and k2 in a decreasing order, while the variance of V0 obtained from the covariance matrices was the smallest, followed by those of K1a, K1p and k2 in an increasing order. The magnitude of the sensitivity function and the variance increased and decreased, respectively, with increasing disease severity and decreased
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.
de Brauw, L M; van de Velde, C J; Tjaden, U R; de Bruijn, E A; Bell, A V; Hermans, J; Zwaveling, A
1988-02-01
An in vivo method of isolated rat liver perfusion was developed with true vascular isolation and recirculating perfusate. This new surgical technique to temporarily isolate the liver vascularly, and the perfusion procedure are described in depth. Twelve inbred WAG/RIJ rats were subjected to 25 min of normothermic liver perfusion without chemotherapy, and all rats survived the procedure. Hepatic functional and histological integrity were not significantly altered during perfusion. To determine the role of isolated liver perfusion (ILP) as a means of improved targeting of antitumor agents, 5-fluorouracil (5-FU) concentrations were monitored in hepatic tumor and liver tissues and in systemic plasma using high-performance liquid chromatography. Fifty-one rats with hepatic tumors of colonic origin were randomly assigned to one of three dosage groups (20, 40, or 80 mg/kg) receiving 5-FU by ILP, hepatic artery infusion (HAI), or jugular vein infusion (JVI). ILP resulted in significantly increased 5-FU concentrations in liver tissue. However, no significant differences were found in tumor tissue concentrations of 5-FU between the three treatment modalities. 5-FU concentrations in tumor tissue increased as a function of the dose with ILP, HAI, and JVI. ILP was associated with the lowest systemic drug concentrations. The low systemic 5-FU concentrations with ILP suggest a higher maximum tolerable dose. This mode of treatment deserves to be studied further in our model before conclusions can be drawn regarding its therapeutic potential. PMID:3339874
Niccoli-Asabella, Artor; Ferlan, Giovanni; Crovace, Antonio; Notaristefano, Antonio; Rubini, Domenico; Altini, Corinna; Pisani, Antonio; Rubini, Giuseppe
2012-01-01
Autologous bone marrow stromal cells (BMSC) implant after swine experimental myocardial infarct (MI) was investigated by serial technetium-99m ((99m)Tc)-tetrofosmin gated single photon emission tomography (G-SPET) and compared with immuno-histochemical findings. The aim was to evaluate if intramyocardial BMSC implant produces any prolonged effect in the left ventricle (LV) perfusion and function. Eleven pigs underwent left anterior descending artery (LAD) ligature; in seven of them BMSC were injected in the border zone of the MI, while in the remaining four saline solution was injected at the same site. After LAD ligature G-SPET scans at 48h and at 5 and 10 weeks (w) after the implant were performed. Uptake defect size and LV function analysis were performed comparing 48h to 5w and 10w studies. Statistical evaluation was performed with Friedman test and unpaired Wilcoxon test. The comparison between a progressive reduction of Perfusion Image Score was observed from 48h to 5w and to 10w in the treated group (Friedman test: χ²= 13.56; P=0.01). No variation was observed in the control group (Friedman test: χ²=3; P= 0.223). Comparison of the absolute variation (Δ) between treated and control group resulted significant (Wilcoxon test W=10; P=0.007). Similar positive results were also observed for the relative extension of the uptake defect, wall motion and LVEF analysis. Histological data of our swine model demonstrated that autologous BMSC implanted in the damaged myocardium area had survived and differentiated into cells with typical features of myocardiocytes. Gated SPET is a reliable tool to evaluate prolonged positive effects of autologous BMSC implant in swine experimental MI model. In conclusion, autologous BMSC implanted can improve perfusion, induce cell regeneration, reduce wall motion abnormalities and prevent severe LV dysfunction in swines.
Use of perfusion bioreactors and large animal models for long bone tissue engineering.
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.
Jonas, Jost B.; Wang, Ningli; Nangia, Vinay
2015-01-01
Purpose: To test the hypothesis that taking translamina pressure difference into consideration changes associations between ocular perfusion pressure and glaucomatous optic neuropathy. Methods: The population-based Central India Eye and Medical Study included 4711 subjects. Ocular perfusion pressure was calculated as follows: ⅔ [diastolic blood pressure + ⅓ × (systolic blood pressure – diastolic blood pressure)] – IOP. Cerebrospinal fluid pressure (mm Hg) was estimated as follows: 0.44 body mass index (kg/m2) + 0.16 diastolic blood pressure (mm Hg) − 0.18 × age (years) − 1.91. Translamina pressure difference was IOP minus cerebrospinal fluid pressure. Results: In multivariate analysis, higher open-angle glaucoma prevalence was associaed with higher IOP (P<.001; odds ratio [OR], 1.19; 95% CI, 1.15, 1.24) or with higher translamina pressure difference (P<.001; OR, 1.15; 95% CI, 1.10, 1.19), but not with ocular perfusion pressure (P<.37). A smaller neuroretinal rim area was correlated with higher IOP (P<.001; standardized coefficient beta −0.09) or larger translamina pressure difference (P<.001; β −0.10), but not with ocular perfusion pressure (P=.26). Greater prevalence of angle-closure glaucoma was associated with higher IOP (P<.001; OR, 1.22; 95% CI, 1.15, 1.28) or higher translamina pressure difference (P<.001; OR, 1.19; 95% CI, 1.13, 1.25) or lower ocular perfusion pressure (P<.04; OR, 0.95; 95% CI, 0.90, 0.996). Correlation coefficients were highest for the association with IOP and lowest for ocular perfusion pressure. A smaller rim area was correlated with higher IOP (P<.001; beta −0.08) and higher translamina pressure difference (P<.001; beta −0.08); rim area and ocular perfusion pressure were not significantly associated (P=.25). Conclusions: The present study provides information on the relationship of translamina pressure difference to the development of optic nerve damage in what is presently called glaucoma. It does not provide
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.
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
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
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.
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.
Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers.
Grosse-Siestrup, Christian; Unger, Volker; Pfeffer, Jeanette; Dinh, Q Thai; Nagel, Stefan; Springer, Jochen; Witt, Christian; Wussow, Anke; Groneberg, David A
2004-12-01
Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. Polidocanol was administered via the hepatic artery and portal vein and the effects of the sclerosant on organ function parameters were compared with those in an untreated control group. In contrast to the untreated control organs, significant differences were found in the polidocanol group for parameters such as alanine aminotransferase or organ weight after perfusion. The most striking differences were found for hepatic bile flow, which dropped in the polidocanol group to 0.24+/-0.02 ml/min per 1000 g after administration of the compound compared with 3.80+/-1.08 ml/min per 1000 g in the control group. In summary, the present observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians should be aware of this problem and the use of polidocanol for intrahepatic sclerosing should be restricted to specialized centers.
Modeling of landslide volume estimation
NASA Astrophysics Data System (ADS)
Amirahmadi, Abolghasem; Pourhashemi, Sima; Karami, Mokhtar; Akbari, Elahe
2016-06-01
Mass displacement of materials such as landslide is considered among problematic phenomena in Baqi Basin located at southern slopes of Binaloud, Iran; since, it destroys agricultural lands and pastures and also increases deposits at the basin exit. Therefore, it is necessary to identify areas which are sensitive to landslide and estimate the significant volume. In the present study, in order to estimate the volume of landslide, information about depth and area of slides was collected; then, considering regression assumptions, a power regression model was given which was compared with 17 suggested models in various regions in different countries. The results showed that values of estimated mass obtained from the suggested model were consistent with observed data (P value= 0.000 and R = 0.692) and some of the existing relations which implies on efficiency of the suggested model. Also, relations that were created in small-area landslides were more suitable rather than the ones created in large-area landslides for using in Baqi Basin. According to the suggested relation, average depth value of landslides was estimated 3.314 meters in Baqi Basin which was close to the observed value, 4.609 m.
2013-01-01
Background The first crucial step in transplantation appears to be the effective rinsing of the graft during organ procurement. Even though there is strong suspicion that ex situ perfusion results in better rinsing of the graft, there is no proof for this hypothesis. The aim of this study was to analyse the differences of in situ and ex situ kidney perfusion in a porcine model. Methods Standardised multiorgan procurement was performed in 15 German landrace pigs. Perfusion was carried out using histidine–tryptophan–ketoglutarate solution (HTK) under the application of pressure. In one kidney, in situ perfusion via the aorta was carried out while the second kidney received ex situ perfusion via the renal artery (RA). Perfusate flow inside the aorta and the RA was recorded at different pressure steps. In order to visualise the effect on the microcirculation, different coloured microparticles (MPs; 10 μm) were administered via the aorta or RA. Subsequently, frozen sections of the explanted kidneys were analysed histologically and MPs were evaluated quantitatively. Results Ex situ kidney perfusion resulted in significantly improved flow rates (P<0.0001) compared with in situ perfusion. By applying ex situ perfusion it was even possible to attain physiological flow levels on the RA under the application of external pressure of 150 to 200 mmHg. The amount of MPs was able to highlight the positive impact of ex situ perfusion on microcirculation of the kidney graft (P<0.0001). Conclusions The use of MPs represents a valuable tool for quantitative investigation and illustration of kidney perfusion in experimental setups. Additional ex situ perfusion is able to improve the quality of kidney perfusion. PMID:23837545
Cardiac and coronary function in the Langendorff-perfused mouse heart model.
Reichelt, Melissa E; Willems, Laura; Hack, Benjamin A; Peart, Jason N; Headrick, John P
2009-01-01
The Langendorff mouse heart model is widely employed in studies of myocardial function and responses to injury (e.g. ischaemia). Nonetheless, marked variability exists in its preparation and functional properties. We examined the impact of early growth (8, 16, 20 and 24 weeks), sex, perfusion fluid [Ca(2+)] and pacing rate on contractile function and responses to 20 min ischaemia followed by 45 min reperfusion. We also assessed the impact of strain, and tested the utility of the model in studying coronary function. Under normoxic conditions, hearts from 8-week-old male C57BL/6 mice (2 mm free perfusate [Ca(2+)], 420 beats min(-1)) exhibited 145 +/- 2 mmHg left ventricular developed pressure (LVDP). Force development declined by approximately 15% (126 +/- 5 mmHg) with a reduction in free [Ca(2+)] to 1.35 mm, and by 25% (108 +/- 3 mmHg) with increased pacing to 600 beats min(-1). While elevated heart rate failed to modify ischaemic outcome, the lower [Ca(2+)] significantly improved contractile recovery (by >30%). We detected minimal sex-dependent differences in normoxic function between 8 and 24 weeks, although age modified contractile function in males (increased LVDP at 24 versus 8 weeks) but not females. Both male and female hearts exhibited age-related reductions in ischaemic tolerance, with a significant decline in recovery evident at 16 weeks in males and later, at 20-24 weeks, in females (versus recoveries in hearts at 8 weeks). Strain also modified tolerance to ischaemia, with similar responses in hearts from C57BL/6, 129/sv, Quackenbush Swiss and FVBN mice, but substantially greater tolerance in BALB/c hearts. In terms of vascular function, baseline coronary flow (20-25 ml min(-1) g(-1)) was 50-60% of maximally dilated flows, and coronary reactive and functional hyperaemic responses were pronounced (up to 4-fold elevations in flow in hearts lacking ventricular balloons). These data indicate that attention to age (and sex) of mice will reduce variability in
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.
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
HIFU Therapy Compared with Other Thermal Ablation Methods in a Perfused Organ Model
NASA Astrophysics Data System (ADS)
Jenne, Jürgen W.; Risse, Frank; Häcker, Axel; Peters, Kristina; Siegler, Peter; Divkovic, Gabriela Wilzbach; Huber, Peter E.
2007-05-01
Therapy with high intensity focused ultrasound (HIFU) has been shown to be both safe and clinically practical in a growing number of patient studies for a variety of different target organs. Especially in cancer therapy there are comparable ablation methods like radio frequency (RFA) or laser (LITT) ablation, which are clinically more accepted. In an ongoing study we compare HIFU with RF- and laser ablation under MRI guidance in a perfused organ model. All evaluated techniques were appropriate to induce defined and localized ablation necrosis in the renal cortex. Our HIFU system and the laser system were completely MRI compatible. The tested RF- system showed local needle artefacts and disturbed the MR images during operation. The ablation rate of HIFU using a spot scanning technique was clearly lower compared to the other ablation techniques. However, advanced HIFU scanning methods might overcome this limitation. In addition HIFU is the only complete non-invasive ablation technique.
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
Yoda, Shunichi; Nakanishi, Kanae; Tano, Ayako; Hori, Yusuke; Hayase, Misa; Mineki, Takashi; Suzuki, Yasuyuki; Matsumoto, Naoya; Hirayama, Atsushi
2016-07-27
We published a cardiac event risk score (CERS) predicting the risk of major cardiac events (MCEs) within 3 years. The purpose of this study was to verify the prognostic value of the CERS before and after treatment in Japanese patients with coronary artery disease.We retrospectively investigated 612 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2013 and who had a significant stenosis with ≥ 75% narrowing of the arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia with the SPECT. The patients underwent treatment including revascularization and medication, and thereafter, were re-evaluated with SPECT during a chronic phase and followed-up to confirm prognosis for ≥ 1 year. The endpoint was the onset of MCEs during the follow-up.During the follow-up (36.7 ± 14.5 months), 50 patients (8.7%) experienced MCEs comprising cardiac death (n = 16), non-fatal myocardial infarction (n = 4), and unstable angina pectoris (n = 30). The multivariate Cox proportional hazards regression model analysis for the actual occurrence of MCEs showed the summed difference score % and MCE risks estimated with the CERS after treatment to be significant independent variables. Ischemic reduction after treatment contributed significantly to a decrease in the MCE risks. The MCE risks estimated with the CERS after treatment were generally consistent with the incidence of the MCEs actually observed.The CERS after treatment is a valuable formula for predicting prognosis in Japanese patients with coronary artery disease. PMID:27357436
Lofthouse, E. M.; Perazzolo, S.; Brooks, S.; Crocker, I. P.; Glazier, J. D.; Johnstone, E. D.; Panitchob, N.; Sibley, C. P.; Widdows, K. L.; Sengers, B. G.
2015-01-01
Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer. PMID:26676251
Tissue-specific sparse deconvolution for brain CT perfusion.
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. PMID:26055434
Tissue-specific sparse deconvolution for brain CT perfusion.
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.
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
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
Sawyer, R T; Horst, M N; Garner, R E; Hudson, J; Jenkins, P R; Richardson, A L
1990-09-01
The adherence of Candida albicans was studied in situ by using the perfused mouse liver model. After exhaustive washing, 10(6) C. albicans were infused into mouse livers. At the time of recovery, 62 +/- 5% (mean +/- standard error of the mean) of the infused C. albicans were recovered from the liver and 14 +/- 3% were recovered from the effluent for a total recovery of 76 +/- 4%. This indicates that 86 +/- 3% of the original inoculum was trapped by the liver and that 24 +/- 4% was killed within the liver. Chemical pretreatment of C. albicans with 8 M urea, 12 mM dithiothreitol, 2% beta-mercaptoethanol, 1% sodium dodecyl sulfate, 10% Triton X-100, or 3 M potassium chloride or enzyme pretreatment with alpha-mannosidase, alpha-chymotrypsin, subtilisin, beta-N-acetyl-glucosaminidase, pronase, trypsin, papain, or lipase did not alter adherence of C. albicans to hepatic tissue. By contrast, pepsin pretreatment significantly decreased hepatic trapping. Simultaneous perfusion with either 100 mg of C. albicans glycoprotein per liter or 100 mg of C. albicans mannan per liter also decreased trapping. Furthermore, both substances eluted previously trapped C. albicans from hepatic tissue. Chemical pretreatment with 8 M urea, 12 mM dithiothreitol, or 3 M KCI or enzymatic pretreatment with alpha-mannosidase, subtilisin, alpha-chymotrypsin, or papain increased killing of C. albicans three- to fivefold within hepatic tissue. The data suggest that mannose-containing structures on the surface of C. albicans, for example. mannans or glucomannoproteins, mediate adherence of C. albicans within the liver. Indirectly, chemical and enzymatic pretreatment renders C. albicans more susceptible to hepatic killing.
Postpartum Vascular Dysfunction in the Reduced Uteroplacental Perfusion Model of Preeclampsia
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
2014-01-01
Background Exact drug dosing in isolated limb perfusion (ILP) and infusion (ILI) is essential. We developed and evaluated a model for calculating the volume of extremities and compared this model with body weight- and height-dependent parameters. Methods The extremity was modeled by a row of coupled truncated cones. The sizes of the truncated cone bases were derived from the circumference measurements of the extremity at predefined levels (5 cm). The resulting volumes were added. This extremity volume model was correlated to the computed tomography (CT) volume data of the extremity (total limb volume). The extremity volume was also correlated with the patient’s body weight, body mass index (BMI) and ideal body weight (IBW). The no-fat CT limb volume was correlated with the circumference-measured limb volume corrected by the ideal-body-weight to actual-body-weight ratio (IBW corrected-limb-volume). Results The correlation between the CT volume and the volume measured by the circumference was high and significant. There was no correlation between the limb volume and the bare body weight, BMI or IBW. The correlation between the no-fat CT volume and IBW-corrected limb volume was high and significant. Conclusions An appropriate drug dosing in ILP can be achieved by combining the limb volume with the simple circumference measurements and the IBW to body-weight ratio. PMID:24684972
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...
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
Novel Perfused Compression Bioreactor System as an in vitro Model to Investigate Fracture Healing
Hoffmann, Waldemar; Feliciano, Sandra; Martin, Ivan; de Wild, Michael; Wendt, David
2015-01-01
Secondary bone fracture healing is a physiological process that leads to functional tissue regeneration via endochondral bone formation. In vivo studies have demonstrated that early mobilization and the application of mechanical loads enhances the process of fracture healing. However, the influence of specific mechanical stimuli and particular effects during specific phases of fracture healing remain to be elucidated. In this work, we have developed and provided proof-of-concept of an in vitro human organotypic model of physiological loading of a cartilage callus, based on a novel perfused compression bioreactor (PCB) system. We then used the fracture callus model to investigate the regulatory role of dynamic mechanical loading. Our findings provide a proof-of-principle that dynamic mechanical loading applied by the PCB can enhance the maturation process of mesenchymal stromal cells toward late hypertrophic chondrocytes and the mineralization of the deposited extracellular matrix. The PCB provides a promising tool to study fracture healing and for the in vitro assessment of alternative fracture treatments based on engineered tissue grafts or pharmaceutical compounds, allowing for the reduction of animal experiments. PMID:25699254
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.
Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.
Boyle, Erin C; Dombrowsky, Heike; Sarau, Jürgen; Braun, Janin; Aepfelbacher, Martin; Lautenschläger, Ingmar; Grassl, Guntram A
2016-01-15
Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine. PMID:26564721
Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.
Boyle, Erin C; Dombrowsky, Heike; Sarau, Jürgen; Braun, Janin; Aepfelbacher, Martin; Lautenschläger, Ingmar; Grassl, Guntram A
2016-01-15
Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine.
Fast nonlinear regression method for CT brain perfusion analysis.
Bennink, Edwin; Oosterbroek, Jaap; Kudo, Kohsuke; Viergever, Max A; Velthuis, Birgitta K; de Jong, Hugo W A M
2016-04-01
Although computed tomography (CT) perfusion (CTP) imaging enables rapid diagnosis and prognosis of ischemic stroke, current CTP analysis methods have several shortcomings. We propose a fast nonlinear regression method with a box-shaped model (boxNLR) that has important advantages over the current state-of-the-art method, block-circulant singular value decomposition (bSVD). These advantages include improved robustness to attenuation curve truncation, extensibility, and unified estimation of perfusion parameters. The method is compared with bSVD and with a commercial SVD-based method. The three methods were quantitatively evaluated by means of a digital perfusion phantom, described by Kudo et al. and qualitatively with the aid of 50 clinical CTP scans. All three methods yielded high Pearson correlation coefficients ([Formula: see text]) with the ground truth in the phantom. The boxNLR perfusion maps of the clinical scans showed higher correlation with bSVD than the perfusion maps from the commercial method. Furthermore, it was shown that boxNLR estimates are robust to noise, truncation, and tracer delay. The proposed method provides a fast and reliable way of estimating perfusion parameters from CTP scans. This suggests it could be a viable alternative to current commercial and academic methods. PMID:27413770
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.
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
Bouet, G; Cruel, M; Laurent, C; Vico, L; Malaval, L; Marchat, D
2015-01-01
An engineered three dimensional (3D) in vitro cell culture system was designed with the goal of inducing and controlling in vitro osteogenesis in a reproducible manner under conditions more similar to the in vivo bone microenvironment than traditional two-dimensional (2D) models. This bioreactor allows efficient mechanical loading and perfusion of an original cubic calcium phosphate bioceramic of highly controlled composition and structure. This bioceramic comprises an internal portion containing homogeneously interconnected macropores surrounded by a dense layer, which minimises fluid flow bypass around the scaffold. This dense and flat layer permits the application of a homogeneous loading on the bioceramic while also enhancing its mechanical strength. Numerical modelling of constraints shows that the system provides direct mechanical stimulation of cells within the scaffold. Experimental results establish that under perfusion at a steady flow of 2 µL/min, corresponding to 3 ≤ Medium velocity ≤ 23 µm/s, mouse calvarial cells grow and differentiate as osteoblasts in a reproducible manner, and lay down a mineralised matrix. Moreover, cells respond to mechanical loading by increasing C-fos expression, which demonstrates the effective mechanical stimulation of the culture within the scaffold. In summary, we provide a "proof-of-concept" for osteoblastic cell culture in a controlled 3D culture system under perfusion and mechanical loading. This model will be a tool to analyse bone cell functions in vivo, and will provide a bench testing system for the clinical assessment of bioactive bone-targeting molecules under load.
Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging
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
Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging
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
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.
Pham, Martin; Kale, Aydemir; Marquez, Yvette; Winer, Jesse; Lee, Brian; Harris, Brianna; Minnetti, Michael; Carey, Joseph; Giannotta, Steven; Zada, Gabriel
2014-10-01
Objective To create and develop a reproducible and realistic training environment to prepare residents and trainees for arterial catastrophes during endoscopic endonasal surgery. Design An artificial blood substitute was perfused at systolic blood pressures in eight fresh human cadavers to mimic intraoperative scenarios. Setting The USC Keck School of Medicine Fresh Tissue Dissection Laboratory was used as the training site. Participants Trainees were USC neurosurgery residents and junior faculty. Main Outcome A 5-point questionnaire was used to assess pre- and posttraining confidence scores. Results High-pressure extravasation at normal arterial blood pressure mimicked real intraoperative internal carotid artery (ICA) injury. Residents developed psychomotor skills required to achieve hemostasis using suction, cottonoids, and muscle grafts. Questionnaire responses from all trainees reported a realistic experience enhanced by the addition of the perfusion model. Conclusions The addition of an arterial perfusion system to fresh tissue cadavers is among the most realistic training models available. This enables the simulation of rare intraoperative scenarios such as ICA injury. Strategies for rapid hemostasis and implementation of techniques including endoscope manipulation, suction, and packing can all be rehearsed via this novel paradigm. PMID:25301092
Kaufman, Christopher L.; Baetiong, Alvin; Radhakrishnan, Jeejabai
2016-01-01
Background Several characteristics of the ventricular fibrillation (VF) waveform have been found predictive of successful defibrillation and hypothesized to reflect the myocardial energy state. In an open-chest swine model of VF, we modeled “average CPR” using extracorporeal circulation (ECC) and assessed the time course of coronary blood flow, myocardial metabolism, and myocardial structure in relation to the amplitude spectral area (AMSA) of the VF waveform without artifacts related to chest compression. Methods VF was induced and left untreated for 8 minutes in 16 swine. ECC was then started adjusting its flow to maintain a coronary perfusion pressure of 10 mmHg for 10 minutes. AMSA was calculated in the frequency domain and analyzed continuously with a 2.1 s timeframe and a Tukey window that moved ahead every 0.5 s. Results AMSA progressively declined during untreated VF. With ECC, AMSA increased from 7.0 ± 1.9 mV·Hz (at minute 8) to 12.8 ± 3.3 mV·Hz (at minute 14) (p < 0.05) without subsequent increase and showing a modest correlation with coronary blood flow of borderline statistical significance (r = 0.489, p = 0.0547). Myocardial energy measurements showed marked reduction in phosphocreatine and moderate reduction in ATP with increases in ADP, AMP, and adenosine along with myocardial lactate, all indicative of ischemia. Yet, ischemia did not resolve during ECC despite a coronary blood flow of ~ 30% of baseline. Conclusion AMSA increased upon return of coronary blood flow during ECC. However, the maximal level was reached after ~ 6 minutes without further change. The significance of the findings for determining the optimal timing for delivering an electrical shock during resuscitation from VF remains to be further explored. PMID:27536996
Glutamate and hypoxia as a stress model for the isolated perfused vertebrate retina.
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
Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...
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.
Zarinabad, Niloufar; Chiribiri, Amedeo; Hautvast, Gilion L T F; Ishida, Masaki; Schuster, Andreas; Cvetkovic, Zoran; Batchelor, Philip G; Nagel, Eike
2012-12-01
The purpose of this study is to enable high spatial resolution voxel-wise quantitative analysis of myocardial perfusion in dynamic contrast-enhanced cardiovascular MR, in particular by finding the most favorable quantification algorithm in this context. Four deconvolution algorithms--Fermi function modeling, deconvolution using B-spline basis, deconvolution using exponential basis, and autoregressive moving average modeling--were tested to calculate voxel-wise perfusion estimates. The algorithms were developed on synthetic data and validated against a true gold-standard using a hardware perfusion phantom. The accuracy of each method was assessed for different levels of spatial averaging and perfusion rate. Finally, voxel-wise analysis was used to generate high resolution perfusion maps on real data acquired from five patients with suspected coronary artery disease and two healthy volunteers. On both synthetic and perfusion phantom data, the B-spline method had the highest error in estimation of myocardial blood flow. The autoregressive moving average modeling and exponential methods gave accurate estimates of myocardial blood flow. The Fermi model was the most robust method to noise. Both simulations and maps in the patients and hardware phantom showed that voxel-wise quantification of myocardium perfusion is feasible and can be used to detect abnormal regions.
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.
2012-01-01
Background Machine perfusion (MP) of kidney graft provides benefits against preservation injury, however decreased graft quality requires optimization of the method. We examined the chronic benefits of MP on kidney grafts and the potential improvements provided by IGL-1 solution. Method We used an established autotransplantation pig kidney model to study the effects of MP against the deleterious effects of warm ischemia (WI: 60 minutes) followed by 22 hours of cold ischemia in MP or static cold storage (CS) followed by autotransplantation. MPS and IGL-1 solutions were compared. Results Animal survival was higher in MPS-MP and both IGL groups. Creatinine measurement did not discriminate between the groups, however MPS-MP and both IGL groups showed decreased proteinuria. Chronic fibrosis level was equivalent between the groups. RTqPCR and immunohistofluorescent evaluation showed that MP and IGL-1 provided some protection against epithelial to mesenchymal transition and chronic lesions. IGL-1 was protective with both MP and CS, particularly against chronic inflammation, with only small differences between the groups. Conclusion IGL-1 used in either machine or static preservation offers similar levels of protection than standard MP. The compatibility of IGL-1 with both machine perfusion and static storage could represent an advantage for clinical teams when choosing the correct solution to use for multi-organ collection. The path towards improving machine perfusion, and organ quality, may involve the optimization of the solution and the correct use of colloids. PMID:23171422
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.
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. PMID:24771348
Eichten, Alexandra; Adler, Alexander P; Cooper, Blerta; Griffith, Jennifer; Wei, Yi; Yancopoulos, George D; Lin, Hsin Chieh; Thurston, Gavin
2013-04-01
Vascular endothelial growth factor (VEGF) is a key upstream mediator of tumor angiogenesis, and blockade of VEGF can inhibit tumor angiogenesis and decrease tumor growth. However, not all tumors respond well to anti-VEGF therapy. Despite much effort, identification of early response biomarkers that correlate with long-term efficacy of anti-VEGF therapy has been difficult. These difficulties arise in part because the functional effects of VEGF inhibition on tumor vessels are still unclear. We therefore assessed rapid molecular, morphologic and functional vascular responses following treatment with aflibercept (also known as VEGF Trap or ziv-aflibercept in the United States) in preclinical tumor models with a range of responses to anti-VEGF therapy, including Colo205 human colorectal carcinoma (highly sensitive), C6 rat glioblastoma (moderately sensitive), and HT1080 human fibrosarcoma (resistant), and correlated these changes to long-term tumor growth inhibition. We found that an overall decrease in tumor vessel perfusion, assessed by dynamic contrast-enhanced ultrasound (DCE-US), and increases in tumor hypoxia correlated well with long-term tumor growth inhibition, whereas changes in vascular gene expression and microvessel density did not. Our findings support previous clinical studies showing that decreased tumor perfusion after anti-VEGF therapy (measured by DCE-US) correlated with response. Thus, measuring tumor perfusion changes shortly after treatment with VEGF inhibitors, or possibly other anti-angiogenic therapies, may be useful to predict treatment efficacy. PMID:23238831
Sawyer, R T; Garner, R E; Hudson, J A
1992-01-01
The isolated perfused mouse liver model was used to study the effect of Arg-Gly-Asp (RGD)-containing peptides on hepatic trapping and killing of Candida albicans. After extensive washing, 10(6) C. albicans CFU were infused into mouse livers. At the time of recovery, 63% +/- 2% (mean +/- standard error of the mean) of the infused C. albicans CFU were recovered from the liver and 14% +/- 1% were recovered from the effluent for a total recovery of 77% +/- 2%. This indicates that 86% +/- 9% of the original inoculum was trapped by the liver and that 23% +/- 2% was killed within the liver. Prior to their infusion into livers, 10(7) CFU of C. albicans were incubated at 37 degrees C for 30 min in the presence of various RGD peptides (0.1 mg/ml). Repeatedly, more than 90% of the infused RGD-treated C. albicans was trapped by the perfused liver. In comparison with the 23% killing rate observed in control livers, perfused livers killed approximately 40 to 50% of the infused C. albicans treated either with fibronectin, PepTite 2000, RGD, or RGDS. Hepatic killing of C. albicans treated with PepTite 2000 or fibronectin was dose dependent. Treatment of C. albicans with GRGDTP, GRGDSP, GRADSP, or GRGESP did not alter the ability of the perfused liver to kill C. albicans, suggesting that a degree of specificity for RGD peptides is associated with an increased ability of liver to kill RGD-treated C. albicans. Together, the data suggest that RGD peptides bind to a receptor on the surface of C. albicans, thereby increasing hepatic, and presumably Kupffer cell, killing of C. albicans. Natural or synthetic RGD peptides may serve as opsonins promoting C. albicans killing by Kupffer cells.
Identification and Estimation of Hedonic Models
ERIC Educational Resources Information Center
Ekeland, Ivar; Heckman, James J.; Nesheim, Lars
2004-01-01
This paper considers the identification and estimation of hedonic models. We establish that in an additive version of the hedonic model, technology and preferences are generically nonparametrically identified from data on demand and supply in a single hedonic market. The empirical literature that claims that hedonic models estimated on data from a…
Estimating recharge rates with analytic element models and parameter estimation
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).
Outlier robust nonlinear mixed model estimation.
Williams, James D; Birch, Jeffrey B; Abdel-Salam, Abdel-Salam G
2015-04-15
In standard analyses of data well-modeled by a nonlinear mixed model, an aberrant observation, either within a cluster, or an entire cluster itself, can greatly distort parameter estimates and subsequent standard errors. Consequently, inferences about the parameters are misleading. This paper proposes an outlier robust method based on linearization to estimate fixed effects parameters and variance components in the nonlinear mixed model. An example is given using the four-parameter logistic model and bioassay data, comparing the robust parameter estimates with the nonrobust estimates given by SAS(®).
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.
Saad, S; Hewett, K; Greenman, J
2012-03-01
An in vitro matrix biofilm perfusion model of tongue-derived microcosms for studying volatile sulfur compound (VSC) biogenesis has been previously described. The model was modified in order to monitor H(2)S in situ by use of a specialized electrode assembly based on microbial fuel cell technology. This system was designed to give real-time measurements expressed as electrode power output, which were proportional to H(2)S levels, measured by other means. In addition to the model modifications, the aim of this study was to demonstrate the biofilm responses following single or multiple exposure to biocidal, biostatic or VSC-inhibiting active compounds used in products. Tongue-derived biofilms (n = 6 per experiment) were perfused with one-fifth strength BHI at 20 ml h(-1) pH 7.2 and pulsed with putative treatment agent, placebo and controls including Zn(2+) ions and chlorhexidine (CHX). Compared with their pre-treatment conditions, all biofilms responded to the treatments in terms of reductions in hydrogen sulfide generation (as detected by the biofilm-electrode response) and other microbial volatile organic compounds (VOCs) as detected using a selected ion flow tube mass spectrometry analyser. The microbiological analysis of the treated and control biofilms show that test products (formulations with active agents) all gave reduced cell populations compared to the control biofilm. An order of effects (magnitude and duration) suggests that both the test agent and CHX produced the strongest reductions, distinct from the responses obtained for the placebo and water controls, which were largely similar. It is concluded that the in vitro perfusion model may be used to replicate many of the activities and reactions believed to be occurring by the tongue biofilm microflora within a real mouth, including H(2)S and VOC biogenesis and their inhibition by exposure to active agents.
Cypel, Marcelo; Keshavjee, Shaf
2012-01-01
Isolated lung perfusion (ILP) has been historically used as a method to study basic lung physiologic concepts using animal models. More recently, ILP has been applied in lung transplantation and thoracic oncology. In lung transplantation, ILP has been used to assess physiological integrity of donor lungs after the organ is removed from the donor. This procedure is called Ex vivo Lung Perfusion (EVLP), and it has also been proposed as a method for active treatment and repair of injured unsuitable donor organs ex vivo. In oncology, ILP is an attractive method to deliver high dose chemotherapy to treat pulmonary metastatic disease. Since the lung vasculature is isolated in vivo, this technique is called in vivo lung perfusion (IVLP). This review will focus on the rationale, technical aspects, experimental and clinical experience of EVLP and IVLP. A perspective on the future use of these techniques is described. PMID:22202033
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.
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).
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.
Schuster, Andreas; Sinclair, Matthew; Zarinabad, Niloufar; Ishida, Masaki; van den Wijngaard, Jeroen P.H.M.; Paul, Matthias; van Horssen, Pepijn; Hussain, Shazia T.; Perera, Divaka; Schaeffter, Tobias; Spaan, Jos A.E.; Siebes, Maria; Nagel, Eike; Chiribiri, Amedeo
2015-01-01
Aims To assess the feasibility of high-resolution quantitative cardiovascular magnetic resonance (CMR) voxel-wise perfusion imaging using clinical 1.5 and 3 T sequences and to validate it using fluorescently labelled microspheres in combination with a state of the art imaging cryomicrotome in a novel, isolated blood-perfused MR-compatible free beating pig heart model without respiratory motion. Methods and results MR perfusion imaging was performed in pig hearts at 1.5 (n = 4) and 3 T (n = 4). Images were acquired at physiological flow (‘rest’), reduced flow (‘ischaemia’), and during adenosine-induced hyperaemia (‘stress’) in control and coronary occlusion conditions. Fluorescently labelled microspheres and known coronary myocardial blood flow represented the reference standards for quantitative perfusion validation. For the comparison with microspheres, the LV was divided into 48 segments based on a subdivision of the 16 AHA segments into subendocardial, midmyocardial, and subepicardial subsegments. Perfusion quantification of the time-signal intensity curves was performed using a Fermi function deconvolution. High-resolution quantitative voxel-wise perfusion assessment was able to distinguish between occluded and remote myocardium (P < 0.001) and between rest, ischaemia, and stress perfusion conditions at 1.5 T (P < 0.001) and at 3 T (P < 0.001). CMR-MBF estimates correlated well with the microspheres at the AHA segmental level at 1.5 T (r = 0.94, P < 0.001) and at 3 T (r = 0.96, P < 0.001) and at the subendocardial, midmyocardial, and subepicardial level at 1.5 T (r = 0.93, r = 0.9, r = 0.88, P < 0.001, respectively) and at 3 T (r = 0.91, r = 0.95, r = 0.84, P < 0.001, respectively). Conclusion CMR-derived voxel-wise quantitative blood flow assessment is feasible and very accurate compared with microspheres. This technique is suitable for both clinically used field strengths and may provide the tools to assess extent and severity of myocardial
Improved diagnostic model for estimating wind energy
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.
Variance estimation for nucleotide substitution models.
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.
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.
Bradford, B U; Marotto, M; Lemasters, J J; Thurman, R G
1986-01-01
Models were developed to study zone-specific damage in periportal and pericentral regions of the liver lobule due to hypoxia produced in the perfused liver by ischemia, nitrogen or perfusion with low flow followed by reflow. Damage was assessed by lactate dehydrogenase release and trypan blue uptake in specific regions. Perfusion for up to 120 min under the conditions employed in all models failed to damage liver from well fed rats. In contrast, perfusion of livers from fasted rats for 30 min with N2-saturated buffer produced dye uptake of 37% and 66% in periportal and pericentral regions, respectively. Damage tended to be greater in this model when calcium was omitted from the perfusate (69% and 88% staining of periportal and pericentral regions, respectively). Release of lactate dehydrogenase correlated well with the percentage of cells stained with dye. In livers from fasted rats, 90 min of low flow (ca. 1 ml/g/min) followed by 30 min of reflow at normal flow rates (ca. 4 ml/g/min) produced damage exclusively to pericental regions of the liver lobule. On the average, about 40% of hepatocytes were stained with the dye under these conditions. Sixty minutes of ischemia followed by 13 min of reflow produced damage in 12% of periportal and 32% of pericentral regions of the liver lobule. When perfusion was in the retrograde direction (60 min low flow, 30 min reflow), periportal areas were damaged but pericentral regions were spared. Thus, models have been developed to study zone-specific damage due to hypoxia in the perfused liver. The data indicate that nutritional status is an important determinant of damage to hepatocytes due to hypoxia.
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
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.
Parameter Estimation of Partial Differential Equation Models.
Xun, Xiaolei; Cao, Jiguo; Mallick, Bani; Carroll, Raymond J; Maity, Arnab
2013-01-01
Partial differential equation (PDE) models are commonly used to model complex dynamic systems in applied sciences such as biology and finance. The forms of these PDE models are usually proposed by experts based on their prior knowledge and understanding of the dynamic system. Parameters in PDE models often have interesting scientific interpretations, but their values are often unknown, and need to be estimated from the measurements of the dynamic system in the present of measurement errors. Most PDEs used in practice have no analytic solutions, and can only be solved with numerical methods. Currently, methods for estimating PDE parameters require repeatedly solving PDEs numerically under thousands of candidate parameter values, and thus the computational load is high. In this article, we propose two methods to estimate parameters in PDE models: a parameter cascading method and a Bayesian approach. In both methods, the underlying dynamic process modeled with the PDE model is represented via basis function expansion. For the parameter cascading method, we develop two nested levels of optimization to estimate the PDE parameters. For the Bayesian method, we develop a joint model for data and the PDE, and develop a novel hierarchical model allowing us to employ Markov chain Monte Carlo (MCMC) techniques to make posterior inference. Simulation studies show that the Bayesian method and parameter cascading method are comparable, and both outperform other available methods in terms of estimation accuracy. The two methods are demonstrated by estimating parameters in a PDE model from LIDAR data. PMID:24363476
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
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
Karki, Kishor; Hugo, Geoffrey D.; Ford, John C.; Olsen, Kathryn M.; Saraiya, Siddharth; Groves, Robert; Weiss, Elisabeth
2015-01-01
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 1.5T 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/µm2, 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/µm2 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/µm2 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/µm2 were significantly different from the ADCIVIM values. From Rician noise simulation using b-value pairs, there was a wide range of
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
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.
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.
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
Estimation of Cerebral Blood Flow From Dynamic Susceptibility Contrast MRI Using A Tissue Model
NASA Astrophysics Data System (ADS)
Shimony, Joshua S.; Lee, John J.; Bretthorst, G. Larry
2005-11-01
Cerebral perfusion measurements are of great clinical and research interest. Positron emission tomography (PET) is considered the gold standard for cerebral perfusion measurement, but is not widely available and entails exposure of the subject to radioactivity. Dynamic susceptibility contrast (DSC) MRI methods are becoming more widely available on the newest generation of MRI scanners. The standard analysis methods of this data have significant disadvantages that include the use of a single, difficult to measure, arterial input function for the entire brain and the need to perform a numerical deconvolution on the logarithm of noisy data. These methods are not yet fully validated and remain qualitative in nature. Using a modification of the standard tracer kinetic principles we implemented a tissue perfusion model that has several advantages over standard methods. The model parameters were estimated using Bayes probability theory in a group of patients with varying degrees of hemodynamic impairment and were found to provide additional physiologic information that was not available using standard techniques.
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 (ADC_{IVIM}) 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 ADC_{IVIM} 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: ADC_{IVIM}, 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 ADC_{IVIM}(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 ADC_{IVIM}, 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 ADC_{IVIM} was 23.3%. Conclusion: ADC values of two 3 b-value sets
Model feedback in Bayesian propensity score estimation.
Zigler, Corwin M; Watts, Krista; Yeh, Robert W; Wang, Yun; Coull, Brent A; Dominici, Francesca
2013-03-01
Methods based on the propensity score comprise one set of valuable tools for comparative effectiveness research and for estimating causal effects more generally. These methods typically consist of two distinct stages: (1) a propensity score stage where a model is fit to predict the propensity to receive treatment (the propensity score), and (2) an outcome stage where responses are compared in treated and untreated units having similar values of the estimated propensity score. Traditional techniques conduct estimation in these two stages separately; estimates from the first stage are treated as fixed and known for use in the second stage. Bayesian methods have natural appeal in these settings because separate likelihoods for the two stages can be combined into a single joint likelihood, with estimation of the two stages carried out simultaneously. One key feature of joint estimation in this context is "feedback" between the outcome stage and the propensity score stage, meaning that quantities in a model for the outcome contribute information to posterior distributions of quantities in the model for the propensity score. We provide a rigorous assessment of Bayesian propensity score estimation to show that model feedback can produce poor estimates of causal effects absent strategies that augment propensity score adjustment with adjustment for individual covariates. We illustrate this phenomenon with a simulation study and with a comparative effectiveness investigation of carotid artery stenting versus carotid endarterectomy among 123,286 Medicare beneficiaries hospitlized for stroke in 2006 and 2007. PMID:23379793
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.
Roofed grooves: Rapid layer engineering of perfusion channels in collagen tissue models
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
USE OF A PROGRAMMABLE CALCULATOR IN CARDIOPULMONARY PERFUSION
Mills, J. David; Tallent, Jerome H.
1978-01-01
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. PMID:15216068
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.
Tuzun, Egemen; Chorpenning, Katherine; Liu, Maxine Qun; Bonugli, Katherine; Tamez, Dan; Lenox, Mark; Miller, Matthew W; Fossum, Theresa W
2014-01-01
The effects of the continuous-flow output on renal and intestinal microcirculation have not been extensively studied. To address this, the Heartware HVAD pump loaded with continuous and intermittent reduced speed (IRS) modes was implanted in four sheep and then operated at low and high speeds to mimic partial and complete unloading of the left ventricle. Then microsphere and positron emission tomography/computed tomography (PET/CT) studies were used to assess renal and intestinal tissue perfusion at various pump speeds and flow modes as compared with baseline (pump off). Arterial and venous oxygen (T02) and carbon dioxide (TCO2) contents were measured to assess changes in intestinal metabolism. Renal and intestinal regional blood flows did not produce any significant changes compared with baseline values in either continuous or IRS modes and speeds. The venous TO2 and TCO2 significantly increased in continuous and IRS modes and speeds compared with baseline. Our data suggested that renal and intestinal tissue perfusions were not adversely affected by continuous and IRS modes either in partial or complete unloading. Intestinal venous hyperoxia and increased TCO2 may be the evidence of intestinal arteriovenous shunting along with increased intestinal tissue metabolism. Longer-term studies are warranted in chronic heart failure models.
Joint estimation of multiple graphical models
Guo, Jian; Levina, Elizaveta; Michailidis, George; Zhu, Ji
2011-01-01
Summary Gaussian graphical models explore dependence relationships between random variables, through the estimation of the corresponding inverse covariance matrices. In this paper we develop an estimator for such models appropriate for data from several graphical models that share the same variables and some of the dependence structure. In this setting, estimating a single graphical model would mask the underlying heterogeneity, while estimating separate models for each category does not take advantage of the common structure. We propose a method that jointly estimates the graphical models corresponding to the different categories present in the data, aiming to preserve the common structure, while allowing for differences between the categories. This is achieved through a hierarchical penalty that targets the removal of common zeros in the inverse covariance matrices across categories. We establish the asymptotic consistency and sparsity of the proposed estimator in the high-dimensional case, and illustrate its performance on a number of simulated networks. An application to learning semantic connections between terms from webpages collected from computer science departments is included. PMID:23049124
Does machine perfusion decrease ischemia reperfusion injury?
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.
Metzger, Anja; Rees, Jennifer; Kwon, Young; Matsuura, Timothy; McKnite, Scott; Lurie, Keith G
2015-08-01
Brain injury is a leading cause of death and disability in children and adults in their most productive years. Use of intrathoracic pressure regulation (IPR) to generate negative intrathoracic pressure during the expiratory phase of positive pressure ventilation improves mean arterial pressure and 24-h survival in porcine models of hemorrhagic shock and cardiac arrest and has been demonstrated to decrease intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these models. Application of IPR for 240 min in a porcine model of intracranial hypertension (ICH) will increase CPP when compared with controls. Twenty-three female pigs were subjected to focal brain injury by insertion of an epidural Foley catheter inflated with 3 mL of saline. Animals were randomized to treatment for 240 min with IPR set to a negative expiratory phase pressure of -12 cmH2O or no IPR therapy. Intracranial pressure, mean arterial pressure, CPP, and cerebral blood flow (CBF) were evaluated. Intrathoracic pressure regulation significantly improved mean CPP and CBF. Specifically, mean CPP after 90, 120, 180, and 240 min of IPR use was 43.7 ± 2.8 mmHg, 44.0 ± 2.7 mmHg, 44.5 ± 2.8 mmHg, and 43.1 ± 1.9 mmHg, respectively; a significant increase from ICH study baseline (39.5 ± 1.7 mmHg) compared with control animals in which mean CPP was 36.7 ± 1.4 mmHg (ICH study baseline) and then 35.9 ± 2.1 mmHg, 33.7 ± 2.8 mmHg, 33.9 ± 3.0 mmHg, and 36.0 ± 2.7 mmHg at 90, 120, 180, and 240 min, respectively (P < 0.05 for all time points). Cerebral blood flow, as measured by an invasive CBF probe, increased in the IPR group (34 ± 4 mL/100 g-min to 49 ± 7 mL/100 g-min at 90 min) but not in controls (27 ± 1 mL/100 g-min to 25 ± 5 mL/100 g-min at 90 min) (P = 0.01). Arterial pH remained unchanged during the entire period of IPR compared with baseline values and control values. In this anesthetized pig model of ICH, treatment with IPR significantly improved CPP and CBF. This therapy may be
Ricken, T; Werner, D; Holzhütter, H G; König, M; Dahmen, U; Dirsch, O
2015-06-01
This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending hydro-diffusion-advection-reaction description. We consider a solid-phase (tissue) containing glycogen and a fluid-phase (blood) containing glucose as well as lactate. The five-component model is enhanced by a two-scale approach including a macroscale (sinusoidal level) and a microscale (cell level). The perfusion on the macroscale within the lobules is described by a homogenized multiphasic approach based on the theory of porous media (mixture theory combined with the concept of volume fraction). On macro level, we recall the basic mixture model, the governing equations as well as the constitutive framework including the solid (tissue) stress, blood pressure and solutes chemical potential. In view of the transport phenomena, we discuss the blood flow including transverse isotropic permeability, as well as the transport of solute concentrations including diffusion and advection. The continuum multicomponent model on the macroscale finally leads to a coupled system of partial differential equations (PDE). In contrast, the hepatic metabolism on the microscale (cell level) was modeled via a coupled system of ordinary differential equations (ODE). Again, we recall the constitutive relations for cell metabolism level. A finite element implementation of this framework is used to provide an illustrative example, describing the spatial and time-depending perfusion-metabolism processes in liver lobules that integrates perfusion and metabolism of the liver.
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
Adaptive Estimation with Partially Overlapping Models
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
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.
EXPOSURE RELATED DOSE ESTIMATING MODEL (ERDEM)
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...
Causal Indicator Models: Identification, Estimation, and Testing
ERIC Educational Resources Information Center
Bollen, Kenneth A.; Davis, Walter R.
2009-01-01
We discuss the identification, estimation, and testing of structural equation models that have causal indicators. We first provide 2 rules of identification that are particularly helpful in models with causal indicators--the 2C emitted paths rule and the exogenous X rule. We demonstrate how these rules can help us distinguish identified from…
Estimating solar radiation for plant simulation models
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.
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
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.
Dombrowsky, Heike; Zitta, Karina; Bein, Berthold; Krause, Thorsten; Goldmann, Torsten; Frerichs, Inez; Steinfath, Markus; Weiler, Norbert; Albrecht, Martin
2015-01-01
Background The application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine. Methods An isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups. Results Compared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces. Conclusion A vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small
Challenges for non-invasive brain perfusion quantification using arterial spin labeling.
Sousa, I; Santos, N; Sanches, J; Figueiredo, P
2011-03-29
Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed.
Challenges for non-invasive brain perfusion quantification using arterial spin labeling.
Sousa, I; Santos, N; Sanches, J; Figueiredo, P
2011-03-29
Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed. PMID:24059574
Kernel bandwidth estimation for nonparametric modeling.
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.
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.
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
Lee, Taek-Soo; Frey, Eric C; Tsui, Benjamin M W
2015-04-01
This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of (99m)Tc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman's rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the
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.
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
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
Estimation and uncertainty of reversible Markov models.
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. PMID:26547152
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.
Microfluidic perfusion culture.
Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki
2014-01-01
Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion culture system is convenient technique to carry out the perfusion culture of animal cells in a microfluidic device. Here, we describe a general theory on microfluid network design, microfabrication technique, and experimental technique for pressure-driven perfusion culture in an 8 × 8 microchamber array on a glass slide-sized microchip made out of PDMS. PMID:24297421
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.
Predicting radiotherapy-induced cardiac perfusion defects
Das, Shiva K.; Baydush, Alan H.; Zhou Sumin; Miften, Moyed; Yu Xiaoli; Craciunescu, Oana; Oldham, Mark; Light, Kim; Wong, Terence; Blazing, Michael; Borges-Neto, Salvador; Dewhirst, Mark W.; Marks, Lawrence B.
2005-01-01
The purpose of this work is to compare the efficacy of mathematical models in predicting the occurrence of radiotherapy-induced left ventricular perfusion defects assessed using single-photon emission computed tomography (SPECT). The basis of this study is data from 73 left-sided breast/chestwall patients treated with tangential photon fields. The mathematical models compared were three commonly used parametric models [Lyman normal tissue complication probability (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and a nonparametric model (Linear discriminant analysis--LDA). Data used by the models were the left ventricular dose--volume histograms, or SPECT-based dose-function histograms, and the presence/absence of SPECT perfusion defects 6 months postradiation therapy (21 patients developed defects). For the parametric models, maximum likelihood estimation and F-tests were used to fit the model parameters. The nonparametric LDA model step-wise selected features (volumes/function above dose levels) using a method based on receiver operating characteristics (ROC) analysis to best separate the groups with and without defects. Optimistic (upper bound) and pessimistic (lower bound) estimates of each model's predictive capability were generated using ROC curves. A higher area under the ROC curve indicates a more accurate model (a model that is always accurate has area=1). The areas under these curves for different models were used to statistically test for differences between them. Pessimistic estimates of areas under the ROC curve using dose-volume histogram/dose-function histogram inputs, in order of increasing prediction accuracy, were LNTCP (0.79/0.75), RS (0.80/0.77), gEUD (0.81/0.78), and LDA (0.84/0.86). Only the LDA model benefited from SPECT-based regional functional information. In general, the LDA model was statistically superior to the parametric models. The LDA model selected as features the left ventricular volumes above
Robust estimation procedure in panel data model
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.
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.
Fieselmann, Andreas; Dennerlein, Frank; Deuerling-Zheng, Yu; Boese, Jan; Fahrig, Rebecca; Hornegger, Joachim
2011-06-21
Filtered backprojection is the basis for many CT reconstruction tasks. It assumes constant attenuation values of the object during the acquisition of the projection data. Reconstruction artifacts can arise if this assumption is violated. For example, contrast flow in perfusion imaging with C-arm CT systems, which have acquisition times of several seconds per C-arm rotation, can cause this violation. In this paper, we derived and validated a novel spatio-temporal model to describe these kinds of artifacts. The model separates the temporal dynamics due to contrast flow from the scan and reconstruction parameters. We introduced derivative-weighted point spread functions to describe the spatial spread of the artifacts. The model allows prediction of reconstruction artifacts for given temporal dynamics of the attenuation values. Furthermore, it can be used to systematically investigate the influence of different reconstruction parameters on the artifacts. We have shown that with optimized redundancy weighting function parameters the spatial spread of the artifacts around a typical arterial vessel can be reduced by about 70%. Finally, an inversion of our model could be used as the basis for novel dynamic reconstruction algorithms that further minimize these artifacts.
de Lange, J; van Eck, P; Elliott, G R; de Kort, W L; Wolthuis, O L
1992-04-01
To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose consumption and lactate production as metabolic parameters, Na+ and K+ ions, as well as lactate dehydrogenase activity in blood as markers for cell damage, whereas vasomotor reactivity was assessed by administering noradrenaline and isoxsuprine. After 60 min of equilibration, only insignificant changes in these parameters were observed during the subsequent 3-hr test period (longer periods were not tested). A slight weight increase was noted during the total period 4 hr, presumably due to slight edema formation. On the basis of several types of measurements, such as in vivo blood flow and ear temperature and in vitro glucose metabolism, standard procedures were developed. It is concluded that this technique offers an easy to handle, cost-efficient, and animal-saving model for skin penetration studies that lacks most of the disadvantages of existing models.
NASA Astrophysics Data System (ADS)
Fieselmann, Andreas; Dennerlein, Frank; Deuerling-Zheng, Yu; Boese, Jan; Fahrig, Rebecca; Hornegger, Joachim
2011-06-01
Filtered backprojection is the basis for many CT reconstruction tasks. It assumes constant attenuation values of the object during the acquisition of the projection data. Reconstruction artifacts can arise if this assumption is violated. For example, contrast flow in perfusion imaging with C-arm CT systems, which have acquisition times of several seconds per C-arm rotation, can cause this violation. In this paper, we derived and validated a novel spatio-temporal model to describe these kinds of artifacts. The model separates the temporal dynamics due to contrast flow from the scan and reconstruction parameters. We introduced derivative-weighted point spread functions to describe the spatial spread of the artifacts. The model allows prediction of reconstruction artifacts for given temporal dynamics of the attenuation values. Furthermore, it can be used to systematically investigate the influence of different reconstruction parameters on the artifacts. We have shown that with optimized redundancy weighting function parameters the spatial spread of the artifacts around a typical arterial vessel can be reduced by about 70%. Finally, an inversion of our model could be used as the basis for novel dynamic reconstruction algorithms that further minimize these artifacts.
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
McCommis, Kyle S.; Zhang, Haosen; Herrero, Pilar; Gropler, Robert J.; Zheng, Jie
2008-01-01
The purpose of this study was to examine the feasibility of quantifying myocardial blood flow (MBF) and rate of myocardial oxygen consumption (MVO2) during pharmacologically induced stress without using a contrast agent. The former was measured by the arterial spin labeling (ASL) method and the later was obtained by measuring the oxygen extraction fraction (OEF) with the magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) effect and Fick's law. The MRI results were compared with the established positron emission tomography (PET) methods. Six mongrel dogs with induced acute moderate left coronary artery stenosis were scanned using a clinical PET and a 1.5T MRI system, in the same day. Regional MBF, myocardial OEF, and MVO2 were measured with both imaging modalities. Correlation coefficients (R2) of the three myocardial indexes (MBF, OEF, and MVO2) between MRI and PET methods ranged from 0.70 to 0.93. Bland-Altman statistics demonstrated that the estimated precision of the limits of agreement between MRI and PET measurements varied from 18% (OEF), to 37% (MBF), and 45% (MVO2). The detected changes in these indexes, at rest and during dobutamine stress, were similar between two image modalities. The proposed non-contrast MRI technique is a promising method to quantitatively assess myocardial perfusion and oxygenation. PMID:17566684
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. PMID:23213770
Model-based estimation of knee stiffness.
Pfeifer, Serge; Vallery, Heike; Hardegger, Michael; Riener, Robert; Perreault, Eric J
2012-09-01
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 toward our ultimate goal of quantifying knee stiffness during gait.
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
Model-Based Estimation of Knee Stiffness
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
Extreme Earthquake Risk Estimation by Hybrid Modeling
NASA Astrophysics Data System (ADS)
Chavez, M.; Cabrera, E.; Ashworth, M.; Garcia, S.; Emerson, D.; Perea, N.; Salazar, A.; Moulinec, C.
2012-12-01
The estimation of the hazard and the economical consequences i.e. the risk associated to the occurrence of extreme magnitude earthquakes in the neighborhood of urban or lifeline infrastructure, such as the 11 March 2011 Mw 9, Tohoku, Japan, represents a complex challenge as it involves the propagation of seismic waves in large volumes of the earth crust, from unusually large seismic source ruptures up to the infrastructure location. The large number of casualties and huge economic losses observed for those earthquakes, some of which have a frequency of occurrence of hundreds or thousands of years, calls for the development of new paradigms and methodologies in order to generate better estimates, both of the seismic hazard, as well as of its consequences, and if possible, to estimate the probability distributions of their ground intensities and of their economical impacts (direct and indirect losses), this in order to implement technological and economical policies to mitigate and reduce, as much as possible, the mentioned consequences. Herewith, we propose a hybrid modeling which uses 3D seismic wave propagation (3DWP) and neural network (NN) modeling in order to estimate the seismic risk of extreme earthquakes. The 3DWP modeling is achieved by using a 3D finite difference code run in the ~100 thousands cores Blue Gene Q supercomputer of the STFC Daresbury Laboratory of UK, combined with empirical Green function (EGF) techniques and NN algorithms. In particular the 3DWP is used to generate broadband samples of the 3D wave propagation of extreme earthquakes (plausible) scenarios corresponding to synthetic seismic sources and to enlarge those samples by using feed-forward NN. We present the results of the validation of the proposed hybrid modeling for Mw 8 subduction events, and show examples of its application for the estimation of the hazard and the economical consequences, for extreme Mw 8.5 subduction earthquake scenarios with seismic sources in the Mexican
Payabvash, Seyedmehdi; Kamalian, Shahmir; Fung, Steve; Wang, Yifei; Passanese, John; Kamalian, Shervin; Souza, Leticia CS; Kemmling, Andre; Harris, Gordon J.; Halpern, Elkan F.; Gonzalez, R. Gilberto; Furie, Karen L.; Lev, Michael H.
2013-01-01
Purpose To construct a multivariate model for prediction of early aphasia improvement in stroke patients using admission CT perfusion (CTP) and CT angiography (CTA). Methods Fifty-eight consecutive patients with aphasia due to first-time ischemic stroke of the left hemisphere were included. Language function was assessed based on patients’ admission and discharge NIHSS and clinical records. All patients had brain CTP and CTA within 9 hours of symptom onset. For image analysis, all CTPs were automatically coregistered to MNI-152 brain space and parcellated into mirrored cortical and subcortical regions. Multiple logistic regression analysis was used to find independent imaging and clinical predictors of language recovery. Results By the time of discharge, 21 (36%) patients demonstrated improvement of language. Independent factors predicting improvement in language included relative cerebral blood flow of angular gyrus gray matter (Brodmann’s area 39) and lower third of insular ribbon, proximal cerebral artery occlusion on admission CTA, and aphasia score on admission NIHSS exam. Using these 4 variables, we developed a multivariate logistic regression model that could estimate the probability of early improvement in stroke patients presenting with aphasia and predict functional outcome with 91% accuracy. Conclusion An imaging-based location weighted multivariate model is developed to predict early language improvement of aphasic patients using admission data collected within 9-hours of stroke onset. This pilot model should be validated in a larger, prospective study; however, the semi-automated atlas-based analysis of brain CTP, along with the statistical approach, could be generalized for prediction of other outcome measures in stroke patients. PMID:20488905
Parameter estimation, model reduction and quantum filtering
NASA Astrophysics Data System (ADS)
Chase, Bradley A.
This thesis explores the topics of parameter estimation and model reduction in the context of quantum filtering. The last is a mathematically rigorous formulation of continuous quantum measurement, in which a stream of auxiliary quantum systems is used to infer the state of a target quantum system. Fundamental quantum uncertainties appear as noise which corrupts the probe observations and therefore must be filtered in order to extract information about the target system. This is analogous to the classical filtering problem in which techniques of inference are used to process noisy observations of a system in order to estimate its state. Given the clear similarities between the two filtering problems, I devote the beginning of this thesis to a review of classical and quantum probability theory, stochastic calculus and filtering. This allows for a mathematically rigorous and technically adroit presentation of the quantum filtering problem and solution. Given this foundation, I next consider the related problem of quantum parameter estimation, in which one seeks to infer the strength of a parameter that drives the evolution of a probe quantum system. By embedding this problem in the state estimation problem solved by the quantum filter, I present the optimal Bayesian estimator for a parameter when given continuous measurements of the probe system to which it couples. For cases when the probe takes on a finite number of values, I review a set of sufficient conditions for asymptotic convergence of the estimator. For a continuous-valued parameter, I present a computational method called quantum particle filtering for practical estimation of the parameter. Using these methods, I then study the particular problem of atomic magnetometry and review an experimental method for potentially reducing the uncertainty in the estimate of the magnetic field beyond the standard quantum limit. The technique involves double-passing a probe laser field through the atomic system, giving
Pulmonary ventilation/perfusion scan
V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health care ...
Nishino, Asuka; Tajima, Yosuke; Takuwa, Hiroyuki; Masamoto, Kazuto; Taniguchi, Junko; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Urushihata, Takuya; Aoki, Ichio; Kanno, Iwao; Tomita, Yutaka; Suzuki, Norihiro; Ikoma, Yoko; Ito, Hiroshi
2016-04-27
We investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [(11)C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before, and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO.
Nishino, Asuka; Tajima, Yosuke; Takuwa, Hiroyuki; Masamoto, Kazuto; Taniguchi, Junko; Wakizaka, Hidekatsu; Kokuryo, Daisuke; Urushihata, Takuya; Aoki, Ichio; Kanno, Iwao; Tomita, Yutaka; Suzuki, Norihiro; Ikoma, Yoko; Ito, Hiroshi
2016-01-01
We investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [11C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before, and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO. PMID:27116932
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
Background A standard quantitative imaging approach to evaluate peripheral arterial disease (PAD) 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. Methods and Results Serial changes in lower extremity arteriogenesis and muscle perfusion were evaluated following femoral artery occlusion in a porcine model using SPECT/CT imaging with post-mortem validation of in vivo findings using gamma counting, post-mortem imaging, and histological analysis. Hybrid thallium-201 (201Tl) SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately post-occlusion, and at 1 and 4 weeks post-occlusion. CT imaging was used to identify muscle regions of interest in the ischemic (I) and non-ischemic (NI) hindlimbs for quantification of regional changes in CT defined arteriogenesis and quantification of 201Tl perfusion. Four weeks post-occlusion, post-mortem tissue 201Tl activity was measured by gamma counting and immunohistochemistry was performed to assess capillary density. Relative 201Tl retention (I/NI) was reduced immediately post-occlusion 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). Conclusions 201Tl SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion following limb ischemia. This approach may be effective for detection of disease and monitoring therapy in PAD. PMID:24170237
Model-based estimation of individual fitness
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).
Model-based estimation of individual fitness
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).
Entropy Based Modelling for Estimating Demographic Trends.
Li, Guoqi; Zhao, Daxuan; Xu, Yi; Kuo, Shyh-Hao; Xu, Hai-Yan; Hu, Nan; Zhao, Guangshe; Monterola, Christopher
2015-01-01
In this paper, an entropy-based method is proposed to forecast the demographical changes of countries. We formulate the estimation of future demographical profiles as a constrained optimization problem, anchored on the empirically validated assumption that the entropy of age distribution is increasing in time. The procedure of the proposed method involves three stages, namely: 1) Prediction of the age distribution of a country's population based on an "age-structured population model"; 2) Estimation the age distribution of each individual household size with an entropy-based formulation based on an "individual household size model"; and 3) Estimation the number of each household size based on a "total household size model". The last stage is achieved by projecting the age distribution of the country's population (obtained in stage 1) onto the age distributions of individual household sizes (obtained in stage 2). The effectiveness of the proposed method is demonstrated by feeding real world data, and it is general and versatile enough to be extended to other time dependent demographic variables. PMID:26382594
Estimating population trends with a linear model
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.
Uncertainty estimation in reconstructed deformable models
Hanson, K.M.; Cunningham, G.S.; McKee, R.
1996-12-31
One of the hallmarks of the Bayesian approach to modeling is the posterior probability, which summarizes all uncertainties regarding the analysis. Using a Markov Chain Monte Carlo (MCMC) technique, it is possible to generate a sequence of objects that represent random samples drawn from the posterior distribution. We demonstrate this technique for reconstructions of two-dimensional objects from noisy projections taken from two directions. The reconstructed object is modeled in terms of a deformable geometrically-defined boundary with a constant interior density yielding a nonlinear reconstruction problem. We show how an MCMC sequence can be used to estimate uncertainties in the location of the edge of the reconstructed object.
Mariotti, E; Orton, M R; Eerbeek, O; Ashruf, J F; Zuurbier, C J; Southworth, R; Eykyn, T R
2016-04-01
Hyperpolarized (13)C MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-(13)C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-(13)C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. PMID:26777799
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
Long term perfusion system supporting adipogenesis.
Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L
2015-08-01
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 adipogenesis, 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
Long term perfusion system supporting adipogenesis
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
Long term perfusion system supporting adipogenesis.
Abbott, Rosalyn D; Raja, Waseem K; Wang, Rebecca Y; Stinson, Jordan A; Glettig, Dean L; Burke, Kelly A; Kaplan, David L
2015-08-01
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 adipogenesis, 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.
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.
Beaufigeau, M; Wolf, P; Azimzadeh, A; Godfrin, Y; Beller, J P; Boudjema, K; Jaeck, D; Kieny, R; Cinqualbre, J
1996-01-01
With the increasing success of liver transplantation there is an urgent need for developing an artificial liver support system to be used in patients with liver failure. An extracorporeal porcine liver perfusion machine was successfully tested in animals with experimental liver failure. Livers were flushed, removed from 35 kg pigs and placed in a heated sterile cassette. The portal vein and the hepatic artery of the graft were connected to the arterial system of the animals. The perfusion pressure of the hepatic artery was regulated via a pressure-flow computerized feed-back device. The venous flow was reinfused from the hepatic veins of the graft to the jugular vein of the animals. The experimental work consisted in two steps: 1. evaluation of clinical and biological consequences of liver perfusion in healthy animals (Group A = pigs, n = 3; group B = primates, n = 3); 2. evaluation of the efficiency of the liver perfusion in animals with ischemic liver failure (Groupe D = pigs, n = 6). The control group (Group C = pigs, n = 7) consisted of pigs with ischemic liver failure without hepatic support. No major clinical or biological adverse effects are reported in groups A and B excepted a thrombocytmia and a marked increase in serum transaminases levels in group B. Liver function as assessed by the bile flow was good in both groups. Comatose pigs with ischemic hepatic failure (group D) recovered a subnormal neurological status in five out of six cases. Serum ammoniemia level were significantly decreased (from 1076 +/- 163 to 255 +/- 32 umol/l). A decrease in serum bilirubine levels and an improvement in the coagulation profile were observed in the perfused animals. Pigs and primates tolerated the perfusion procedure well and beneficial effects were observed in perfused pigs with experimental liver failure.
Selection and estimation for mixed graphical models
Chen, Shizhe; Witten, Daniela M.; shojaie, Ali
2016-01-01
Summary We consider the problem of estimating the parameters in a pairwise graphical model in which the distribution of each node, conditioned on the others, may have a different exponential family form. We identify restrictions on the parameter space required for the existence of a well-defined joint density, and establish the consistency of the neighbourhood selection approach for graph reconstruction in high dimensions when the true underlying graph is sparse. Motivated by our theoretical results, we investigate the selection of edges between nodes whose conditional distributions take different parametric forms, and show that efficiency can be gained if edge estimates obtained from the regressions of particular nodes are used to reconstruct the graph. These results are illustrated with examples of Gaussian, Bernoulli, Poisson and exponential distributions. Our theoretical findings are corroborated by evidence from simulation studies.
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.
Selection and estimation for mixed graphical models
Chen, Shizhe; Witten, Daniela M.; shojaie, Ali
2016-01-01
Summary We consider the problem of estimating the parameters in a pairwise graphical model in which the distribution of each node, conditioned on the others, may have a different exponential family form. We identify restrictions on the parameter space required for the existence of a well-defined joint density, and establish the consistency of the neighbourhood selection approach for graph reconstruction in high dimensions when the true underlying graph is sparse. Motivated by our theoretical results, we investigate the selection of edges between nodes whose conditional distributions take different parametric forms, and show that efficiency can be gained if edge estimates obtained from the regressions of particular nodes are used to reconstruct the graph. These results are illustrated with examples of Gaussian, Bernoulli, Poisson and exponential distributions. Our theoretical findings are corroborated by evidence from simulation studies. PMID:27625437
Validation of Kp Estimation and Prediction Models
NASA Astrophysics Data System (ADS)
McCollough, J. P., II; Young, S. L.; Frey, W.
2014-12-01
Specifification and forecast of geomagnetic indices is an important capability for space weather operations. The University Partnering for Operational Support (UPOS) effort at the Applied Physics Laboratory of Johns Hopkins University (JHU/APL) produced many space weather models, including the Kp Predictor and Kp Estimator. We perform a validation of index forecast products against definitive indices computed by the Deutches GeoForschungsZentstrum Potsdam (GFZ). We compute continuous predictant skill scores, as well as 2x2 contingency tables and associated scalar quantities for different index thresholds. We also compute a skill score against a nowcast persistence model. We discuss various sources of error for the models and how they may potentially be improved.
Solar sails: Modeling, estimation, and trajectory control
NASA Astrophysics Data System (ADS)
Rios-Reyes, Leonel
There has been great interest in developing solar sail technology and missions by several international space agencies in recent years. However, at present there is no consensus on how one can mathematically model forces and moments acting on a solar sail. Traditional analytical models and finite element methods are not feasible for integration into a precise navigation system. This dissertation takes a step toward resolving this issue by developing tools and concepts that can be integrated into a precise solar sail navigation system. These steps are the derivation of a generalized sail model, a linear estimation method for estimating and predicting forces and moments acting on a solar sail, and a new trajectory control methodology for tracking a nominal trajectory when the sail performance exceeds the nominal design performance. The main contributions of this dissertation follow. First, the generalized sail model (GSM) is defined to analytically describe the forces and moments acting on a solar sail of arbitrary shape. The GSM is derived by performing an integration, of all the differential forces and moments acting on the sail, over the sail surface. Next, the GSM is applied to several examples to illustrate the use of the GSM's analytic equations. These examples allow comparisons of forces and moments generated by different solar sails, the computation of force derivatives, and the application of the model to orbital mechanics problems. Since it is difficult to model the sail geometry based on ground measurements; errors in the sail model are expected once the sail is deployed in space. Due to this difficulty; a least-squares estimation method for the force and moment coefficients of the GSM is derived. For realistic implementation of a sail trajectory, the deployed sail must have an excess thrust capacity. We develop and implement a control methodology for flying a nominal mission profile with such an excess capacity. Control laws for maintaining a flat, ideal
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...
Taeger, Christian D; Müller-Seubert, Wibke; Horch, Raymund E; Präbst, Konstantin; Münch, Frank; Geppert, Carol I; Birkholz, Torsten; Dragu, Adrian
2014-01-01
Tissue undergoing free transfer in transplant or reconstructive surgery always is at high risk of ischaemia-related cell damage. This study aims at assessing different procedures using an extracorporeal perfusion and oxygenation system to investigate the expression of hypoxia inducible factor (HIF)-1-α as marker for hypoxia and of the pro-apoptotic protein Caspase-3 in skeletal muscle to elucidate potential improvements in tissue conservation. Twenty-four porcine rectus abdominis muscles were assigned to five different groups and examined after they had been extracorporeally preserved for 60 min. time. Group I was left untreated (control), group II was perfused with a cardioplegic solution, group III was flushed with 10 ml of a cardioplegic solution and then left untreated. Group IV and V were perfused and oxygenated with either an isotone crystalloid solution or a cardioplegic solution. Among others, immunohistochemistry (Caspase-3 and HIF-1-α) of muscle samples was performed. Furthermore, oxygen partial pressure in the perfusate at the arterial and venous branch was measured. Expression of Caspase-3 after 60 min. was reduced in all groups compared to the control group. Furthermore, all groups (except group III) expressed less HIF-1-α than the control group. Oxygenation leads to higher oxygen levels at the venous branch compared to groups without oxygenation. Using an extracorporeal perfusion and oxygenation system cell damage could be reduced as indicated by stabilized expressions of Caspase-3 and HIF-1-α for 60 min. of tissue preservation. Complete depletion of oxygen at the venous branch can be prevented by oxygenation of the perfusate with ambient air. PMID:24636195
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.
Eigler, N L; Pfaff, J M; Zeiher, A; Whiting, J S; Forrester, J S
1989-05-01
The system mean transit time (Tsys) of the impulse response function describing contrast material transit through the coronary circulation was determined from serial digital angiographic images. The linearity, reproducibility, and relations with regional myocardial perfusion and conventional time-density curve parameters, time to peak concentration (TPC), and exponential washout rate (k) were assessed in a dynamic flow x-ray phantom (n = 46) and in six open-chest dogs (n = 102) while coronary flow was altered by stenosis and/or hyperemic stimuli. In the phantom studies, the inverse of the system mean transit time (Tsys-1) closely predicted flow/volume (r = 0.99, slope = 0.99). In dogs, Tsys-1 was independent of the shape of the contrast bolus injection (single or double-peaked), class of contrast agent (ionic or nonionic), the type of hyperemic stimulus (dipyridamole, dipyridamole plus norepinephrine, transient total occlusion, or ionic contrast media), and was highly reproducible between adjacent myocardial regions served by the same artery (r = 0.98 +/- 0.01). There was a strong correlation between Tsys-1 and regional coronary flow for stenotic and/or hyperemic vessels (r = 0.94, distribution volume = 14.9 ml/100 g) over a wide range (0-514 ml/min/100 g). Tsys-1 performed better than conventional time-density curve parameters TPC-1 and k for predicting phantom flow/volume ratios and regional myocardial blood flow in the dog. These data suggest that both digital coronary angiography and coronary contrast transit can be modeled as linear systems and that impulse response analysis may provide accurate and reproducible estimates of regional myocardial blood flow.
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.
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…
Personality factors correlate with regional cerebral perfusion.
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.
Proost, J H; Nijssen, H M; Strating, C B; Meijer, D K; Groothuis, G M
1993-08-01
This study contains a pharmacokinetic analysis on the efflux of organic anions from the liver into the bloodstream (sinusoidal efflux) with specific reference to the influence of albumin. The net sinusoidal efflux rate of dibromosulfophthalein (DBSP) from preloaded livers, being the resultant of sinusoidal efflux and reuptake of ligand by hepatocytes downstream the sinusoid, can be strongly increased by the presence of bovine serum albumin (BSA), a protein having multiple binding sites for DBSP. We previously attributed this effect to a reduction of reuptake through extracellular binding of the organic anion to the protein, rather than to an intrinsic stimulatory effect on the actual membrane transport process from the cells. In the present study we tested this hypothesis using a pharmacokinetic multicompartment liver model. This model resembles the parallel tube model in that the liver is described by several compartments placed in series instead of a single well-stirred compartment and it takes into account rates of dissociation and association in binding to proteins in the sinusoidal space. The model parameters were fitted from the sinusoidal efflux and biliary excretion data from efflux experiments measuring the stimulatory effect of various concentrations of BSA. Equilibrium binding of DBSP to albumin as well as the dissociation rate constant (koff) were determined in vitro with rapid filtration techniques. The experimental data could not be fitted satisfactorily when using the experimentally obtained values of the protein association and dissociation rate constants (kon and koff). However, they could be simulated accurately assuming 16 times higher values for the association and dissociation rate constant compared to those determined in vitro. Time constants of the perfusate flow, liver (re)uptake, and protein association and dissociation indicate that binding equilibrium does not exist within the sinusoids and that, in particular at low protein
Li, Chunxia; Zhang, Xiaodong; Komery, Amelia; Li, Yingxia; Novembre, Francis J; Herndon, James G
2011-09-01
The Simian immunodeficiency virus (SIV) infected macaque model exhibits neuropathological symptoms similar to those of HIV(+) patients, and is ideal for studying cognitive impairment and neuropathological sequelae of disease in repeated measurements. The aim of this study is to use Diffusion Tensor Imaging (DTI) and perfusion MRI to longitudinally access the disease development in SIV-infected monkeys under controlled conditions and to cross-validate our finding with MRI studies in HIV(+) patients. Three adult male pig-tailed macaques (Macaca nemestrina) were inoculated with the SIVsmmFGb virus. Blood was collected for enumeration of CD4+ and CD8+ T-cells. Serial time-sensitive high-resolution T(2)- weighted structural images, Cerebral Blood Flow (CBF) maps measured with the Continuous Arterial Spin Labeling (CASL) technique, and DTI images were obtained. Animals were sacrificed after 24 weeks. Cognitive behavioral tests were also carried out at each time point. Longitudinal changes in brain volume, CBF, and DTI in selected regions were analyzed statistically. In this study, CD4+ T-cell counts were found declined significantly after SIV infection in all macaques. No significant neurological behavior and brain volume changes were observed following virus inoculation. The CBF was found reduced in the caudate, inferior parietal cortex, and the prefrontal cortex. Fractional Anisotropy (FA) values in the whole brain and several Regions of Interest (ROIs) decreased significantly. These longitudinal changes in CBF and FA are correlated with CD4+ T-cell depletion and/or CD4:CD8 ratio. The MRI findings from this pilot study agree with previous results in HIV(+) patients.
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.
Guyot, Y; Luyten, F P; Schrooten, J; Papantoniou, I; Geris, L
2015-12-01
Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the scaffold pores leading a fully filled scaffold following the scaffold's geometric characteristics. Current computational fluid dynamic approaches for tissue engineering bioreactor systems have been mostly carried out for empty scaffolds. The effect of 3D cell growth and extracellular matrix formation (termed in this study as neotissue growth), on its surrounding fluid flow field is a challenge yet to be tackled. In this work a combined approach was followed linking curvature driven cell growth to fluid dynamics modeling. The level-set method (LSM) was employed to capture neotissue growth driven by curvature, while the Stokes and Darcy equations, combined in the Brinkman equation, provided information regarding the distribution of the shear stress profile at the neotissue/medium interface and within the neotissue itself during growth. The neotissue was assumed to be micro-porous allowing flow through its structure while at the same time allowing the simulation of complete scaffold filling without numerical convergence issues. The results show a significant difference in the amplitude of shear stress for cells located within the micro-porous neo-tissue or at the neotissue/medium interface, demonstrating the importance of taking along the neotissue in the calculation of the mechanical stimulation of cells during culture.The presented computational framework is used on different scaffold pore geometries demonstrating its potential to be used a design as tool for scaffold architecture taking into account the growing neotissue. Biotechnol. Bioeng. 2015;112: 2591-2600. © 2015 Wiley Periodicals, Inc. PMID:26059101
Dyke, Jonathan P; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K
2015-03-01
This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown.
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
Dyke, Jonathan P.; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K.
2014-01-01
Purpose This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. Methods We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Results Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. Discussion MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523
Estimating Resolution Lengths of Hybrid Turbulence Models
NASA Technical Reports Server (NTRS)
Abdol-Hamid, Khaled S.; Girimaji, Sharath S.
2006-01-01
A two-stage procedure has been devised for estimating the spatial resolution achievable in the simulation of a given flow on a given computational grid by a computational fluid dynamics (CFD) code that incorporates a hybrid model of turbulence. The hybrid models to which this procedure is especially relevant are those of the Reynolds-averaged Navier-Stokes (RANS) and the partial-averaged Navier-Stokes (PANS) approaches. This procedure represents the first step toward adding variable-resolution turbulence-modeling capabilities to CFD codes as part of a continuing effort to increase the accuracy and robustness of CFD simulations of unsteady flows. Some background information is prerequisite to a meaningful summary of the procedure. Among experts in CFD, it is well known that combination of the Reynolds-averaged Navier-Stokes (RANS) approach and eddy-viscosity turbulence models offers limited capability for simulating unsteady and complex flows. The RANS approach includes an assumption that most of the energy in a given flow is modeled through turbulence-transport equations and is resolved in a computational grid used to simulate the flow. RANS also overpredicts eddy viscosity, thereby yielding excessive damping of unsteady motion. The eddy viscosity attains an unphysically large value because of unresolved scales, and suppresses most temporal and spatial fluctuations in the resolved flow field. One approach used to overcome this deficiency is to provide a mechanism for the RANS equations to resolve motion only on the largest scales and to use a hybrid model to represent effects at smaller scales. The RANS approach involves the use of a standard two-equation turbulence model in which the effect of turbulence is summarized by a viscosity that is a function of (1) the time-averaged kinetic- energy density (k) associated with the local fluctuating (turbulent) component of flow and (2) the time-averaged rate of dissipation of the turbulent-kinetic- energy density ( ). In
3D functional and perfusable microvascular networks for organotypic microfluidic models.
Bersini, Simone; Moretti, Matteo
2015-05-01
The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases. PMID:25893395
The Mayfield method of estimating nesting success: A model, estimators and simulation results
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.
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.
Zerbi, Valerio; Jansen, Diane; Wiesmann, Maximilian; Fang, Xiaotian; Broersen, Laus M; Veltien, Andor; Heerschap, Arend; Kiliaan, Amanda J
2014-03-01
Nutritional intervention may retard the development of Alzheimer's disease (AD). In this study we tested the effects of 2 multi-nutrient diets in an AD mouse model (APPswe/PS1dE9). One diet contained membrane precursors such as omega-3 fatty acids and uridine monophosphate (DEU), whereas another diet contained cofactors for membrane synthesis as well (Fortasyn); the diets were developed to enhance synaptic membranes synthesis, and contain components that may improve vascular health. We measured cerebral blood flow (CBF) and water diffusivity with ultra-high-field magnetic resonance imaging, as alterations in these parameters correlate with clinical symptoms of the disease. APPswe/PS1dE9 mice on control diet showed decreased CBF and changes in brain water diffusion, in accordance with findings of hypoperfusion, axonal disconnection and neuronal loss in patients with AD. Both multinutrient diets were able to increase cortical CBF in APPswe/PS1dE9 mice and Fortasyn reduced water diffusivity, particularly in the dentate gyrus and in cortical regions. We suggest that a specific diet intervention has the potential to slow AD progression, by simultaneously improving cerebrovascular health and enhancing neuroprotective mechanisms. PMID:24210253
Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling
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
Rajeev, Rahul; Gamblin, T Clark; Turaga, Kiran K
2016-04-01
Isolated hepatic perfusion uses the unique vascular supply of hepatic malignancies to deliver cytotoxic chemotherapy. The procedure involves vascular isolation of the liver and delivery of chemotherapy via the hepatic artery and extraction from retrohepatic vena cava. Benefits of hepatic perfusion have been observed in hepatic metastases of ocular melanoma and colorectal cancer and primary hepatocellular carcinoma. Percutaneous and prophylactic perfusions are avenues of ongoing research.
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)…
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.
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
Ex vivo lung perfusion and reconditioning.
Yeung, Jonathan C; Cypel, Marcelo; Massad, Ehab; Keshavjee, Shaf
2011-01-01
Normothermic ex vivo lung perfusion can act as a platform for the evaluation and repair of donor lungs. An acellular hyperosmolar solution is perfused anterograde through the donor lungs at 40% of the estimated cardiac output. Following oxygenation of the perfusate by the lung, it passes through a hollow fiber oxygenator supplied with a hypoxic gas mixture to remove oxygen and to maintain physiological carbon dioxide levels. Flow through a heat exchanger to maintain normothermia and a leukocyte filter to remove demarginated leukocytes completes the circuit. Lung function can be measured by the difference in PO2 between the perfusate postlung and postmembrane and by physiological parameters. Utilization of this method of ex vivo donor lung evaluation should reduce concerns of primary graft dysfunction and increase utilization rates of donor lungs. PMID:24412979
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.
On population size estimators in the Poisson mixture model.
Mao, Chang Xuan; Yang, Nan; Zhong, Jinhua
2013-09-01
Estimating population sizes via capture-recapture experiments has enormous applications. The Poisson mixture model can be adopted for those applications with a single list in which individuals appear one or more times. We compare several nonparametric estimators, including the Chao estimator, the Zelterman estimator, two jackknife estimators and the bootstrap estimator. The target parameter of the Chao estimator is a lower bound of the population size. Those of the other four estimators are not lower bounds, and they may produce lower confidence limits for the population size with poor coverage probabilities. A simulation study is reported and two examples are investigated. PMID:23865502
On population size estimators in the Poisson mixture model.
Mao, Chang Xuan; Yang, Nan; Zhong, Jinhua
2013-09-01
Estimating population sizes via capture-recapture experiments has enormous applications. The Poisson mixture model can be adopted for those applications with a single list in which individuals appear one or more times. We compare several nonparametric estimators, including the Chao estimator, the Zelterman estimator, two jackknife estimators and the bootstrap estimator. The target parameter of the Chao estimator is a lower bound of the population size. Those of the other four estimators are not lower bounds, and they may produce lower confidence limits for the population size with poor coverage probabilities. A simulation study is reported and two examples are investigated.
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
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
Wang, Kai; Zhou, Xiaorong; Huang, Yanming; Khalil, Mazen; Wiktor, Dominik; van Giezen, J J J; Penn, Marc S
2010-09-01
Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. PMID:20694285
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…
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…
Bubble dynamics in perfused tissue undergoing decompression.
Meisel, S; Nir, A; Kerem, D
1981-02-01
A mathematical model describing bubble dynamics in a perfused tissue undergoing decompression is presented, taking into account physical expansion and inward diffusion from surrounding supersaturated tissue as growth promoting factors and tissue gas elimination by perfusion, tissue elasticity, surface tension and inherent unsaturation as resolving driving forces. The expected behavior after a step reduction of pressure of a bubble initially existing in the tissue, displaying both growth and resolution has been demonstrated. A strong perfusion-dependence of bubble resolution time at low perfusion rates is apparent. The model can account for various exposure pressures and saturation fractions of any inert gas-tissue combination for which a set of physical and physiological parameters is available.
Gao, Ying; Goodnough, Candida L; Erokwu, Bernadette O; Farr, George W; Darrah, Rebecca; Lu, Lan; Dell, Katherine M; Yu, Xin; Flask, Chris A
2014-08-01
Arterial spin labeling (ASL) is a valuable non-contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo-planar imaging (EPI) or true fast imaging with steady-state free precession (true FISP) readouts, which are prone to off-resonance artifacts on high-field MRI scanners. We have developed a rapid ASL-FISP MRI acquisition for high-field preclinical MRI scanners providing perfusion-weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow-sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL-FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high-field MRI scanners with minimal image artifacts.
Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Akbarzadeh, Aram; Sabetkish, Shabnam; Sabetkish, Nastaran; Saadat, Paria; Tehrani, Mona
2015-01-01
The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body. PMID:26031202
Kajbafzadeh, Abdol-Mohammad; Khorramirouz, Reza; Akbarzadeh, Aram; Sabetkish, Shabnam; Sabetkish, Nastaran; Saadat, Paria; Tehrani, Mona
2015-04-01
The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body. PMID:26031202
Bayram-Weston, Zubeyde; Olsen, Elliott; Harrison, David J.; Dunnett, Stephen B.; Brooks, Simon P.
2016-01-01
Background The Golgi–Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured. New methods Conventional rapid Golgi and Golgi–Cox methods all require fresh impregnation in unfixed brain blocks. Here, we describe a modified method that gives high quality staining on brain tissue blocks perfusion-fixed with 4% paraformaldehyde (PFA) and post-fixed by immersion for 24 h. Results Tissue perfused with 4% PFA and post fixed for 24 h remained viable for the modified Golgi–Cox silver impregnation staining of mouse striatum from perfused wild type and zQ175. It was not found necessary to impregnate tissue blocks with Golgi solutions prior to sectioning, as post-sectioned tissues yielded equally good impregnation. Impregnation for 14 days resulted in optimal visualisation of striatal neuron and dendritic morphology. Although no modifications applied to the rapid Golgi method were reliable, the modified Golgi–Cox method yielded consistently reliable high-quality staining. Comparison with existing methods The current method used fixed tissues to reduce damage and preserve cell morphology. The revised method was found to be fast, reliable and cost effective without the need for expensive staining kits and could be performed in any neuroscience lab with limited specialist equipment. Conclusions The present study introduces a robust reproducible and inexpensive staining method for identifying neuronal morphological changes in the post fixed mouse brain, and is suitable for assessing changes in cell morphology in models of neurodegeneration and in response to experimental treatment. PMID:26459195
Pottecher, Julien; Santelmo, Nicola; Noll, Eric; Charles, Anne-Laure; Benahmed, Malika; Canuet, Matthieu; Frossard, Nelly; Namer, Izzie J; Geny, Bernard; Massard, Gilbert; Diemunsch, Pierre
2013-10-01
The aim of this study was to assess the functional preservation of the lung graft with anterograde lung perfusion in a model of donation after cardiac death. Thirty minutes after cardiac arrest, in situ anterograde selective pulmonary cold perfusion was started in six swine. The alveolo-capillary membrane was challenged at 3, 6, and 8 h with measurements of the mean pulmonary arterial pressure (mPAP), the pulmonary vascular resistance (PVR), the PaO2 /FiO2 ratio, the transpulmonary oxygen output (tpVO2 ), and the transpulmonary CO2 clearance (tpCO2 ). Mitochondrial homeostasis was investigated by measuring maximal oxidative capacity (Vmax ) and the coupling of phosphorylation to oxidation (ACR, acceptor control ratio) in lung biopsies. Inflammation and induction of primary immune response were assessed by measurement of tumor necrosis factor alpha (TNFα), interleukine-6 (IL-6) and receptor for advanced glycation endproducts (RAGE) in bronchoalveolar lavage fluid. Data were compared using repeated measures Anova. Pulmonary hemodynamics (mPAP: P = 0.69; PVR: P = 0.46), oxygenation (PaO2 /FiO2 : P = 0.56; tpVO2 : P = 0.46), CO2 diffusion (tpCO2 : P = 0.24), mitochondrial homeostasis (Vmax : P = 0.42; ACR: P = 0.8), and RAGE concentrations (P = 0.24) did not significantly change up to 8 h after cardiac arrest. TNFα and IL-6 were undetectable. Unaffected pulmonary hemodynamics, sustained oxygen and carbon dioxide diffusion, preserved mitochondrial homeostasis, and lack of inflammation suggest a long-lasting functional preservation of the graft with selective anterograde in situ pulmonary perfusion.
Estimates of Acausal Joint Impedance Models
Perreault, Eric J.
2013-01-01
Estimates of joint or limb impedance are commonly used in the study of how the nervous system controls posture and movement, and how that control is altered by injury to the neural or musculoskeletal systems. Impedance characterizes the dynamic relationship between an imposed perturbation of joint position and the torques generated in response. While there are many practical reasons for estimating impedance rather than its inverse, admittance, it is an acausal representation of the limb mechanics that can lead to difficulties in interpretation or use. The purpose of this study was to explore the acausal nature of nonparametric estimates of joint impedance representations to determine how they are influenced by common experimental and computational choices. This was accomplished by deriving discrete-time realizations of first-and second-order derivatives to illustrate two key difficulties in the physical interpretation of impedance impulse response functions. These illustrations were provided using both simulated and experimental data. It was found that the shape of the impedance impulse response depends critically on the selected sampling rate, and on the bandwidth and noise characteristics of the position perturbation used during the estimation process. These results provide important guidelines for designing experiments in which nonparametric estimates of impedance will be obtained, especially when those estimates are to be used in a multistep identification process. PMID:22907963
Multi-Cone Model for Estimating GPS Ionospheric Delays
NASA Technical Reports Server (NTRS)
Sparks, Lawrence; Komjathy, Attila; Mannucci, Anthony
2009-01-01
The multi-cone model is a computational model for estimating ionospheric delays of Global Positioning System (GPS) signals. It is a direct descendant of the conical-domain model. A primary motivation for the development of this model is the need to find alternatives for modeling slant delays at low latitudes, where ionospheric behavior poses an acute challenge for GPS signal-delay estimates based upon the thin-shell model of the ionosphere.
Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank
2010-08-01
Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.
Simultaneous estimation of parameters in the bivariate Emax model.
Magnusdottir, Bergrun T; Nyquist, Hans
2015-12-10
In this paper, we explore inference in multi-response, nonlinear models. By multi-response, we mean models with m > 1 response variables and accordingly m relations. Each parameter/explanatory variable may appear in one or more of the relations. We study a system estimation approach for simultaneous computation and inference of the model and (co)variance parameters. For illustration, we fit a bivariate Emax model to diabetes dose-response data. Further, the bivariate Emax model is used in a simulation study that compares the system estimation approach to equation-by-equation estimation. We conclude that overall, the system estimation approach performs better for the bivariate Emax model when there are dependencies among relations. The stronger the dependencies, the more we gain in precision by using system estimation rather than equation-by-equation estimation.
Pal, Sushanta; Sen, Srabani; Das, Debasis; Basu, Sandip
2016-10-01
A hypothetical quantitative model of analyzing gated myocardial perfusion SPECT is proposed and examined for the feasibility of its use as a predictor of diseased coronary artery and approximating the site of stenosis to determine whether it could serve as a useful noninvasive complement for coronary angiography. The extent and severity of perfusion defects on rest gated myocardial perfusion imaging SPECT-images were assessed on a five-point scale in a standard 17-segment model and total perfusion deficit was quantified by automated software. The first step was to locate the diseased coronary artery using a quantitative method: for this, the score of each segment belonging to a particular coronary artery was determined using a systematic presumptive approach. After determination of specific coronary artery segments, the scores of the contiguous segments in three short axis slices (apical, middle, and basal) were summed for six subdivisions (anterior, anterolateral, inferolateral, inferior, anteroseptal, and inferoseptal). The site of stenosis was determined from (a) the initial approximation of the involved segments with a defect score of 2-4 and (b) subsequent calculation of the defect score of each of the six subdivisions and allocating the site through a preassigned number for each coronary artery. For each coronary artery, only the subdivision with the highest defect score was considered. Proximal, middle, and distal segments of left anterior descending artery (LAD) were considered to be represented when the summed value of a subdivision within a particular arterial territory was more than or equal to 7, between 5 and 7, 5 and 3, respectively. For the left circumflex and right coronary artery, summed scores (of respective subdivisions) of more than or equal to 5 and between 3 and 5 were preassigned to proximal and distal stenosis, respectively. The results were then correlated with the coronary angiographic data. On coronary angiography, proximal LAD occlusion
INVERSE MODEL ESTIMATION AND EVALUATION OF SEASONAL NH 3 EMISSIONS
The presentation topic is inverse modeling for estimate and evaluation of emissions. The case study presented is the need for seasonal estimates of NH_{3} emissions for air quality modeling. The inverse modeling application approach is first described, and then the NH
Otton, James; Morton, Geraint; Schuster, Andreas; Bigalke, Boris; Marano, Riccardo; Olivotti, Luca; Nagel, Eike; Chiribiri, Amedeo
2013-01-01
Background Direct comparison of CT and magnetic resonance (MR) perfusion techniques has been limited and in vivo assessment is affected by physiological variability, timing of image acquisition, and parameter selection. Objective We precisely compared high-resolution k-t SENSE MR cardiac perfusion at 3 T with single-phase CT perfusion (CTP) under identical imaging conditions. Methods We used a customized MR imaging and CT compatible dynamic myocardial perfusion phantom to represent the human circulation. CT perfusion studies were performed with a Philips iCT (256 slice) CT, with isotropic resolution of 0.6 mm3. MR perfusion was performed with k-t SENSE acceleration at 3 T and spatial resolution of 1.2 × 1.2 × 10 mm. The image contrast between normal and underperfused myocardial compartments was quantified at various perfusion and photon energy settings. Noise estimates were based on published clinical data. Results Contrast by CTP highly depends on photon energy and also timing of imaging within the myocardial perfusion upslope. For an identical myocardial perfusion deficit, the native image contrast-to-noise ratio (CNR) generated by CT and MR are similar. If slice averaging is used, the CNR of a perfusion deficit is expected to be greater for CTP than MR perfusion (MRP). Perfect timing during single time point CTP imaging is difficult to achieve, and CNR by CT decreases by 24%–31% two seconds from the optimal imaging time point. Although single-phase CT perfusion offers higher spatial resolution, MRP allows multiple time point sampling and quantitative analysis. Conclusion The ability of CTP and current optimal MRP techniques to detect simulated myocardial perfusion deficits is similar. PMID:23622506
Wu, Ming-Che; Tsai, Cheng-Ting; Lin, Hui-Chun; Sun, Fang-Ju; Lin, Ku-Hung
2015-11-01
We analyzed the left-ventricular functional data obtained by cardiac-gated single-photon emission computed tomography myocardial perfusion imaging (MPI) with thallium-201 (Tl-201) and technetium-99m-sestamibi (MIBI) protocols in different groups of patients, and compared the data between Tl-201 and MIBI. Two hundred and seventy-two patients undergoing dipyridamole stress/redistribution Tl-201 MPI and 563 patients undergoing 1-day rest/dipyridamole stress MIBI MPI were included. Higher mean stress ejection fraction (EF), rest EF, and change in EF (ΔEF) were noticed in the normal MPI groups by both Tl-201 and MIBI protocols. Higher mean EF was observed in the females with normal MPI results despite their higher mean age. Comparisons between the Tl-201 and MIBI groups suggested a significant difference in all functional parameters, except for the rest end diastolic volume/end systolic volume and ΔEF between groups with negative MPI results. For the positive MPI groups, there was no significant difference in all parameters, except for the change in end diastolic volume and change in end systolic volume after stress between both protocols. The Tl-201 provides comparable left-ventricular functional data to MIBI cardiac-gated single-photon emission computed tomography in patients with positive MPI results, and may therefore be undertaken routinely for incremental functional information that is especially valuable to this patient group.
Wu, Ming-Che; Tsai, Cheng-Ting; Lin, Hui-Chun; Sun, Fang-Ju; Lin, Ku-Hung
2015-11-01
We analyzed the left-ventricular functional data obtained by cardiac-gated single-photon emission computed tomography myocardial perfusion imaging (MPI) with thallium-201 (Tl-201) and technetium-99m-sestamibi (MIBI) protocols in different groups of patients, and compared the data between Tl-201 and MIBI. Two hundred and seventy-two patients undergoing dipyridamole stress/redistribution Tl-201 MPI and 563 patients undergoing 1-day rest/dipyridamole stress MIBI MPI were included. Higher mean stress ejection fraction (EF), rest EF, and change in EF (ΔEF) were noticed in the normal MPI groups by both Tl-201 and MIBI protocols. Higher mean EF was observed in the females with normal MPI results despite their higher mean age. Comparisons between the Tl-201 and MIBI groups suggested a significant difference in all functional parameters, except for the rest end diastolic volume/end systolic volume and ΔEF between groups with negative MPI results. For the positive MPI groups, there was no significant difference in all parameters, except for the change in end diastolic volume and change in end systolic volume after stress between both protocols. The Tl-201 provides comparable left-ventricular functional data to MIBI cardiac-gated single-photon emission computed tomography in patients with positive MPI results, and may therefore be undertaken routinely for incremental functional information that is especially valuable to this patient group. PMID:26678935
Doubly robust estimation in missing data and causal inference models.
Bang, Heejung; Robins, James M
2005-12-01
The goal of this article is to construct doubly robust (DR) estimators in ignorable missing data and causal inference models. In a missing data model, an estimator is DR if it remains consistent when either (but not necessarily both) a model for the missingness mechanism or a model for the distribution of the complete data is correctly specified. Because with observational data one can never be sure that either a missingness model or a complete data model is correct, perhaps the best that can be hoped for is to find a DR estimator. DR estimators, in contrast to standard likelihood-based or (nonaugmented) inverse probability-weighted estimators, give the analyst two chances, instead of only one, to make a valid inference. In a causal inference model, an estimator is DR if it remains consistent when either a model for the treatment assignment mechanism or a model for the distribution of the counterfactual data is correctly specified. Because with observational data one can never be sure that a model for the treatment assignment mechanism or a model for the counterfactual data is correct, inference based on DR estimators should improve upon previous approaches. Indeed, we present the results of simulation studies which demonstrate that the finite sample performance of DR estimators is as impressive as theory would predict. The proposed method is applied to a cardiovascular clinical trial.
Cano, I; Roca, J; Wagner, P D
2015-01-01
Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation–perfusion and skeletal muscle metabolism–perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake ( and on mitochondrial (). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial () at sea level by 32 mmHg, but muscle by only 122 ml min−1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced by less than 1 mmHg and by 32 ml min−1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential among muscle regions, a range that becomes narrower as increases, and in regions with a low ratio of metabolic capacity to blood flow, can exceed that of mixed muscle venous blood. For patients with severe COPD, peak was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known. PMID:25640017
Consistency of Rasch Model Parameter Estimation: A Simulation Study.
ERIC Educational Resources Information Center
van den Wollenberg, Arnold L.; And Others
1988-01-01
The unconditional--simultaneous--maximum likelihood (UML) estimation procedure for the one-parameter logistic model produces biased estimators. The UML method is inconsistent and is not a good alternative to conditional maximum likelihood method, at least with small numbers of items. The minimum Chi-square estimation procedure produces unbiased…
Performance of Random Effects Model Estimators under Complex Sampling Designs
ERIC Educational Resources Information Center
Jia, Yue; Stokes, Lynne; Harris, Ian; Wang, Yan
2011-01-01
In this article, we consider estimation of parameters of random effects models from samples collected via complex multistage designs. Incorporation of sampling weights is one way to reduce estimation bias due to unequal probabilities of selection. Several weighting methods have been proposed in the literature for estimating the parameters of…
Intestinal perfusion monitoring using photoplethysmography
NASA Astrophysics Data System (ADS)
Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.
2013-08-01
In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.
Maximum likelihood estimation of finite mixture model for economic data
NASA Astrophysics Data System (ADS)
Phoong, Seuk-Yen; Ismail, Mohd Tahir
2014-06-01
Finite mixture model is a mixture model with finite-dimension. This models are provides a natural representation of heterogeneity in a finite number of latent classes. In addition, finite mixture models also known as latent class models or unsupervised learning models. Recently, maximum likelihood estimation fitted finite mixture models has greatly drawn statistician's attention. The main reason is because maximum likelihood estimation is a powerful statistical method which provides consistent findings as the sample sizes increases to infinity. Thus, the application of maximum likelihood estimation is used to fit finite mixture model in the present paper in order to explore the relationship between nonlinear economic data. In this paper, a two-component normal mixture model is fitted by maximum likelihood estimation in order to investigate the relationship among stock market price and rubber price for sampled countries. Results described that there is a negative effect among rubber price and stock market price for Malaysia, Thailand, Philippines and Indonesia.
Distributed Damage Estimation for Prognostics based on Structural Model Decomposition
NASA Technical Reports Server (NTRS)
Daigle, Matthew; Bregon, Anibal; Roychoudhury, Indranil
2011-01-01
Model-based prognostics approaches capture system knowledge in the form of physics-based models of components, and how they fail. These methods consist of a damage estimation phase, in which the health state of a component is estimated, and a prediction phase, in which the health state is projected forward in time to determine end of life. However, the damage estimation problem is often multi-dimensional and computationally intensive. We propose a model decomposition approach adapted from the diagnosis community, called possible conflicts, in order to both improve the computational efficiency of damage estimation, and formulate a damage estimation approach that is inherently distributed. Local state estimates are combined into a global state estimate from which prediction is performed. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the approach.
Student Models for Prior Knowledge Estimation
ERIC Educational Resources Information Center
Nižnan, Juraj; Pelánek, Radek; Rihák, Jirí
2015-01-01
Intelligent behavior of adaptive educational systems is based on student models. Most research in student modeling focuses on student learning (acquisition of skills). We focus on prior knowledge, which gets much less attention in modeling and yet can be highly varied and have important consequences for the use of educational systems. We describe…
Obtaining Diagnostic Classification Model Estimates Using Mplus
ERIC Educational Resources Information Center
Templin, Jonathan; Hoffman, Lesa
2013-01-01
Diagnostic classification models (aka cognitive or skills diagnosis models) have shown great promise for evaluating mastery on a multidimensional profile of skills as assessed through examinee responses, but continued development and application of these models has been hindered by a lack of readily available software. In this article we…
The use of models in the estimation of disease epidemiology.
Kruijshaar, Michelle E.; Barendregt, Jan J.; Hoeymans, Nancy
2002-01-01
OBJECTIVE: To explore the usefulness of incidence-prevalence-mortality (IPM) models in improving estimates of disease epidemiology. METHODS: Two artificial and four empirical data sets (for breast, prostate, colorectal, and stomach cancer) were employed in IPM models. FINDINGS: The internally consistent artificial data sets could be reproduced virtually identically by the models. Our estimates often differed considerably from the empirical data sets, especially for breast and prostate cancer and for older ages. Only for stomach cancer did the estimates approximate to the data, except at older ages. CONCLUSION: There is evidence that the discrepancies between model estimates and observations are caused both by data inaccuracies and past trends in incidence or mortality. Because IPM models cannot distinguish these effects, their use in improving disease estimates becomes complicated. Expert opinion is indispensable in assessing whether the use of these models improves data quality or, inappropriately, removes the effect of trends. PMID:12219152
A simulation of water pollution model parameter estimation
NASA Technical Reports Server (NTRS)
Kibler, J. F.
1976-01-01
A parameter estimation procedure for a water pollution transport model is elaborated. A two-dimensional instantaneous-release shear-diffusion model serves as representative of a simple transport process. Pollution concentration levels are arrived at via modeling of a remote-sensing system. The remote-sensed data are simulated by adding Gaussian noise to the concentration level values generated via the transport model. Model parameters are estimated from the simulated data using a least-squares batch processor. Resolution, sensor array size, and number and location of sensor readings can be found from the accuracies of the parameter estimates.
Assessing Uncertainty of Interspecies Correlation Estimation Models for Aromatic Compounds
We developed Interspecies Correlation Estimation (ICE) models for aromatic compounds containing 1 to 4 benzene rings to assess uncertainty in toxicity extrapolation in two data compilation approaches. ICE models are mathematical relationships between surrogate and predicted test ...
Mixture Rasch Models with Joint Maximum Likelihood Estimation
ERIC Educational Resources Information Center
Willse, John T.
2011-01-01
This research provides a demonstration of the utility of mixture Rasch models. Specifically, a model capable of estimating a mixture partial credit model using joint maximum likelihood is presented. Like the partial credit model, the mixture partial credit model has the beneficial feature of being appropriate for analysis of assessment data…
Frog intestinal perfusion to evaluate drug permeability: application to p-gp and cyp3a4 substrates
Yerasi, Neelima; Vurimindi, Himabindu; Devarakonda, Krishna
2015-01-01
To evaluate the reliability of using in situ frog intestinal perfusion technique for permeability assessment of carrier transported drugs which are also substrates for CYP enzymes. Single Pass Intestinal Perfusion (SPIP) studies were performed in frogs of the species Rana tigrina using established method for rats with some modifications after inducing anesthesia. Effective permeability coefficient (Peff) of losartan and midazolam was calculated in the presence and absence of inhibitors using the parallel-tube model. Peff of losartan when perfused alone was found to be 0.427 ± 0.27 × 10-4cm/s and when it was co-perfused with inhibitors, significant change in Peff was observed. Peff of midazolam when perfused alone was found to be 2.03 ± 0.07 × 10-4cm/s and when it was co-perfused with inhibitors, no significant change in Peff was observed. Comparison of Peff calculated in frog with that of other available models and also humans suggested that the Peff-values are comparable and reflected well with human intestinal permeability. It is possible to determine the Peff-value for compounds which are dual substrates of P-glycoprotein and CYP3A4 using in situ frog intestinal perfusion technique. The calculated Peff-values correlated well with reported Peff-values of probe drugs. comparison of the Peff-value of losartan obtained with that of reported human’s Peff and Caco 2 cell data, and comparison of the Peff-value of midazolam with that of reported rat’s Peff, we could conclude that SPIP from model can be reliably used in preclinical studies for permeability estimation. This model may represent a valuable alternative to the low speed and high cost of conventional animal models (typically rodents) for the assessment of intestinal permeability. PMID:26236236
Estimating Lead (Pb) Bioavailability In A Mouse Model
Children are exposed to Pb through ingestion of Pb-contaminated soil. Soil Pb bioavailability is estimated using animal models or with chemically defined in vitro assays that measure bioaccessibility. However, bioavailability estimates in a large animal model (e.g., swine) can be...
Meteorological models for estimating phenology of corn
NASA Technical Reports Server (NTRS)
Daughtry, C. S. T.; Cochran, J. C.; Hollinger, S. E.
1984-01-01
Knowledge of when critical crop stages occur and how the environment affects them should provide useful information for crop management decisions and crop production models. Two sources of data were evaluated for predicting dates of silking and physiological maturity of corn (Zea mays L.). Initial evaluations were conducted using data of an adapted corn hybrid grown on a Typic Agriaquoll at the Purdue University Agronomy Farm. The second phase extended the analyses to large areas using data acquired by the Statistical Reporting Service of USDA for crop reporting districts (CRD) in Indiana and Iowa. Several thermal models were compared to calendar days for predicting dates of silking and physiological maturity. Mixed models which used a combination of thermal units to predict silking and days after silking to predict physiological maturity were also evaluated. At the Agronomy Farm the models were calibrated and tested on the same data. The thermal models were significantly less biased and more accurate than calendar days for predicting dates of silking. Differences among the thermal models were small. Significant improvements in both bias and accuracy were observed when the mixed models were used to predict dates of physiological maturity. The results indicate that statistical data for CRD can be used to evaluate models developed at agricultural experiment stations.
ESTIMATING UNCERTAINITIES IN FACTOR ANALYTIC MODELS
When interpreting results from factor analytic models as used in receptor modeling, it is important to quantify the uncertainties in those results. For example, if the presence of a species on one of the factors is necessary to interpret the factor as originating from a certain ...
Improved Subspace Estimation for Low-Rank Model-Based Accelerated Cardiac Imaging
Hitchens, T. Kevin; Wu, Yijen L.; Ho, Chien; Liang, Zhi-Pei
2014-01-01
Sparse sampling methods have emerged as effective tools to accelerate cardiac magnetic resonance imaging (MRI). Low-rank model-based cardiac imaging uses a pre-determined temporal subspace for image reconstruction from highly under-sampled (k, t)-space data and has been demonstrated effective for high-speed cardiac MRI. The accuracy of the temporal subspace is a key factor in these methods, yet little work has been published on data acquisition strategies to improve subspace estimation. This paper investigates the use of non-Cartesian k-space trajectories to replace the Cartesian trajectories which are omnipresent but are highly sensitive to readout direction. We also propose “self-navigated” pulse sequences which collect both navigator data (for determining the temporal subspace) and imaging data after every RF pulse, allowing for even greater acceleration. We investigate subspace estimation strategies through analysis of phantom images and demonstrate in vivo cardiac imaging in rats and mice without the use of ECG or respiratory gating. The proposed methods achieved 3-D imaging of wall motion, first-pass myocardial perfusion, and late gadolinium enhancement in rats at 74 frames per second (fps), as well as 2-D imaging of wall motion in mice at 97 fps. PMID:24801352
Estimation of population size using open capture-recapture models
McDonald, T.L.; Amstrup, Steven C.
2001-01-01
One of the most important needs for wildlife managers is an accurate estimate of population size. Yet, for many species, including most marine species and large mammals, accurate and precise estimation of numbers is one of the most difficult of all research challenges. Open-population capture-recapture models have proven useful in many situations to estimate survival probabilities but typically have not been used to estimate population size. We show that open-population models can be used to estimate population size by developing a Horvitz-Thompson-type estimate of population size and an estimator of its variance. Our population size estimate keys on the probability of capture at each trap occasion and therefore is quite general and can be made a function of external covariates measured during the study. Here we define the estimator and investigate its bias, variance, and variance estimator via computer simulation. Computer simulations make extensive use of real data taken from a study of polar bears (Ursus maritimus) in the Beaufort Sea. The population size estimator is shown to be useful because it was negligibly biased in all situations studied. The variance estimator is shown to be useful in all situations, but caution is warranted in cases of extreme capture heterogeneity.
Yifat, Jonathan; Gannot, Israel
2015-03-01
Early detection of malignant tumors plays a crucial role in the survivability chances of the patient. Therefore, new and innovative tumor detection methods are constantly searched for. Tumor-specific magnetic-core nano-particles can be used with an alternating magnetic field to detect and treat tumors by hyperthermia. For the analysis of the method effectiveness, the bio-heat transfer between the nanoparticles and the tissue must be carefully studied. Heat diffusion in biological tissue is usually analyzed using the Pennes Bio-Heat Equation, where blood perfusion plays an important role. Malignant tumors are known to initiate an angiogenesis process, where endothelial cell migration from neighboring vasculature eventually leads to the formation of a thick blood capillary network around them. This process allows the tumor to receive its extensive nutrition demands and evolve into a more progressive and potentially fatal tumor. In order to assess the effect of angiogenesis on the bio-heat transfer problem, we have developed a discrete stochastic 3D model & simulation of tumor-induced angiogenesis. The model elaborates other angiogenesis models by providing high resolution 3D stochastic simulation, capturing of fine angiogenesis morphological features, effects of dynamic sprout thickness functions, and stochastic parent vessel generator. We show that the angiogenesis realizations produced are well suited for numerical bio-heat transfer analysis. Statistical study on the angiogenesis characteristics was derived using Monte Carlo simulations. According to the statistical analysis, we provide analytical expression for the blood perfusion coefficient in the Pennes equation, as a function of several parameters. This updated form of the Pennes equation could be used for numerical and analytical analyses of the proposed detection and treatment method.
Yifat, Jonathan; Gannot, Israel
2015-03-01
Early detection of malignant tumors plays a crucial role in the survivability chances of the patient. Therefore, new and innovative tumor detection methods are constantly searched for. Tumor-specific magnetic-core nano-particles can be used with an alternating magnetic field to detect and treat tumors by hyperthermia. For the analysis of the method effectiveness, the bio-heat transfer between the nanoparticles and the tissue must be carefully studied. Heat diffusion in biological tissue is usually analyzed using the Pennes Bio-Heat Equation, where blood perfusion plays an important role. Malignant tumors are known to initiate an angiogenesis process, where endothelial cell migration from neighboring vasculature eventually leads to the formation of a thick blood capillary network around them. This process allows the tumor to receive its extensive nutrition demands and evolve into a more progressive and potentially fatal tumor. In order to assess the effect of angiogenesis on the bio-heat transfer problem, we have developed a discrete stochastic 3D model & simulation of tumor-induced angiogenesis. The model elaborates other angiogenesis models by providing high resolution 3D stochastic simulation, capturing of fine angiogenesis morphological features, effects of dynamic sprout thickness functions, and stochastic parent vessel generator. We show that the angiogenesis realizations produced are well suited for numerical bio-heat transfer analysis. Statistical study on the angiogenesis characteristics was derived using Monte Carlo simulations. According to the statistical analysis, we provide analytical expression for the blood perfusion coefficient in the Pennes equation, as a function of several parameters. This updated form of the Pennes equation could be used for numerical and analytical analyses of the proposed detection and treatment method. PMID:24462603
Estimating parameters for generalized mass action models with connectivity information
Ko, Chih-Lung; Voit, Eberhard O; Wang, Feng-Sheng
2009-01-01
Background Determining the parameters of a mathematical model from quantitative measurements is the main bottleneck of modelling biological systems. Parameter values can be estimated from steady-state data or from dynamic data. The nature of suitable data for these two types of estimation is rather different. For instance, estimations of parameter values in pathway models, such as kinetic orders, rate constants, flux control coefficients or elasticities, from steady-state data are generally based on experiments that measure how a biochemical system responds to small perturbations around the steady state. In contrast, parameter estimation from dynamic data requires time series measurements for all dependent variables. Almost no literature has so far discussed the combined use of both steady-state and transient data for estimating parameter values of biochemical systems. Results In this study we introduce a constrained optimization method for estimating parameter values of biochemical pathway models using steady-state information and transient measurements. The constraints are derived from the flux connectivity relationships of the system at the steady state. Two case studies demonstrate the estimation results with and without flux connectivity constraints. The unconstrained optimal estimates from dynamic data may fit the experiments well, but they do not necessarily maintain the connectivity relationships. As a consequence, individual fluxes may be misrepresented, which may cause problems in later extrapolations. By contrast, the constrained estimation accounting for flux connectivity information reduces this misrepresentation and thereby yields improved model parameters. Conclusion The method combines transient metabolic profiles and steady-state information and leads to the formulation of an inverse parameter estimation task as a constrained optimization problem. Parameter estimation and model selection are simultaneously carried out on the constrained
These model-based estimates use two surveys, the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS). The two surveys are combined using novel statistical methodology.
Comparison of Estimation Procedures for Multilevel AR(1) Models.
Krone, Tanja; Albers, Casper J; Timmerman, Marieke E
2016-01-01
To estimate a time series model for multiple individuals, a multilevel model may be used. In this paper we compare two estimation methods for the autocorrelation in Multilevel AR(1) models, namely Maximum Likelihood Estimation (MLE) and Bayesian Markov Chain Monte Carlo. Furthermore, we examine the difference between modeling fixed and random individual parameters. To this end, we perform a simulation study with a fully crossed design, in which we vary the length of the time series (10 or 25), the number of individuals per sample (10 or 25), the mean of the autocorrelation (-0.6 to 0.6 inclusive, in steps of 0.3) and the standard deviation of the autocorrelation (0.25 or 0.40). We found that the random estimators of the population autocorrelation show less bias and higher power, compared to the fixed estimators. As expected, the random estimators profit strongly from a higher number of individuals, while this effect is small for the fixed estimators. The fixed estimators profit slightly more from a higher number of time points than the random estimators. When possible, random estimation is preferred to fixed estimation. The difference between MLE and Bayesian estimation is nearly negligible. The Bayesian estimation shows a smaller bias, but MLE shows a smaller variability (i.e., standard deviation of the parameter estimates). Finally, better results are found for a higher number of individuals and time points, and for a lower individual variability of the autocorrelation. The effect of the size of the autocorrelation differs between outcome measures. PMID:27242559
Estimating Neuronal Ageing with Hidden Markov Models
NASA Astrophysics Data System (ADS)
Wang, Bing; Pham, Tuan D.
2011-06-01
Neuronal degeneration is widely observed in normal ageing, meanwhile the neurode-generative disease like Alzheimer's disease effects neuronal degeneration in a faster way which is considered as faster ageing. Early intervention of such disease could benefit subjects with potentials of positive clinical outcome, therefore, early detection of disease related brain structural alteration is required. In this paper, we propose a computational approach for modelling the MRI-based structure alteration with ageing using hidden Markov model. The proposed hidden Markov model based brain structural model encodes intracortical tissue/fluid distribution using discrete wavelet transformation and vector quantization. Further, it captures gray matter volume loss, which is capable of reflecting subtle intracortical changes with ageing. Experiments were carried out on healthy subjects to validate its accuracy and robustness. Results have shown its ability of predicting the brain age with prediction error of 1.98 years without training data, which shows better result than other age predition methods.
Recharge estimation for transient ground water modeling.
Jyrkama, Mikko I; Sykes, Jon F; Normani, Stefano D
2002-01-01
Reliable ground water models require both an accurate physical representation of the system and appropriate boundary conditions. While physical attributes are generally considered static, boundary conditions, such as ground water recharge rates, can be highly variable in both space and time. A practical methodology incorporating the hydrologic model HELP3 in conjunction with a geographic information system was developed to generate a physically based and highly detailed recharge boundary condition for ground water modeling. The approach uses daily precipitation and temperature records in addition to land use/land cover and soils data. The importance of the method in transient ground water modeling is demonstrated by applying it to a MODFLOW modeling study in New Jersey. In addition to improved model calibration, the results from the study clearly indicate the importance of using a physically based and highly detailed recharge boundary condition in ground water quality modeling, where the detailed knowledge of the evolution of the ground water flowpaths is imperative. The simulated water table is within 0.5 m of the observed values using the method, while the water levels can differ by as much as 2 m using uniform recharge conditions. The results also show that the combination of temperature and precipitation plays an important role in the amount and timing of recharge in cooler climates. A sensitivity analysis further reveals that increasing the leaf area index, the evaporative zone depth, or the curve number in the model will result in decreased recharge rates over time, with the curve number having the greatest impact.
Tran-Dinh, S; Hoerter, J A; Mateo, P; Bouet, F; Herve, M
1997-04-15
We propose a simple mathematical model and a practical approach for evaluating the flux constant and the absolute value of flux in the citric acid cycle in perfused organs by 13C-NMR and 1H-NMR spectroscopy. We demonstrate that 13C-NMR glutamate spectra are independent of the relative sizes of the mitochondrial and cytosolic compartments and the exchange rates of glutamates, unless there is a difference in 13C chemical shifts of glutamate carbons between the two compartments. Wistar rat hearts (five beating and four KCl-arrested hearts) were aerobically perfused with 100% enriched [2-(13)C]acetate and the kinetics of glutamate carbon labeling from perchloric acid extracts were studied at various perfusion times. Under our experimental conditions, the citric acid cycle flux constant, which represents the fraction of glutamate in exchange with the citric acid cycle per unit time, is about 0.350 +/- 0.003 min(-1) for beating hearts and 0.0741 +/- 0.004 min(-1) for KCl-arrested hearts. The absolute values of the citric acid flux for beating hearts and for KCl-arrested hearts are 1.06 +/- 0.06 micromol x min(-1) x mg(-1) and 0.21 +/- 0.02 micromol x min(-1) x g(-1), respectively. The fraction of unlabeled acetate determined from the proton signal of the methyl group is small and essentially the same in beating and arrested hearts (7.4 +/- 1.7% and 8.8 +/- 2.1%, respectively). Thus, the large difference in the Glu C2/C4 between beating and arrested hearts is not due to the important contribution from anaplerotic sources in arrested hearts but simply to a substantial difference in citric acid cycle fluxes. Our model fits the experimental data well, indicating a fast exchange between 2-oxoglutarate and glutamate in the mitochondria of rat hearts. Analysis of the flux constant, calculated from the half-time of glutamate C4 labeling given in the literature, allows for a comparison of the citric acid flux for various working conditions in different animal species.
Modelling approaches to dose estimation in children
Johnson, Trevor N
2005-01-01
Introduction Most of the drugs on the market are originally developed for adults and dosage selection is based on an optimal balance between clinical efficacy and safety. The aphorism ‘children are not small adults’ not only holds true for the selection of suitable drugs and dosages for use in children but also their susceptibility to adverse drug reactions [1]. Since children may not be subject to dose escalation studies similar to those carried out in the adult population, some initial estimation of dose in paediatrics should be obtained via extrapolation approaches. However, following such an exercise, well-conducted PK-PD or PK studies will still be needed to determine the most appropriate doses for neonates, infants, children and adolescents. PMID:15948929
A regression model to estimate regional ground water recharge
Lorenz, D.L.; Delin, G.N.
2007-01-01
A regional regression model was developed to estimate the spatial distribution of ground water recharge in subhumid regions. The regional regression recharge (RRR) model was based on a regression of basin-wide estimates of recharge from surface water drainage basins, precipitation, growing degree days (GDD), and average basin specific yield (SY). Decadal average recharge, precipitation, and GDD were used in the RRR model. The RRR estimates were derived from analysis of stream base flow using a computer program that was based on the Rorabaugh method. As expected, there was a strong correlation between recharge and precipitation. The model was applied to statewide data in Minnesota. Where precipitation was least in the western and northwestern parts of the state (50 to 65 cm/year), recharge computed by the RRR model also was lowest (0 to 5 cm/year). A strong correlation also exists between recharge and SY. SY was least in areas where glacial lake clay occurs, primarily in the northwest part of the state; recharge estimates in these areas were in the 0- to 5-cm/year range. In sand-plain areas where SY is greatest, recharge estimates were in the 15- to 29-cm/year range on the basis of the RRR model. Recharge estimates that were based on the RRR model compared favorably with estimates made on the basis of other methods. The RRR model can be applied in other subhumid regions where region wide data sets of precipitation, streamflow, GDD, and soils data are available.
A regression model to estimate regional ground water recharge.
Lorenz, David L; Delin, Geoffrey N
2007-01-01
A regional regression model was developed to estimate the spatial distribution of ground water recharge in subhumid regions. The regional regression recharge (RRR) model was based on a regression of basin-wide estimates of recharge from surface water drainage basins, precipitation, growing degree days (GDD), and average basin specific yield (SY). Decadal average recharge, precipitation, and GDD were used in the RRR model. The RRR estimates were derived from analysis of stream base flow using a computer program that was based on the Rorabaugh method. As expected, there was a strong correlation between recharge and precipitation. The model was applied to statewide data in Minnesota. Where precipitation was least in the western and northwestern parts of the state (50 to 65 cm/year), recharge computed by the RRR model also was lowest (0 to 5 cm/year). A strong correlation also exists between recharge and SY. SY was least in areas where glacial lake clay occurs, primarily in the northwest part of the state; recharge estimates in these areas were in the 0- to 5-cm/year range. In sand-plain areas where SY is greatest, recharge estimates were in the 15- to 29-cm/year range on the basis of the RRR model. Recharge estimates that were based on the RRR model compared favorably with estimates made on the basis of other methods. The RRR model can be applied in other subhumid regions where region wide data sets of precipitation, streamflow, GDD, and soils data are available.
Adjoint method for estimating Jiles-Atherton hysteresis model parameters
NASA Astrophysics Data System (ADS)
Zaman, Mohammad Asif; Hansen, Paul C.; Neustock, Lars T.; Padhy, Punnag; Hesselink, Lambertus
2016-09-01
A computationally efficient method for identifying the parameters of the Jiles-Atherton hysteresis model is presented. Adjoint analysis is used in conjecture with an accelerated gradient descent optimization algorithm. The proposed method is used to estimate the Jiles-Atherton model parameters of two different materials. The obtained results are found to be in good agreement with the reported values. By comparing with existing methods of model parameter estimation, the proposed method is found to be computationally efficient and fast converging.
Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.
2016-01-01
Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This
DEVELOPMENT OF RESIDENTIAL WOOD COMSUMPTION ESTIMATION MODELS
The report gives data on the distribution and usage of firewood, obtained from a pool of household wood use surveys. ased on a series of regression models developed using the STEPWISE procedure in the SAS statistical package, two variables appear to be most predictive of wood use...
Chen, Ying; Liu, Xinmin; Pan, Ruile; Zhu, Xiaoxin; Steinmetz, André; Liao, Yonghong; Wang, Ning; Peng, Bo; Chang, Qi
2013-10-01
3,6'-Disinapoylsucrose is a major active component of the herb Polygala tenuifolia which has long been used for relieving tranquilization, uneasiness of the mind, and improving learning and memory. Our previous study found that 3,6'-disinapoylsucrose had a very low oral bioavailability. Its mechanisms of absorption in the small intestine have so far been unclear. In the present study, the absorption mechanisms of 3,6'-disinapoylsucrose were investigated by using the Caco-2 cell monolayer and in situ rat intestinal perfusion models. The 3,6'-disinapoylsucrose concentration was determined by an LC/MS/MS method. In a Caco-2 cell transport study, the results showed that 3,6'-disinapoylsucrose had very limited intestinal permeability with average apparent permeability coefficient values around (1.11-1.34) × 10(-7) cm/s from the apical (A) to the basolateral (B) side and (1.37-1.42) × 10(-7) cm/s from B to A, at concentrations of 5, 20, and 33 µM. No concentration dependence in the 3,6'-disinapoylsucrose transport was observed. The apparent permeability coefficient value of 3,6'-disinapoylsucrose (5 µM) from A to B greatly increased to 4.49 × 10(-7) and 1.81 × 10(-7) cm/s, respectively, when the cells were preincubated with EDTA (17 mM) and sodium caprate (5.14 mM). No significant effect on the 3,6'-disinapoylsucrose transport by the inhibitors including verapamil, cyclosporine A, and sodium azide was observed. Similar results were found in the small intestinal perfusion study. The apparent permeability coefficient value of 3,6'-disinapoylsucrose greatly increased from 3.97 × 10(-6) to 23.4 × 10(-6) and 20.0 × 10(-6) cm/s in the presence of EDTA (17 mM) and sodium caprate (5.14 mM), respectively, in perfusion buffer. An in vitro stability evaluation of 3,6'-disinapoylsucrose in the gastrointestinal tract showed that it was relatively stable both in the stomach and small intestine contents, while it was found to be more instable in the colon contents. All of the
Chen, Ying; Liu, Xinmin; Pan, Ruile; Zhu, Xiaoxin; Steinmetz, André; Liao, Yonghong; Wang, Ning; Peng, Bo; Chang, Qi
2013-10-01
3,6'-Disinapoylsucrose is a major active component of the herb Polygala tenuifolia which has long been used for relieving tranquilization, uneasiness of the mind, and improving learning and memory. Our previous study found that 3,6'-disinapoylsucrose had a very low oral bioavailability. Its mechanisms of absorption in the small intestine have so far been unclear. In the present study, the absorption mechanisms of 3,6'-disinapoylsucrose were investigated by using the Caco-2 cell monolayer and in situ rat intestinal perfusion models. The 3,6'-disinapoylsucrose concentration was determined by an LC/MS/MS method. In a Caco-2 cell transport study, the results showed that 3,6'-disinapoylsucrose had very limited intestinal permeability with average apparent permeability coefficient values around (1.11-1.34) × 10(-7) cm/s from the apical (A) to the basolateral (B) side and (1.37-1.42) × 10(-7) cm/s from B to A, at concentrations of 5, 20, and 33 µM. No concentration dependence in the 3,6'-disinapoylsucrose transport was observed. The apparent permeability coefficient value of 3,6'-disinapoylsucrose (5 µM) from A to B greatly increased to 4.49 × 10(-7) and 1.81 × 10(-7) cm/s, respectively, when the cells were preincubated with EDTA (17 mM) and sodium caprate (5.14 mM). No significant effect on the 3,6'-disinapoylsucrose transport by the inhibitors including verapamil, cyclosporine A, and sodium azide was observed. Similar results were found in the small intestinal perfusion study. The apparent permeability coefficient value of 3,6'-disinapoylsucrose greatly increased from 3.97 × 10(-6) to 23.4 × 10(-6) and 20.0 × 10(-6) cm/s in the presence of EDTA (17 mM) and sodium caprate (5.14 mM), respectively, in perfusion buffer. An in vitro stability evaluation of 3,6'-disinapoylsucrose in the gastrointestinal tract showed that it was relatively stable both in the stomach and small intestine contents, while it was found to be more instable in the colon contents. All of the
Gaussian estimation for discretely observed Cox-Ingersoll-Ross model
NASA Astrophysics Data System (ADS)
Wei, Chao; Shu, Huisheng; Liu, Yurong
2016-07-01
This paper is concerned with the parameter estimation problem for Cox-Ingersoll-Ross model based on discrete observation. First, a new discretized process is built based on the Euler-Maruyama scheme. Then, the parameter estimators are obtained by employing the maximum likelihood method and the explicit expressions of the error of estimation are given. Subsequently, the consistency property of all parameter estimators are proved by applying the law of large numbers for martingales, Holder's inequality, B-D-G inequality and Cauchy-Schwarz inequality. Finally, a numerical simulation example for estimators and the absolute error between estimators and true values is presented to demonstrate the effectiveness of the estimation approach used in this paper.
Battery Calendar Life Estimator Manual Modeling and Simulation
Jon P. Christophersen; Ira Bloom; Ed Thomas; Vince Battaglia
2012-10-01
The Battery Life Estimator (BLE) Manual has been prepared to assist developers in their efforts to estimate the calendar life of advanced batteries for automotive applications. Testing requirements and procedures are defined by the various manuals previously published under the United States Advanced Battery Consortium (USABC). The purpose of this manual is to describe and standardize a method for estimating calendar life based on statistical models and degradation data acquired from typical USABC battery testing.
Stochastic Wireless Channel Modeling, Estimation and Identification from Measurements
Olama, Mohammed M; Djouadi, Seddik M; Li, Yanyan
2008-07-01
This paper is concerned with stochastic modeling of wireless fading channels, parameter estimation, and system identification from measurement data. Wireless channels are represented by stochastic state-space form, whose parameters and state variables are estimated using the expectation maximization algorithm and Kalman filtering, respectively. The latter are carried out solely from received signal measurements. These algorithms estimate the channel inphase and quadrature components and identify the channel parameters recursively. The proposed algorithm is tested using measurement data, and the results are presented.
Reeb, Jeremie; Cypel, Marcelo
2016-03-01
Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. PMID:26700566
Estimating restricted mean treatment effects with stacked survival models.
Wey, Andrew; Vock, David M; Connett, John; Rudser, Kyle
2016-08-30
The difference in restricted mean survival times between two groups is a clinically relevant summary measure. With observational data, there may be imbalances in confounding variables between the two groups. One approach to account for such imbalances is estimating a covariate-adjusted restricted mean difference by modeling the covariate-adjusted survival distribution and then marginalizing over the covariate distribution. Because the estimator for the restricted mean difference is defined by the estimator for the covariate-adjusted survival distribution, it is natural to expect that a better estimator of the covariate-adjusted survival distribution is associated with a better estimator of the restricted mean difference. We therefore propose estimating restricted mean differences with stacked survival models. Stacked survival models estimate a weighted average of several survival models by minimizing predicted error. By including a range of parametric, semi-parametric, and non-parametric models, stacked survival models can robustly estimate a covariate-adjusted survival distribution and, therefore, the restricted mean treatment effect in a wide range of scenarios. We demonstrate through a simulation study that better performance of the covariate-adjusted survival distribution often leads to better mean squared error of the restricted mean difference although there are notable exceptions. In addition, we demonstrate that the proposed estimator can perform nearly as well as Cox regression when the proportional hazards assumption is satisfied and significantly better when proportional hazards is violated. Finally, the proposed estimator is illustrated with data from the United Network for Organ Sharing to evaluate post-lung transplant survival between large-volume and small-volume centers. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26934835
Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.
2014-01-01
Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422
Model-Based Estimation of Active Knee Stiffness
Pfeifer, Serge; Hardegger, Michael; Vallery, Heike; List, Renate; Foresti, Mauro; Riener, Robert; Perreault, Eric J.
2013-01-01
Knee joint impedance varies substantially during physiological gait. Quantifying this modulation is critical for the design of transfemoral prostheses that aim to mimic physiological limb behavior. Conventional methods for quantifying joint impedance typically involve perturbing the joint in a controlled manner, and describing impedance as the dynamic relationship between applied perturbations and corresponding joint torques. These experimental techniques, however, are difficult to apply during locomotion without impeding natural movements. In this paper, we propose a method to estimate the elastic component of knee joint impedance that depends on muscle activation, often referred to as active knee stiffness. The method estimates stiffness using a musculoskeletal model of the leg and a model for activation-dependent short-range muscle stiffness. Muscle forces are estimated from measurements including limb kinematics, kinetics and muscle electromyograms. For isometric validation, we compare model estimates to measurements involving joint perturbations; measured stiffness is 17% lower than model estimates for extension, and 42% lower for flexion torques. We show that sensitivity of stiffness estimates to common approaches for estimating muscle force is small in isometric conditions. We also make initial estimates of how knee stiffness is modulated during gait, illustrating how this approach may be used to obtain parameters relevant to the design of transfemoral prostheses. PMID:22275672
Kuo, Yur-Ren; Wang, Chun-Ting; Wang, Feng-Sheng; Chiang, Yuan-Cheng; Wang, Ching-Jen
2009-01-01
Extracorporeal shock-wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio-mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 x 5 cm) in a streptozotocin-induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW-1) on day 3 (800 impulses at 0.09 mJ/mm(2)) postwounding; group IV included rats that underwent two sessions of ESWT (ESW-2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW-3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT-treated rats, especially in the ESW-2 and ESW-3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro-inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW-2 and ESW-3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo-angiogenesis and tissue regeneration, and topical anti-inflammatory response.
Klabusay, Martin; Scheer, Peter; Doubek, Michael; Rehakova, Kristina; Coupek, Petr; Horky, Drahomir
2009-02-01
Cell therapy of myocardial infarction (MI) is under clinical investigation, yet little is known about its underlying mechanism of function. Our aims were to induce a sub-lethal myocardial infarction in a rabbit, to evaluate the abilities of labeled bone marrow mononuclear cells to migrate from the vessel bed into extracellular space of the myocardium, and to evaluate the short-term distribution of cells in the damaged left ventricle. Sub-lethal myocardial infarction was induced in rabbits by ligation of the left coronary vessel branch (in vivo). The Langendorff heart perfusion model (ex vivo) was used in the next phase. The hearts subjected to MI induction were divided into 3 groups (P1-P3), and hearts without MI formed a control group (C). Nanoparticles-labeled bone marrow mononuclear cells were injected into coronary arteries via the aorta. Perfusion after application lasted 2 minutes in the P1 group, 10 minutes in the P2 and C groups, and 25 minutes in the P3 group. The myocardium of the left ventricle was examined histologically, and the numbers of labeled cells in vessels, myocardium, and combined were determined. The numbers of detected cells in the P1 and C groups were significantly lower than in the P2 and P3 groups. In the P2 and P3 groups, the numbers of cells found distally from the ligation were significantly higher than proximally from the ligation site. Bone marrow mononuclear cells labeled with iron oxide nanoparticles proved the ability to migrate in the myocardium interstitium with significantly higher affinity for the tissue damaged by infarction.
Perfusion Electronic Record Documentation Using Epic Systems Software.
Riley, Jeffrey B; Justison, George A
2015-12-01
The authors comment on Steffens and Gunser's article describing the University of Wisconsin adoption of the Epic anesthesia record to include perfusion information from the cardiopulmonary bypass patient experience. We highlight the current-day lessons and the valuable quality and safety principles the Wisconsin-Epic model anesthesia-perfusion record provides.
Cardiac tissue engineering using perfusion bioreactor systems
Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana
2009-01-01
This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955
Robust Estimation of Ability in the Rasch Model.
ERIC Educational Resources Information Center
Wainer, Howard; Wright, Benjamin D.
The pure Rasch model was compared with four modifications of the model in a number of different simulations in order to ascertain the comparative efficiencies of the parameter estimations of these modifications. Because there is always noise in test score data, some individuals may have response patterns that do not fit the model and their…
Local Solutions in the Estimation of Growth Mixture Models
ERIC Educational Resources Information Center
Hipp, John R.; Bauer, Daniel J.
2006-01-01
Finite mixture models are well known to have poorly behaved likelihood functions featuring singularities and multiple optima. Growth mixture models may suffer from fewer of these problems, potentially benefiting from the structure imposed on the estimated class means and covariances by the specified growth model. As demonstrated here, however,…
Assumptions of Value-Added Models for Estimating School Effects
ERIC Educational Resources Information Center
Reardon, Sean F.; Raudenbush, Stephen W.
2009-01-01
The ability of school (or teacher) value-added models to provide unbiased estimates of school (or teacher) effects rests on a set of assumptions. In this article, we identify six assumptions that are required so that the estimands of such models are well defined and the models are able to recover the desired parameters from observable data. These…
Parameter Estimates in Differential Equation Models for Population Growth
ERIC Educational Resources Information Center
Winkel, Brian J.
2011-01-01
We estimate the parameters present in several differential equation models of population growth, specifically logistic growth models and two-species competition models. We discuss student-evolved strategies and offer "Mathematica" code for a gradient search approach. We use historical (1930s) data from microbial studies of the Russian biologist,…
Jaworski, Jacek; Redlarski, Grzegorz
2014-08-01
This paper presents a model of alveolar-capillary oxygen diffusion with dynamics of air transport through the respiratory tract. For this purpose electrical model representing the respiratory tract mechanics and differential equations representing oxygen membrane diffusion are combined. Relevant thermodynamic relations describing the mass of oxygen transported into the human body are proposed as the connection between these models, as well as the influence of ventilation-perfusion mismatch on the oxygen diffusion. The model is verified based on simulation results of varying exercise intensities and statistical calculations of the results obtained during various clinical trials. The benefit of the approach proposed is its application in simulation-based research aimed to generate quantitative data of normal and pathological conditions. Based on the model presented, taking into account many essential physiological processes and air transport dynamics, comprehensive and combined studies of the respiratory efficiency can be performed. The impact of physical exercise, precise changes in respiratory tract mechanics and alterations in breathing pattern can be analyzed together with the impact of various changes in alveolar-capillary oxygen diffusion. This may be useful in simulation of effects of many severe medical conditions and increased activity level.
NEFDS contamination model parameter estimation of powder contaminated surfaces
NASA Astrophysics Data System (ADS)
Gibbs, Timothy J.; Messinger, David W.
2016-05-01
Hyperspectral signatures of powdered contaminated surfaces are challenging to characterize due to intimate mixing between materials. Most radiometric models have diﬃculties in recreating these signatures due to non-linear interactions between particles with diﬀerent physical properties. The Nonconventional Exploitation Factors Data System (NEFDS) Contamination Model is capable of recreating longwave hyperspectral signatures at any contamination mixture amount, but only for a limited selection of materials currently in the database. A method has been developed to invert the NEFDS model and perform parameter estimation on emissivity measurements from a variety of powdered materials on substrates. This model was chosen for its potential to accurately determine contamination coverage density as a parameter in the inverted model. Emissivity data were measured using a Designs and Prototypes fourier transform infrared spectrometer model 102 for diﬀerent levels of contamination. Temperature emissivity separation was performed to convert data from measure radiance to estimated surface emissivity. Emissivity curves were then input into the inverted model and parameters were estimated for each spectral curve. A comparison of measured data with extrapolated model emissivity curves using estimated parameter values assessed performance of the inverted NEFDS contamination model. This paper will present the initial results of the experimental campaign and the estimated surface coverage parameters.
Liu, Q; Nassar, A; Farias, K; Buccini, L; Mangino, M J; Baldwin, W; Bennett, A; O'Rourke, C; Iuppa, G; Soliman, B G; Urcuyo-Llanes, D; Okamoto, T; Uso, T D; Fung, J; Abu-Elmagd, K; Miller, C; Quintini, C
2016-03-01
The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs. PMID:26663737
Parameter estimation in deformable models using Markov chain Monte Carlo
NASA Astrophysics Data System (ADS)
Chalana, Vikram; Haynor, David R.; Sampson, Paul D.; Kim, Yongmin
1997-04-01
Deformable models have gained much popularity recently for many applications in medical imaging, such as image segmentation, image reconstruction, and image registration. Such models are very powerful because various kinds of information can be integrated together in an elegant statistical framework. Each such piece of information is typically associated with a user-defined parameter. The values of these parameters can have a significant effect on the results generated using these models. Despite the popularity of deformable models for various applications, not much attention has been paid to the estimation of these parameters. In this paper we describe systematic methods for the automatic estimation of these deformable model parameters. These methods are derived by posing the deformable models as a Bayesian inference problem. Our parameter estimation methods use Markov chain Monte Carlo methods for generating samples from highly complex probability distributions.
Estimating the number of species in a stochastic abundance model.
Chao, Anne; Bunge, John
2002-09-01
Consider a stochastic abundance model in which the species arrive in the sample according to independent Poisson processes, where the abundance parameters of the processes follow a gamma distribution. We propose a new estimator of the number of species for this model. The estimator takes the form of the number of duplicated species (i.e., species represented by two or more individuals) divided by an estimated duplication fraction. The duplication fraction is estimated from all frequencies including singleton information. The new estimator is closely related to the sample coverage estimator presented by Chao and Lee (1992, Journal of the American Statistical Association 87, 210-217). We illustrate the procedure using the Malayan butterfly data discussed by Fisher, Corbet, and Williams (1943, Journal of Animal Ecology 12, 42-58) and a 1989 Christmas Bird Count dataset collected in Florida, U.S.A. Simulation studies show that this estimator compares well with maximum likelihood estimators (i.e., empirical Bayes estimators from the Bayesian viewpoint) for which an iterative numerical procedure is needed and may be infeasible.
Z-estimation and stratified samples: application to survival models.
Breslow, Norman E; Hu, Jie; Wellner, Jon A
2015-10-01
The infinite dimensional Z-estimation theorem offers a systematic approach to joint estimation of both Euclidean and non-Euclidean parameters in probability models for data. It is easily adapted for stratified sampling designs. This is important in applications to censored survival data because the inverse probability weights that modify the standard estimating equations often depend on the entire follow-up history. Since the weights are not predictable, they complicate the usual theory based on martingales. This paper considers joint estimation of regression coefficients and baseline hazard functions in the Cox proportional and Lin-Ying additive hazards models. Weighted likelihood equations are used for the former and weighted estimating equations for the latter. Regression coefficients and baseline hazards may be combined to estimate individual survival probabilities. Efficiency is improved by calibrating or estimating the weights using information available for all subjects. Although inefficient in comparison with likelihood inference for incomplete data, which is often difficult to implement, the approach provides consistent estimates of desired population parameters even under model misspecification.
Parametric Estimation in a Recurrent Competing Risks Model
Peña, Edsel A.
2014-01-01
A resource-efficient approach to making inferences about the distributional properties of the failure times in a competing risks setting is presented. Efficiency is gained by observing recurrences of the competing risks over a random monitoring period. The resulting model is called the recurrent competing risks model (RCRM) and is coupled with two repair strategies whenever the system fails. Maximum likelihood estimators of the parameters of the marginal distribution functions associated with each of the competing risks and also of the system lifetime distribution function are presented. Estimators are derived under perfect and partial repair strategies. Consistency and asymptotic properties of the estimators are obtained. The estimation methods are applied to a data set of failures for cars under warranty. Simulation studies are used to ascertain the small sample properties and the efficiency gains of the resulting estimators. PMID:25346751
Intestinal perfusion monitoring using photoplethysmography
Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.
2013-01-01
Abstract. In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed. PMID:23942635
Nonlinear modeling and estimation of slew induced structural deformations
NASA Technical Reports Server (NTRS)
Dwyer, T. A. W., III; Karray, F.
1988-01-01
A model of the nonlinear dynamics of a deformable maneuvering multibody system is described, whereby elastic deformation are modeled by restoring forces and dissipative forces at point mass appendages. This model is brought into bilinear form. Estimation of deformations occasioned by rapid slewing maneuvers is carried out by a filter based on a globally equivalent linear model of the bilinear dynamics, and is shown to be an improvement over the extended Kalman filter. To further alleviate the computational burden, the estimated deformation state is propagated between observations by a low dimensional operator spline interpolator of bilinear system Volterra series, which is easily implemented.
Development of CSAMT impedance modeling and its estimation
NASA Astrophysics Data System (ADS)
Sutarno, D.
2015-04-01
Accurate modeling and estimation of impedance functions is essential for the correct interpretation of Controlled Source Audio Magnetotelluric (CSAMT) measurements. Non plane wave effect of CSAMT source and noises are inevitably encountered when CSAMT observations are conducted and, consequently, impedance estimates are usually based on least-squares (LS) approximation, and the resulting estimates need to be corrected for the non plane wave field fraction. However, estimation procedure based on LS would not be statistically optimal, as outliers (abnormal data) are frequently superimposed on a normal ambient CSAMT noise field. In this situation, the estimation can be seriously misleading, while plane wave correction has also limited application, as the non plane wave field fraction is reasonably strong. This paper briefly discus the recent development of alternative methods for the CSAMT impedance modeling and its estimation, those are efficient in nature. The means for accomplishing the non plane wave problem is based on full solution numerical modeling of CSAMT impedance function that accommodates the non plane wave effect in the function. Whilst, one appealing approach to dealing with outliers is to make the estimation procedure robust. This is based on the M-estimation and the Hilbert transform operating on the causal CSAMT impedance functions. As demonstrated, the full solution based modeling for CSAMT impedance function is applied for all measurement zones, including near-, transition- as well as the far-field zones, and suitably, the plane wave correction is no longer needed for the impedance function. In the resulting impedance estimates, outlier contamination is removed and the self consistency between the real and imaginary parts of the impedance estimates is guaranteed. Using synthetic data, it is shown that the proposed methods can produce usable CSAMT impedance functions for all measurement zones, even under condition of severe noise contamination.
Fast model-based estimation of ancestry in unrelated individuals.
Alexander, David H; Novembre, John; Lange, Kenneth
2009-09-01
Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure. Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure. We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure. However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies.
Estimation of growth parameters using a nonlinear mixed Gompertz model.
Wang, Z; Zuidhof, M J
2004-06-01
In order to maximize the utility of simulation models for decision making, accurate estimation of growth parameters and associated variances is crucial. A mixed Gompertz growth model was used to account for between-bird variation and heterogeneous variance. The mixed model had several advantages over the fixed effects model. The mixed model partitioned BW variation into between- and within-bird variation, and the covariance structure assumed with the random effect accounted for part of the BW correlation across ages in the same individual. The amount of residual variance decreased by over 55% with the mixed model. The mixed model reduced estimation biases that resulted from selective sampling. For analysis of longitudinal growth data, the mixed effects growth model is recommended.
Error Estimation for Reduced Order Models of Dynamical systems
Homescu, C; Petzold, L R; Serban, R
2003-12-16
The use of reduced order models to describe a dynamical system is pervasive in science and engineering. Often these models are used without an estimate of their error or range of validity. In this paper we consider dynamical systems and reduced models built using proper orthogonal decomposition. We show how to compute estimates and bounds for these errors, by a combination of the small sample statistical condition estimation method and of error estimation using the adjoint method. More importantly, the proposed approach allows the assessment of so-called regions of validity for reduced models, i.e., ranges of perturbations in the original system over which the reduced model is still appropriate. This question is particularly important for applications in which reduced models are used not just to approximate the solution to the system that provided the data used in constructing the reduced model, but rather to approximate the solution of systems perturbed from the original one. Numerical examples validate our approach: the error norm estimates approximate well the forward error while the derived bounds are within an order of magnitude.
A hierarchical model for estimating change in American Woodcock populations
Sauer, J.R.; Link, W.A.; Kendall, W.L.; Kelley, J.R.; Niven, D.K.
2008-01-01
The Singing-Ground Survey (SGS) is a primary source of information on population change for American woodcock (Scolopax minor). We analyzed the SGS using a hierarchical log-linear model and compared the estimates of change and annual indices of abundance to a route regression analysis of SGS data. We also grouped SGS routes into Bird Conservation Regions (BCRs) and estimated population change and annual indices using BCRs within states and provinces as strata. Based on the hierarchical model?based estimates, we concluded that woodcock populations were declining in North America between 1968 and 2006 (trend = -0.9%/yr, 95% credible interval: -1.2, -0.5). Singing-Ground Survey results are generally similar between analytical approaches, but the hierarchical model has several important advantages over the route regression. Hierarchical models better accommodate changes in survey efficiency over time and space by treating strata, years, and observers as random effects in the context of a log-linear model, providing trend estimates that are derived directly from the annual indices. We also conducted a hierarchical model analysis of woodcock data from the Christmas Bird Count and the North American Breeding Bird Survey. All surveys showed general consistency in patterns of population change, but the SGS had the shortest credible intervals. We suggest that population management and conservation planning for woodcock involving interpretation of the SGS use estimates provided by the hierarchical model.
Performance-based selection of likelihood models for phylogeny estimation.
Minin, Vladimir; Abdo, Zaid; Joyce, Paul; Sullivan, Jack
2003-10-01
Phylogenetic estimation has largely come to rely on explicitly model-based methods. This approach requires that a model be chosen and that that choice be justified. To date, justification has largely been accomplished through use of likelihood-ratio tests (LRTs) to assess the relative fit of a nested series of reversible models. While this approach certainly represents an important advance over arbitrary model selection, the best fit of a series of models may not always provide the most reliable phylogenetic estimates for finite real data sets, where all available models are surely incorrect. Here, we develop a novel approach to model selection, which is based on the Bayesian information criterion, but incorporates relative branch-length error as a performance measure in a decision theory (DT) framework. This DT method includes a penalty for overfitting, is applicable prior to running extensive analyses, and simultaneously compares all models being considered and thus does not rely on a series of pairwise comparisons of models to traverse model space. We evaluate this method by examining four real data sets and by using those data sets to define simulation conditions. In the real data sets, the DT method selects the same or simpler models than conventional LRTs. In order to lend generality to the simulations, codon-based models (with parameters estimated from the real data sets) were used to generate simulated data sets, which are therefore more complex than any of the models we evaluate. On average, the DT method selects models that are simpler than those chosen by conventional LRTs. Nevertheless, these simpler models provide estimates of branch lengths that are more accurate both in terms of relative error and absolute error than those derived using the more complex (yet still wrong) models chosen by conventional LRTs. This method is available in a program called DT-ModSel. PMID:14530134
Accuracy of Aerodynamic Model Parameters Estimated from Flight Test Data
NASA Technical Reports Server (NTRS)
Morelli, Eugene A.; Klein, Vladislav
1997-01-01
An important put of building mathematical models based on measured date is calculating the accuracy associated with statistical estimates of the model parameters. Indeed, without some idea of this accuracy, the parameter estimates themselves have limited value. An expression is developed for computing quantitatively correct parameter accuracy measures for maximum likelihood parameter estimates when the output residuals are colored. This result is important because experience in analyzing flight test data reveals that the output residuals from maximum likelihood estimation are almost always colored. The calculations involved can be appended to conventional maximum likelihood estimation algorithms. Monte Carlo simulation runs were used to show that parameter accuracy measures from the new technique accurately reflect the quality of the parameter estimates from maximum likelihood estimation without the need for correction factors or frequency domain analysis of the output residuals. The technique was applied to flight test data from repeated maneuvers flown on the F-18 High Alpha Research Vehicle. As in the simulated cases, parameter accuracy measures from the new technique were in agreement with the scatter in the parameter estimates from repeated maneuvers, whereas conventional parameter accuracy measures were optimistic.
Inverse estimation of parameters for an estuarine eutrophication model
Shen, J.; Kuo, A.Y.
1996-11-01
An inverse model of an estuarine eutrophication model with eight state variables is developed. It provides a framework to estimate parameter values of the eutrophication model by assimilation of concentration data of these state variables. The inverse model using the variational technique in conjunction with a vertical two-dimensional eutrophication model is general enough to be applicable to aid model calibration. The formulation is illustrated by conducting a series of numerical experiments for the tidal Rappahannock River, a western shore tributary of the Chesapeake Bay. The numerical experiments of short-period model simulations with different hypothetical data sets and long-period model simulations with limited hypothetical data sets demonstrated that the inverse model can be satisfactorily used to estimate parameter values of the eutrophication model. The experiments also showed that the inverse model is useful to address some important questions, such as uniqueness of the parameter estimation and data requirements for model calibration. Because of the complexity of the eutrophication system, degrading of speed of convergence may occur. Two major factors which cause degradation of speed of convergence are cross effects among parameters and the multiple scales involved in the parameter system.
Comparing interval estimates for small sample ordinal CFA models.
Natesan, Prathiba
2015-01-01
Robust maximum likelihood (RML) and asymptotically generalized least squares (AGLS) methods have been recommended for fitting ordinal structural equation models. Studies show that some of these methods underestimate standard errors. However, these studies have not investigated the coverage and bias of interval estimates. An estimate with a reasonable standard error could still be severely biased. This can only be known by systematically investigating the interval estimates. The present study compares Bayesian, RML, and AGLS interval estimates of factor correlations in ordinal confirmatory factor analysis models (CFA) for small sample data. Six sample sizes, 3 factor correlations, and 2 factor score distributions (multivariate normal and multivariate mildly skewed) were studied. Two Bayesian prior specifications, informative and relatively less informative were studied. Undercoverage of confidence intervals and underestimation of standard errors was common in non-Bayesian methods. Underestimated standard errors may lead to inflated Type-I error rates. Non-Bayesian intervals were more positive biased than negatively biased, that is, most intervals that did not contain the true value were greater than the true value. Some non-Bayesian methods had non-converging and inadmissible solutions for small samples and non-normal data. Bayesian empirical standard error estimates for informative and relatively less informative priors were closer to the average standard errors of the estimates. The coverage of Bayesian credibility intervals was closer to what was expected with overcoverage in a few cases. Although some Bayesian credibility intervals were wider, they reflected the nature of statistical uncertainty that comes with the data (e.g., small sample). Bayesian point estimates were also more accurate than non-Bayesian estimates. The results illustrate the importance of analyzing coverage and bias of interval estimates, and how ignoring interval estimates can be misleading
Chia, Yen Lin; Salzman, Peter; Plevritis, Sylvia K; Glynn, Peter W
2004-12-01
Simulation-based parameter estimation offers a powerful means of estimating parameters in complex stochastic models. We illustrate the application of these ideas in the setting of a natural history model for breast cancer. Our model assumes that the tumor growth process follows a geometric Brownian motion; parameters are estimated from the SEER registry. Our discussion focuses on the use of simulation for computing the maximum likelihood estimator for this class of models. The analysis shows that simulation provides a straightforward means of computing such estimators for models of substantial complexity.
Estimating tree height-diameter models with the Bayesian method.
Zhang, Xiongqing; Duan, Aiguo; Zhang, Jianguo; Xiang, Congwei
2014-01-01
Six candidate height-diameter models were used to analyze the height-diameter relationships. The common methods for estimating the height-diameter models have taken the classical (frequentist) approach based on the frequency interpretation of probability, for example, the nonlinear least squares method (NLS) and the maximum likelihood method (ML). The Bayesian method has an exclusive advantage compared with classical method that the parameters to be estimated are regarded as random variables. In this study, the classical and Bayesian methods were used to estimate six height-diameter models, respectively. Both the classical method and Bayesian method showed that the Weibull model was the "best" model using data1. In addition, based on the Weibull model, data2 was used for comparing Bayesian method with informative priors with uninformative priors and classical method. The results showed that the improvement in prediction accuracy with Bayesian method led to narrower confidence bands of predicted value in comparison to that for the classical method, and the credible bands of parameters with informative priors were also narrower than uninformative priors and classical method. The estimated posterior distributions for parameters can be set as new priors in estimating the parameters using data2.
Hydrological model uncertainty due to spatial evapotranspiration estimation methods
NASA Astrophysics Data System (ADS)
Yu, Xuan; Lamačová, Anna; Duffy, Christopher; Krám, Pavel; Hruška, Jakub
2016-05-01
Evapotranspiration (ET) continues to be a difficult process to estimate in seasonal and long-term water balances in catchment models. Approaches to estimate ET typically use vegetation parameters (e.g., leaf area index [LAI], interception capacity) obtained from field observation, remote sensing data, national or global land cover products, and/or simulated by ecosystem models. In this study we attempt to quantify the uncertainty that spatial evapotranspiration estimation introduces into hydrological simulations when the age of the forest is not precisely known. The Penn State Integrated Hydrologic Model (PIHM) was implemented for the Lysina headwater catchment, located 50°03‧N, 12°40‧E in the western part of the Czech Republic. The spatial forest patterns were digitized from forest age maps made available by the Czech Forest Administration. Two ET methods were implemented in the catchment model: the Biome-BGC forest growth sub-model (1-way coupled to PIHM) and with the fixed-seasonal LAI method. From these two approaches simulation scenarios were developed. We combined the estimated spatial forest age maps and two ET estimation methods to drive PIHM. A set of spatial hydrologic regime and streamflow regime indices were calculated from the modeling results for each method. Intercomparison of the hydrological responses to the spatial vegetation patterns suggested considerable variation in soil moisture and recharge and a small uncertainty in the groundwater table elevation and streamflow. The hydrologic modeling with ET estimated by Biome-BGC generated less uncertainty due to the plant physiology-based method. The implication of this research is that overall hydrologic variability induced by uncertain management practices was reduced by implementing vegetation models in the catchment models.
Identification of Neurofuzzy models using GTLS parameter estimation.
Jakubek, Stefan; Hametner, Christoph
2009-10-01
In this paper, nonlinear system identification utilizing generalized total least squares (GTLS) methodologies in neurofuzzy systems is addressed. The problem involved with the estimation of the local model parameters of neurofuzzy networks is the presence of noise in measured data. When some or all input channels are subject to noise, the GTLS algorithm yields consistent parameter estimates. In addition to the estimation of the parameters, the main challenge in the design of these local model networks is the determination of the region of validity for the local models. The method presented in this paper is based on an expectation-maximization algorithm that uses a residual from the GTLS parameter estimation for proper partitioning. The performance of the resulting nonlinear model with local parameters estimated by weighted GTLS is a product both of the parameter estimation itself and the associated residual used for the partitioning process. The applicability and benefits of the proposed algorithm are demonstrated by means of illustrative examples and an automotive application. PMID:19336320
Estimating Independent Locally Shifted Random Utility Models for Ranking Data
ERIC Educational Resources Information Center
Lam, Kar Yin; Koning, Alex J.; Franses, Philip Hans
2011-01-01
We consider the estimation of probabilistic ranking models in the context of conjoint experiments. By using approximate rather than exact ranking probabilities, we avoided the computation of high-dimensional integrals. We extended the approximation technique proposed by Henery (1981) in the context of the Thurstone-Mosteller-Daniels model to any…
Estimating demographic parameters using hidden process dynamic models.
Gimenez, Olivier; Lebreton, Jean-Dominique; Gaillard, Jean-Michel; Choquet, Rémi; Pradel, Roger
2012-12-01
Structured population models are widely used in plant and animal demographic studies to assess population dynamics. In matrix population models, populations are described with discrete classes of individuals (age, life history stage or size). To calibrate these models, longitudinal data are collected at the individual level to estimate demographic parameters. However, several sources of uncertainty can complicate parameter estimation, such as imperfect detection of individuals inherent to monitoring in the wild and uncertainty in assigning a state to an individual. Here, we show how recent statistical models can help overcome these issues. We focus on hidden process models that run two time series in parallel, one capturing the dynamics of the true states and the other consisting of observations arising from these underlying possibly unknown states. In a first case study, we illustrate hidden Markov models with an example of how to accommodate state uncertainty using Frequentist theory and maximum likelihood estimation. In a second case study, we illustrate state-space models with an example of how to estimate lifetime reproductive success despite imperfect detection, using a Bayesian framework and Markov Chain Monte Carlo simulation. Hidden process models are a promising tool as they allow population biologists to cope with process variation while simultaneously accounting for observation error. PMID:22373775
Yield estimation of sugarcane based on agrometeorological-spectral models
NASA Technical Reports Server (NTRS)
Rudorff, Bernardo Friedrich Theodor; Batista, Getulio Teixeira
1990-01-01
This work has the objective to assess the performance of a yield estimation model for sugarcane (Succharum officinarum). The model uses orbital gathered spectral data along with yield estimated from an agrometeorological model. The test site includes the sugarcane plantations of the Barra Grande Plant located in Lencois Paulista municipality in Sao Paulo State. Production data of four crop years were analyzed. Yield data observed in the first crop year (1983/84) were regressed against spectral and agrometeorological data of that same year. This provided the model to predict the yield for the following crop year i.e., 1984/85. The model to predict the yield of subsequent years (up to 1987/88) were developed similarly, incorporating all previous years data. The yield estimations obtained from these models explained 69, 54, and 50 percent of the yield variation in the 1984/85, 1985/86, and 1986/87 crop years, respectively. The accuracy of yield estimations based on spectral data only (vegetation index model) and on agrometeorological data only (agrometeorological model) were also investigated.
Estimation of an Occupational Choice Model when Occupations Are Misclassified
ERIC Educational Resources Information Center
Sullivan, Paul
2009-01-01
This paper develops an empirical occupational choice model that corrects for misclassification in occupational choices and measurement error in occupation-specific work experience. The model is used to estimate the extent of measurement error in occupation data and quantify the bias that results from ignoring measurement error in occupation codes…
Model-based approach for elevator performance estimation
NASA Astrophysics Data System (ADS)
Esteban, E.; Salgado, O.; Iturrospe, A.; Isasa, I.
2016-02-01
In this paper, a dynamic model for an elevator installation is presented in the state space domain. The model comprises both the mechanical and the electrical subsystems, including the electrical machine and a closed-loop field oriented control. The proposed model is employed for monitoring the condition of the elevator installation. The adopted model-based approach for monitoring employs the Kalman filter as an observer. A Kalman observer estimates the elevator car acceleration, which determines the elevator ride quality, based solely on the machine control signature and the encoder signal. Finally, five elevator key performance indicators are calculated based on the estimated car acceleration. The proposed procedure is experimentally evaluated, by comparing the key performance indicators calculated based on the estimated car acceleration and the values obtained from actual acceleration measurements in a test bench. Finally, the proposed procedure is compared with the sliding mode observer.
Estimating classification images with generalized linear and additive models.
Knoblauch, Kenneth; Maloney, Laurence T
2008-12-22
Conventional approaches to modeling classification image data can be described in terms of a standard linear model (LM). We show how the problem can be characterized as a Generalized Linear Model (GLM) with a Bernoulli distribution. We demonstrate via simulation that this approach is more accurate in estimating the underlying template in the absence of internal noise. With increasing internal noise, however, the advantage of the GLM over the LM decreases and GLM is no more accurate than LM. We then introduce the Generalized Additive Model (GAM), an extension of GLM that can be used to estimate smooth classification images adaptively. We show that this approach is more robust to the presence of internal noise, and finally, we demonstrate that GAM is readily adapted to estimation of higher order (nonlinear) classification images and to testing their significance.
Spatial Distribution of Hydrologic Ecosystem Service Estimates: Comparing Two Models
NASA Astrophysics Data System (ADS)
Dennedy-Frank, P. J.; Ghile, Y.; Gorelick, S.; Logsdon, R. A.; Chaubey, I.; Ziv, G.
2014-12-01
We compare estimates of the spatial distribution of water quantity provided (annual water yield) from two ecohydrologic models: the widely-used Soil and Water Assessment Tool (SWAT) and the much simpler water models from the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) toolbox. These two models differ significantly in terms of complexity, timescale of operation, effort, and data required for calibration, and so are often used in different management contexts. We compare two study sites in the US: the Wildcat Creek Watershed (2083 km2) in Indiana, a largely agricultural watershed in a cold aseasonal climate, and the Upper Upatoi Creek Watershed (876 km2) in Georgia, a mostly forested watershed in a temperate aseasonal climate. We evaluate (1) quantitative estimates of water yield to explore how well each model represents this process, and (2) ranked estimates of water yield to indicate how useful the models are for management purposes where other social and financial factors may play significant roles. The SWAT and InVEST models provide very similar estimates of the water yield of individual subbasins in the Wildcat Creek Watershed (Pearson r = 0.92, slope = 0.89), and a similar ranking of the relative water yield of those subbasins (Spearman r = 0.86). However, the two models provide relatively different estimates of the water yield of individual subbasins in the Upper Upatoi Watershed (Pearson r = 0.25, slope = 0.14), and very different ranking of the relative water yield of those subbasins (Spearman r = -0.10). The Upper Upatoi watershed has a significant baseflow contribution due to its sandy, well-drained soils. InVEST's simple seasonality terms, which assume no change in storage over the time of the model run, may not accurately estimate water yield processes when baseflow provides such a strong contribution. Our results suggest that InVEST users take care in situations where storage changes are significant.
The Federal Highway Administration Gasohol Consumption Estimation Model
Hwang, HL
2003-08-28
The Federal Highway Administration (FHWA) is responsible for estimating the portion of Federal highway funds attributable to each State. The process involves use of State-reported data (gallons) and a set of estimation models when accurate State data is unavailable. To ensure that the distribution of funds is equitable, FHWA periodically reviews the estimation models. Estimation of the use of gasohol is difficult because of State differences in the definition of gasohol, inability of many States to separate and report gasohol usage from other fuel types, changes in fuel composition in nonattainment areas to address concerns over the use of certain fuel additives, and the lack of a valid State-level surrogate data set for gasohol use. Under the sponsorship of FHWA, Oak Ridge National Laboratory (ORNL) reviewed the regression-based gasohol estimation model that has been in use for several years. Based on an analytical assessment of that model and an extensive review of potential data sets, ORNL developed an improved rule-based model. The new model uses data from Internal Revenue Service, Energy Information Administration, Environmental Protection Agency, Department of Energy, ORNL, and FHWA sources. The model basically consists of three parts: (1) development of a controlled total of national gasohol usage, (2) determination of reliable State gasohol consumption data, and (3) estimation of gasohol usage for all other States. The new model will be employed for the 2004 attribution process. FHWA is currently soliciting comments and inputs from interested parties. Relevant data, as identified, will be pursued and refinements will be made by the research team if warranted.
Development on electromagnetic impedance function modeling and its estimation
Sutarno, D.
2015-09-30
Today the Electromagnetic methods such as magnetotellurics (MT) and controlled sources audio MT (CSAMT) is used in a broad variety of applications. Its usefulness in poor seismic areas and its negligible environmental impact are integral parts of effective exploration at minimum cost. As exploration was forced into more difficult areas, the importance of MT and CSAMT, in conjunction with other techniques, has tended to grow continuously. However, there are obviously important and difficult problems remaining to be solved concerning our ability to collect process and interpret MT as well as CSAMT in complex 3D structural environments. This talk aim at reviewing and discussing the recent development on MT as well as CSAMT impedance functions modeling, and also some improvements on estimation procedures for the corresponding impedance functions. In MT impedance modeling, research efforts focus on developing numerical method for computing the impedance functions of three dimensionally (3-D) earth resistivity models. On that reason, 3-D finite elements numerical modeling for the impedances is developed based on edge element method. Whereas, in the CSAMT case, the efforts were focused to accomplish the non-plane wave problem in the corresponding impedance functions. Concerning estimation of MT and CSAMT impedance functions, researches were focused on improving quality of the estimates. On that objective, non-linear regression approach based on the robust M-estimators and the Hilbert transform operating on the causal transfer functions, were used to dealing with outliers (abnormal data) which are frequently superimposed on a normal ambient MT as well as CSAMT noise fields. As validated, the proposed MT impedance modeling method gives acceptable results for standard three dimensional resistivity models. Whilst, the full solution based modeling that accommodate the non-plane wave effect for CSAMT impedances is applied for all measurement zones, including near-, transition
Development on electromagnetic impedance function modeling and its estimation
NASA Astrophysics Data System (ADS)
Sutarno, D.
2015-09-01
Today the Electromagnetic methods such as magnetotellurics (MT) and controlled sources audio MT (CSAMT) is used in a broad variety of applications. Its usefulness in poor seismic areas and its negligible environmental impact are integral parts of effective exploration at minimum cost. As exploration was forced into more difficult areas, the importance of MT and CSAMT, in conjunction with other techniques, has tended to grow continuously. However, there are obviously important and difficult problems remaining to be solved concerning our ability to collect process and interpret MT as well as CSAMT in complex 3D structural environments. This talk aim at reviewing and discussing the recent development on MT as well as CSAMT impedance functions modeling, and also some improvements on estimation procedures for the corresponding impedance functions. In MT impedance modeling, research efforts focus on developing numerical method for computing the impedance functions of three dimensionally (3-D) earth resistivity models. On that reason, 3-D finite elements numerical modeling for the impedances is developed based on edge element method. Whereas, in the CSAMT case, the efforts were focused to accomplish the non-plane wave problem in the corresponding impedance functions. Concerning estimation of MT and CSAMT impedance functions, researches were focused on improving quality of the estimates. On that objective, non-linear regression approach based on the robust M-estimators and the Hilbert transform operating on the causal transfer functions, were used to dealing with outliers (abnormal data) which are frequently superimposed on a normal ambient MT as well as CSAMT noise fields. As validated, the proposed MT impedance modeling method gives acceptable results for standard three dimensional resistivity models. Whilst, the full solution based modeling that accommodate the non-plane wave effect for CSAMT impedances is applied for all measurement zones, including near-, transition
[Hyperspectral estimation models of chlorophyll content in apple leaves].
Liang, Shuang; Zhao, Geng-xing; Zhu, Xi-cun
2012-05-01
The present study chose the apple orchard of Shandong Agricultural University as the study area to explore the method of apple leaf chlorophyll content estimation by hyperspectral analysis technology. Through analyzing the characteristics of apple leaves' hyperspectral curve, transforming the original spectral into first derivative, red edge position and leaf chlorophyll index (LCI) respectively, and making the correlation analysis and regression analysis of these variables with the chlorophyll content to establish the estimation models and test to select the high fitting precision models. Results showed that the fitting precision of the estimation model with variable of LCI and the estimation model with variable of the first derivative in the band of 521 and 523 nm was the highest. The coefficients of determination R2 were 0.845 and 0.839, the root mean square errors RMSE were 2.961 and 2.719, and the relative errors RE% were 4.71% and 4.70%, respectively. Therefore LCI and the first derivative are the important index for apple leaf chlorophyll content estimation. The models have positive significance to guide the production of apple cultivation.
Estimation of Unsteady Aerodynamic Models from Dynamic Wind Tunnel Data
NASA Technical Reports Server (NTRS)
Murphy, Patrick; Klein, Vladislav
2011-01-01
Demanding aerodynamic modelling requirements for military and civilian aircraft have motivated researchers to improve computational and experimental techniques and to pursue closer collaboration in these areas. Model identification and validation techniques are key components for this research. This paper presents mathematical model structures and identification techniques that have been used successfully to model more general aerodynamic behaviours in single-degree-of-freedom dynamic testing. Model parameters, characterizing aerodynamic properties, are estimated using linear and nonlinear regression methods in both time and frequency domains. Steps in identification including model structure determination, parameter estimation, and model validation, are addressed in this paper with examples using data from one-degree-of-freedom dynamic wind tunnel and water tunnel experiments. These techniques offer a methodology for expanding the utility of computational methods in application to flight dynamics, stability, and control problems. Since flight test is not always an option for early model validation, time history comparisons are commonly made between computational and experimental results and model adequacy is inferred by corroborating results. An extension is offered to this conventional approach where more general model parameter estimates and their standard errors are compared.
Combined Estimation of Hydrogeologic Conceptual Model and Parameter Uncertainty
Meyer, Philip D.; Ye, Ming; Neuman, Shlomo P.; Cantrell, Kirk J.
2004-03-01
The objective of the research described in this report is the development and application of a methodology for comprehensively assessing the hydrogeologic uncertainties involved in dose assessment, including uncertainties associated with conceptual models, parameters, and scenarios. This report describes and applies a statistical method to quantitatively estimate the combined uncertainty in model predictions arising from conceptual model and parameter uncertainties. The method relies on model averaging to combine the predictions of a set of alternative models. Implementation is driven by the available data. When there is minimal site-specific data the method can be carried out with prior parameter estimates based on generic data and subjective prior model probabilities. For sites with observations of system behavior (and optionally data characterizing model parameters), the method uses model calibration to update the prior parameter estimates and model probabilities based on the correspondence between model predictions and site observations. The set of model alternatives can contain both simplified and complex models, with the requirement that all models be based on the same set of data. The method was applied to the geostatistical modeling of air permeability at a fractured rock site. Seven alternative variogram models of log air permeability were considered to represent data from single-hole pneumatic injection tests in six boreholes at the site. Unbiased maximum likelihood estimates of variogram and drift parameters were obtained for each model. Standard information criteria provided an ambiguous ranking of the models, which would not justify selecting one of them and discarding all others as is commonly done in practice. Instead, some of the models were eliminated based on their negligibly small updated probabilities and the rest were used to project the measured log permeabilities by kriging onto a rock volume containing the six boreholes. These four
Models and estimation methods for clinical HIV-1 data
NASA Astrophysics Data System (ADS)
Verotta, Davide
2005-12-01
Clinical HIV-1 data include many individual factors, such as compliance to treatment, pharmacokinetics, variability in respect to viral dynamics, race, sex, income, etc., which might directly influence or be associated with clinical outcome. These factors need to be taken into account to achieve a better understanding of clinical outcome and mathematical models can provide a unifying framework to do so. The first objective of this paper is to demonstrate the development of comprehensive HIV-1 dynamics models that describe viral dynamics and also incorporate different factors influencing such dynamics. The second objective of this paper is to describe alternative estimation methods that can be applied to the analysis of data with such models. In particular, we consider: (i) simple but effective two-stage estimation methods, in which data from each patient are analyzed separately and summary statistics derived from the results, (ii) more complex nonlinear mixed effect models, used to pool all the patient data in a single analysis. Bayesian estimation methods are also considered, in particular: (iii) maximum posterior approximations, MAP, and (iv) Markov chain Monte Carlo, MCMC. Bayesian methods incorporate prior knowledge into the models, thus avoiding some of the model simplifications introduced when the data are analyzed using two-stage methods, or a nonlinear mixed effect framework. We demonstrate the development of the models and the different estimation methods using real AIDS clinical trial data involving patients receiving multiple drugs regimens.
Estimation of Time-Varying Pilot Model Parameters
NASA Technical Reports Server (NTRS)
Zaal, Peter M. T.; Sweet, Barbara T.
2011-01-01
Human control behavior is rarely completely stationary over time due to fatigue or loss of attention. In addition, there are many control tasks for which human operators need to adapt their control strategy to vehicle dynamics that vary in time. In previous studies on the identification of time-varying pilot control behavior wavelets were used to estimate the time-varying frequency response functions. However, the estimation of time-varying pilot model parameters was not considered. Estimating these parameters can be a valuable tool for the quantification of different aspects of human time-varying manual control. This paper presents two methods for the estimation of time-varying pilot model parameters, a two-step method using wavelets and a windowed maximum likelihood estimation method. The methods are evaluated using simulations of a closed-loop control task with time-varying pilot equalization and vehicle dynamics. Simulations are performed with and without remnant. Both methods give accurate results when no pilot remnant is present. The wavelet transform is very sensitive to measurement noise, resulting in inaccurate parameter estimates when considerable pilot remnant is present. Maximum likelihood estimation is less sensitive to pilot remnant, but cannot detect fast changes in pilot control behavior.
Model Year 2013 Fuel Economy Guide: EPA Fuel Economy Estimates
2012-12-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles.
Model Year 2012 Fuel Economy Guide: EPA Fuel Economy Estimates
2011-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles.
Model Year 2011 Fuel Economy Guide: EPA Fuel Economy Estimates
2010-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles.
Estimating Energy Expenditure With Multiple Models Using Different Wearable Sensors.
Cvetkovic, Bozidara; Milic, Radoje; Lustrek, Mitja
2016-07-01
This paper presents an approach to designing a method for the estimation of human energy expenditure (EE). The approach first evaluates different sensors and their combinations. After that, multiple regression models are trained utilizing data from different sensors. The EE estimation method designed in this way was evaluated on a dataset containing a wide range of activities. It was compared against three competing state-of-the-art approaches, including the BodyMedia Fit armband, the leading consumer EE estimation device. The results show that the proposed method outperforms the competition by up to 10.2 percentage points.
Srivastava, Shashikant; Pasipanodya, Jotam G; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E; Cirrincione, Kayle N; Sherman, Carleton M; Swaminathan, Soumya; Gumbo, Tawanda
2016-04-01
Treatment of disseminated tuberculosis in children≤6years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose-response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children≤6years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555
Srivastava, Shashikant; Pasipanodya, Jotam G.; Ramachandran, Geetha; Deshpande, Devyani; Shuford, Stephen; Crosswell, Howland E.; Cirrincione, Kayle N.; Sherman, Carleton M.; Swaminathan, Soumya; Gumbo, Tawanda
2016-01-01
Treatment of disseminated tuberculosis in children ≤ 6 years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose–response studies in children. We designed a hollow fiber system model of disseminated intracellular tuberculosis with co-perfused three-dimensional organotypic liver modules to simultaneously test for efficacy and toxicity. We utilized pediatric pharmacokinetics of pyrazinamide and acetaminophen to determine dose-dependent pyrazinamide efficacy and hepatotoxicity. Acetaminophen concentrations that cause hepatotoxicity in children led to elevated liver function tests, while 100 mg/kg pyrazinamide did not. Surprisingly, pyrazinamide did not kill intracellular Mycobacterium tuberculosis up to fourfold the standard dose as monotherapy or as combination therapy, despite achieving high intracellular concentrations. Host-pathogen RNA-sequencing revealed lack of a pyrazinamide exposure transcript signature in intracellular bacteria or of phagolysosome acidification on pH imaging. Artificial intelligence algorithms confirmed that pyrazinamide was not predictive of good clinical outcomes in children ≤ 6 years who had extrapulmonary tuberculosis. Thus, adding a drug that works inside macrophages could benefit children with disseminated tuberculosis. Our in vitro model can be used to identify such new regimens that could accelerate cure while minimizing toxicity. PMID:27211555
Random effects and shrinkage estimation in capture-recapture models
Royle, J. Andrew; Link, W.A.
2002-01-01
We discuss the analysis of random effects in capture-recapture models, and outline Bayesian and frequentists approaches to their analysis. Under a normal model, random effects estimators derived from Bayesian or frequentist considerations have a common form as shrinkage estimators. We discuss some of the difficulties of analysing random effects using traditional methods, and argue that a Bayesian formulation provides a rigorous framework for dealing with these difficulties. In capture-recapture models, random effects may provide a parsimonious compromise between constant and completely time-dependent models for the parameters (e.g. survival probability). We consider application of random effects to band-recovery models, although the principles apply to more general situations, such as Cormack-Jolly-Seber models. We illustrate these ideas using a commonly analysed band recovery data set.
Estimation of exposure to toxic releases using spatial interaction modeling
2011-01-01
Background The United States Environmental Protection Agency's Toxic Release Inventory (TRI) data are frequently used to estimate a community's exposure to pollution. However, this estimation process often uses underdeveloped geographic theory. Spatial interaction modeling provides a more realistic approach to this estimation process. This paper uses four sets of data: lung cancer age-adjusted mortality rates from the years 1990 through 2006 inclusive from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, TRI releases of carcinogens from 1987 to 1996, covariates associated with lung cancer, and the EPA's Risk-Screening Environmental Indicators (RSEI) model. Results The impact of the volume of carcinogenic TRI releases on each county's lung cancer mortality rates was calculated using six spatial interaction functions (containment, buffer, power decay, exponential decay, quadratic decay, and RSEI estimates) and evaluated with four multivariate regression methods (linear, generalized linear, spatial lag, and spatial error). Akaike Information Criterion values and P values of spatial interaction terms were computed. The impacts calculated from the interaction models were also mapped. Buffer and quadratic interaction functions had the lowest AIC values (22298 and 22525 respectively), although the gains from including the spatial interaction terms were diminished with spatial error and spatial lag regression. Conclusions The use of different methods for estimating the spatial risk posed by pollution from TRI sites can give different results about the impact of those sites on health outcomes. The most reliable estimates did not always come from the most complex methods. PMID:21418644
Stochastic algorithms for Markov models estimation with intermittent missing data.
Deltour, I; Richardson, S; Le Hesran, J Y
1999-06-01
Multistate Markov models are frequently used to characterize disease processes, but their estimation from longitudinal data is often hampered by complex patterns of incompleteness. Two algorithms for estimating Markov chain models in the case of intermittent missing data in longitudinal studies, a stochastic EM algorithm and the Gibbs sampler, are described. The first can be viewed as a random perturbation of the EM algorithm and is appropriate when the M step is straightforward but the E step is computationally burdensome. It leads to a good approximation of the maximum likelihood estimates. The Gibbs sampler is used for a full Bayesian inference. The performances of the two algorithms are illustrated on two simulated data sets. A motivating example concerned with the modelling of the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of 105 young children in Cameroon is described and briefly analyzed.
Synchronous Generator Model Parameter Estimation Based on Noisy Dynamic Waveforms
NASA Astrophysics Data System (ADS)
Berhausen, Sebastian; Paszek, Stefan
2016-01-01
In recent years, there have occurred system failures in many power systems all over the world. They have resulted in a lack of power supply to a large number of recipients. To minimize the risk of occurrence of power failures, it is necessary to perform multivariate investigations, including simulations, of power system operating conditions. To conduct reliable simulations, the current base of parameters of the models of generating units, containing the models of synchronous generators, is necessary. In the paper, there is presented a method for parameter estimation of a synchronous generator nonlinear model based on the analysis of selected transient waveforms caused by introducing a disturbance (in the form of a pseudorandom signal) in the generator voltage regulation channel. The parameter estimation was performed by minimizing the objective function defined as a mean square error for deviations between the measurement waveforms and the waveforms calculated based on the generator mathematical model. A hybrid algorithm was used for the minimization of the objective function. In the paper, there is described a filter system used for filtering the noisy measurement waveforms. The calculation results of the model of a 44 kW synchronous generator installed on a laboratory stand of the Institute of Electrical Engineering and Computer Science of the Silesian University of Technology are also given. The presented estimation method can be successfully applied to parameter estimation of different models of high-power synchronous generators operating in a power system.
Improved Estimation of Human Lipoprotein Kinetics with Mixed Effects Models
Berglund, Martin; Adiels, Martin; Taskinen, Marja-Riitta; Borén, Jan; Wennberg, Bernt
2015-01-01
Context Mathematical models may help the analysis of biological systems by providing estimates of otherwise un-measurable quantities such as concentrations and fluxes. The variability in such systems makes it difficult to translate individual characteristics to group behavior. Mixed effects models offer a tool to simultaneously assess individual and population behavior from experimental data. Lipoproteins and plasma lipids are key mediators for cardiovascular disease in metabolic disorders such as diabetes mellitus type 2. By the use of mathematical models and tracer experiments fluxes and production rates of lipoproteins may be estimated. Results We developed a mixed effects model to study lipoprotein kinetics in a data set of 15 healthy individuals and 15 patients with type 2 diabetes. We compare the traditional and the mixed effects approach in terms of group estimates at various sample and data set sizes. Conclusion We conclude that the mixed effects approach provided better estimates using the full data set as well as with both sparse and truncated data sets. Sample size estimates showed that to compare lipoprotein secretion the mixed effects approach needed almost half the sample size as the traditional method. PMID:26422201
Coupling Hydrologic and Hydrodynamic Models to Estimate PMF
NASA Astrophysics Data System (ADS)
Felder, G.; Weingartner, R.
2015-12-01
Most sophisticated probable maximum flood (PMF) estimations derive the PMF from the probable maximum precipitation (PMP) by applying deterministic hydrologic models calibrated with observed data. This method is based on the assumption that the hydrological system is stationary, meaning that the system behaviour during the calibration period or the calibration event is presumed to be the same as it is during the PMF. However, as soon as a catchment-specific threshold is reached, the system is no longer stationary. At or beyond this threshold, retention areas, new flow paths, and changing runoff processes can strongly affect downstream peak discharge. These effects can be accounted for by coupling hydrologic and hydrodynamic models, a technique that is particularly promising when the expected peak discharge may considerably exceed the observed maximum discharge. In such cases, the coupling of hydrologic and hydraulic models has the potential to significantly increase the physical plausibility of PMF estimations. This procedure ensures both that the estimated extreme peak discharge does not exceed the physical limit based on riverbed capacity and that the dampening effect of inundation processes on peak discharge is considered. Our study discusses the prospect of considering retention effects on PMF estimations by coupling hydrologic and hydrodynamic models. This method is tested by forcing PREVAH, a semi-distributed deterministic hydrological model, with randomly generated, physically plausible extreme precipitation patterns. The resulting hydrographs are then used to externally force the hydraulic model BASEMENT-ETH (riverbed in 1D, potential inundation areas in 2D). Finally, the PMF estimation results obtained using the coupled modelling approach are compared to the results obtained using ordinary hydrologic modelling.
Combining Empirical and Stochastic Models for Extreme Floods Estimation
NASA Astrophysics Data System (ADS)
Zemzami, M.; Benaabidate, L.
2013-12-01
Hydrological models can be defined as physical, mathematical or empirical. The latter class uses mathematical equations independent of the physical processes involved in the hydrological system. The linear regression and Gradex (Gradient of Extreme values) are classic examples of empirical models. However, conventional empirical models are still used as a tool for hydrological analysis by probabilistic approaches. In many regions in the world, watersheds are not gauged. This is true even in developed countries where the gauging network has continued to decline as a result of the lack of human and financial resources. Indeed, the obvious lack of data in these watersheds makes it impossible to apply some basic empirical models for daily forecast. So we had to find a combination of rainfall-runoff models in which it would be possible to create our own data and use them to estimate the flow. The estimated design floods would be a good choice to illustrate the difficulties facing the hydrologist for the construction of a standard empirical model in basins where hydrological information is rare. The construction of the climate-hydrological model, which is based on frequency analysis, was established to estimate the design flood in the Anseghmir catchments, Morocco. The choice of using this complex model returns to its ability to be applied in watersheds where hydrological information is not sufficient. It was found that this method is a powerful tool for estimating the design flood of the watershed and also other hydrological elements (runoff, volumes of water...).The hydrographic characteristics and climatic parameters were used to estimate the runoff, water volumes and design flood for different return periods.
Man power/cost estimation model: Automated planetary projects
NASA Technical Reports Server (NTRS)
Kitchen, L. D.
1975-01-01
A manpower/cost estimation model is developed which is based on a detailed level of financial analysis of over 30 million raw data points which are then compacted by more than three orders of magnitude to the level at which the model is applicable. The major parameter of expenditure is manpower (specifically direct labor hours) for all spacecraft subsystem and technical support categories. The resultant model is able to provide a mean absolute error of less than fifteen percent for the eight programs comprising the model data base. The model includes cost saving inheritance factors, broken down in four levels, for estimating follow-on type programs where hardware and design inheritance are evident or expected.
Regionalized rainfall-runoff model to estimate low flow indices
NASA Astrophysics Data System (ADS)
Garcia, Florine; Folton, Nathalie; Oudin, Ludovic
2016-04-01
Estimating low flow indices is of paramount importance to manage water resources and risk assessments. These indices are derived from river discharges which are measured at gauged stations. However, the lack of observations at ungauged sites bring the necessity of developing methods to estimate these low flow indices from observed discharges in neighboring catchments and from catchment characteristics. Different estimation methods exist. Regression or geostatistical methods performed on the low flow indices are the most common types of methods. Another less common method consists in regionalizing rainfall-runoff model parameters, from catchment characteristics or by spatial proximity, to estimate low flow indices from simulated hydrographs. Irstea developed GR2M-LoiEau, a conceptual monthly rainfall-runoff model, combined with a regionalized model of snow storage and melt. GR2M-LoiEau relies on only two parameters, which are regionalized and mapped throughout France. This model allows to cartography monthly reference low flow indices. The inputs data come from SAFRAN, the distributed mesoscale atmospheric analysis system, which provides daily solid and liquid precipitation and temperature data from everywhere in the French territory. To exploit fully these data and to estimate daily low flow indices, a new version of GR-LoiEau has been developed at a daily time step. The aim of this work is to develop and regionalize a GR-LoiEau model that can provide any daily, monthly or annual estimations of low flow indices, yet keeping only a few parameters, which is a major advantage to regionalize them. This work includes two parts. On the one hand, a daily conceptual rainfall-runoff model is developed with only three parameters in order to simulate daily and monthly low flow indices, mean annual runoff and seasonality. On the other hand, different regionalization methods, based on spatial proximity and similarity, are tested to estimate the model parameters and to simulate
2010-01-01
Background Quantitative estimates of myocardial perfusion generally require accurate measurement of the arterial input function (AIF). The saturation of signal intensity in the blood that occurs with most doses of contrast agent makes obtaining an accurate AIF challenging. This work seeks to evaluate the performance of a method that uses a radial k-space perfusion sequence and multiple saturation recovery times (SRT) to quantify myocardial perfusion with cardiovascular magnetic resonance (CMR). Methods Perfusion CMR was performed at 3 Tesla with a saturation recovery radial turboFLASH sequence with 72 rays. Fourteen subjects were given a low dose (0.004 mmol/kg) of dilute (1/5 concentration) contrast agent (Gd-BOPTA) and then a higher non-dilute dose of the same volume (0.02 mmol/kg). AIFs were calculated from the blood signal in three sub-images with differing effective saturation recovery times. The full and sub-images were reconstructed iteratively with a total variation constraint. The images from the full 72 ray data were processed to obtain six tissue enhancement curves in two slices of the left ventricle in each subject. A 2-compartment model was used to determine absolute flows Results The proposed multi-SRT method resulted in AIFs that were similar to those obtained with the dual-bolus method. Myocardial blood flow (MBF) estimates from the dual-bolus and the multi-SRT methods were related by MBFmulti-SRT = 0.85MBFdual-bolus + 0.18 (r = 0.91). Conclusions The multi-SRT method, which uses a radial k-space perfusion sequence, can be used to obtain an accurate AIF and thus quantify myocardial perfusion for doses of contrast agent that result in a relatively saturated AIF. PMID:20653961
Parameter Estimation and Parameterization Uncertainty Using Bayesian Model Averaging
NASA Astrophysics Data System (ADS)
Tsai, F. T.; Li, X.
2007-12-01
This study proposes Bayesian model averaging (BMA) to address parameter estimation uncertainty arisen from non-uniqueness in parameterization methods. BMA provides a means of incorporating multiple parameterization methods for prediction through the law of total probability, with which an ensemble average of hydraulic conductivity distribution is obtained. Estimation uncertainty is described by the BMA variances, which contain variances within and between parameterization methods. BMA shows the facts that considering more parameterization methods tends to increase estimation uncertainty and estimation uncertainty is always underestimated using a single parameterization method. Two major problems in applying BMA to hydraulic conductivity estimation using a groundwater inverse method will be discussed in the study. The first problem is the use of posterior probabilities in BMA, which tends to single out one best method and discard other good methods. This problem arises from Occam's window that only accepts models in a very narrow range. We propose a variance window to replace Occam's window to cope with this problem. The second problem is the use of Kashyap information criterion (KIC), which makes BMA tend to prefer high uncertain parameterization methods due to considering the Fisher information matrix. We found that Bayesian information criterion (BIC) is a good approximation to KIC and is able to avoid controversial results. We applied BMA to hydraulic conductivity estimation in the 1,500-foot sand aquifer in East Baton Rouge Parish, Louisiana.
Modeling an exhumed basin: A method for estimating eroded overburden
Poelchau, H.S.
2001-01-01
The Alberta Deep Basin in western Canada has undergone a large amount of erosion following deep burial in the Eocene. Basin modeling and simulation of burial and temperature history require estimates of maximum overburden for each gridpoint in the basin model. Erosion can be estimated using shale compaction trends. For instance, the widely used Magara method attempts to establish a sonic log gradient for shales and uses the extrapolation to a theoretical uncompacted shale value as a first indication of overcompaction and estimation of the amount of erosion. Because such gradients are difficult to establish in many wells, an extension of this method was devised to help map erosion over a large area. Sonic A; values of one suitable shale formation are calibrated with maximum depth of burial estimates from sonic log extrapolation for several wells. This resulting regression equation then can be used to estimate and map maximum depth of burial or amount of erosion for all wells in which this formation has been logged. The example from the Alberta Deep Basin shows that the magnitude of erosion calculated by this method is conservative and comparable to independent estimates using vitrinite reflectance gradient methods. ?? 2001 International Association for Mathematical Geology.
Parameter Estimation for Single Diode Models of Photovoltaic Modules
Hansen, Clifford
2015-03-01
Many popular models for photovoltaic system performance employ a single diode model to compute the I - V curve for a module or string of modules at given irradiance and temperature conditions. A single diode model requires a number of parameters to be estimated from measured I - V curves. Many available parameter estimation methods use only short circuit, o pen circuit and maximum power points for a single I - V curve at standard test conditions together with temperature coefficients determined separately for individual cells. In contrast, module testing frequently records I - V curves over a wide range of irradi ance and temperature conditions which, when available , should also be used to parameterize the performance model. We present a parameter estimation method that makes use of a fu ll range of available I - V curves. We verify the accuracy of the method by recov ering known parameter values from simulated I - V curves . We validate the method by estimating model parameters for a module using outdoor test data and predicting the outdoor performance of the module.
NASA Astrophysics Data System (ADS)
Perrin, Muriel; Vaillant, Regis; Gavit-Houdant, Laurence; Lienard, Jean; Benali, Karim
2002-04-01
Discordance between lesion severity from angiocardiography and physiological effects has been reported elsewhere. Quantification of myocardial perfusion during the angiography procedure may supply additional information about short- and long-term outcomes and may be helpful for clinical decision making. In previous works, myocardial perfusion has been assessed using time density curves (TDC), which represent the contrast medium dilution over time in the myocardium. The mean transit time (MTT), derived from the TDC, has been reported as a good indicator of the regional myocardial perfusion. Our objective is to estimate the accuracy and reproducibility of MTT estimation on digital flat panel (DFP) images. We have simulated typical myocardium TDC obtained with a DFP cardiac system (Innova 2000, GE), taking into account scatter and noise. Logarithmic or linear subtractions have been applied to derive a contrast medium concentration proportional quantity from image intensity. A non-linear minimisation realises the model curve fitting. MTT estimates are more stable with linear subtraction in presence of scatter. However logarithmic subtraction presents smaller bias when scatter level is small. Both approaches are equally sensible to image noise. Linear subtraction should be preferred. Image noise has a high influence on MTT accuracy and we may reduce.
Model Error Estimation for the CPTEC Eta Model
NASA Technical Reports Server (NTRS)
Tippett, Michael K.; daSilva, Arlindo
1999-01-01
Statistical data assimilation systems require the specification of forecast and observation error statistics. Forecast error is due to model imperfections and differences between the initial condition and the actual state of the atmosphere. Practical four-dimensional variational (4D-Var) methods try to fit the forecast state to the observations and assume that the model error is negligible. Here with a number of simplifying assumption, a framework is developed for isolating the model error given the forecast error at two lead-times. Two definitions are proposed for the Talagrand ratio tau, the fraction of the forecast error due to model error rather than initial condition error. Data from the CPTEC Eta Model running operationally over South America are used to calculate forecast error statistics and lower bounds for tau.
Inbreeding estimation from population data: models, procedures and implications.
Spielman, R S; Neel, J V; Li, F H
1977-02-01
Four different estimation procedures for models of population structure are compared. The parameters of the models are shown to be equivalent and, in most cases, easily expressed in terms of the parameters WRIGHT calls "F-statistics." We have estimated the parameters of each of these models with data on nine codominant allele pairs in 47 Yanomama villages, and we find that the different estimators for a given parameter all yield more or less equivalent results. F-statistics are often equated to inbreeding coefficients that are definid as the probability of identity by descent from alleles taken to be unique in some founding population. However, we are led to infer from computer simulation and general historical considerations that all estimates from genotype frequencies greatly underestimate the inbreeding coefficient for alleles in the founding population of American Indians in the western hemisphere. We surmise that in the highly subdivided tribal populations which prevailed until the recent advent of civilization, the probability of identity by descent for homologous alleles was roughly 0.5. We consider some consequences of working with the customary, much lower, estimates--0.005 to 0.01--if, on the time scale of human evolution, these represent only a very recent departure from the inbreeding intensity that prevailed before civilization.
Models for estimating daily rainfall erosivity in China
NASA Astrophysics Data System (ADS)
Xie, Yun; Yin, Shui-qing; Liu, Bao-yuan; Nearing, Mark A.; Zhao, Ying
2016-04-01
The rainfall erosivity factor (R) represents the multiplication of rainfall energy and maximum 30 min intensity by event (EI30) and year. This rainfall erosivity index is widely used for empirical soil loss prediction. Its calculation, however, requires high temporal resolution rainfall data that are not readily available in many parts of the world. The purpose of this study was to parameterize models suitable for estimating erosivity from daily rainfall data, which are more widely available. One-minute resolution rainfall data recorded in sixteen stations over the eastern water erosion impacted regions of China were analyzed. The R-factor ranged from 781.9 to 8258.5 MJ mm ha-1 h-1 y-1. A total of 5942 erosive events from one-minute resolution rainfall data of ten stations were used to parameterize three models, and 4949 erosive events from the other six stations were used for validation. A threshold of daily rainfall between days classified as erosive and non-erosive was suggested to be 9.7 mm based on these data. Two of the models (I and II) used power law functions that required only daily rainfall totals. Model I used different model coefficients in the cool season (Oct.-Apr.) and warm season (May-Sept.), and Model II was fitted with a sinusoidal curve of seasonal variation. Both Model I and Model II estimated the erosivity index for average annual, yearly, and half-month temporal scales reasonably well, with the symmetric mean absolute percentage error MAPEsym ranging from 10.8% to 32.1%. Model II predicted slightly better than Model I. However, the prediction efficiency for the daily erosivity index was limited, with the symmetric mean absolute percentage error being 68.0% (Model I) and 65.7% (Model II) and Nash-Sutcliffe model efficiency being 0.55 (Model I) and 0.57 (Model II). Model III, which used the combination of daily rainfall amount and daily maximum 60-min rainfall, improved predictions significantly, and produced a Nash-Sutcliffe model efficiency
Conical-Domain Model for Estimating GPS Ionospheric Delays
NASA Technical Reports Server (NTRS)
Sparks, Lawrence; Komjathy, Attila; Mannucci, Anthony
2009-01-01
The conical-domain model is a computational model, now undergoing development, for estimating ionospheric delays of Global Positioning System (GPS) signals. Relative to the standard ionospheric delay model described below, the conical-domain model offers improved accuracy. In the absence of selective availability, the ionosphere is the largest source of error for single-frequency users of GPS. Because ionospheric signal delays contribute to errors in GPS position and time measurements, satellite-based augmentation systems (SBASs) have been designed to estimate these delays and broadcast corrections. Several national and international SBASs are currently in various stages of development to enhance the integrity and accuracy of GPS measurements for airline navigation. In the Wide Area Augmentation System (WAAS) of the United States, slant ionospheric delay errors and confidence bounds are derived from estimates of vertical ionospheric delay modeled on a grid at regularly spaced intervals of latitude and longitude. The estimate of vertical delay at each ionospheric grid point (IGP) is calculated from a planar fit of neighboring slant delay measurements, projected to vertical using a standard, thin-shell model of the ionosphere. Interpolation on the WAAS grid enables estimation of the vertical delay at the ionospheric pierce point (IPP) corresponding to any arbitrary measurement of a user. (The IPP of a given user s measurement is the point where the GPS signal ray path intersects a reference ionospheric height.) The product of the interpolated value and the user s thin-shell obliquity factor provides an estimate of the user s ionospheric slant delay. Two types of error that restrict the accuracy of the thin-shell model are absent in the conical domain model: (1) error due to the implicit assumption that the electron density is independent of the azimuthal angle at the IPP and (2) error arising from the slant-to-vertical conversion. At low latitudes or at mid
Adaptive Error Estimation in Linearized Ocean General Circulation Models
NASA Technical Reports Server (NTRS)
Chechelnitsky, Michael Y.
1999-01-01
Data assimilation methods are routinely used in oceanography. The statistics of the model and measurement errors need to be specified a priori. This study addresses the problem of estimating model and measurement error statistics from observations. We start by testing innovation based methods of adaptive error estimation with low-dimensional models in the North Pacific (5-60 deg N, 132-252 deg E) to TOPEX/POSEIDON (TIP) sea level anomaly data, acoustic tomography data from the ATOC project, and the MIT General Circulation Model (GCM). A reduced state linear model that describes large scale internal (baroclinic) error dynamics is used. The methods are shown to be sensitive to the initial guess for the error statistics and the type of observations. A new off-line approach is developed, the covariance matching approach (CMA), where covariance matrices of model-data residuals are "matched" to their theoretical expectations using familiar least squares methods. This method uses observations directly instead of the innovations sequence and is shown to be related to the MT method and the method of Fu et al. (1993). Twin experiments using the same linearized MIT GCM suggest that altimetric data are ill-suited to the estimation of internal GCM errors, but that such estimates can in theory be obtained using acoustic data. The CMA is then applied to T/P sea level anomaly data and a linearization of a global GFDL GCM which uses two vertical modes. We show that the CMA method can be used with a global model and a global data set, and that the estimates of the error statistics are robust. We show that the fraction of the GCM-T/P residual variance explained by the model error is larger than that derived in Fukumori et al.(1999) with the method of Fu et al.(1993). Most of the model error is explained by the barotropic mode. However, we find that impact of the change in the error statistics on the data assimilation estimates is very small. This is explained by the large
Thyrotropin-releasing hormone metabolism and extraction by the perfused guinea pig placenta
Nogimori, T.; Alex, S.; Baker, S.; Emerson, C.H.
1985-08-01
This report describes the extraction of synthetic TRH and its metabolic conversion in the perfused guinea pig placenta. These studies were performed to obtain an estimate of fractional fetal TRH losses through the placenta and to determine if some of these losses are due to TRH metabolism. Experiments were performed in which the perfusion buffer contained 0.01, 1, and 10 micrograms/ml or no synthetic TRH. In experiments in which TRH was perfused, the perfusion reservoir contents and placental effluent fractions were counted for TH, and TRH and deamido-TRH were determined by RIA. Similarly, cyclo(His-Pro) was measured when 10 micrograms/ml TRH were perfused. When synthetic TRH was perfused, steady state TRH concentrations were achieved in placental effluent fractions by 20-30 min. The single pass extraction of TRH by the placenta was 11.4 +/- 2.6% (mean +/- SE) compared to 56.9 +/- 7.0% for TH22O. No significant difference was detected regardless of whether 10, 1, or 0.01 micrograms/ml TRH were perfused. A portion of the TRH that perfused the placenta was converted to deamido-TRH at all concentrations of perfused TRH. The conversion of TRH to TRH-OH was 4.2 +/- 0.7% in a single pass. When the perfusion buffer was devoid of synthetic TRH, a small but significant increase in the content of TRH immunoreactivity was noted in the placental effluent compared to that in the perfusion reservoir.
Estimation of traffic accident costs: a prompted model.
Hejazi, Rokhshad; Shamsudin, Mad Nasir; Radam, Alias; Rahim, Khalid Abdul; Ibrahim, Zelina Zaitun; Yazdani, Saeed
2013-01-01
Traffic accidents are the reason for 25% of unnatural deaths in Iran. The main objective of this study is to find a simple model for the estimation of economic costs especially in Islamic countries (like Iran) in a straightforward manner. The model can show the magnitude of traffic accident costs with monetary equivalent. Data were collected from different sources that included traffic police records, insurance companies and hospitals. The conceptual framework, in our study, was based on the method of Ayati. He used this method for the estimation of economic costs in Iran. We promoted his method via minimum variables. Our final model has only three available variables which can be taken from insurance companies and police records. The running model showed that the traffic accident costs were US$2.2 million in 2007 for our case study route.
MAXIMUM LIKELIHOOD ESTIMATION FOR PERIODIC AUTOREGRESSIVE MOVING AVERAGE MODELS.
Vecchia, A.V.
1985-01-01
A useful class of models for seasonal time series that cannot be filtered or standardized to achieve second-order stationarity is that of periodic autoregressive moving average (PARMA) models, which are extensions of ARMA models that allow periodic (seasonal) parameters. An approximation to the exact likelihood for Gaussian PARMA processes is developed, and a straightforward algorithm for its maximization is presented. The algorithm is tested on several periodic ARMA(1, 1) models through simulation studies and is compared to moment estimation via the seasonal Yule-Walker equations. Applicability of the technique is demonstrated through an analysis of a seasonal stream-flow series from the Rio Caroni River in Venezuela.
Modeling hypoxia in the Chesapeake Bay: Ensemble estimation using a Bayesian hierarchical model
NASA Astrophysics Data System (ADS)
Stow, Craig A.; Scavia, Donald
2009-02-01
Quantifying parameter and prediction uncertainty in a rigorous framework can be an important component of model skill assessment. Generally, models with lower uncertainty will be more useful for prediction and inference than models with higher uncertainty. Ensemble estimation, an idea with deep roots in the Bayesian literature, can be useful to reduce model uncertainty. It is based on the idea that simultaneously estimating common or similar parameters among models can result in more precise estimates. We demonstrate this approach using the Streeter-Phelps dissolved oxygen sag model fit to 29 years of data from Chesapeake Bay. Chesapeake Bay has a long history of bottom water hypoxia and several models are being used to assist management decision-making in this system. The Bayesian framework is particularly useful in a decision context because it can combine both expert-judgment and rigorous parameter estimation to yield model forecasts and a probabilistic estimate of the forecast uncertainty.
Hybrid Simulation Modeling to Estimate U.S. Energy Elasticities
NASA Astrophysics Data System (ADS)
Baylin-Stern, Adam C.
This paper demonstrates how an U.S. application of CIMS, a technologically explicit and behaviourally realistic energy-economy simulation model which includes macro-economic feedbacks, can be used to derive estimates of elasticity of substitution (ESUB) and autonomous energy efficiency index (AEEI) parameters. The ability of economies to reduce greenhouse gas emissions depends on the potential for households and industry to decrease overall energy usage, and move from higher to lower emissions fuels. Energy economists commonly refer to ESUB estimates to understand the degree of responsiveness of various sectors of an economy, and use estimates to inform computable general equilibrium models used to study climate policies. Using CIMS, I have generated a set of future, 'pseudo-data' based on a series of simulations in which I vary energy and capital input prices over a wide range. I then used this data set to estimate the parameters for transcendental logarithmic production functions using regression techniques. From the production function parameter estimates, I calculated an array of elasticity of substitution values between input pairs. Additionally, this paper demonstrates how CIMS can be used to calculate price-independent changes in energy-efficiency in the form of the AEEI, by comparing energy consumption between technologically frozen and 'business as usual' simulations. The paper concludes with some ideas for model and methodological improvement, and how these might figure into future work in the estimation of ESUBs from CIMS. Keywords: Elasticity of substitution; hybrid energy-economy model; translog; autonomous energy efficiency index; rebound effect; fuel switching.
An Instructional Cost Estimation Model for the XYZ Community College.
ERIC Educational Resources Information Center
Edmonson, William F.
An enrollment-driven model for estimating instructional costs is presented in this paper as developed by the Western Interstate Commission for Higher Education (WICHE). After stating the principles of the WICHE planning system (i.e., various categories of data are gathered, segmented, and then cross-tabulated against one another to yield certain…
A model for estimating the life of electrical submersible pumps
Patterson, M.M.
1993-11-01
This paper presents a mathematical model to estimate the life expectancy of an electrical submersible pump (ESP). The premise uses a statistical method known as the Poisson pure death process, which calculates the probability of system failure on the basis of sparse data. The technique needs only one parameter and was tested on ESP failure data from a west Texas field.
A method of estimating optimal catchment model parameters
NASA Astrophysics Data System (ADS)
Ibrahim, Yaacob; Liong, Shie-Yui
1993-09-01
A review of a calibration method developed earlier (Ibrahim and Liong, 1992) is presented. The method generates optimal values for single events. It entails randomizing the calibration parameters over bounds such that a system response under consideration is bounded. Within the bounds, which are narrow and generated automatically, explicit response surface representation of the response is obtained using experimental design techniques and regression analysis. The optimal values are obtained by searching on the response surface for a point at which the predicted response is equal to the measured response and the value of the joint probability density function at that point in a transformed space is the highest. The method is demonstrated on a catchment in Singapore. The issue of global optimal values is addressed by applying the method on wider bounds. The results indicate that the optimal values arising from the narrow set of bounds are, indeed, global. Improvements which are designed to achieve comparably accurate estimates but with less expense are introduced. A linear response surface model is used. Two approximations of the model are studied. The first is to fit the model using data points generated from simple Monte Carlo simulation; the second is to approximate the model by a Taylor series expansion. Very good results are obtained from both approximations. Two methods of obtaining a single estimate from the individual event's estimates of the parameters are presented. The simulated and measured hydrographs of four verification storms using these estimates compare quite well.
DEVELOPING SEASONAL AMMONIA EMISSION ESTIMATES WITH AN INVERSE MODELING TECHNIQUE
Significant uncertainty exists in magnitude and variability of ammonia (NH3) emissions, which are needed for air quality modeling of aerosols and deposition of nitrogen compounds. Approximately 85% of NH3 emissions are estimated to come from agricultural non-point sources. We sus...
A mathematical model for efficient estimation of aircraft motions
NASA Technical Reports Server (NTRS)
Bach, R. E., Jr.
1983-01-01
In the usual formulation of the aircraft state-estimation problem, motions along a flight trajectory are represented by a plant consisting of nonlinear state and measurement models. Problem solution using this formulation requires that both state- and measurement-dependent Jacobian matrices be evaluated along any trajectory. In this paper it is shown that a set of state variables can be chosen to realize a linear state model of very simple form, such that all nonlinearities appear in the measurement model. The potential advantage of the new formulation is computational: the Jacobian matrix corresponding to a linear state model is constant, a feature that should outweigh the fact that the measurement model is more complicated than in the conventinal formulation. To compare the modeling methods, aircraft motions from typical flight-test and accident data were estimated, using each formulation with the same off-line (smoothing) algorithm. The results of these experiments, reported in the paper, demonstrate clearly the computational superiority of the linear state-variable formulation. The procedure advocated here may be extended to other nonlinear estimation problems, including on-line (filtering) applications.
Estimating Predictive Variance for Statistical Gas Distribution Modelling
Lilienthal, Achim J.; Asadi, Sahar; Reggente, Matteo
2009-05-23
Recent publications in statistical gas distribution modelling have proposed algorithms that model mean and variance of a distribution. This paper argues that estimating the predictive concentration variance entails not only a gradual improvement but is rather a significant step to advance the field. This is, first, since the models much better fit the particular structure of gas distributions, which exhibit strong fluctuations with considerable spatial variations as a result of the intermittent character of gas dispersal. Second, because estimating the predictive variance allows to evaluate the model quality in terms of the data likelihood. This offers a solution to the problem of ground truth evaluation, which has always been a critical issue for gas distribution modelling. It also enables solid comparisons of different modelling approaches, and provides the means to learn meta parameters of the model, to determine when the model should be updated or re-initialised, or to suggest new measurement locations based on the current model. We also point out directions of related ongoing or potential future research work.
Estimating Predictive Variance for Statistical Gas Distribution Modelling
NASA Astrophysics Data System (ADS)
Lilienthal, Achim J.; Asadi, Sahar; Reggente, Matteo
2009-05-01
Recent publications in statistical gas distribution modelling have proposed algorithms that model mean and variance of a distribution. This paper argues that estimating the predictive concentration variance entails not only a gradual improvement but is rather a significant step to advance the field. This is, first, since the models much better fit the particular structure of gas distributions, which exhibit strong fluctuations with considerable spatial variations as a result of the intermittent character of gas dispersal. Second, because estimating the predictive variance allows to evaluate the model quality in terms of the data likelihood. This offers a solution to the problem of ground truth evaluation, which has always been a critical issue for gas distribution modelling. It also enables solid comparisons of different modelling approaches, and provides the means to learn meta parameters of the model, to determine when the model should be updated or re-initialised, or to suggest new measurement locations based on the current model. We also point out directions of related ongoing or potential future research work.
Cost estimation model for advanced planetary programs, fourth edition
NASA Technical Reports Server (NTRS)
Spadoni, D. J.
1983-01-01
The development of the planetary program cost model is discussed. The Model was updated to incorporate cost data from the most recent US planetary flight projects and extensively revised to more accurately capture the information in the historical cost data base. This data base is comprised of the historical cost data for 13 unmanned lunar and planetary flight programs. The revision was made with a two fold objective: to increase the flexibility of the model in its ability to deal with the broad scope of scenarios under consideration for future missions, and to maintain and possibly improve upon the confidence in the model's capabilities with an expected accuracy of 20%. The Model development included a labor/cost proxy analysis, selection of the functional forms of the estimating relationships, and test statistics. An analysis of the Model is discussed and two sample applications of the cost model are presented.
Parameterized modeling and estimation of spatially varying optical blur
NASA Astrophysics Data System (ADS)
Simpkins, Jonathan D.; Stevenson, Robert L.
2015-02-01
Optical blur can display significant spatial variation across the image plane, even for constant camera settings and object depth. Existing solutions to represent this spatially varying blur requires a dense sampling of blur kernels across the image, where each kernel is defined independent of the neighboring kernels. This approach requires a large amount of data collection, and the estimation of the kernels is not as robust as if it were possible to incorporate knowledge of the relationship between adjacent kernels. A novel parameterized model is presented which relates the blur kernels at different locations across the image plane. The model is motivated by well-established optical models, including the Seidel aberration model. It is demonstrated that the proposed model can unify a set of hundreds of blur kernel observations across the image plane under a single 10-parameter model, and the accuracy of the model is demonstrated with simulations and measurement data collected by two separate research groups.
Linear systems, compartmental modeling, and estimability issues in IAQ studies
Evans, W.C.
1996-12-31
Many IAQ models are expressed as coupled systems of linear, ordinary differential equations. In this paper, the linear-systems or state-variable format for these systems will be reviewed, and some useful information will be presented which can be obtained from this formulation without explicitly solving the differential equation system. Much information concerning linear systems analysis is available in the literature of various disciplines, particularly biomathematics, wherein there is a specialization called compartmental modeling. It is important to recognize that there exists a great deal of directly usable mathematical information which can immediately be applied to IAQ modeling problems. In compartmental modeling, an issue called identifiability has long been recognized as a potential problem with experiments that are intended to extract information about a linear system`s parameters from observations of that system`s response to a forcing function. It can happen that the system`s parameters cannot be uniquely estimated from an experiment, no matter how good (noise-free) the measurements are. With a linear-systems formulation of the experimental configuration, this condition can be detected before the experiment is conducted. A related issue is termed redundancy, which refers to the inability to obtain unique parameter estimates from the data, even if the experiment is identifiable. This problem occurs for sums-of-exponentials models, fitted via nonlinear estimation to the observations. Taken together, identifiability and redundancy can be termed estimability. These difficulties can affect chamber testing in particular, since this is the context where they are attempting to estimate system parameters from observations. This paper will present an overview of these issues, with selected examples.
Can modeling improve estimation of desert tortoise population densities?
Nussear, K.E.; Tracy, C.R.
2007-01-01
The federally listed desert tortoise (Gopherus agassizii) is currently monitored using distance sampling to estimate population densities. Distance sampling, as with many other techniques for estimating population density, assumes that it is possible to quantify the proportion of animals available to be counted in any census. Because desert tortoises spend much of their life in burrows, and the proportion of tortoises in burrows at any time can be extremely variable, this assumption is difficult to meet. This proportion of animals available to be counted is used as a correction factor (g0) in distance sampling and has been estimated from daily censuses of small populations of tortoises (6-12 individuals). These censuses are costly and produce imprecise estimates of g0 due to small sample sizes. We used data on tortoise activity from a large (N = 150) experimental population to model activity as a function of the biophysical attributes of the environment, but these models did not improve the precision of estimates from the focal populations. Thus, to evaluate how much of the variance in tortoise activity is apparently not predictable, we assessed whether activity on any particular day can predict activity on subsequent days with essentially identical environmental conditions. Tortoise activity was only weakly correlated on consecutive days, indicating that behavior was not repeatable or consistent among days with similar physical environments. ?? 2007 by the Ecological Society of America.
Tyre pressure monitoring using a dynamical model-based estimator
NASA Astrophysics Data System (ADS)
Reina, Giulio; Gentile, Angelo; Messina, Arcangelo
2015-04-01
In the last few years, various control systems have been investigated in the automotive field with the aim of increasing the level of safety and stability, avoid roll-over, and customise handling characteristics. One critical issue connected with their integration is the lack of state and parameter information. As an example, vehicle handling depends to a large extent on tyre inflation pressure. When inflation pressure drops, handling and comfort performance generally deteriorate. In addition, it results in an increase in fuel consumption and in a decrease in lifetime. Therefore, it is important to keep tyres within the normal inflation pressure range. This paper introduces a model-based approach to estimate online tyre inflation pressure. First, basic vertical dynamic modelling of the vehicle is discussed. Then, a parameter estimation framework for dynamic analysis is presented. Several important vehicle parameters including tyre inflation pressure can be estimated using the estimated states. This method aims to work during normal driving using information from standard sensors only. On the one hand, the driver is informed about the inflation pressure and he is warned for sudden changes. On the other hand, accurate estimation of the vehicle states is available as possible input to onboard control systems.
Single-View Food Portion Estimation Based on Geometric Models
Fang, Shaobo; Liu, Chang; Zhu, Fengqing; Delp, Edward J.; Boushey, Carol J.
2016-01-01
In this paper we present a food portion estimation technique based on a single-view food image used for the estimation of the amount of energy (in kilocalories) consumed at a meal. Unlike previous methods we have developed, the new technique is capable of estimating food portion without manual tuning of parameters. Although single-view 3D scene reconstruction is in general an ill-posed problem, the use of geometric models such as the shape of a container can help to partially recover 3D parameters of food items in the scene. Based on the estimated 3D parameters of each food item and a reference object in the scene, the volume of each food item in the image can be determined. The weight of each food can then be estimated using the density of the food item. We were able to achieve an error of less than 6% for energy estimation of an image of a meal assuming accurate segmentation and food classification. PMID:27672682
Parameter Estimation for Groundwater Models under Uncertain Irrigation Data.
Demissie, Yonas; Valocchi, Albert; Cai, Ximing; Brozovic, Nicholas; Senay, Gabriel; Gebremichael, Mekonnen
2015-01-01
The success of modeling groundwater is strongly influenced by the accuracy of the model parameters that are used to characterize the subsurface system. However, the presence of uncertainty and possibly bias in groundwater model source/sink terms may lead to biased estimates of model parameters and model predictions when the standard regression-based inverse modeling techniques are used. This study first quantifies the levels of bias in groundwater model parameters and predictions due to the presence of errors in irrigation data. Then, a new inverse modeling technique called input uncertainty weighted least-squares (IUWLS) is presented for unbiased estimation of the parameters when pumping and other source/sink data are uncertain. The approach uses the concept of generalized least-squares method with the weight of the objective function depending on the level of pumping uncertainty and iteratively adjusted during the parameter optimization process. We have conducted both analytical and numerical experiments, using irrigation pumping data from the Republican River Basin in Nebraska, to evaluate the performance of ordinary least-squares (OLS) and IUWLS calibration methods under different levels of uncertainty of irrigation data and calibration conditions. The result from the OLS method shows the presence of statistically significant (p < 0.05) bias in estimated parameters and model predictions that persist despite calibrating the models to different calibration data and sample sizes. However, by directly accounting for the irrigation pumping uncertainties during the calibration procedures, the proposed IUWLS is able to minimize the bias effectively without adding significant computational burden to the calibration processes.
Parameter Estimation for Groundwater Models under Uncertain Irrigation Data.
Demissie, Yonas; Valocchi, Albert; Cai, Ximing; Brozovic, Nicholas; Senay, Gabriel; Gebremichael, Mekonnen
2015-01-01
The success of modeling groundwater is strongly influenced by the accuracy of the model parameters that are used to characterize the subsurface system. However, the presence of uncertainty and possibly bias in groundwater model source/sink terms may lead to biased estimates of model parameters and model predictions when the standard regression-based inverse modeling techniques are used. This study first quantifies the levels of bias in groundwater model parameters and predictions due to the presence of errors in irrigation data. Then, a new inverse modeling technique called input uncertainty weighted least-squares (IUWLS) is presented for unbiased estimation of the parameters when pumping and other source/sink data are uncertain. The approach uses the concept of generalized least-squares method with the weight of the objective function depending on the level of pumping uncertainty and iteratively adjusted during the parameter optimization process. We have conducted both analytical and numerical experiments, using irrigation pumping data from the Republican River Basin in Nebraska, to evaluate the performance of ordinary least-squares (OLS) and IUWLS calibration methods under different levels of uncertainty of irrigation data and calibration conditions. The result from the OLS method shows the presence of statistically significant (p < 0.05) bias in estimated parameters and model predictions that persist despite calibrating the models to different calibration data and sample sizes. However, by directly accounting for the irrigation pumping uncertainties during the calibration procedures, the proposed IUWLS is able to minimize the bias effectively without adding significant computational burden to the calibration processes. PMID:25040235
Bayesian Model Averaging of Artificial Intelligence Models for Hydraulic Conductivity Estimation
NASA Astrophysics Data System (ADS)
Nadiri, A.; Chitsazan, N.; Tsai, F. T.; Asghari Moghaddam, A.
2012-12-01
This research presents a Bayesian artificial intelligence model averaging (BAIMA) method that incorporates multiple artificial intelligence (AI) models to estimate hydraulic conductivity and evaluate estimation uncertainties. Uncertainty in the AI model outputs stems from error in model input as well as non-uniqueness in selecting different AI methods. Using one single AI model tends to bias the estimation and underestimate uncertainty. BAIMA employs Bayesian model averaging (BMA) technique to address the issue of using one single AI model for estimation. BAIMA estimates hydraulic conductivity by averaging the outputs of AI models according to their model weights. In this study, the model weights were determined using the Bayesian information criterion (BIC) that follows the parsimony principle. BAIMA calculates the within-model variances to account for uncertainty propagation from input data to AI model output. Between-model variances are evaluated to account for uncertainty due to model non-uniqueness. We employed Takagi-Sugeno fuzzy logic (TS-FL), artificial neural network (ANN) and neurofuzzy (NF) to estimate hydraulic conductivity for the Tasuj plain aquifer, Iran. BAIMA combined three AI models and produced better fitting than individual models. While NF was expected to be the best AI model owing to its utilization of both TS-FL and ANN models, the NF model is nearly discarded by the parsimony principle. The TS-FL model and the ANN model showed equal importance although their hydraulic conductivity estimates were quite different. This resulted in significant between-model variances that are normally ignored by using one AI model.
Negative binomial models for abundance estimation of multiple closed populations
Boyce, Mark S.; MacKenzie, Darry I.; Manly, Bryan F.J.; Haroldson, Mark A.; Moody, David W.
2001-01-01
Counts of uniquely identified individuals in a population offer opportunities to estimate abundance. However, for various reasons such counts may be burdened by heterogeneity in the probability of being detected. Theoretical arguments and empirical evidence demonstrate that the negative binomial distribution (NBD) is a useful characterization for counts from biological populations with heterogeneity. We propose a method that focuses on estimating multiple populations by simultaneously using a suite of models derived from the NBD. We used this approach to estimate the number of female grizzly bears (Ursus arctos) with cubs-of-the-year in the Yellowstone ecosystem, for each year, 1986-1998. Akaike's Information Criteria (AIC) indicated that a negative binomial model with a constant level of heterogeneity across all years was best for characterizing the sighting frequencies of female grizzly bears. A lack-of-fit test indicated the model adequately described the collected data. Bootstrap techniques were used to estimate standard errors and 95% confidence intervals. We provide a Monte Carlo technique, which confirms that the Yellowstone ecosystem grizzly bear population increased during the period 1986-1998.
Estimating genetic parameters in natural populations using the "animal model".
Kruuk, Loeske E B
2004-01-01
Estimating the genetic basis of quantitative traits can be tricky for wild populations in natural environments, as environmental variation frequently obscures the underlying evolutionary patterns. I review the recent application of restricted maximum-likelihood "animal models" to multigenerational data from natural populations, and show how the estimation of variance components and prediction of breeding values using these methods offer a powerful means of tackling the potentially confounding effects of environmental variation, as well as generating a wealth of new areas of investigation. PMID:15306404
Inversion of canopy reflectance models for estimation of vegetation parameters
NASA Technical Reports Server (NTRS)
Goel, Narendra S.
1987-01-01
One of the keys to successful remote sensing of vegetation is to be able to estimate important agronomic parameters like leaf area index (LAI) and biomass (BM) from the bidirectional canopy reflectance (CR) data obtained by a space-shuttle or satellite borne sensor. One approach for such an estimation is through inversion of CR models which relate these parameters to CR. The feasibility of this approach was shown. The overall objective of the research carried out was to address heretofore uninvestigated but important fundamental issues, develop the inversion technique further, and delineate its strengths and limitations.
Estimation of nonlinear pilot model parameters including time delay.
NASA Technical Reports Server (NTRS)
Schiess, J. R.; Roland, V. R.; Wells, W. R.
1972-01-01
Investigation of the feasibility of using a Kalman filter estimator for the identification of unknown parameters in nonlinear dynamic systems with a time delay. The problem considered is the application of estimation theory to determine the parameters of a family of pilot models containing delayed states. In particular, the pilot-plant dynamics are described by differential-difference equations of the retarded type. The pilot delay, included as one of the unknown parameters to be determined, is kept in pure form as opposed to the Pade approximations generally used for these systems. Problem areas associated with processing real pilot response data are included in the discussion.
Rothbarth, Joost; Sparidans, Rolf W; Beijnen, Jos H; Schultze-Kool, Leo J; Putter, Hein; van de Velde, Cornelis J H; Mulder, Gerard J
2002-11-01
Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction male WAG/Rij rats were inoculated with CC531 cells, a colorectal tumor cell line. After 11 to 12 days the tumor-bearing rat livers were perfused by single-pass perfusion through either the portal (orthograde) or caval vein (retrograde) for different time periods. During perfusion melphalan (160 Schultze) was infused in the hepatic artery. Melphalan concentrations were measured by high-performance liquid chromatography. A rapid extraction of melphalan by the liver occurred in the first 5 min, reaching steady state after 10 to 20 min for both perfusion directions. The melphalan concentration of the outflow perfusate was significantly higher in the retrograde perfusion compared with the orthograde perfusion. The melphalan content of the tumor tissue was unaffected by perfusion direction at any time point. To the contrary, the melphalan uptake in liver tissue was strongly influenced: the melphalan content after 40-min retrograde perfusion was 12% of that after orthograde perfusion. The average tumor/liver concentration ratio was 6 for orthograde perfusion and 30 for retrograde perfusion. In conclusion, retrograde IHP with continuous melphalan infusion in the hepatic artery provides a high tumor uptake of melphalan with potentially reduced liver toxicity compared with orthograde IHP. PMID:12388659
Multi-criteria parameter estimation for the Unified Land Model
NASA Astrophysics Data System (ADS)
Livneh, B.; Lettenmaier, D. P.
2012-08-01
We describe a parameter estimation framework for the Unified Land Model (ULM) that utilizes multiple independent data sets over the continental United States. These include a satellite-based evapotranspiration (ET) product based on MODerate resolution Imaging Spectroradiometer (MODIS) and Geostationary Operational Environmental Satellites (GOES) imagery, an atmospheric-water balance based ET estimate that utilizes North American Regional Reanalysis (NARR) atmospheric fields, terrestrial water storage content (TWSC) data from the Gravity Recovery and Climate Experiment (GRACE), and streamflow (Q) primarily from the United States Geological Survey (USGS) stream gauges. The study domain includes 10 large-scale (≥105 km2) river basins and 250 smaller-scale (<104 km2) tributary basins. ULM, which is essentially a merger of the Noah Land Surface Model and Sacramento Soil Moisture Accounting Model, is the basis for these experiments. Calibrations were made using each of the data sets individually, in addition to combinations of multiple criteria, with multi-criteria skill scores computed for all cases. At large scales, calibration to Q resulted in the best overall performance, whereas certain combinations of ET and TWSC calibrations lead to large errors in other criteria. At small scales, about one-third of the basins had their highest Q performance from multi-criteria calibrations (to Q and ET) suggesting that traditional calibration to Q may benefit by supplementing observed Q with remote sensing estimates of ET. Model streamflow errors using optimized parameters were mostly due to over (under) estimation of low (high) flows. Overall, uncertainties in remote-sensing data proved to be a limiting factor in the utility of multi-criteria parameter estimation.
Multi-criteria parameter estimation for the unified land model
NASA Astrophysics Data System (ADS)
Livneh, B.; Lettenmaier, D. P.
2012-04-01
We describe a parameter estimation framework for the Unified Land Model (ULM) that utilizes multiple independent data sets over the Continental United States. These include a satellite-based evapotranspiration (ET) product based on MODerate resolution Imaging Spectroradiometer (MODIS) and Geostationary Operation Environmental Satellites (GOES) imagery, an atmospheric-water balance based ET estimate that utilizes North American Regional Reanalysis (NARR) atmospheric fields, terrestrial water storage content (TWSC) data from the Gravity Recovery and Climate Experiment (GRACE), and streamflow (Q) primarily from the United States Geological Survey (USGS) stream gauges. The study domain includes 10 large-scale (≥105 km2) river basins and 250 smaller-scale (<104 km2) tributary basins. ULM, which is essentially a merger of the Noah Land Surface Model and Sacramento Soil Moisture Accounting model, is the basis for these experiments. Calibrations were made using each of the criteria individually, in addition to combinations of multiple criteria, with multi-criteria skill scores computed for all cases. At large-scales calibration to Q resulted in the best overall performance, whereas certain combinations of ET and TWSC calibrations lead to large errors in other criteria. At small scales, about one-third of the basins had their highest Q performance from multi-criteria calibrations (to Q and ET) suggesting that traditional calibration to Q may benefit by supplementing observed Q with remote sensing estimates of ET. Model streamflow errors using optimized parameters were mostly due to over (under) estimation of low (high) flows. Overall, uncertainties in remote-sensing data proved to be a limiting factor in the utility of multi-criteria parameter estimation.
Evaluation of Black Carbon Estimations in Global Aerosol Models
Koch, D.; Schulz, M.; Kinne, Stefan; McNaughton, C. S.; Spackman, J. R.; Balkanski, Y.; Bauer, S.; Berntsen, T.; Bond, Tami C.; Boucher, Olivier; Chin, M.; Clarke, A. D.; De Luca, N.; Dentener, F.; Diehl, T.; Dubovik, O.; Easter, Richard C.; Fahey, D. W.; Feichter, J.; Fillmore, D.; Freitag, S.; Ghan, Steven J.; Ginoux, P.; Gong, S.; Horowitz, L.; Iversen, T.; Kirkevag, A.; Klimont, Z.; Kondo, Yutaka; Krol, M.; Liu, Xiaohong; Miller, R.; Montanaro, V.; Moteki, N.; Myhre, G.; Penner, J.; Perlwitz, Ja; Pitari, G.; Reddy, S.; Sahu, L.; Sakamoto, H.; Schuster, G.; Schwarz, J. P.; Seland, O.; Stier, P.; Takegawa, Nobuyuki; Takemura, T.; Textor, C.; van Aardenne, John; Zhao, Y.
2009-11-27
We evaluate black carbon (BC) model predictions from the AeroCom model intercomparison project by considering the diversity among year 2000 model simulations and comparing model predictions with available measurements. These model-measurement intercomparisons include BC surface and aircraft concentrations, aerosol absorption optical depth (AAOD) from AERONET and OMI retrievals and BC column estimations based on AERONET. In regions other than Asia, most models are biased high compared to surface concentration measurements. However compared with (column) AAOD or BC burden retreivals, the models are generally biased low. The average ratio of model to retrieved AAOD is less than 0.7 in South American and 0.6 in African biomass burning regions; both of these regions lack surface concentration measurements. In Asia the average model to observed ratio is 0.6 for AAOD and 0.5 for BC surface concentrations. Compared with aircraft measurements over the Americas at latitudes between 0 and 50N, the average model is a factor of 10 larger than observed, and most models exceed the measured BC standard deviation in the mid to upper troposphere. At higher latitudes the average model to aircraft BC is 0.6 and underestimate the observed BC loading in the lower and middle troposphere associated with springtime Arctic haze. Low model bias for AAOD but overestimation of surface and upper atmospheric BC concentrations at lower latitudes suggests that most models are underestimating BC absorption and should improve estimates for refractive index, particle size, and optical effects of BC coating. Retrieval uncertainties and/or differences with model diagnostic treatment may also contribute to the model-measurement disparity. Largest AeroCom model diversity occurred in northern Eurasia and the remote Arctic, regions influenced by anthropogenic sources. Changing emissions, aging, removal, or optical properties within a single model generated a smaller change in model predictions than the
Ressler, Noel; Rider, Alan R; Kunselman, Allen R; Richardson, J Scott; Dasse, Kurt A; Wang, Shigang; Undar, Akif
2009-01-01
The hemodynamic comparison of the Jostra HL-20 and the Levitronix PediVAS blood pumps is the focus this study, where pressure-flow waveforms and hemodynamic energy values are analyzed in the confines of a pediatric cardiopulmonary bypass circuit.The pseudo pediatric patient was perfused with flow rates between 500 and 900 ml/min (100 ml/min increments) under pulsatile and nonpulsatile mode. The Levitronix continuous flow pump utilized a customized controller to engage in pulsatile perfusion with equivalent pulse settings to the Jostra HL-20 roller pump. Hemodynamic measurements and waveforms were recorded at the precannula location, while the mean arterial pressure was maintained at 40 mm Hg for each test. Glycerin water was used as the blood analog circuit perfusate. At each flow rate 24 trials were conducted yielding a total of 120 experiments (n=60 pulsatile and n=60 nonpulsatile).Under nonpulsatile perfusion the Jostra roller pump produced small values for surplus hemodynamic energy (SHE) due to its inherent pulsatility, while the Levitronix produced values of essentially zero for SHE. When switching to pulsatile perfusion, the SHE levels for both the Jostra and Levitronix pump made considerable increases. In comparing the two pumps under pulsatile perfusion, the Levitronix PediVAS produced significantly more surplus and total hemodynamic energy than did the Jostra roller pump each pump flow rate.The study suggests that the Levitronix PediVAS centrifugal pump has the capability of achieving quality pulsatile waveforms and delivering more SHE to the pseudo patient than the Jostra HL-20 roller pump. Further studies are warranted to investigate the Levitronix under bovine blood studies and with various pulsatile settings.
Error estimates for the Skyrme-Hartree-Fock model
NASA Astrophysics Data System (ADS)
Erler, J.; Reinhard, P.-G.
2015-03-01
There are many complementary strategies to estimate the extrapolation errors of a model calibrated in least-squares fits. We consider the Skyrme-Hartree-Fock model for nuclear structure and dynamics and exemplify the following five strategies: uncertainties from statistical analysis, covariances between observables, trends of residuals, variation of fit data, and dedicated variation of model parameters. This gives useful insight into the impact of the key fit data as they consist of binding energies, charge rms radii, and charge formfactor. Amongst others, we check in particular the predictive value for observables in the stable nucleus 208Pb, the super-heavy element 266Hs, r-process nuclei, and neutron stars.
Hidden Markov Modeling for Weigh-In-Motion Estimation
Abercrombie, Robert K; Ferragut, Erik M; Boone, Shane
2012-01-01
This paper describes a hidden Markov model to assist in the weight measurement error that arises from complex vehicle oscillations of a system of discrete masses. Present reduction of oscillations is by a smooth, flat, level approach and constant, slow speed in a straight line. The model uses this inherent variability to assist in determining the true total weight and individual axle weights of a vehicle. The weight distribution dynamics of a generic moving vehicle were simulated. The model estimation converged to within 1% of the true mass for simulated data. The computational demands of this method, while much greater than simple averages, took only seconds to run on a desktop computer.
Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps
Fichter, Andreas M.; Ritschl, Lucas M.; Borgmann, Anna; Humbs, Martin; Luppa, Peter B.; Wolff, Klaus-Dietrich; Mücke, Thomas
2016-01-01
Background Extracorporeal perfusion (ECP) might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps. Methods After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood) were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7. Results ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27%) was even lower than after in vivo perfusion (49%), although not statistically significant (P = 0,083). After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%). Angiographic and histological findings confirmed these observations. Conclusions Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies. PMID:26808996
NASA Technical Reports Server (NTRS)
Morrison, Dennis R.
1990-01-01
Perfusion bioreactor module, self-contained, closed-loop cell-culture system that operates in microgravity or on Earth. Equipment supports growth or long-term maintenance of cultures of human or other fragile cells for experiments in basic cell biology or process technology. Designed to support proliferation (initially at exponential rates of growth) of cells in complex growth medium and to maintain confluent cells in defined medium under conditions optimized to permit or encourage selected functions of cells, including secretion of products of cells into medium.
Model Year 2016 Fuel Economy Guide: EPA Fuel Economy Estimates
2015-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2007 Fuel Economy Guide: EPA Fuel Economy Estimates
2007-10-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2006 Fuel Economy Guide: EPA Fuel Economy Estimates
2005-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2008 Fuel Economy Guide: EPA Fuel Economy Estimates
2007-10-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2005 Fuel Economy Guide: EPA Fuel Economy Estimates
2004-11-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2010 Fuel Economy Guide: EPA Fuel Economy Estimates
2009-10-14
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2009 Fuel Economy Guide: EPA Fuel Economy Estimates
2008-10-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Model Year 2014 Fuel Economy Guide: EPA Fuel Economy Estimates
2013-12-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Modeling of Closed-Die Forging for Estimating Forging Load
NASA Astrophysics Data System (ADS)
Sheth, Debashish; Das, Santanu; Chatterjee, Avik; Bhattacharya, Anirban
2016-05-01
Closed die forging is one common metal forming process used for making a range of products. Enough load is to exert on the billet for deforming the material. This forging load is dependent on work material property and frictional characteristics of the work material with the punch and die. Several researchers worked on estimation of forging load for specific products under different process variables. Experimental data on deformation resistance and friction were used to calculate the load. In this work, theoretical estimation of forging load is made to compare this value with that obtained through LS-DYNA model facilitating the finite element analysis. Theoretical work uses slab method to assess forging load for an axi-symmetric upsetting job made of lead. Theoretical forging load estimate shows slightly higher value than the experimental one; however, simulation shows quite close matching with experimental forging load, indicating possibility of wide use of this simulation software.
Model Year 2015 Fuel Economy Guide: EPA Fuel Economy Estimates
2014-12-01
The Fuel Economy Guide is published by the U.S. Department of Energy as an aid to consumers considering the purchase of a new vehicle. The Guide lists estimates of miles per gallon (mpg) for each vehicle available for the new model year. These estimates are provided by the U.S. Environmental Protection Agency in compliance with Federal Law. By using this Guide, consumers can estimate the average yearly fuel cost for any vehicle. The Guide is intended to help consumers compare the fuel economy of similarly sized cars, light duty trucks and special purpose vehicles. The vehicles listed have been divided into three classes of cars, three classes of light duty trucks, and three classes of special purpose vehicles.
Parameter and uncertainty estimation for mechanistic, spatially explicit epidemiological models
NASA Astrophysics Data System (ADS)
Finger, Flavio; Schaefli, Bettina; Bertuzzo, Enrico; Mari, Lorenzo; Rinaldo, Andrea
2014-05-01
Epidemiological models can be a crucially important tool for decision-making during disease outbreaks. The range of possible applications spans from real-time forecasting and allocation of health-care resources to testing alternative intervention mechanisms such as vaccines, antibiotics or the improvement of sanitary conditions. Our spatially explicit, mechanistic models for cholera epidemics have been successfully applied to several epidemics including, the one that struck Haiti in late 2010 and is still ongoing. Calibration and parameter estimation of such models represents a major challenge because of properties unusual in traditional geoscientific domains such as hydrology. Firstly, the epidemiological data available might be subject to high uncertainties due to error-prone diagnosis as well as manual (and possibly incomplete) data collection. Secondly, long-term time-series of epidemiological data are often unavailable. Finally, the spatially explicit character of the models requires the comparison of several time-series of model outputs with their real-world counterparts, which calls for an appropriate weighting scheme. It follows that the usual assumption of a homoscedastic Gaussian error distribution, used in combination with classical calibration techniques based on Markov chain Monte Carlo algorithms, is likely to be violated, whereas the construction of an appropriate formal likelihood function seems close to impossible. Alternative calibration methods, which allow for accurate estimation of total model uncertainty, particularly regarding the envisaged use of the models for decision-making, are thus needed. Here we present the most recent developments regarding methods for parameter and uncertainty estimation to be used with our mechanistic, spatially explicit models for cholera epidemics, based on informal measures of goodness of fit.
Estimation of effective connectivity via data-driven neural modeling
Freestone, Dean R.; Karoly, Philippa J.; Nešić, Dragan; Aram, Parham; Cook, Mark J.; Grayden, David B.
2014-01-01
This research introduces a new method for functional brain imaging via a process of model inversion. By estimating parameters of a computational model, we are able to track effective connectivity and mean membrane potential dynamics that cannot be directly measured using electrophysiological measurements alone. The ability to track the hidden aspects of neurophysiology will have a profound impact on the way we understand and treat epilepsy. For example, under the assumption the model captures the key features of the cortical circuits of interest, the framework will provide insights into seizure initiation and termination on a patient-specific basis. It will enable investigation into the effect a particular drug has on specific neural populations and connectivity structures using minimally invasive measurements. The method is based on approximating brain networks using an interconnected neural population model. The neural population model is based on a neural mass model that describes the functional activity of the brain, capturing the mesoscopic biophysics and anatomical structure. The model is made subject-specific by estimating the strength of intra-cortical connections within a region and inter-cortical connections between regions using a novel Kalman filtering method. We demonstrate through simulation how the framework can be used to track the mechanisms involved in seizure initiation and termination. PMID:25506315
Survivorship models for estimating the risk of decompression sickness.
Kumar, K V; Powell, M R
1994-07-01
Several approaches have been used for modeling the incidence of decompression sickness (DCS) such as Hill's dose-response and logistic regression. Most of these methods do not include the time-to-onset information in the model. Survival analysis (failure time analysis) is appropriate when the time to onset of an event is of interest. The applicability of survival analysis for modeling the risk of DCS is illustrated by using data obtained from hypobaric chamber exposures simulating extravehicular activities (n = 426). Univariate analysis of incidence-free survival proportions were obtained for Doppler-detectable circulating microbubbles (CMB), symptoms of DCS and test aborts. A log-linear failure time regression model with 360-min half-time tissue ratio (TR) as covariate was constructed, and estimated probabilities for various TR values were calculated. Further regression analysis by including CMB status in this model showed significant improvement (p < 0.05) in the estimation of DCS over the previous model. Since DCS is dependent on the exposure pressure as well as the duration of exposure, we recommend the use of survival analysis for modeling the risk of DCS. PMID:7945136
Estimating a geographically explicit model of population divergence.
Knowles, L Lacey; Carstens, Bryan C
2007-03-01
Patterns of genetic variation can provide valuable insights for deciphering the relative roles of different evolutionary processes in species differentiation. However, population-genetic models for studying divergence in geographically structured species are generally lacking. Since these are the biogeographic settings where genetic drift is expected to predominate, not only are population-genetic tests of hypotheses in geographically structured species constrained, but generalizations about the evolutionary processes that promote species divergence may also be potentially biased. Here we estimate a population-divergence model in montane grasshoppers from the sky islands of the Rocky Mountains. Because this region was directly impacted by Pleistocene glaciation, both the displacement into glacial refugia and recolonization of montane habitats may contribute to differentiation. Building on the tradition of using information from the genealogical relationships of alleles to infer the geography of divergence, here the additional consideration of the process of gene-lineage sorting is used to obtain a quantitative estimate of population relationships and historical associations (i.e., a population tree) from the gene trees of five anonymous nuclear loci and one mitochondrial locus in the broadly distributed species Melanoplus oregonensis. Three different approaches are used to estimate a model of population divergence; this comparison allows us to evaluate specific methodological assumptions that influence the estimated history of divergence. A model of population divergence was identified that significantly fits the data better compared to the other approaches, based on per-site likelihood scores of the multiple loci, and that provides clues about how divergence proceeded in M. oregonensis during the dynamic Pleistocene. Unlike the approaches that either considered only the most recent coalescence (i.e., information from a single individual per population) or did not
Channel mismatch estimation in time-interleaved ADCs based on input dependent estimating model
NASA Astrophysics Data System (ADS)
Liu, Sujuan; Wang, Junshan; Qi, Peipei; Chen, Jianxin
2012-04-01
Time-interleaved Analog-to-Digital Converter (TIADC) is an efficient way to achieve higher sampling rates for medium-to-high resolution applications. However, the performance of a TIADC suffers from mismatch errors among the sub-channels. This paper presents a method to estimate the channel mismatch errors using the sub-channels' output data. The proposed method introduces an input dependent estimating model (IDEM) based on an equivalent transfer function including the mismatch errors to calculate the standard deviation of the mismatch errors. The spurious-free dynamic range (SFDR) is then evaluated by applying multi-tone sinusoids signal to input. The simulated results show that the method in this work can get about 45dB SFDR enhancement.
Virtual patient simulator for the perfusion resource management drill.
Ninomiya, Shinji; Tokaji, Megumi; Tokumine, Asako; Kurosaki, Tatsuya
2009-12-01
Perfusionists require a detailed understanding of a patient's physiological status while comprehending the mechanics and engineering of the cardiopulmonary bypass system, so it is beneficial for them to obtain relevant practical skills using extracorporeal circulation technology and educational physiological simulators. We designed a perfusion simulator system (ECCSIM: Extracorporeal Circulation SIMulator system) based on a hybrid of a simple hydraulic mock circulation loop linked to a computer simulation model. Patient physiological conditions (height, weight, and cardiac indices) were determined by a parameter estimation procedure and used to accurately reproduce hemodynamic conditions. Extracorporeal circulation trainees in pre-clinical education were able to maintain venous oxygen saturation levels above 50%, except during cardiac standstill and a brief resumption of pulsation. Infant amplitudes of reservoir volume oscillation and flow rate were greatly increased compared with adult cardiovascular parameters, this enabled the instructor to control the difficulty level of the operation using different hemodynamic variations. High-fidelity simulator systems with controllable difficulty levels and high physiological reproducibility are useful in constructing a perfusion resource management environment that enable basic training and periodic crisis management drills to be performed. PMID:20092074
Virtual Patient Simulator for the Perfusion Resource Management Drill
Ninomiya, Shinji; Tokaji, Megumi; Tokumine, Asako; Kurosaki, Tatsuya
2009-01-01
Abstract: Perfusionists require a detailed understanding of a patient’s physiological status while comprehending the mechanics and engineering of the cardiopulmonary bypass system, so it is beneficial for them to obtain relevant practical skills using extra-corporeal circulation technology and educational physiological simulators. We designed a perfusion simulator system (ECCSIM: Extracorporeal Circulation SIMulator system) based on a hybrid of a simple hydraulic mock circulation loop linked to a computer simulation model. Patient physiological conditions (height, weight, and cardiac indices) were determined by a parameter estimation procedure and used to accurately reproduce hemodynamic conditions. Extracorporeal circulation trainees in pre-clinical education were able to maintain venous oxygen saturation levels above 50%, except during cardiac standstill and a brief resumption of pulsation. Infant amplitudes of reservoir volume oscillation and flow rate were greatly increased compared with adult cardiovascular parameters, this enabled the instructor to control the difficulty level of the operation using different hemodynamic variations. High-fidelity simula tor systems with controllable difficulty levels and high physiological reproducibility are useful in constructing a perfusion resource management environment that enable basic training and periodic crisis management drills to be performed. PMID:20092074
Forward Models and State Estimation in Compensatory Eye Movements
Frens, Maarten A.; Donchin, Opher
2009-01-01
The compensatory eye movement (CEM) system maintains a stable retinal image, integrating information from different sensory modalities to compensate for head movements. Inspired by recent models of the physiology of limb movements, we suggest that CEM can be modeled as a control system with three essential building blocks: a forward model that predicts the effects of motor commands; a state estimator that integrates sensory feedback into this prediction; and, a feedback controller that translates a state estimate into motor commands. We propose a specific mapping of nuclei within the CEM system onto these control functions. Specifically, we suggest that the Flocculus is responsible for generating the forward model prediction and that the Vestibular Nuclei integrate sensory feedback to generate an estimate of current state. Finally, the brainstem motor nuclei – in the case of horizontal compensation this means the Abducens Nucleus and the Nucleus Prepositus Hypoglossi – implement a feedback controller, translating state into motor commands. While these efforts to understand the physiological control system as a feedback control system are in their infancy, there is the intriguing possibility that CEM and targeted voluntary movements use the same cerebellar circuitry in fundamentally different ways. PMID:19956563
Time-to-Compromise Model for Cyber Risk Reduction Estimation
Miles A. McQueen; Wayne F. Boyer; Mark A. Flynn; George A. Beitel
2005-09-01
We propose a new model for estimating the time to compromise a system component that is visible to an attacker. The model provides an estimate of the expected value of the time-to-compromise as a function of known and visible vulnerabilities, and attacker skill level. The time-to-compromise random process model is a composite of three subprocesses associated with attacker actions aimed at the exploitation of vulnerabilities. In a case study, the model was used to aid in a risk reduction estimate between a baseline Supervisory Control and Data Acquisition (SCADA) system and the baseline system enhanced through a specific set of control system security remedial actions. For our case study, the total number of system vulnerabilities was reduced by 86% but the dominant attack path was through a component where the number of vulnerabilities was reduced by only 42% and the time-to-compromise of that component was increased by only 13% to 30% depending on attacker skill level.
Urban scale air quality modelling using detailed traffic emissions estimates
NASA Astrophysics Data System (ADS)
Borrego, C.; Amorim, J. H.; Tchepel, O.; Dias, D.; Rafael, S.; Sá, E.; Pimentel, C.; Fontes, T.; Fernandes, P.; Pereira, S. R.; Bandeira, J. M.; Coelho, M. C.
2016-04-01
The atmospheric dispersion of NOx and PM10 was simulated with a second generation Gaussian model over a medium-size south-European city. Microscopic traffic models calibrated with GPS data were used to derive typical driving cycles for each road link, while instantaneous emissions were estimated applying a combined Vehicle Specific Power/Co-operative Programme for Monitoring and Evaluation of the Long-range Transmission of Air Pollutants in Europe (VSP/EMEP) methodology. Site-specific background concentrations were estimated using time series analysis and a low-pass filter applied to local observations. Air quality modelling results are compared against measurements at two locations for a 1 week period. 78% of the results are within a factor of two of the observations for 1-h average concentrations, increasing to 94% for daily averages. Correlation significantly improves when background is added, with an average of 0.89 for the 24 h record. The results highlight the potential of detailed traffic and instantaneous exhaust emissions estimates, together with filtered urban background, to provide accurate input data to Gaussian models applied at the urban scale.
Uncertainty Analysis and Parameter Estimation For Nearshore Hydrodynamic Models
NASA Astrophysics Data System (ADS)
Ardani, S.; Kaihatu, J. M.
2012-12-01
Numerical models represent deterministic approaches used for the relevant physical processes in the nearshore. Complexity of the physics of the model and uncertainty involved in the model inputs compel us to apply a stochastic approach to analyze the robustness of the model. The Bayesian inverse problem is one powerful way to estimate the important input model parameters (determined by apriori sensitivity analysis) and can be used for uncertainty analysis of the outputs. Bayesian techniques can be used to find the range of most probable parameters based on the probability of the observed data and the residual errors. In this study, the effect of input data involving lateral (Neumann) boundary conditions, bathymetry and off-shore wave conditions on nearshore numerical models are considered. Monte Carlo simulation is applied to a deterministic numerical model (the Delft3D modeling suite for coupled waves and flow) for the resulting uncertainty analysis of the outputs (wave height, flow velocity, mean sea level and etc.). Uncertainty analysis of outputs is performed by random sampling from the input probability distribution functions and running the model as required until convergence to the consistent results is achieved. The case study used in this analysis is the Duck94 experiment, which was conducted at the U.S. Army Field Research Facility at Duck, North Carolina, USA in the fall of 1994. The joint probability of model parameters relevant for the Duck94 experiments will be found using the Bayesian approach. We will further show that, by using Bayesian techniques to estimate the optimized model parameters as inputs and applying them for uncertainty analysis, we can obtain more consistent results than using the prior information for input data which means that the variation of the uncertain parameter will be decreased and the probability of the observed data will improve as well. Keywords: Monte Carlo Simulation, Delft3D, uncertainty analysis, Bayesian techniques
Evaporation Estimation of Rift Valley Lakes: Comparison of Models
Melesse, Assefa M.; Abtew, Wossenu; Dessalegne, Tibebe
2009-01-01
Evapotranspiration (ET) accounts for a substantial amount of the water flux in the arid and semi-arid regions of the World. Accurate estimation of ET has been a challenge for hydrologists, mainly because of the spatiotemporal variability of the environmental and physical parameters governing the latent heat flux. In addition, most available ET models depend on intensive meteorological information for ET estimation. Such data are not available at the desired spatial and temporal scales in less developed and remote parts of the world. This limitation has necessitated the development of simple models that are less data intensive and provide ET estimates with acceptable level of accuracy. Remote sensing approach can also be applied to large areas where meteorological data are not available and field scale data collection is costly, time consuming and difficult. In areas like the Rift Valley regions of Ethiopia, the applicability of the Simple Method (Abtew Method) of lake evaporation estimation and surface energy balance approach using remote sensing was studied. The Simple Method and a remote sensing-based lake evaporation estimates were compared to the Penman, Energy balance, Pan, Radiation and Complementary Relationship Lake Evaporation (CRLE) methods applied in the region. Results indicate a good correspondence of the models outputs to that of the above methods. Comparison of the 1986 and 2000 monthly lake ET from the Landsat images to the Simple and Penman Methods show that the remote sensing and surface energy balance approach is promising for large scale applications to understand the spatial variation of the latent heat flux. PMID:22303142
Neural Net Gains Estimation Based on an Equivalent Model.
Aguilar Cruz, Karen Alicia; Medel Juárez, José de Jesús; Fernández Muñoz, José Luis; Esmeralda Vigueras Velázquez, Midory
2016-01-01
A model of an Equivalent Artificial Neural Net (EANN) describes the gains set, viewed as parameters in a layer, and this consideration is a reproducible process, applicable to a neuron in a neural net (NN). The EANN helps to estimate the NN gains or parameters, so we propose two methods to determine them. The first considers a fuzzy inference combined with the traditional Kalman filter, obtaining the equivalent model and estimating in a fuzzy sense the gains matrix A and the proper gain K into the traditional filter identification. The second develops a direct estimation in state space, describing an EANN using the expected value and the recursive description of the gains estimation. Finally, a comparison of both descriptions is performed; highlighting the analytical method describes the neural net coefficients in a direct form, whereas the other technique requires selecting into the Knowledge Base (KB) the factors based on the functional error and the reference signal built with the past information of the system.
Causal Estimation using Semiparametric Transformation Models under Prevalent Sampling
Cheng, Yu-Jen; Wang, Mei-Cheng
2015-01-01
Summary This paper develops methods and inference for causal estimation in semiparametric transformation models for prevalent survival data. Through estimation of the transformation models and covariate distribution, we propose analytical procedures to estimate the causal survival function. As the data are observational, the unobserved potential outcome (survival time) may be associated with the treatment assignment, and therefore there may exist a systematic imbalance between the data observed from each treatment arm. Further, due to prevalent sampling, subjects are observed only if they have not experienced the failure event when data collection began, causing the prevalent sampling bias. We propose a unified approach which simultaneously corrects the bias from the prevalent sampling and balances the systematic differences from the observational data. We illustrate in the simulation study that standard analysis without proper adjustment would result in biased causal inference. Large sample properties of the proposed estimation procedures are established by techniques of empirical processes and examined by simulation studies. The proposed methods are applied to the Surveillance, Epidemiology, and End Results (SEER) and Medicare linked data for women diagnosed with breast cancer. PMID:25715045
Change-point models to estimate the limit of detection.
May, Ryan C; Chu, Haitao; Ibrahim, Joseph G; Hudgens, Michael G; Lees, Abigail C; Margolis, David M
2013-12-10
In many biological and environmental studies, measured data is subject to a limit of detection. The limit of detection is generally defined as the lowest concentration of analyte that can be differentiated from a blank sample with some certainty. Data falling below the limit of detection is left censored, falling below a level that is easily quantified by a measuring device. A great deal of interest lies in estimating the limit of detection for a particular measurement device. In this paper, we propose a change-point model to estimate the limit of detection by using data from an experiment with known analyte concentrations. Estimation of the limit of detection proceeds by a two-stage maximum likelihood method. Extensions are considered that allow for censored measurements and data from multiple experiments. A simulation study is conducted demonstrating that in some settings the change-point model provides less biased estimates of the limit of detection than conventional methods. The proposed method is then applied to data from an HIV pilot study.
Neural Net Gains Estimation Based on an Equivalent Model.
Aguilar Cruz, Karen Alicia; Medel Juárez, José de Jesús; Fernández Muñoz, José Luis; Esmeralda Vigueras Velázquez, Midory
2016-01-01
A model of an Equivalent Artificial Neural Net (EANN) describes the gains set, viewed as parameters in a layer, and this consideration is a reproducible process, applicable to a neuron in a neural net (NN). The EANN helps to estimate the NN gains or parameters, so we propose two methods to determine them. The first considers a fuzzy inference combined with the traditional Kalman filter, obtaining the equivalent model and estimating in a fuzzy sense the gains matrix A and the proper gain K into the traditional filter identification. The second develops a direct estimation in state space, describing an EANN using the expected value and the recursive description of the gains estimation. Finally, a comparison of both descriptions is performed; highlighting the analytical method describes the neural net coefficients in a direct form, whereas the other technique requires selecting into the Knowledge Base (KB) the factors based on the functional error and the reference signal built with the past information of the system. PMID:27366146
Estimating vehicle roadside encroachment frequency using accident prediction models
Miaou, S.-P.
1996-07-01
The existing data to support the development of roadside encroachment- based accident models are extremely limited and largely outdated. Under the sponsorship of the Federal Highway Administration and Transportation Research Board, several roadside safety projects have attempted to address this issue by providing rather comprehensive data collection plans and conducting pilot data collection efforts. It is clear from the results of these studies that the required field data collection efforts will be expensive. Furthermore, the validity of any field collected encroachment data may be questionable because of the technical difficulty to distinguish intentional from unintentional encroachments. This paper proposes an alternative method for estimating the basic roadside encroachment data without actually field collecting them. The method is developed by exploring the probabilistic relationships between a roadside encroachment event and a run-off-the-road event With some mild assumptions, the method is capable of providing a wide range of basic encroachment data from conventional accident prediction models. To illustrate the concept and use of such a method, some basic encroachment data are estimated for rural two-lane undivided roads. In addition, the estimated encroachment data are compared with the existing collected data. The illustration shows that the method described in this paper can be a viable approach to estimating basic encroachment data without actually collecting them which can be very costly.
Neural Net Gains Estimation Based on an Equivalent Model
Aguilar Cruz, Karen Alicia; Medel Juárez, José de Jesús; Fernández Muñoz, José Luis; Esmeralda Vigueras Velázquez, Midory
2016-01-01
A model of an Equivalent Artificial Neural Net (EANN) describes the gains set, viewed as parameters in a layer, and this consideration is a reproducible process, applicable to a neuron in a neural net (NN). The EANN helps to estimate the NN gains or parameters, so we propose two methods to determine them. The first considers a fuzzy inference combined with the traditional Kalman filter, obtaining the equivalent model and estimating in a fuzzy sense the gains matrix A and the proper gain K into the traditional filter identification. The second develops a direct estimation in state space, describing an EANN using the expected value and the recursive description of the gains estimation. Finally, a comparison of both descriptions is performed; highlighting the analytical method describes the neural net coefficients in a direct form, whereas the other technique requires selecting into the Knowledge Base (KB) the factors based on the functional error and the reference signal built with the past information of the system. PMID:27366146
Improving a regional model using reduced complexity and parameter estimation
Kelson, Victor A.; Hunt, Randall J.; Haitjema, Henk M.
2002-01-01
The availability of powerful desktop computers and graphical user interfaces for ground water flow models makes possible the construction of ever more complex models. A proposed copper-zinc sulfide mine in northern Wisconsin offers a unique case in which the same hydrologic system has been modeled using a variety of techniques covering a wide range of sophistication and complexity. Early in the permitting process, simple numerical models were used to evaluate the necessary amount of water to be pumped from the mine, reductions in streamflow, and the drawdowns in the regional aquifer. More complex models have subsequently been used in an attempt to refine the predictions. Even after so much modeling effort, questions regarding the accuracy and reliability of the predictions remain. We have performed a new analysis of the proposed mine using the two-dimensional analytic element code GFLOW coupled with the nonlinear parameter estimation code UCODE. The new model is parsimonious, containing fewer than 10 parameters, and covers a region several times larger in areal extent than any of the previous models. The model demonstrates the suitability of analytic element codes for use with parameter estimation codes. The simplified model results are similar to the more complex models; predicted mine inflows and UCODE-derived 95% confidence intervals are consistent with the previous predictions. More important, the large areal extent of the model allowed us to examine hydrological features not included in the previous models, resulting in new insights about the effects that far-field boundary conditions can have on near-field model calibration and parameterization. In this case, the addition of surface water runoff into a lake in the headwaters of a stream while holding recharge constant moved a regional ground watershed divide and resulted in some of the added water being captured by the adjoining basin. Finally, a simple analytical solution was used to clarify the GFLOW model
Tommasi, C.; May, C.
2010-09-30
The DKL-optimality criterion has been recently proposed for the dual problem of model discrimination and parameter estimation, for the case of two rival models. A sequential version of the DKL-optimality criterion is herein proposed in order to discriminate and efficiently estimate more than two nested non-linear models. Our sequential method is inspired by the procedure of Biswas and Chaudhuri (2002), which is however useful only in the set up of nested linear models.
Lung Ventilation/Perfusion Scan
... from the NHLBI on Twitter. What Is a Lung Ventilation/Perfusion Scan? A lung ventilation/perfusion scan, or VQ scan, is a ... that measures air and blood flow in your lungs. A VQ scan most often is used to ...
Van Raemdonck, Dirk; Neyrinck, Arne; Cypel, Marcelo; Keshavjee, Shaf
2015-06-01
This review outlines the new and promising technique of ex vivo lung perfusion and its clinical potential to increase the number of transplantable lungs and to improve the early and late outcome after transplantation. The rationale, the experimental background, the technique and protocols, and available devices for ex vivo lung perfusion are discussed. The current clinical experience worldwide and ongoing clinical trials are reviewed.
Estimation of the fractional coverage of rainfall in climate models
NASA Technical Reports Server (NTRS)
Eltahir, E. A. B.; Bras, R. L.
1993-01-01
The fraction of the grid cell area covered by rainfall, mu, is an essential parameter in descriptions of land surface hydrology in climate models. A simple procedure is presented for estimating this fraction, based on extensive observations of storm areas and rainfall volumes. Storm area and rainfall volume are often linearly related; this relation can be used to compute the storm area from the volume of rainfall simulated by a climate model. A formula is developed for computing mu, which describes the dependence of the fractional coverage of rainfall on the season of the year, the geographical region, rainfall volume, and the spatial and temporal resolution of the model. The new formula is applied in computing mu over the Amazon region. Significant temporal variability in the fractional coverage of rainfall is demonstrated. The implications of this variability for the modeling of land surface hydrology in climate models are discussed.
Model and Parameter Discretization Impacts on Estimated ASR Recovery Efficiency
NASA Astrophysics Data System (ADS)
Forghani, A.; Peralta, R. C.
2015-12-01
We contrast computed recovery efficiency of one Aquifer Storage and Recovery (ASR) well using several modeling situations. Test situations differ in employed finite difference grid discretization, hydraulic conductivity, and storativity. We employ a 7-layer regional groundwater model calibrated for Salt Lake Valley. Since the regional model grid is too coarse for ASR analysis, we prepare two local models with significantly smaller discretization capable of analyzing ASR recovery efficiency. Some addressed situations employ parameters interpolated from the coarse valley model. Other situations employ parameters derived from nearby well logs or pumping tests. The intent of the evaluations and subsequent sensitivity analysis is to show how significantly the employed discretization and aquifer parameters affect estimated recovery efficiency. Most of previous studies to evaluate ASR recovery efficiency only consider hypothetical uniform specified boundary heads and gradient assuming homogeneous aquifer parameters. The well is part of the Jordan Valley Water Conservancy District (JVWCD) ASR system, that lies within Salt Lake Valley.
Low dose CT perfusion using k-means clustering
NASA Astrophysics Data System (ADS)
Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc
2016-03-01
We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.
NASA Astrophysics Data System (ADS)
Bindschadler, Michael; Modgil, Dimple; Branch, Kelley R.; La Riviere, Patrick J.; Alessio, Adam M.
2015-03-01
Cardiac CT acquisitions for perfusion assessment can be performed in a dynamic or static mode. In this simulation study, we evaluate the relative classification and quantification performance of these modes for assessing myocardial blood flow (MBF). In the dynamic method, a series of low dose cardiac CT acquisitions yields data on contrast bolus dynamics over time; these data are fit with a model to give a quantitative MBF estimate. In the static method, a single CT acquisition is obtained, and the relative CT numbers in the myocardium are used to infer perfusion states. The static method does not directly yield a quantitative estimate of MBF, but these estimates can be roughly approximated by introducing assumed linear relationships between CT number and MBF, consistent with the ways such images are typically visually interpreted. Data obtained by either method may be used for a variety of clinical tasks, including 1) stratifying patients into differing categories of ischemia and 2) using the quantitative MBF estimate directly to evaluate ischemic disease severity. Through simulations, we evaluate the performance on each of these tasks. The dynamic method has very low bias in MBF estimates, making it particularly suitable for quantitative estimation. At matched radiation dose levels, ROC analysis demonstrated that the static method, with its high bias but generally lower variance, has superior performance in stratifying patients, especially for larger patients.
An aerial sightability model for estimating ferruginous hawk population size
Ayers, L.W.; Anderson, S.H.
1999-01-01
Most raptor aerial survey projects have focused on numeric description of visibility bias without identifying the contributing factors or developing predictive models to account for imperfect detection rates. Our goal was to develop a sightability model for nesting ferruginous hawks (Buteo regalis) that could account for nests missed during aerial surveys and provide more accurate population estimates. Eighteen observers, all unfamiliar with nest locations in a known population, searched for nests within 300 m of flight transects via a Maule fixed-wing aircraft. Flight variables tested for their influence on nest-detection rates included aircraft speed, height, direction of travel, time of day, light condition, distance to nest, and observer experience level. Nest variables included status (active vs. inactive), condition (i.e., excellent, good, fair, poor, bad), substrate type, topography, and tree density. A multiple logistic regression model identified nest substrate type, distance to nest, and observer experience level as significant predictors of detection rates (P < 0.05). The overall model was significant (??26 = 124.4, P < 0.001, n = 255 nest observations), and the correct classification rate was 78.4%. During 2 validation surveys, observers saw 23.7% (14/59) and 36.5% (23/63) of the actual population. Sightability model predictions, with 90% confidence intervals, captured the true population in both tests. Our results indicate standardized aerial surveys, when used in conjunction with the predictive sightability model, can provide unbiased population estimates for nesting ferruginous hawks.
Som, P.; Oster, Z.H.; Knapp, F.F. Jr.
1987-01-01
We have studied two animal models of non-coronary heart disease. The salt-sensitive Dahl strain hypertensive rats and their genetically matched normotensive controls and the cardiomyopathic BIO 53.58 (CM) strain Syrian hamsters with age and sex-matched RB strain controls. The CM strain hamster seems to be a very good model of human congestive cardiomyopathy and the Dahl strain hypertensive rats have also been found to be good models for studying the effects of hypertension on the myocardium. In our studies we compared the utilization of various metabolic substrates, viz., fatty acids, glucose analogs, and the early distribution of /sup 201/Tl, as an indicator of myocardial flow. The routine studies involving dissection of animals for assaying the radioactivity following the injection of radiopharmaceuticals is not suitable for assessing regional changes in metabolism and flow. The use of quantitative autoradiographic microimaging (ARG) enables the visualization of discrete regional as well as global changes from normal and to quantitate them. This paper describes the methodology and results of these investigations. 14 refs., 5 figs.
Mazzuca, Enrico; Aliverti, Andrea; Miserocchi, Giuseppe
2016-07-01
A computational model of a morphologically-based alveolar capillary unit (ACU) in the rabbit is developed to relate lung fluid balance to mechanical forces between capillary surface and interstitium during development of interstitial edema. We hypothesize that positive values of interstitial liquid pressure Pliq impact on capillary transmural pressure and on blood flow. ACU blood flow, capillary recruitment and filtration are computed by modulating vascular and interstitial pressures. Model results are compared with experimental data of Pliq increasing from ~-10 (control) up to ~4cmH2O in two conditions, hypoxia and collagenase injection. For hypoxia exposure, fitting data requires a linear increase in hydraulic conductivity Lp and capillary pressure PC, that fulfils the need of increase in oxygen delivery. For severe fragmentation of capillary endothelial barrier (collagenase injection), fitting requires a rapid increase in both hydraulic and protein permeability, causing ACU de-recruitment, followed by an increase in PC as a late response to restore blood flow. In conclusion, the model allows to describe the lung adaptive response to edemagenic perturbations; the increase in Pliq, related to the low interstitial compliance, provides an efficient control of extravascular water, by limiting microvascular filtration. PMID:27059893
Robust image reconstruction enhancement based on Gaussian mixture model estimation
NASA Astrophysics Data System (ADS)
Zhao, Fan; Zhao, Jian; Han, Xizhen; Wang, He; Liu, Bochao
2016-03-01
The low quality of an image is often characterized by low contrast and blurred edge details. Gradients have a direct relationship with image edge details. More specifically, the larger the gradients, the clearer the image details become. Robust image reconstruction enhancement based on Gaussian mixture model estimation is proposed here. First, image is transformed to its gradient domain, obtaining the gradient histogram. Second, the gradient histogram is estimated and extended using a Gaussian mixture model, and the predetermined function is constructed. Then, using histogram specification technology, the gradient field is enhanced with the constraint of the predetermined function. Finally, a matrix sine transform-based method is applied to reconstruct the enhanced image from the enhanced gradient field. Experimental results show that the proposed algorithm can effectively enhance different types of images such as medical image, aerial image, and visible image, providing high-quality image information for high-level processing.
Occupancy estimation and modeling with multiple states and state uncertainty
Nichols, J.D.; Hines, J.E.; MacKenzie, D.I.; Seamans, M.E.; Gutierrez, R.J.
2007-01-01
The distribution of a species over space is of central interest in ecology, but species occurrence does not provide all of the information needed to characterize either the well-being of a population or the suitability of occupied habitat. Recent methodological development has focused on drawing inferences about species occurrence in the face of imperfect detection. Here we extend those methods by characterizing occupied locations by some additional state variable ( e. g., as producing young or not). Our modeling approach deals with both detection probabilities,1 and uncertainty in state classification. We then use the approach with occupancy and reproductive rate data from California Spotted Owls (Strix occidentalis occidentalis) collected in the central Sierra Nevada during the breeding season of 2004 to illustrate the utility of the modeling approach. Estimates of owl reproductive rate were larger than naive estimates, indicating the importance of appropriately accounting for uncertainty in detection and state classification.
Occupancy estimation and modeling with multiple states and state uncertainty.
Nichols, James D; Hines, A James E; Mackenzie, Darryl I; Seamans, Mark E; Gutiérrez, R J
2007-06-01
The distribution of a species over space is of central interest in ecology, but species occurrence does not provide all of the information needed to characterize either the well-being of a population or the suitability of occupied habitat. Recent methodological development has focused on drawing inferences about species occurrence in the face of imperfect detection. Here we extend those methods by characterizing occupied locations by some additional state variable (e.g., as producing young or not). Our modeling approach deals with both detection probabilities <1 and uncertainty in state classification. We then use the approach with occupancy and reproductive rate data from California Spotted Owls (Strix occidentalis occidentalis) collected in the central Sierra Nevada during the breeding season of 2004 to illustrate the utility of the modeling approach. Estimates of owl reproductive rate were larger than naïve estimates, indicating the importance of appropriately accounting for uncertainty in detection and state classification. PMID:17601132
Chen, J C; Rhee, K K; Beaudry, D M; Ramirez, V D
1984-05-01
In the present experiment we used push-pull perfusion (PPP) on-line with high performance liquid chromatography with electrochemical detection (HPLC-EC) to measure the concentration of neuroactive substances collected in perfusates from the caudate nucleus (CN) of conscious, freely moving rats. To validate the suitability of such an approach, both chromatographic and biological procedures were used. The chromatographic performances of four pure standards, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) were examined under the conditions of the experiment and the release of these four chemicals by amphetamine (AMPH) locally infused into the CN or systemically administered to conscious rats used as an index of biological validation. Distinct dose-response curves were obtained for each standard injected into the HPLC-EC singly or mixed together in perfusion medium (modified Krebs-Ringer's Phosphate, KRP , pH 7.4). Moreover, each standard in the chromatogram appeared as a well-defined elution band with a different retention time. The brain perfusate samples did not contain factors interfering with the normal operation of the HPLC-EC or measurement of the concentration of added standards. The recovery of pure DA, DOPAC, 5-HIAA and HVA added to the perfusate samples was 97, 87, 98 and 114%, respectively. No decrements in peak heights were observed in the chromatograms when a 1-ng dose mixture of the four standards dissolved in medium and maintained at 4 degrees C was injected into the HPLC-EC at regular intervals for a 60-min period after initial preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
Zou, Li-Hua; Liu, Jin-Ping; Zhang, Hao; Wu, Shu-Bin; Ji, Bing-Yang
2016-01-01
Background: Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA). However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods: To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group, n = 6) and without (DHCA [D] group, n = 6) ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student's t-test was applied to test for statistical significance between the two groups. Results: Metabolic profiling of brain was distinctive significantly between the two groups (Q2Y = 0.88 for partial least squares-DA model). In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine (P = 0.0019), 5-methoxyindole-3-acetic acid (P = 0.0499), and 5-hydroxyindole-3-acetic acid (P = 0.0495) in tryptophan metabolism pathways were decreased, and citrulline (P = 0.0158) in urea cycle was increased in group DA comparing to group D. Conclusions: The present study applied metabolomics analysis to identify the cerebral