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

PubMed Central

Das, Marco; Haberland, Ulrike; Slump, Cees; Handayani, Astri; van Tuijl, Sjoerd; Stijnen, Marco; 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

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.

Model-based estimation for dynamic cardiac studies using ECT.

PubMed

Chiao, P C; Rogers, W L; Clinthorne, N H; Fessler, J A; Hero, A O

1994-01-01

The authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (emission computed tomography). They 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. They 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, the authors discuss model assumptions and potential uses of the joint estimation strategy.

GPU-Accelerated Voxelwise Hepatic Perfusion Quantification

PubMed Central

Wang, H; Cao, Y

2012-01-01

Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using CUDA-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, non-linear least squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626400 voxels in a patient’s liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10−6. The method will be useful for generating liver perfusion images in clinical settings. PMID:22892645

Modeling of nanotherapeutics delivery based on tumor perfusion

PubMed Central

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

2013-01-01

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

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.

Assessment of the spatial pattern of colorectal tumour perfusion estimated at perfusion CT using two-dimensional fractal analysis.

PubMed

Goh, Vicky; Sanghera, Bal; Wellsted, David M; Sundin, Josefin; Halligan, Steve

2009-06-01

The aim was to evaluate the feasibility of fractal analysis for assessing the spatial pattern of colorectal tumour perfusion at dynamic contrast-enhanced CT (perfusion CT). Twenty patients with colorectal adenocarcinoma underwent a 65-s perfusion CT study from which a perfusion parametric map was generated using validated commercial software. The tumour was identified by an experienced radiologist, segmented via thresholding and fractal analysis applied using in-house software: fractal dimension, abundance and lacunarity were assessed for the entire outlined tumour and for selected representative areas within the tumour of low and high perfusion. Comparison was made with ten patients with normal colons, processed in a similar manner, using two-way mixed analysis of variance with statistical significance at the 5% level. Fractal values were higher in cancer than normal colon (p < or = 0.001): mean (SD) 1.71 (0.07) versus 1.61 (0.07) for fractal dimension and 7.82 (0.62) and 6.89 (0.47) for fractal abundance. Fractal values were lower in 'high' than 'low' perfusion areas. Lacunarity curves were shifted to the right for cancer compared with normal colon. In conclusion, colorectal cancer mapped by perfusion CT demonstrates fractal properties. Fractal analysis is feasible, potentially providing a quantitative measure of the spatial pattern of tumour perfusion.

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

PubMed

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

2017-01-01

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

Model-based estimation for dynamic cardiac studies using ECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiao, P.C.; Rogers, W.L.; Clinthorne, N.H.

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 performancemore » to the Cramer-Rao lower bound. Finally, model assumptions and potential uses of the joint estimation strategy are discussed.« less

A noninvasive estimation of cerebral perfusion pressure using critical closing pressure.

PubMed

Varsos, Georgios V; Kolias, Angelos G; Smielewski, Peter; Brady, Ken M; Varsos, Vassilis G; Hutchinson, Peter J; Pickard, John D; Czosnyka, Marek

2015-09-01

Cerebral blood flow is associated with cerebral perfusion pressure (CPP), which is clinically monitored through arterial blood pressure (ABP) and invasive measurements of intracranial pressure (ICP). Based on critical closing pressure (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP (eCPP). Data from 280 head-injured patients with ABP, ICP, and transcranial Doppler ultrasonography measurements were retrospectively examined. CrCP was calculated with a noninvasive version of the cerebrovascular impedance method. The eCPP was refined with a predictive regression model of CrCP-based estimation of ICP from known ICP using data from 232 patients, and validated with data from the remaining 48 patients. Cohort analysis showed eCPP to be correlated with measured CPP (R = 0.851, p < 0.001), with a mean ± SD difference of 4.02 ± 6.01 mm Hg, and 83.3% of the cases with an estimation error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area under the curve of 0.913 (95% CI 0.883-0.944). When each recording session of a patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD for estimating CPP between multiple recording sessions of 1.89-5.01 mm Hg. Overall, CrCP-based eCPP was strongly correlated with invasive CPP, with sensitivity and specificity for detection of low CPP that show promise for clinical use.

Concurrent hyperthermia estimation schemes based on extended Kalman filtering and reduced-order modelling.

PubMed

Potocki, J K; Tharp, H S

1993-01-01

The success of treating cancerous tissue with heat depends on the temperature elevation, the amount of tissue elevated to that temperature, and the length of time that the tissue temperature is elevated. In clinical situations the temperature of most of the treated tissue volume is unknown, because only a small number of temperature sensors can be inserted into the tissue. A state space model based on a finite difference approximation of the bioheat transfer equation (BHTE) is developed for identification purposes. A full-order extended Kalman filter (EKF) is designed to estimate both the unknown blood perfusion parameters and the temperature at unmeasured locations. Two reduced-order estimators are designed as computationally less intensive alternatives to the full-order EKF. Simulation results show that the success of the estimation scheme depends strongly on the number and location of the temperature sensors. Superior results occur when a temperature sensor exists in each unknown blood perfusion zone, and the number of sensors is at least as large as the number of unknown perfusion zones. Unacceptable results occur when there are more unknown perfusion parameters than temperature sensors, or when the sensors are placed in locations that do not sample the unknown perfusion information.

Metabolomic Perfusate Analysis during Kidney Machine Perfusion: The Pig Provides an Appropriate Model for Human Studies

PubMed Central

Nath, Jay; Guy, Alison; Smith, Thomas B.; Cobbold, Mark; Inston, Nicholas G.; Hodson, James; Tennant, Daniel A.

2014-01-01

Introduction Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies. PMID:25502759

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

PubMed Central

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

2004-01-01

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

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

PubMed

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

2004-11-17

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

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

PubMed

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

2015-11-01

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

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

PubMed

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

2011-03-28

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

The human placental perfusion model: a systematic review and development of a model to predict in vivo transfer of therapeutic drugs.

PubMed

Hutson, J R; Garcia-Bournissen, F; Davis, A; Koren, G

2011-07-01

Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.

Non-Invasive Blood Perfusion Measurements Using a Combined Temperature and Heat Flux Surface Probe

PubMed Central

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

2009-01-01

Non-invasive blood perfusion measurement systems have been developed and tested in a phantom tissue and an animal model. The probes use a small sensor with a laminated flat thermocouple to measure the heat transfer and temperature response to an arbitrary thermal event (convective or conductive) imposed on the tissue surface. Blood perfusion and thermal contact resistance are estimated by comparing heat flux data with a mathematical model of the tissue. The perfusion probes were evaluated for repeatability and sensitivity using both a phantom tissue test stand and exposed rat liver tests. Perfusion in the phantom tissue tests was varied by controlling the flow of water into the phantom tissue test section, and the perfusion in the exposed liver tests was varied by temporarily occluding blood flow through the portal vein. The phantom tissue tests indicated that the probes can be used to detect small changes in perfusion (0.005 ml/ml/s). The probes qualitatively tracked the changes in the perfusion of the liver model due to occlusion of the portal vein. PMID:19885372

Coupled modelling of tumour angiogenesis, tumour growth and blood perfusion.

PubMed

Cai, Yan; Xu, Shixiong; Wu, Jie; Long, Quan

2011-06-21

We propose a mathematical modelling system to investigate the dynamic process of tumour cell proliferation, death and tumour angiogenesis by fully coupling the vessel growth, tumour growth and blood perfusion. Tumour growth and angiogenesis are coupled by the chemical microenvironment and the cell-matrix interaction. The haemodynamic calculation is carried out on the updated vasculature. The domains of intravascular, transcapillary and interstitial fluid flow were coupled in the model to provide a comprehensive solution of blood perfusion variables. An estimation of vessel collapse is made according to the wall shear stress criterion to provide feedback on vasculature remodelling. The simulation can show the process of tumour angiogenesis and the spatial distribution of tumour cells for periods of up to 24 days. It can show the major features of tumour and tumour microvasculature during the period such as the formation of a large necrotic core in the tumour centre with few functional vessels passing through, and a well circulated tumour periphery regions in which the microvascular density is high and associated with more aggressive proliferating cells of the growing tumour which are all consistent with physiological observations. The study also demonstrated that the simulation results are not dependent on the initial tumour and networks, which further confirms the application of the coupled model feedback mechanisms. The model enables us to examine the interactions between angiogenesis and tumour growth, and to study the dynamic response of a solid tumour to the changes in the microenvironment. This simulation framework can be a foundation for further applications such as drug delivery and anti-angiogenic therapies. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2006-01-01

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

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

PubMed Central

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

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

PubMed

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

2014-11-01

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

Perfusion CT of the Brain and Liver and of Lung Tumors: Use of Monte Carlo Simulation for Patient Dose Estimation for Examinations With a Cone-Beam 320-MDCT Scanner.

PubMed

Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal

2016-01-01

The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.

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

PubMed

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

2017-12-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hubbard, L; Ziemer, B; Sadeghi, B

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

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.

Rapid perfusion quantification using Welch-Satterthwaite approximation and analytical spectral filtering

NASA Astrophysics Data System (ADS)

Krishnan, Karthik; Reddy, Kasireddy V.; Ajani, Bhavya; Yalavarthy, Phaneendra K.

2017-02-01

CT and MR perfusion weighted imaging (PWI) enable quantification of perfusion parameters in stroke studies. These parameters are calculated from the residual impulse response function (IRF) based on a physiological model for tissue perfusion. The standard approach for estimating the IRF is deconvolution using oscillatory-limited singular value decomposition (oSVD) or Frequency Domain Deconvolution (FDD). FDD is widely recognized as the fastest approach currently available for deconvolution of CT Perfusion/MR PWI. In this work, three faster methods are proposed. The first is a direct (model based) crude approximation to the final perfusion quantities (Blood flow, Blood volume, Mean Transit Time and Delay) using the Welch-Satterthwaite approximation for gamma fitted concentration time curves (CTC). The second method is a fast accurate deconvolution method, we call Analytical Fourier Filtering (AFF). The third is another fast accurate deconvolution technique using Showalter's method, we call Analytical Showalter's Spectral Filtering (ASSF). Through systematic evaluation on phantom and clinical data, the proposed methods are shown to be computationally more than twice as fast as FDD. The two deconvolution based methods, AFF and ASSF, are also shown to be quantitatively accurate compared to FDD and oSVD.

Intraoperative fluorescence-based enhanced reality laparoscopic real-time imaging to assess bowel perfusion at the anastomotic site in an experimental model.

PubMed

Diana, M; Agnus, V; Halvax, P; Liu, Y-Y; Dallemagne, B; Schlagowski, A-I; Geny, B; Diemunsch, P; Lindner, V; Marescaux, J

2015-01-01

relevance Clinical assessment has limited accuracy in evaluating bowel perfusion before anastomosis. Fluorescence videography estimates intestinal perfusion based on the fluorescence intensity of injected fluorophores, which is proportional to bowel vascularization. However, evaluation of fluorescence intensity remains a static and subjective measure. Fluorescence-based enhanced reality (FLER) is a dynamic fluorescence videography technique integrating near-infrared endoscopy and specific software. The software generates a virtual perfusion cartogram based on time to peak fluorescence, which can be superimposed on to real-time laparoscopic images. This experimental study demonstrates the accuracy of FLER in detecting differences in bowel perfusion in a survival model of laparoscopic small bowel resection-anastomosis, based on biochemical and histopathological data. It is concluded that real-time imaging of bowel perfusion is easy to use and accurate, and should be translated into clinical use. © 2015 BJS Society Ltd. Published by John Wiley & Sons Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rupcich, Franco; Badal, Andreu; Kyprianou, Iacovos

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 tablesmore » 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

The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion.

PubMed

Laing, Richard W; Bhogal, Ricky H; Wallace, Lorraine; Boteon, Yuri; Neil, Desley A H; Smith, Amanda; Stephenson, Barney T F; Schlegel, Andrea; Hübscher, Stefan G; Mirza, Darius F; Afford, Simon C; Mergental, Hynek

2017-11-01

Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions while maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury. The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2 extraction ratio 13.75 vs 9.43 % ×10 per gram of tissue, P = 0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species, and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure. Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid.

A non-linear regression method for CT brain perfusion analysis

NASA Astrophysics Data System (ADS)

Bennink, E.; Oosterbroek, J.; Viergever, M. A.; Velthuis, B. K.; de Jong, H. W. A. M.

2015-03-01

CT perfusion (CTP) imaging allows for rapid diagnosis of ischemic stroke. Generation of perfusion maps from CTP data usually involves deconvolution algorithms providing estimates for the impulse response function in the tissue. We propose the use of a fast non-linear regression (NLR) method that we postulate has similar performance to the current academic state-of-art method (bSVD), but that has some important advantages, including the estimation of vascular permeability, improved robustness to tracer-delay, and very few tuning parameters, that are all important in stroke assessment. The aim of this study is to evaluate the fast NLR method against bSVD and a commercial clinical state-of-art method. The three methods were tested against a published digital perfusion phantom earlier used to illustrate the superiority of bSVD. In addition, the NLR and clinical methods were also tested against bSVD on 20 clinical scans. Pearson correlation coefficients were calculated for each of the tested methods. All three methods showed high correlation coefficients (>0.9) with the ground truth in the phantom. With respect to the clinical scans, the NLR perfusion maps showed higher correlation with bSVD than the perfusion maps from the clinical method. Furthermore, the perfusion maps showed that the fast NLR estimates are robust to tracer-delay. In conclusion, the proposed fast NLR method provides a simple and flexible way of estimating perfusion parameters from CT perfusion scans, with high correlation coefficients. This suggests that it could be a better alternative to the current clinical and academic state-of-art methods.

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

NASA Astrophysics Data System (ADS)

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

2004-02-01

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

The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion

PubMed Central

Wallace, Lorraine; Boteon, Yuri; Neil, Desley AH; Smith, Amanda; Stephenson, Barney TF; Schlegel, Andrea; Hübscher, Stefan G; Mirza, Darius F

2017-01-01

Background Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions whilst maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. Methods Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury. Results The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2ER 13.75 vs 9.43 % x105 per gram of tissue, p=0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure. Conclusion Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid. PMID:28520579

Towards robust deconvolution of low-dose perfusion CT: sparse perfusion deconvolution using online dictionary learning.

PubMed

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C

2013-05-01

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

PubMed Central

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

Parameterisation of multi-scale continuum perfusion models from discrete vascular networks.

PubMed

Hyde, Eoin R; Michler, Christian; Lee, Jack; Cookson, Andrew N; Chabiniok, Radek; Nordsletten, David A; Smith, Nicolas P

2013-05-01

Experimental data and advanced imaging techniques are increasingly enabling the extraction of detailed vascular anatomy from biological tissues. Incorporation of anatomical data within perfusion models is non-trivial, due to heterogeneous vessel density and disparate radii scales. Furthermore, previous idealised networks have assumed a spatially repeating motif or periodic canonical cell, thereby allowing for a flow solution via homogenisation. However, such periodicity is not observed throughout anatomical networks. In this study, we apply various spatial averaging methods to discrete vascular geometries in order to parameterise a continuum model of perfusion. Specifically, a multi-compartment Darcy model was used to provide vascular scale separation for the fluid flow. Permeability tensor fields were derived from both synthetic and anatomically realistic networks using (1) porosity-scaled isotropic, (2) Huyghe and Van Campen, and (3) projected-PCA methods. The Darcy pressure fields were compared via a root-mean-square error metric to an averaged Poiseuille pressure solution over the same domain. The method of Huyghe and Van Campen performed better than the other two methods in all simulations, even for relatively coarse networks. Furthermore, inter-compartment volumetric flux fields, determined using the spatially averaged discrete flux per unit pressure difference, were shown to be accurate across a range of pressure boundary conditions. This work justifies the application of continuum flow models to characterise perfusion resulting from flow in an underlying vascular network.

Effects of lung ventilation–perfusion and muscle metabolism–perfusion heterogeneities on maximal O2 transport and utilization

PubMed Central

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

Numerical simulation of blood flow in femoral perfusion: comparison between side-armed femoral artery perfusion and direct femoral artery perfusion.

PubMed

Kitamura, Shingo; Shirota, Minori; Fukuda, Wakako; Inamura, Takao; Fukuda, Ikuo

2016-12-01

Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.

Semi-automatic motion compensation of contrast-enhanced ultrasound images from abdominal organs for perfusion analysis.

PubMed

Schäfer, Sebastian; Nylund, Kim; Sævik, Fredrik; Engjom, Trond; Mézl, Martin; Jiřík, Radovan; Dimcevski, Georg; Gilja, Odd Helge; Tönnies, Klaus

2015-08-01

This paper presents a system for correcting motion influences in time-dependent 2D contrast-enhanced ultrasound (CEUS) images to assess tissue perfusion characteristics. The system consists of a semi-automatic frame selection method to find images with out-of-plane motion as well as a method for automatic motion compensation. Translational and non-rigid motion compensation is applied by introducing a temporal continuity assumption. A study consisting of 40 clinical datasets was conducted to compare the perfusion with simulated perfusion using pharmacokinetic modeling. Overall, the proposed approach decreased the mean average difference between the measured perfusion and the pharmacokinetic model estimation. It was non-inferior for three out of four patient cohorts to a manual approach and reduced the analysis time by 41% compared to manual processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2015-08-28

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

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

PubMed

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

2017-07-01

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

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.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Optical modeling toward optimizing monitoring of intestinal perfusion in trauma patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akl, Tony; Wilson, Mark A.; Ericson, Milton Nance

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. Throughmore » 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.« less

Optical modeling toward optimizing monitoring of intestinal perfusion in trauma patients

NASA Astrophysics Data System (ADS)

Akl, Tony J.; Wilson, Mark A.; Ericson, M. N.; Coté, Gerard L.

2013-02-01

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.

Budget impact of applying appropriateness criteria for myocardial perfusion scintigraphy: The perspective of a developing country.

PubMed

Dos Santos, Mauro Augusto; Santos, Marisa Silva; Tura, Bernardo Rangel; Félix, Renata; Brito, Adriana Soares X; De Lorenzo, Andrea

2016-10-01

Myocardial perfusion imaging is widely used for the risk stratification of coronary artery disease. In view of its cost, besides radiation issues, judicious evaluation of the appropriateness of its indications is essential to prevent an unnecessary economic burden on the health system. We evaluated, at a tertiary-care, public Brazilian hospital, the appropriateness of myocardial perfusion scintigraphy indications, and estimated the budget impact of applying appropriateness criteria. An observational, cross-sectional study of 190 patients with suspected or known coronary artery disease referred for myocardial perfusion imaging was conducted. The appropriateness of myocardial perfusion imaging indications was evaluated with the Appropriate Use Criteria for Cardiac Radionuclide Imaging published in 2009. Budget impact analysis was performed with a deterministic model. The prevalence of appropriate requests was 78%; of inappropriate indications, 12%; and of uncertain indications, 10%. Budget impact analysis showed that the use of appropriateness criteria, applied to the population referred to myocardial perfusion scintigraphy within 1 year, could generate savings of $ 64,252.04 dollars. The 12% inappropriate requests for myocardial perfusion scintigraphy at a tertiary-care hospital suggest that a reappraisal of MPI indications is needed. Budget impact analysis estimated resource savings of 18.6% with the establishment of appropriateness criteria for MPI.

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

DTIC Science & Technology

2001-10-25

Image Analysis aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected with the Dynamic Pulmonary Imaging technique 18,5,17,6. We have proposed and evaluated a multiresolutional method with an explicit ventilation model based on pyramid images for ventilation analysis. We have further extended the method for ventilation analysis to pulmonary perfusion. This paper focuses on the clinical evaluation of our method for

EFFECT ON PERFUSION VALUES OF SAMPLING INTERVAL OF CT PERFUSION ACQUISITIONS IN NEUROENDOCRINE LIVER METASTASES AND NORMAL LIVER

PubMed Central

Ng, Chaan S.; Hobbs, Brian P.; Wei, Wei; Anderson, Ella F.; Herron, Delise H.; Yao, James C.; Chandler, Adam G.

2014-01-01

Objective To assess the effects of sampling interval (SI) of CT perfusion acquisitions on CT perfusion values in normal liver and liver metastases from neuroendocrine tumors. Methods CT perfusion in 16 patients with neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction, for tumor and normal liver. CT perfusion values for the reference sampling interval of 0.5s (SI0.5) were compared with those of SI datasets of 1s, 2s, 3s and 4s, using mixed-effects model analyses. Results Increases in SI beyond 1s were associated with significant and increasing departures of CT perfusion parameters from reference values at SI0.5 (p≤0.0009). CT perfusion values deviated from reference with increasing uncertainty with increasing SIs. Findings for normal liver were concordant. Conclusion Increasing SIs beyond 1s yield significantly different CT perfusion parameter values compared to reference values at SI0.5. PMID:25626401

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

PubMed

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

2010-12-01

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

The effect of time-of-flight and point spread function modeling on 82Rb myocardial perfusion imaging of obese patients.

PubMed

Dasari, Paul K R; Jones, Judson P; Casey, Michael E; Liang, Yuanyuan; Dilsizian, Vasken; Smith, Mark F

2018-06-15

The effect of time-of-flight (TOF) and point spread function (PSF) modeling in image reconstruction has not been well studied for cardiac PET. This study assesses their separate and combined influence on 82 Rb myocardial perfusion imaging in obese patients. Thirty-six obese patients underwent rest-stress 82 Rb cardiac PET. Images were reconstructed with and without TOF and PSF modeling. Perfusion was quantitatively compared using the AHA 17-segment model for patients grouped by BMI, cross-sectional body area in the scanner field of view, gender, and left ventricular myocardial volume. Summed rest scores (SRS), summed stress scores (SSS), and summed difference scores (SDS) were compared. TOF improved polar map visual uniformity and increased septal wall perfusion by up to 10%. This increase was greater for larger patients, more evident for patients grouped by cross-sectional area than by BMI, and more prominent for females. PSF modeling increased perfusion by about 1.5% in all cardiac segments. TOF modeling generally decreased SRS and SSS with significant decreases between 2.4 and 3.0 (P < .05), which could affect risk stratification; SDS remained about the same. With PSF modeling, SRS, SSS, and SDS were largely unchanged. TOF and PSF modeling affect regional and global perfusion, SRS, and SSS. Clinicians should consider these effects and gender-dependent differences when interpreting 82 Rb perfusion studies.

Cerebral perfusion computed tomography deconvolution via structure tensor total variation regularization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, Dong; Zhang, Xinyu; Bian, Zhaoying, E-mail: zybian@smu.edu.cn, E-mail: jhma@smu.edu.cn

Purpose: Cerebral perfusion computed tomography (PCT) imaging as an accurate and fast acute ischemic stroke examination has been widely used in clinic. Meanwhile, a major drawback of PCT imaging is the high radiation dose due to its dynamic scan protocol. The purpose of this work is to develop a robust perfusion deconvolution approach via structure tensor total variation (STV) regularization (PD-STV) for estimating an accurate residue function in PCT imaging with the low-milliampere-seconds (low-mAs) data acquisition. Methods: Besides modeling the spatio-temporal structure information of PCT data, the STV regularization of the present PD-STV approach can utilize the higher order derivativesmore » of the residue function to enhance denoising performance. To minimize the objective function, the authors propose an effective iterative algorithm with a shrinkage/thresholding scheme. A simulation study on a digital brain perfusion phantom and a clinical study on an old infarction patient were conducted to validate and evaluate the performance of the present PD-STV approach. Results: In the digital phantom study, visual inspection and quantitative metrics (i.e., the normalized mean square error, the peak signal-to-noise ratio, and the universal quality index) assessments demonstrated that the PD-STV approach outperformed other existing approaches in terms of the performance of noise-induced artifacts reduction and accurate perfusion hemodynamic maps (PHM) estimation. In the patient data study, the present PD-STV approach could yield accurate PHM estimation with several noticeable gains over other existing approaches in terms of visual inspection and correlation analysis. Conclusions: This study demonstrated the feasibility and efficacy of the present PD-STV approach in utilizing STV regularization to improve the accuracy of residue function estimation of cerebral PCT imaging in the case of low-mAs.« less

A multiphase model for tissue construct growth in a perfusion bioreactor.

PubMed

O'Dea, R D; Waters, S L; Byrne, H M

2010-06-01

The growth of a cell population within a rigid porous scaffold in a perfusion bioreactor is studied, using a three-phase continuum model of the type presented by Lemon et al. (2006, Multiphase modelling of tissue growth using the theory of mixtures. J. Math. Biol., 52, 571-594) to represent the cell population (and attendant extracellular matrix), culture medium and porous scaffold. The bioreactor system is modelled as a 2D channel containing the cell-seeded rigid porous scaffold (tissue construct) which is perfused with culture medium. The study concentrates on (i) the cell-cell and cell-scaffold interactions and (ii) the impact of mechanotransduction mechanisms on construct composition. A numerical and analytical analysis of the model equations is presented and, depending upon the relative importance of cell aggregation and repulsion, markedly different cell movement is revealed. Additionally, mechanotransduction effects due to cell density, pressure and shear stress-mediated tissue growth are shown to generate qualitative differences in the composition of the resulting construct. The results of our simulations indicate that this model formulation (in conjunction with appropriate experimental data) has the potential to provide a means of identifying the dominant regulatory stimuli in a cell population.

Optimization and control of perfusion cultures using a viable cell probe and cell specific perfusion rates.

PubMed

Dowd, Jason E; Jubb, Anthea; Kwok, K Ezra; Piret, James M

2003-05-01

Consistent perfusion culture production requires reliable cell retention and control of feed rates. An on-line cell probe based on capacitance was used to assay viable biomass concentrations. A constant cell specific perfusion rate controlled medium feed rates with a bioreactor cell concentration of approximately 5 x 10(6) cells mL(-1). Perfusion feeding was automatically adjusted based on the cell concentration signal from the on-line biomass sensor. Cell specific perfusion rates were varied over a range of 0.05 to 0.4 nL cell(-1) day(-1). Pseudo-steady-state bioreactor indices (concentrations, cellular rates and yields) were correlated to cell specific perfusion rates investigated to maximize recombinant protein production from a Chinese hamster ovary cell line. The tissue-type plasminogen activator concentration was maximized ( approximately 40 mg L(-1)) at 0.2 nL cell(-1) day(-1). The volumetric protein productivity ( approximately 60 mg L(-1) day(-1) was maximized above 0.3 nL cell(-1) day(-1). The use of cell specific perfusion rates provided a straightforward basis for controlling, modeling and optimizing perfusion cultures.

Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model.

PubMed

Sun, Chang-Jin; Li, Chao; Lv, Hai-Bo; Zhao, Cong; Yu, Jin-Ming; Wang, Guang-Hui; Luo, Yun-Xiu; Li, Yan; Xiao, Mingyong; Yin, Jun; Lang, Jin-Yi

2014-01-01

The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7-124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2-62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14-47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice.

In Search of the Optimal Heart Perfusion Ultrasound Imaging Platform.

PubMed

Grishenkov, Dmitry; Gonon, Adrian; Janerot-Sjoberg, Birgitta

2015-09-01

Quantification of myocardial perfusion by contrast echocardiography remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled. To contribute toward an improvement, we developed a contrast echocardiographic perfusion imaging platform based on an isolated rat heart coupled to an ultrasound scanner. Perfusion was assessed by using 3 different types of contrast agents: dextran-based Promiten (Meda AB, Solna, Sweden), phospholipid-shelled SonoVue (Bracco Diagnostics, Inc, Princeton, NJ), and polymer-shelled MB-pH5-RT, developed in-house. The myocardial video intensity was monitored over time from contrast agent administration to peak, and 2 characteristic constants were calculated by using an exponential fit: A, representing capillary volume; and β, representing inflow velocity. Acquired experimental evidence demonstrates that the application of all 3 contrast agents allows sonographic estimation of myocardial perfusion in the isolated rat heart. Video intensity maps show that an increase in contrast concentration increases the late-plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to A × β, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by a flowmeter attached to the aortic cannula. The contrast echocardiographic perfusion imaging platform described holds promise for standardized evaluation and optimization of contrast perfusion ultrasound imaging in which real-time inflow curves at low acoustic power semiquantitatively reflect coronary flow. © 2015 by the American Institute of Ultrasound in Medicine.

Inflow-weighted pulmonary perfusion: comparison between dynamic contrast-enhanced MRI versus perfusion scintigraphy in complex pulmonary circulation

PubMed Central

2013-01-01

Background Due to the different properties of the contrast agents, the lung perfusion maps as measured by 99mTc-labeled macroaggregated albumin perfusion scintigraphy (PS) are not uncommonly discrepant from those measured by dynamic contrast-enhanced MRI (DCE-MRI) using indicator-dilution analysis in complex pulmonary circulation. Since PS offers the pre-capillary perfusion of the first-pass transit, we hypothesized that an inflow-weighted perfusion model of DCE-MRI could simulate the result by PS. Methods 22 patients underwent DCE-MRI at 1.5T and also PS. Relative perfusion contributed by the left lung was calculated by PS (PSL%), by DCE-MRI using conventional indicator dilution theory for pulmonary blood volume (PBVL%) and pulmonary blood flow (PBFL%) and using our proposed inflow-weighted pulmonary blood volume (PBViwL%). For PBViwL%, the optimal upper bound of the inflow-weighted integration range was determined by correlation coefficient analysis. Results The time-to-peak of the normal lung parenchyma was the optimal upper bound in the inflow-weighted perfusion model. Using PSL% as a reference, PBVL% showed error of 49.24% to −40.37% (intraclass correlation coefficient RI = 0.55) and PBFL% had error of 34.87% to −27.76% (RI = 0.80). With the inflow-weighted model, PBViwL% had much less error of 12.28% to −11.20% (RI = 0.98) from PSL%. Conclusions The inflow-weighted DCE-MRI provides relative perfusion maps similar to that by PS. The discrepancy between conventional indicator-dilution and inflow-weighted analysis represents a mixed-flow component in which pathological flow such as shunting or collaterals might have participated. PMID:23448679

High temporal resolution dynamic contrast-enhanced MRI using compressed sensing-combined sequence in quantitative renal perfusion measurement.

PubMed

Chen, Bin; Zhao, Kai; Li, Bo; Cai, Wenchao; Wang, Xiaoying; Zhang, Jue; Fang, Jing

2015-10-01

To demonstrate the feasibility of the improved temporal resolution by using compressed sensing (CS) combined imaging sequence in dynamic contrast-enhanced MRI (DCE-MRI) of kidney, and investigate its quantitative effects on renal perfusion measurements. Ten rabbits were included in the accelerated scans with a CS-combined 3D pulse sequence. To evaluate the image quality, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the proposed CS strategy and the conventional full sampling method. Moreover, renal perfusion was estimated by using the separable compartmental model in both CS simulation and realistic CS acquisitions. The CS method showed DCE-MRI images with improved temporal resolution and acceptable image contrast, while presenting significantly higher SNR than the fully sampled images (p<.01) at 2-, 3- and 4-X acceleration. In quantitative measurements, renal perfusion results were in good agreement with the fully sampled one (concordance correlation coefficient=0.95, 0.91, 0.88) at 2-, 3- and 4-X acceleration in CS simulation. Moreover, in realistic acquisitions, the estimated perfusion by the separable compartmental model exhibited no significant differences (p>.05) between each CS-accelerated acquisition and the full sampling method. The CS-combined 3D sequence could improve the temporal resolution for DCE-MRI in kidney while yielding diagnostically acceptable image quality, and it could provide effective measurements of renal perfusion. Copyright © 2015 Elsevier Inc. All rights reserved.

Perfusion-induced changes in cardiac contractility depend on capillary perfusion.

PubMed

Dijkman, M A; Heslinga, J W; Sipkema, P; Westerhof, N

1998-02-01

The perfusion-induced increase in cardiac contractility (Gregg phenomenon) is especially found in heart preparations that lack adequate coronary autoregulation and thus protection of changes in capillary pressure. We determined in the isolated perfused papillary muscle of the rat whether cardiac muscle contractility is related to capillary perfusion. Oxygen availability of this muscle is independent of internal perfusion, and perfusion may be varied or even stopped without loss of function. Muscles contracted isometrically at 27 degrees C (n = 7). During the control state stepwise increases in perfusion pressure resulted in all muscles in a significant increase in active tension. Muscle diameter always increased with increased perfusion pressure, but muscle segment length was unaffected. Capillary perfusion was then obstructed by plastic microspheres (15 microns). Flow, at a perfusion pressure of 66.6 +/- 26.2 cmH2O, reduced from 17.6 +/- 5.4 microliters/min in the control state to 3.2 +/- 1.3 microliters/min after microspheres. Active tension developed by the muscle in the unperfused condition before microspheres and after microspheres did not differ significantly (-12.8 +/- 29.4% change). After microspheres similar perfusion pressure steps as in control never resulted in an increase in active tension. Even at the two highest perfusion pressures (89.1 +/- 28.4 and 106.5 +/- 31.7 cmH2O) that were applied a significant decrease in active tension was found. We conclude that the Gregg phenomenon is related to capillary perfusion.

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

NASA Astrophysics Data System (ADS)

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

2011-03-01

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

Inflow-weighted pulmonary perfusion: comparison between dynamic contrast-enhanced MRI versus perfusion scintigraphy in complex pulmonary circulation.

PubMed

Lin, Yi-Ru; Tsai, Shang-Yueh; Huang, Teng-Yi; Chung, Hsiao-Wen; Huang, Yi-Luan; Wu, Fu-Zong; Lin, Chu-Chuan; Peng, Nan-Jing; Wu, Ming-Ting

2013-02-28

Due to the different properties of the contrast agents, the lung perfusion maps as measured by 99mTc-labeled macroaggregated albumin perfusion scintigraphy (PS) are not uncommonly discrepant from those measured by dynamic contrast-enhanced MRI (DCE-MRI) using indicator-dilution analysis in complex pulmonary circulation. Since PS offers the pre-capillary perfusion of the first-pass transit, we hypothesized that an inflow-weighted perfusion model of DCE-MRI could simulate the result by PS. 22 patients underwent DCE-MRI at 1.5T and also PS. Relative perfusion contributed by the left lung was calculated by PS (PS(L%)), by DCE-MRI using conventional indicator dilution theory for pulmonary blood volume (PBV(L%)) and pulmonary blood flow (PBFL%) and using our proposed inflow-weighted pulmonary blood volume (PBV(iw)(L%)). For PBViw(L%), the optimal upper bound of the inflow-weighted integration range was determined by correlation coefficient analysis. The time-to-peak of the normal lung parenchyma was the optimal upper bound in the inflow-weighted perfusion model. Using PSL% as a reference, PBV(L%) showed error of 49.24% to -40.37% (intraclass correlation coefficient R(I) = 0.55) and PBF(L%) had error of 34.87% to -27.76% (R(I) = 0.80). With the inflow-weighted model, PBV(iw)(L%) had much less error of 12.28% to -11.20% (R(I) = 0.98) from PS(L%). The inflow-weighted DCE-MRI provides relative perfusion maps similar to that by PS. The discrepancy between conventional indicator-dilution and inflow-weighted analysis represents a mixed-flow component in which pathological flow such as shunting or collaterals might have participated.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao Yue, E-mail: yuecao@umich.edu; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Wang Hesheng

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 betweenmore » 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

Four Surgical Modifications to the Classic Elastase Perfusion Aneurysm Model Enable Haemodynamic Alterations and Extended Elastase Perfusion.

PubMed

Busch, Albert; Chernogubova, Ekaterina; Jin, Hong; Meurer, Felix; Eckstein, Hans-Henning; Kim, Mia; Maegdefessel, Lars

2018-04-24

Abdominal aortic aneurysm (AAA) is an individual and socioeconomic burden in today's ageing society. Treatment relies on surgical exclusion of the dilated aorta by open or endovascular repair. For research purposes, animal models are necessary and the elastase induced aneurysm model closely mimics end stage human aneurysm disease. To improve the translational value of this model, four modifications to the classic elastase perfusion procedure (PPE) in relation to human aneurysm morphology were conducted. In ten week old male C57BL/6J wild type mice the PPE procedure was modified in four ways using two different techniques. Flow alteration was simulated by partial ligation of the common iliac artery or the distal aorta. Additionally, careful exploration of the abdominal aortic branches allowed PPE induction at the suprarenal and iliac level. Molecular biology, ultrasound, and immunohistochemistry were used to evaluate these pilot results. Two aortic outflow obstructions simulating distal aortic or iliac stenosis significantly increase murine AAA diameter (p = .046), and affect local vascular wall remodelling. Suprarenal aortic dissection allows a juxtarenal aneurysm to be induced, similar to the angiotensin II induced aneurysm model. A separate investigation for canonical activation of transforming growth factor β in the two embryonically distinct juxtarenal and infrarenal segments showed no distinct difference. Creating an aortoiliac bifurcated aneurysm completes the mimicry of human aneurysm morphology. The alteration of the classic PPE aneurysm by outflow modulation and further elastase perfusion to the juxtarenal and aortoiliac segment modifies morphology and diameter, and thus increases the translational value in future research. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Does machine perfusion decrease ischemia reperfusion injury?

PubMed

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

2014-06-01

In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Microfluidic perfusion culture.

PubMed

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.

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

PubMed

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

2016-02-01

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

Large enhancement of perfusion contribution on fMRI signal

PubMed Central

Wang, Xiao; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

2012-01-01

The perfusion contribution to the total functional magnetic resonance imaging (fMRI) signal was investigated using a rat model with mild hypercapnia at 9.4 T, and human subjects with visual stimulation at 4 T. It was found that the total fMRI signal change could be approximated as a linear superposition of ‘true' blood oxygenation level-dependent (BOLD; T2/T2*) effect and the blood flow-related (T1) effect. The latter effect was significantly enhanced by using short repetition time and large radiofrequency pulse flip angle and became comparable to the ‘true' BOLD signal in response to a mild hypercapnia in the rat brain, resulting in an improved contrast-to-noise ratio (CNR). Bipolar diffusion gradients suppressed the intravascular signals but had no significant effect on the flow-related signal. Similar results of enhanced fMRI signal were observed in the human study. The overall results suggest that the observed flow-related signal enhancement is likely originated from perfusion, and this enhancement can improve CNR and the spatial specificity for mapping brain activity and physiology changes. The nature of mixed BOLD and perfusion-related contributions in the total fMRI signal also has implication on BOLD quantification, in particular, the BOLD calibration model commonly used to estimate the change of cerebral metabolic rate of oxygen. PMID:22395206

Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI

NASA Astrophysics Data System (ADS)

Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

2016-10-01

Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7  ±  1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n  =  9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland-Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were  -31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and  -10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p  =  0.0085) and HA fraction (p  <  0.0001), but not other parameters. Improved mean differences and Bland-Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.

An en bloc approach to CT perfusion for the evaluation of limb ischemia.

PubMed

Barfett, Joe; Velauthapillai, Nivethan; Kloeters, Christian; Mikulis, David J; Jaskolka, Jeffrey D

2012-12-01

We examine volumetric CT perfusion in soft tissues of the entire foot with an en bloc technique to provide a meaningful measure of differentiation between mild and major vascular impairment. With Institutional Review Board approval, 22 healthy male subjects between the ages of 21 and 50 (mean 37) were enrolled. Volumetric computed tomography using an en bloc technique was conducted on 14 subjects for validation while unilateral vascular obstruction was simulated in the calves of the remaining 8 subjects. Perfusion estimates were made using in-house software and differences in perfusion estimates between feet were evaluated with Student's t-test at 95% confidence. Subjects with simulated major vascular obstruction (calf blood pressure cuff inflated to 200 mmHg) showed significantly higher ratios of perfusion estimates between the unobstructed and obstructed foot compared to subjects with simulated mild vascular obstruction (cuff inflated to 120 mmHg), mean 4.6, SD 2.6 vs. mean 1.3, SD 0.2; P = 0.05. CT perfusion using an en bloc technique shows promise for the future evaluation of patients with critical limb ischemia and particularly for re-characterization post medical, surgical or endovascular intervention.

Increased visceral tissue perfusion with heated, humidified carbon dioxide insufflation during open abdominal surgery in a rodent model.

PubMed

Robson, Jonathan P; Kokhanenko, Pavlo; Marshall, Jean K; Phillips, Anthony R; van der Linden, Jan

2018-01-01

Tissue perfusion during surgery is important in reducing surgical site infections and promoting healing. This study aimed to determine if insufflation of the open abdomen with heated, humidified (HH) carbon dioxide (CO2) increased visceral tissue perfusion and core body temperature during open abdominal surgery in a rodent model. Using two different rodent models of open abdominal surgery, visceral perfusion and core temperature were measured. Visceral perfusion was investigated using a repeated measures crossover experiment with rodents receiving the same sequence of two alternating treatments: exposure to ambient air (no insufflation) and insufflation with HH CO2. Core body temperature was measured using an independent experimental design with three treatment groups: ambient air, HH CO2 and cold, dry (CD) CO2. Visceral perfusion was measured by laser speckle contrast analysis (LASCA) and core body temperature was measured with a rectal thermometer. Insufflation with HH CO2 into a rodent open abdominal cavity significantly increased visceral tissue perfusion (2.4 perfusion units (PU)/min (95% CI 1.23-3.58); p<0.0001) compared with ambient air, which significantly reduced visceral blood flow (-5.20 PU/min (95% CI -6.83- -3.58); p<0.0001). Insufflation of HH CO2 into the open abdominal cavity significantly increased core body temperature (+1.15 ± 0.14°C) compared with open cavities exposed to ambient air (-0.65 ± 0.52°C; p = 0.037), or cavities insufflated with CD CO2 (-0.73 ± 0.33°C; p = 0.006). Abdominal visceral temperatures also increased with HH CO2 insufflation compared with ambient air or CD CO2, as shown by infrared thermography. This study reports for the first time the use of LASCA to measure visceral perfusion in open abdominal surgery and shows that insufflation of open abdominal cavities with HH CO2 significantly increases visceral tissue perfusion and core body temperature.

The rate of percutaneous permeation of xylene, measured using the "perfused pig ear" model, is dependent on the effective protein concentration in the perfusing medium.

PubMed

de Lange, J; van Eck, P; Bruijnzeel, P L; Elliott, G R

1994-08-01

In order to study the dermal permeation of compounds through the skin, an in vitro model was developed which utilized pig ears perfused with autologous pig blood (de Lange, J., van Eck, P., Elliott, G. R., de Kort, W. L. A. M., and Wolthuis, O. L. (1992). J. Pharmacol. Toxicol. Methods 27, 71-77). In the present article we investigated to what extent the rate of permeation of xylene through pig ear skin is dependent on the perfusion medium used. Pig ears were exposed to xylene (10 cm2 area) for a 4-hr period (30 degrees C, relative humidity of 40-60%) and the perfusate was analyzed for xylene using gas chromatography. The rates of permeation of xylene for whole blood, blood depleted of white blood cells, and a buffer containing 4.5% albumin were similar (+/- 300 ng/min/cm2). The rate of penetration was fivefold higher when pig plasma was used and ninefold lower when albumin was excluded from the buffer. Using the buffer, we found that the rate of permeation of xylene was proportional to flow (constant protein concentration) and protein concentration (constant flow). Our data demonstrate that the measured permeation rate for xylene is, to a large degree, dependent on the effective protein concentration (mg/min) passing through the ear. Differences in this parameter could explain the variations in rates of permeation found using the different perfusion media. To avoid problems associated with the choice of receptor fluid for permeation experiments, we suggest that full blood remains the vehicle of choice, although the practical perfusion period is limited to about 6 hr. If longer perfusion periods are required, then it should be possible to reproduce results obtained with whole blood by choosing an appropriate buffer.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population.

PubMed

Amen, Daniel G; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A

2016-04-25

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. To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. 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. 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. 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 study carries implications for the neurological safety

Microdialysis measurements of lamellar perfusion and energy metabolism during the development of laminitis in the oligofructose model.

PubMed

Medina-Torres, C E; Underwood, C; Pollitt, C C; Castro-Olivera, E M; Hodson, M P; Richardson, D W; van Eps, A W

2016-03-01

Failure of lamellar energy metabolism, with or without ischaemia, may be important in the pathophysiology of sepsis-associated laminitis. To examine lamellar perfusion and energy balance during laminitis development in the oligofructose model using tissue microdialysis. In vivo experiment. Six Standardbred horses underwent laminitis induction using the oligofructose model (OFT group) and 6 horses were untreated controls (CON group). Microdialysis probes were placed in the lamellar tissue of one forelimb (all horses) as well as the skin dermis of the tail in OFT horses. Dialysate and plasma samples were collected every 2 h for 24 h and concentrations of energy metabolites (glucose, lactate, pyruvate) and standard indices of energy metabolism (lactate to glucose ratio [L:G] and lactate to pyruvate ratio [L:P]) determined. Microdialysis urea clearance was used to estimate changes in tissue perfusion. Data were analysed nonparametrically. Median glucose concentration decreased to <30% of baseline by 8 h in OFT lamellar (P = <0.01) and skin (P<0.01) dialysate. Lactate increased mildly in skin dialysate (P = 0.04) and plasma (P = 0.05) but not lamellar dialysate in OFT horses. Median pyruvate concentration decreased to <50% of baseline in OFT lamellar dialysate (P = 0.03). A >5-fold increase in median L:G compared with baseline occurred in OFT lamellar and skin dialysate (P<0.03). From a baseline of <20, median L:P increased to a peak of 80 in OFT skin and 38.7 in OFT lamellar dialysates (P<0.02); however, OFT lamellar dialysate L:P was not significantly different from CON. Urea concentration decreased significantly in OFT lamellar dialysate (increased urea clearance) but not in OFT skin or CON lamellar dialysate. Increased lamellar perfusion occurred during the development of sepsis-associated laminitis in the oligofructose model. Glucose concentrations in the lamellar interstitium decreased, suggesting increased glucose consumption but there was no definitive

Impaired healing of cervical oesophagogastrostomies can be predicted by estimation of gastric serosal blood perfusion by laser Doppler flowmetry.

PubMed

Pierie, J P; De Graaf, P W; Poen, H; Van der Tweel, I; Obertop, H

1994-11-01

To assess the value of relative blood perfusion of the gastric tube in prediction of impaired healing of cervical oesophagogastrostomies. Prospective study. University hospital, The Netherlands. Thirty patients undergoing transhiatal oesophagectomy and partial gastrectomy for cancer of the oesophagus or oesophagogastric junction, with gastric tube reconstruction and cervical oesophagogastrostomy. Operative measurement of gastric blood perfusion at four sites by laser Doppler flowmetry and perfusion of the same sites after construction of the gastric tube expressed as a percentage of preconstruction values. The relative perfusion at the most proximal site of the gastric tube was significantly lower than at the more distal sites (p = 0.001). Nine of 18 patients (50%) in whom the perfusion of the proximal gastric tube was less than 70% of preconstruction values developed an anastomotic stricture, compared with only 1 of 12 patients (8%) with a relative perfusion of 70% or more (p = 0.024). A reduction in perfusion of the gastric tube did not predict leakage. Impaired anastomotic healing is unlikely if relative perfusion is 70% or more of preconstruction values. Perfusion of less than 70% partly predicts the occurrence of anastomotic stricture, but leakage cannot be predicted. Factors other than blood perfusion may have a role in the process of anastomotic healing.

TH-CD-206-01: Expectation-Maximization Algorithm-Based Tissue Mixture Quantification for Perfusion MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, H; Xing, L; Liang, Z

Purpose: To investigate the feasibility of estimating the tissue mixture perfusions and quantifying cerebral blood flow change in arterial spin labeled (ASL) perfusion MR images. Methods: The proposed perfusion MR image analysis framework consists of 5 steps: (1) Inhomogeneity correction was performed on the T1- and T2-weighted images, which are available for each studied perfusion MR dataset. (2) We used the publicly available FSL toolbox to strip off the non-brain structures from the T1- and T2-weighted MR images. (3) We applied a multi-spectral tissue-mixture segmentation algorithm on both T1- and T2-structural MR images to roughly estimate the fraction of eachmore » tissue type - white matter, grey matter and cerebral spinal fluid inside each image voxel. (4) The distributions of the three tissue types or tissue mixture across the structural image array are down-sampled and mapped onto the ASL voxel array via a co-registration operation. (5) The presented 4-dimensional expectation-maximization (4D-EM) algorithm takes the down-sampled three tissue type distributions on perfusion image data to generate the perfusion mean, variance and percentage images for each tissue type of interest. Results: Experimental results on three volunteer datasets demonstrated that the multi-spectral tissue-mixture segmentation algorithm was effective to initialize tissue mixtures from T1- and T2-weighted MR images. Compared with the conventional ASL image processing toolbox, the proposed 4D-EM algorithm not only generated comparable perfusion mean images, but also produced perfusion variance and percentage images, which the ASL toolbox cannot obtain. It is observed that the perfusion contribution percentages may not be the same as the corresponding tissue mixture volume fractions estimated in the structural images. Conclusion: A specific application to brain ASL images showed that the presented perfusion image analysis method is promising for detecting subtle changes in tissue

Ventilation and perfusion imaging by electrical impedance tomography: a comparison with radionuclide scanning.

PubMed

Kunst, P W; Vonk Noordegraaf, A; Hoekstra, O S; Postmus, P E; de Vries, P M

1998-11-01

Electrical impedance tomography (EIT) is a technique that makes it possible to measure ventilation and pulmonary perfusion in a volume that approximates to a 2D plane. The possibility of using EIT for measuring the left-right division of ventilation and perfusion was compared with that of radionuclide imaging. Following routine ventilation (81mKr) and perfusion scanning (99mTc-MAA), EIT measurements were performed at the third and the sixth intercostal level in 14 patients with lung cancer. A correlation (r = 0.98, p < 0.005) between the left-right division for the ventilation measured with EIT and that with 81mKr was found. For the left-right division of pulmonary perfusion a correlation of 0.95 (p < 0.005) was found between the two methods. The reliability coefficient (RC) was calculated for estimating the left-right division with EIT. The RC for the ventilation measurements was 94% and 96% for the perfusion measurements. The correlation analysis for reproducibility of the EIT measurements was 0.95 (p < 0.001) for the ventilation and 0.93 (p < 0.001) for the perfusion measurements. In conclusion, EIT can be regarded as a promising technique to estimate the left-right division of pulmonary perfusion and ventilation.

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

NASA Astrophysics Data System (ADS)

Diana, Michele

2016-03-01

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

Quantitative lung perfusion evaluation using Fourier decomposition perfusion MRI.

PubMed

Kjørstad, Åsmund; Corteville, Dominique M R; Fischer, Andre; Henzler, Thomas; Schmid-Bindert, Gerald; Zöllner, Frank G; Schad, Lothar R

2014-08-01

To quantitatively evaluate lung perfusion using Fourier decomposition perfusion MRI. The Fourier decomposition (FD) method is a noninvasive method for assessing ventilation- and perfusion-related information in the lungs, where the perfusion maps in particular have shown promise for clinical use. However, the perfusion maps are nonquantitative and dimensionless, making follow-ups and direct comparisons between patients difficult. We present an approach to obtain physically meaningful and quantifiable perfusion maps using the FD method. The standard FD perfusion images are quantified by comparing the partially blood-filled pixels in the lung parenchyma with the fully blood-filled pixels in the aorta. The percentage of blood in a pixel is then combined with the temporal information, yielding quantitative blood flow values. The values of 10 healthy volunteers are compared with SEEPAGE measurements which have shown high consistency with dynamic contrast enhanced-MRI. All pulmonary blood flow (PBF) values are within the expected range. The two methods are in good agreement (mean difference = 0.2 mL/min/100 mL, mean absolute difference = 11 mL/min/100 mL, mean PBF-FD = 150 mL/min/100 mL, mean PBF-SEEPAGE = 151 mL/min/100 mL). The Bland-Altman plot shows a good spread of values, indicating no systematic bias between the methods. Quantitative lung perfusion can be obtained using the Fourier Decomposition method combined with a small amount of postprocessing. Copyright © 2013 Wiley Periodicals, Inc.

Renal perfusion scintiscan

MedlinePlus

... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

Arterial Spin Labeling - Fast Imaging with Steady-State Free Precession (ASL-FISP): A Rapid and Quantitative Perfusion Technique for High Field MRI

PubMed Central

Gao, Ying; Goodnough, Candida L.; Erokwu, Bernadette O.; Farr, George W.; Darrah, Rebecca; Lu, Lan; Dell, Katherine M.; Yu, Xin; Flask, Chris A.

2014-01-01

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 that 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 seconds. In this initial implementation, a FAIR (Flow-Sensitive Alternating Inversion Recovery) 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 T and 9.4 T (249±38 ml/min/100g and 241±17 ml/min/100g, respectively). The utility of this method was further demonstrated in detecting 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. PMID:24891124

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population

PubMed Central

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

Patient-specific coronary blood supply territories for quantitative perfusion analysis

PubMed Central

Zakkaroff, Constantine; Biglands, John D.; Greenwood, John P.; Plein, Sven; Boyle, Roger D.; Radjenovic, Aleksandra; Magee, Derek R.

2018-01-01

Abstract Myocardial perfusion imaging, coupled with quantitative perfusion analysis, provides an important diagnostic tool for the identification of ischaemic heart disease caused by coronary stenoses. The accurate mapping between coronary anatomy and under-perfused areas of the myocardium is important for diagnosis and treatment. However, in the absence of the actual coronary anatomy during the reporting of perfusion images, areas of ischaemia are allocated to a coronary territory based on a population-derived 17-segment (American Heart Association) AHA model of coronary blood supply. This work presents a solution for the fusion of 2D Magnetic Resonance (MR) myocardial perfusion images and 3D MR angiography data with the aim to improve the detection of ischaemic heart disease. The key contribution of this work is a novel method for the mediated spatiotemporal registration of perfusion and angiography data and a novel method for the calculation of patient-specific coronary supply territories. The registration method uses 4D cardiac MR cine series spanning the complete cardiac cycle in order to overcome the under-constrained nature of non-rigid slice-to-volume perfusion-to-angiography registration. This is achieved by separating out the deformable registration problem and solving it through phase-to-phase registration of the cine series. The use of patient-specific blood supply territories in quantitative perfusion analysis (instead of the population-based model of coronary blood supply) has the potential of increasing the accuracy of perfusion analysis. Quantitative perfusion analysis diagnostic accuracy evaluation with patient-specific territories against the AHA model demonstrates the value of the mediated spatiotemporal registration in the context of ischaemic heart disease diagnosis. PMID:29392098

Spatio-temporal analysis of blood perfusion by imaging photoplethysmography

NASA Astrophysics Data System (ADS)

Zaunseder, Sebastian; Trumpp, Alexander; Ernst, Hannes; Förster, Michael; Malberg, Hagen

2018-02-01

Imaging photoplethysmography (iPPG) has attracted much attention over the last years. The vast majority of works focuses on methods to reliably extract the heart rate from videos. Only a few works addressed iPPGs ability to exploit spatio-temporal perfusion pattern to derive further diagnostic statements. This work directs at the spatio-temporal analysis of blood perfusion from videos. We present a novel algorithm that bases on the two-dimensional representation of the blood pulsation (perfusion map). The basic idea behind the proposed algorithm consists of a pairwise estimation of time delays between photoplethysmographic signals of spatially separated regions. The probabilistic approach yields a parameter denoted as perfusion speed. We compare the perfusion speed versus two parameters, which assess the strength of blood pulsation (perfusion strength and signal to noise ratio). Preliminary results using video data with different physiological stimuli (cold pressure test, cold face test) show that all measures are influenced by those stimuli (some of them with statistical certainty). The perfusion speed turned out to be more sensitive than the other measures in some cases. However, our results also show that the intraindividual stability and interindividual comparability of all used measures remain critical points. This work proves the general feasibility of employing the perfusion speed as novel iPPG quantity. Future studies will address open points like the handling of ballistocardiographic effects and will try to deepen the understanding of the predominant physiological mechanisms and their relation to the algorithmic performance.

Effects of chlorhexidine on a tongue-flora microcosm and VSC production using an in vitro biofilm perfusion model.

PubMed

Greenman, J; McKenzie, C; Saad, S; Wiegand, B; Zguris, J C

2008-12-01

An in vitro perfusion biofilm model, derived from tongue-scrape microflora removed from one individual, was employed to study sulfide biogenesis and the effects of repeated exposure to chlorhexidine (CHX). Volatile sulfur compounds (VSC) were measured using a carbon veil electrode within the biofilm and a halimeter for liquid and gas phase levels, respectively. The microflora of the perfusate and the biofilm were assessed by microbiological techniques and polymerase chain reaction (PCR) to estimate diversity. Biofilms treated with a 1 mL pulse of 0.1% CHX twice a day for three days showed (1) a large reduction in viable count (>90% kill), (2) a (slow) reduction in the VSC production rate, consistent with the reduction in microbes rather than direct inhibitory effects on the biotransformation steps, and (3) a preferential reduction of strict anaerobes. Treated biofilms allowed to recover over 3-5 days showed a nominal amount of regrowth in some experiments, although population numbers were still well below those found in untreated controls. The microbiological composition of biofilms treated but allowed to recover was markedly different from the controls, with proportionally fewer strict anaerobes. Thus, CHX treatment caused detectable ecological shifts with consequent long-term effects on the response of the biofilm in terms of VSC generation, consistent with clinical observations. The model appears highly suited for testing the efficacy of putative anti-malodour or antimicrobial agents.

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

PubMed

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

2013-07-01

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

Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein in In-situ Cancerous Colon Perfusion Rat Model.

PubMed

Neerati, Prasad; Sudhakar, Yakkanti A; Kanwar, Jagat R

2013-07-08

Studies on p-glycoprotein was carried out world vide with cell lines like Caco2, MDR1-LLC-PK1 and MDR1-MDCK in-vitro , but most of the results were failed to produce similar results in-vivo. In the present study curcumin inhibitory action on p-glycoprotein increased permeability of irinotecan, so in the colon cancer it would be beneficial if curcumin used as add on therapy. Intra-rectal administered of N-Nitroso N-methyl urea (2 mg/Kg) induced colon cancer. Single pass whole length of colon in-situ perfusion was carried out in rats with irinotecan to study the influence of p-glycoprotein modulators like verapamil and curcumin. The rats were divided in to 5 groups (n=6), Group I served as control perfused with 30 μg/ml of irinotecan, propronolol and phenol red. Group II was cancerous group, induced by N-methyl N-nitroso urea. Group III was perfused with irinotican in cancerous rats. Group IV, perfused with irinotican in presence of verapamil and group V was pre-treated with curcumin and then perfused with irinotican and was estimated by HPLC-UV to effective permeability coefficient. Our qRT-PCR and Western blot results confirmed that about 15-fold decreases in the expression of p-glycoprotein (P-gp) in curcumin treated colon cancer cells. Irinotecan was increased to 0.00066 cm/s and about 11-fold increase in verapamil-coperfused group, where curcumin pre-treated group irinotecan was increases 0.00006 cm/s to 0.00042 cm/s that is about 7-fold increase p-glycoprotein inhibitory activity by verapamil and curcumin found to be significantly enhanced the cancerous colon permeability of irinotecan. Any safe suitable p-glycoprotein inhibitors along with irinotecan will enhance the therapeutic benefit in the treatment of the colon cancer.

Impaired Tissue Oxygenation in Metabolic Syndrome Requires Increased Microvascular Perfusion Heterogeneity

PubMed Central

McClatchey, P. Mason; Wu, Fan; Olfert, I. Mark; Ellis, Christopher G.; Goldman, Daniel; Reusch, Jane E. B.

2018-01-01

Metabolic syndrome (MS) in obese Zucker rats (OZR) is associated with impaired skeletal muscle performance and blunted hyperemia. Studies suggest that reduced O2 diffusion capacity is required to explain compromised muscle performance and that heterogeneous microvascular perfusion distribution is critical. We modeled tissue oxygenation during muscle contraction in control and OZR skeletal muscle using physiologically realistic relationships. Using a network model of Krogh cylinders with increasing perfusion asymmetry and increased plasma skimming, we predict increased perfusion heterogeneity and decreased muscle oxygenation in OZR, with partial recovery following therapy. Notably, increasing O2 delivery had less impact on VO2 than equivalent decreases in O2 delivery, providing a mechanism for previous empirical work associating perfusion heterogeneity and impaired O2 extraction. We demonstrate that increased skeletal muscle perfusion asymmetry is a defining characteristic of MS and must be considered to effectively model and understand blood-tissue O2 exchange in this model of human disease. PMID:28168652

Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siva, Shankar, E-mail: shankar.siva@petermac.org; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville; Hardcastle, Nicholas

2015-10-01

Purpose: To investigate {sup 68}Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation andmore » perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D

Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model.

PubMed

Jamshidfar, Sanaz; Ardakani, Yalda H; Lavasani, Hoda; Rouini, Mohammadreza

2017-06-28

Nowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound. Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression. MRZ is extensively metabolized in liver by CYP450 isoenzymes. 8-hydroxymirtazapine (8-OH) is mainly produced by CYP2D6. N-desmethylmirtazapine (NDES) is generated by CYP3A4. MDMA is also metabolized by the mentioned isoenzymes and demonstrates mechanism-based inhibition (MBI) in association with CYP2D6. Several studies revealed that MDMA showed inhibitory effects on CYP3A4. In the present study, our aim was to evaluate the impact of MDMA on the metabolism of MRZ in liver. Therefore, isolated perfused rat liver model was applied as our model of choice in this assessment. The subjects of the study were categorized into two experimental groups. Rats in the control group received MRZ-containing Krebs-Henselit buffer (1 μg/ml). Rats in the treatment group received aqueous solution of 1 mg/ml MDMA (3 mg/kg) intraperitoneally 1 hour before receiving MRZ. Perfusate samples were analyzed by HPLC. Analyses of perfusate samples showed 80% increase in the parent drug concentrations and 50% decrease in the concentrations of both metabolites in our treatment group compared to the control group. In the treatment group compared to the control group, AUC (0-120) of the parent drug demonstrated 50% increase and AUC (0-120) of 8-OH and NDES showed 70% and 60% decrease, respectively. Observed decrease in metabolic ratios were 83% and 79% for 8-OH and NDES in treatment group compared to control group, respectively. Hepatic clearance (CL h ) and intrinsic clearance (Cl int ) showed 20% and 60% decrease in treatment group compared to control group. All findings prove the inhibitory effects of ecstasy on both CYP2D6 and CYP3A4 hepatic isoenzymes. In

A microfluidically perfused three dimensional human liver model.

PubMed

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

2015-12-01

Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Steps for the autologous ex vivo perfused porcine liver-kidney experiment.

PubMed

Chung, Wen Yuan; Eltweri, Amar M; Isherwood, John; Haqq, Jonathan; Ong, Seok Ling; Gravante, Gianpiero; Lloyd, David M; Metcalfe, Matthew S; Dennison, Ashley R

2013-12-18

The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.

Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance.

PubMed

Sammut, Eva C; Villa, Adriana D M; Di Giovine, Gabriella; Dancy, Luke; Bosio, Filippo; Gibbs, Thomas; Jeyabraba, Swarna; Schwenke, Susanne; Williams, Steven E; Marber, Michael; Alfakih, Khaled; Ismail, Tevfik F; Razavi, Reza; Chiribiri, Amedeo

2018-05-01

This study sought to evaluate the prognostic usefulness of visual and quantitative perfusion cardiac magnetic resonance (CMR) ischemic burden in an unselected group of patients and to assess the validity of consensus-based ischemic burden thresholds extrapolated from nuclear studies. There are limited data on the prognostic value of assessing myocardial ischemic burden by CMR, and there are none using quantitative perfusion analysis. Patients with suspected coronary artery disease referred for adenosine-stress perfusion CMR were included (n = 395; 70% male; age 58 ± 13 years). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, aborted sudden death, and revascularization after 90 days. Perfusion scans were assessed visually and with quantitative analysis. Cross-validated Cox regression analysis and net reclassification improvement were used to assess the incremental prognostic value of visual or quantitative perfusion analysis over a baseline clinical model, initially as continuous covariates, then using accepted thresholds of ≥2 segments or ≥10% myocardium. After a median 460 days (interquartile range: 190 to 869 days) follow-up, 52 patients reached the primary endpoint. At 2 years, the addition of ischemic burden was found to increase prognostic value over a baseline model of age, sex, and late gadolinium enhancement (baseline model area under the curve [AUC]: 0.75; visual AUC: 0.84; quantitative AUC: 0.85). Dichotomized quantitative ischemic burden performed better than visual assessment (net reclassification improvement 0.043 vs. 0.003 against baseline model). This study was the first to address the prognostic benefit of quantitative analysis of perfusion CMR and to support the use of consensus-based ischemic burden thresholds by perfusion CMR for prognostic evaluation of patients with suspected coronary artery disease. Quantitative analysis provided incremental prognostic value to visual assessment and

CT Perfusion of the Head

MedlinePlus

... News Physician Resources Professions Site Index A-Z CT Perfusion of the Head Computed tomography (CT) perfusion ... of CT Perfusion of the Head? What is CT Perfusion of the Head? Computed tomography (CT) perfusion ...

[Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy].

PubMed

Fujii, T; Tanaka, M; Yazaki, Y; Kitabayashi, H; Koizumi, T; Kubo, K; Sekiguchi, M; Yano, K

1999-06-01

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09 +/- 1.28 for the normal subjects, 1.97 +/- 0.89 for the patients with lung disease, and 1.59 +/- 0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (> 20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease.

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

PubMed

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

2017-01-10

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

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

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

PubMed Central

2013-01-01

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

Hepatic sinusoid is not well-stirred: estimation of the degree of axial mixing by analysis of lobular concentration gradients formed during uptake of thyroxine by the perfused rat liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisiger, R.A.; Mendel, C.M.; Cavalieri, R.R.

1986-03-01

Two general models have been proposed for predicting the effects of metabolism, protein binding, and plasma flow on the removal of drugs by the liver. These models differ in the degree of plasma mixing assumed to exist within each hepatic sinusoid. The venous equilibrium model treats the sinusoid as a single well-stirred compartment, whereas the sinusoidal model effectively breaks up the sinusoid into a large number of sequentially perfused compartments which do not exchange their contents except through plasma flow. As a consequence, the sinusoidal model, but not the venous equilibrium model, predicts that the concentration of highly extracted drugsmore » will decline as the plasma flows through the hepatic lobule. To determine which of these alternative models best describes the hepatic uptake process, we looked for evidence that concentration gradients are formed during the uptake of (/sup 125/I)thyroxine by the perfused rat liver. Autoradiography of tissue slices after perfusion of the portal vein at physiologic flow rates with protein-free buffer containing (/sup 125/I)thyroxine demonstrated a rapid exponential fall in grain density with distance from the portal venule, declining by half for each 8% of the mean length of the sinusoid. Reversing the direction of perfusate flow reversed the direction of the autoradiographic gradients, indicating that they primarily reflect differences in the concentration of thyroxine within the hepatic sinusoids rather than differences in the uptake capacity of portal and central hepatocytes. Analysis of the data using models in which each sinusoid was represented by different numbers of sequentially perfused compartments (1-20) indicated that at least eight compartments were necessary to account for the magnitude of the gradients seen.« less

Application of a Simplified Method for Estimating Perfusion Derived from Diffusion-Weighted MR Imaging in Glioma Grading.

PubMed

Cao, Mengqiu; Suo, Shiteng; Han, Xu; Jin, Ke; Sun, Yawen; Wang, Yao; Ding, Weina; Qu, Jianxun; Zhang, Xiaohua; Zhou, Yan

2017-01-01

Purpose : To evaluate the feasibility of a simplified method based on diffusion-weighted imaging (DWI) acquired with three b -values to measure tissue perfusion linked to microcirculation, to validate it against from perfusion-related parameters derived from intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging, and to investigate its utility to differentiate low- from high-grade gliomas. Materials and Methods : The prospective study was approved by the local institutional review board and written informed consent was obtained from all patients. From May 2016 and May 2017, 50 patients confirmed with glioma were assessed with multi- b -value DWI and DCE MR imaging at 3.0 T. Besides conventional apparent diffusion coefficient (ADC 0,1000 ) map, perfusion-related parametric maps for IVIM-derived perfusion fraction ( f ) and pseudodiffusion coefficient (D*), DCE MR imaging-derived pharmacokinetic metrics, including K trans , v e and v p , as well as a metric named simplified perfusion fraction (SPF), were generated. Correlation between perfusion-related parameters was analyzed by using the Spearman rank correlation. All imaging parameters were compared between the low-grade ( n = 19) and high-grade ( n = 31) groups by using the Mann-Whitney U test. The diagnostic performance for tumor grading was evaluated with receiver operating characteristic (ROC) analysis. Results : SPF showed strong correlation with IVIM-derived f and D* ( ρ = 0.732 and 0.716, respectively; both P < 0.001). Compared with f , SPF was more correlated with DCE MR imaging-derived K trans ( ρ = 0.607; P < 0.001) and v p ( ρ = 0.397; P = 0.004). Among all parameters, SPF achieved the highest accuracy for differentiating low- from high-grade gliomas, with an area under the ROC curve value of 0.942, which was significantly higher than that of ADC 0,1000 ( P = 0.004). By using SPF as a discriminative index, the diagnostic sensitivity and specificity were

Brain perfusion imaging using a Reconstruction-of-Difference (RoD) approach for cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Mow, M.; Zbijewski, W.; Sisniega, A.; Xu, J.; Dang, H.; Stayman, J. W.; Wang, X.; Foos, D. H.; Koliatsos, V.; Aygun, N.; Siewerdsen, J. H.

2017-03-01

Purpose: To improve the timely detection and treatment of intracranial hemorrhage or ischemic stroke, recent efforts include the development of cone-beam CT (CBCT) systems for perfusion imaging and new approaches to estimate perfusion parameters despite slow rotation speeds compared to multi-detector CT (MDCT) systems. This work describes development of a brain perfusion CBCT method using a reconstruction of difference (RoD) approach to enable perfusion imaging on a newly developed CBCT head scanner prototype. Methods: A new reconstruction approach using RoD with a penalized-likelihood framework was developed to image the temporal dynamics of vascular enhancement. A digital perfusion simulation was developed to give a realistic representation of brain anatomy, artifacts, noise, scanner characteristics, and hemo-dynamic properties. This simulation includes a digital brain phantom, time-attenuation curves and noise parameters, a novel forward projection method for improved computational efficiency, and perfusion parameter calculation. Results: Our results show the feasibility of estimating perfusion parameters from a set of images reconstructed from slow scans, sparse data sets, and arc length scans as short as 60 degrees. The RoD framework significantly reduces noise and time-varying artifacts from inconsistent projections. Proper regularization and the use of overlapping reconstructed arcs can potentially further decrease bias and increase temporal resolution, respectively. Conclusions: A digital brain perfusion simulation with RoD imaging approach has been developed and supports the feasibility of using a CBCT head scanner for perfusion imaging. Future work will include testing with data acquired using a 3D-printed perfusion phantom currently and translation to preclinical and clinical studies.

Perfusion Electronic Record Documentation Using Epic Systems Software.

PubMed

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.

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

PubMed

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

2017-09-01

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

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

PubMed

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

2013-04-01

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

Perfusion directed 3D mineral formation within cell-laden hydrogels.

PubMed

Sawyer, Stephen William; Shridhar, Shivkumar Vishnempet; Zhang, Kairui; Albrecht, Lucas; Filip, Alex; Horton, Jason; Soman, Pranav

2018-06-08

Despite the promise of stem cell engineering and the new advances in bioprinting technologies, one of the major challenges in the manufacturing of large scale bone tissue scaffolds is the inability to perfuse nutrients throughout thick constructs. Here, we report a scalable method to create thick, perfusable bone constructs using a combination of cell-laden hydrogels and a 3D printed sacrificial polymer. Osteoblast-like Saos-2 cells were encapsulated within a gelatin methacrylate (GelMA) hydrogel and 3D printed polyvinyl alcohol (PVA) pipes were used to create perfusable channels. A custom-built bioreactor was used to perfuse osteogenic media directly through the channels in order to induce mineral deposition which was subsequently quantified via microCT. Histological staining was used to verify mineral deposition around the perfused channels, while COMSOL modeling was used to simulate oxygen diffusion between adjacent channels. This information was used to design a scaled-up construct containing a 3D array of perfusable channels within cell-laden GelMA. Progressive matrix mineralization was observed by cells surrounding perfused channels as opposed to random mineral deposition in static constructs. MicroCT confirmed that there was a direct relationship between channel mineralization within perfused constructs and time within the bioreactor. Furthermore, the scalable method presented in this work serves as a model on how large-scale bone tissue replacement constructs could be made using commonly available 3D printers, sacrificial materials, and hydrogels. © 2018 IOP Publishing Ltd.

Reflectance Photoplethysmography as Noninvasive Monitoring of Tissue Blood Perfusion.

PubMed

Abay, Tomas Ysehak; Kyriacou, Panayiotis A

2015-09-01

In the last decades, photoplethysmography (PPG) has been used as a noninvasive technique for monitoring arterial oxygen saturation by pulse oximetry (PO), whereas near-infrared spectroscopy (NIRS) has been employed for monitoring tissue blood perfusion. While NIRS offers more parameters to evaluate oxygen delivery and consumption in deep tissues, PO only assesses the state of oxygen delivery. For a broader assessment of blood perfusion, this paper explores the utilization of dual-wavelength PPG by using the pulsatile (ac) and continuous (dc) PPG for the estimation of arterial oxygen saturation (SpO2) by conventional PO. Additionally, the Beer-Lambert law is applied to the dc components only for the estimation of changes in deoxyhemoglobin (HHb), oxyhemoglobin (HbO2), and total hemoglobin (tHb) as in NIRS. The system was evaluated on the forearm of 21 healthy volunteers during induction of venous occlusion (VO) and total occlusion (TO). A reflectance PPG probe and NIRS sensor were applied above the brachioradialis, PO sensors were applied on the fingers, and all the signals were acquired simultaneously. While NIRS and forearm SpO2 indicated VO, SpO2 from the finger did not exhibit any significant drop from baseline. During TO, all the indexes indicated the change in blood perfusion. HHb, HbO2, and tHb changes estimated by PPG presented high correlation with the same parameters obtained by NIRS during VO (r(2) = 0.960, r(2) = 0.821, and r(2) = 0.974, respectively) and during TO (r(2) = 0.988, r(2) = 0.940, and r(2) = 0.938, respectively). The system demonstrated the ability to extract valuable information from PPG signals for a broader assessment of tissue blood perfusion.

Modeling of the contrast-enhanced perfusion test in liver based on the multi-compartment flow in porous media.

PubMed

Rohan, Eduard; Lukeš, Vladimír; Jonášová, Alena

2018-01-24

The paper deals with modeling the liver perfusion intended to improve quantitative analysis of the tissue scans provided by the contrast-enhanced computed tomography (CT). For this purpose, we developed a model of dynamic transport of the contrast fluid through the hierarchies of the perfusion trees. Conceptually, computed time-space distributions of the so-called tissue density can be compared with the measured data obtained from CT; such a modeling feedback can be used for model parameter identification. The blood flow is characterized at several scales for which different models are used. Flows in upper hierarchies represented by larger branching vessels are described using simple 1D models based on the Bernoulli equation extended by correction terms to respect the local pressure losses. To describe flows in smaller vessels and in the tissue parenchyma, we propose a 3D continuum model of porous medium defined in terms of hierarchically matched compartments characterized by hydraulic permeabilities. The 1D models corresponding to the portal and hepatic veins are coupled with the 3D model through point sources, or sinks. The contrast fluid saturation is governed by transport equations adapted for the 1D and 3D flow models. The complex perfusion model has been implemented using the finite element and finite volume methods. We report numerical examples computed for anatomically relevant geometries of the liver organ and of the principal vascular trees. The simulated tissue density corresponding to the CT examination output reflects a pathology modeled as a localized permeability deficiency.

Effect of multiple perfusion components on pseudo-diffusion coefficient in intravoxel incoherent motion imaging

NASA Astrophysics Data System (ADS)

Kuai, Zi-Xiang; Liu, Wan-Yu; Zhu, Yue-Min

2017-11-01

The aim of this work was to investigate the effect of multiple perfusion components on the pseudo-diffusion coefficient D * in the bi-exponential intravoxel incoherent motion (IVIM) model. Simulations were first performed to examine how the presence of multiple perfusion components influences D *. The real data of livers (n  =  31), spleens (n  =  31) and kidneys (n  =  31) of 31 volunteers was then acquired using DWI for in vivo study and the number of perfusion components in these tissues was determined together with their perfusion fraction and D *, using an adaptive multi-exponential IVIM model. Finally, the bi-exponential model was applied to the real data and the mean, standard variance and coefficient of variation of D * as well as the fitting residual were calculated over the 31 volunteers for each of the three tissues and compared between them. The results of both the simulations and the in vivo study showed that, for the bi-exponential IVIM model, both the variance of D * and the fitting residual tended to increase when the number of perfusion components was increased or when the difference between perfusion components became large. In addition, it was found that the kidney presented the fewest perfusion components among the three tissues. The present study demonstrated that multi-component perfusion is a main factor that causes high variance of D * and the bi-exponential model should be used only when the tissues under investigation have few perfusion components, for example the kidney.

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

PubMed

Clauss, R P; Dormehl, I C; Oliver, D W; Nel, W H; Kilian, E; Louw, W K

2001-01-01

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

Perfusion defects in pulmonary perfusion iodine maps: causes and semiology.

PubMed

Bustos Fiore, A; González Vázquez, M; Trinidad López, C; Mera Fernández, D; Costas Álvarez, M

2017-12-14

to describe the usefulness of dual-energy CT for obtaining pulmonary perfusion maps to provide morphological and functional information in patients with pulmonary embolisms. To review the semiology of perfusion defects due to pulmonary embolism so they can be differentiated from perfusion defects due to other causes: alterations outside the range used in the iodine map caused by other diseases of the lung parenchyma or artifacts. CT angiography of the pulmonary arteries is the technique of choice for the diagnosis of pulmonary embolisms. New dual-energy CT scanners are useful for detecting perfusion defects secondary to complete or partial obstruction of pulmonary arteries and is most useful for detecting pulmonary embolisms in subsegmental branches. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Tokihiro, E-mail: toyamamoto@ucdavis.edu

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

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

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

Robust Low-dose CT Perfusion Deconvolution via Tensor Total-Variation Regularization

PubMed Central

Zhang, Shaoting; Chen, Tsuhan; Sanelli, Pina C.

2016-01-01

Acute brain diseases such as acute strokes and transit ischemic attacks are the leading causes of mortality and morbidity worldwide, responsible for 9% of total death every year. ‘Time is brain’ is a widely accepted concept in acute cerebrovascular disease treatment. Efficient and accurate computational framework for hemodynamic parameters estimation can save critical time for thrombolytic therapy. Meanwhile the high level of accumulated radiation dosage due to continuous image acquisition in CT perfusion (CTP) raised concerns on patient safety and public health. However, low-radiation leads to increased noise and artifacts which require more sophisticated and time-consuming algorithms for robust estimation. In this paper, we focus on developing a robust and efficient framework to accurately estimate the perfusion parameters at low radiation dosage. Specifically, we present a tensor total-variation (TTV) technique which fuses the spatial correlation of the vascular structure and the temporal continuation of the blood signal flow. An efficient algorithm is proposed to find the solution with fast convergence and reduced computational complexity. Extensive evaluations are carried out in terms of sensitivity to noise levels, estimation accuracy, contrast preservation, and performed on digital perfusion phantom estimation, as well as in-vivo clinical subjects. Our framework reduces the necessary radiation dose to only 8% of the original level and outperforms the state-of-art algorithms with peak signal-to-noise ratio improved by 32%. It reduces the oscillation in the residue functions, corrects over-estimation of cerebral blood flow (CBF) and under-estimation of mean transit time (MTT), and maintains the distinction between the deficit and normal regions. PMID:25706579

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

PubMed Central

Andreasson, Anders S.I.; Karamanou, Danai M.; Gillespie, Colin S.; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R.; Green, Nicola J.; Borthwick, Lee A.; Clark, Stephen C.; Pauli, Henning; Gould, Kate F.; Corris, Paul A.; Ali, Simi; Dark, John H.

2017-01-01

Abstract OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. PMID:28082471

Cardiac tissue engineering using perfusion bioreactor systems

PubMed Central

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

Comparing kidney perfusion using noncontrast arterial spin labeling MRI and microsphere methods in an interventional swine model.

PubMed

Artz, Nathan S; Wentland, Andrew L; Sadowski, Elizabeth A; Djamali, Arjang; Grist, Thomas M; Seo, Songwon; Fain, Sean B

2011-02-01

The purpose of this study was to assess the ability of a flow-sensitive alternating inversion recovery-arterial spin labeling (FAIR-ASL) technique to track renal perfusion changes during pharmacologic and physiologic alterations in renal blood flow using microspheres as a gold standard. Fluorescent microsphere and FAIR-ASL perfusion were compared in the cortex of the kidney for 11 swine across 4 interventional time points: (1) under baseline conditions, (2) during an acetylcholine and fluid bolus challenge to increase perfusion, (3) initially after switching to isoflurane anesthesia, and (4) after 2 hours of isoflurane anesthesia. In 10 of the 11 swine, a bag of ice was placed on the hilum of 1 kidney at the beginning of isoflurane administration to further reduce perfusion in 1 kidney. Both ASL and microspheres tracked the expected cortical perfusion changes (P < 0.02) across the interventions, including an increase in perfusion during the acetylcholine challenge and decrease during the administration of isoflurane. Both techniques also measured lower cortical perfusion in the iced compared with the non-iced kidneys (P ≤ 0.01). The ASL values were systematically lower compared with microsphere perfusion. Very good correlation (r = 0.81, P < 0.0001) was observed between the techniques, and the relationship appeared linear for perfusion values in the expected physiologic range (microsphere perfusion <550 mL/min/100 g) although ASL values saturated for perfusion >550 mL/min/100 g. Cortical perfusion measured with ASL correlated with microspheres and reliably detected changes in renal perfusion in response to physiologic challenge.

Simulation of plastic surgery and microvascular procedures using perfused fresh human cadavers.

PubMed

Carey, Joseph N; Rommer, Elizabeth; Sheckter, Clifford; Minneti, Michael; Talving, Peep; Wong, Alex K; Garner, Warren; Urata, Mark M

2014-02-01

Surgical simulation models are often limited by their lack of fidelity, which hinders their essential purpose, making a better surgeon. Fresh cadaveric tissue is a superior model of simulation owing to its approximation of live tissue. One major unresolved difference between dead and live tissue is perfusion. Here, we propose a means of enhancing the fidelity of cadaveric simulation through the development of a perfused cadaveric model whereby simulation is further able to approach life-like surgery and teach one of the more technically demanding skills of plastic surgery: microsurgery. Fresh tissue human cadavers were procured according to university protocol. Perfusion was performed via cannulation of large vessels, and arterial and venous pressure was maintained by centrifugal circulation. Skin perfusion was evaluated with incisions in the perfused regions and was evaluated using indocyanine green angiography. Surgical simulations were selected to broadly evaluate applicability to plastic surgical education. Surgical simulation of 38 procedures ranging in complexity from skin excisions to microsurgical cases was performed with high priority given to the accurate simulation of clinical procedures. Flap dissections included perforator flaps, muscle flaps, and fasciocutaneous flaps. Effective perfusion was noted with ICG angiography and notable bleeding vessels. Microsurgical flap transfer was successfully performed. We report the establishment of a high fidelity surgical simulation using a perfused fresh tissue model in a realistic environment akin to the operating room. We anticipate utilization of this model prior to entering the operating room will enhance surgical ability and offer a valuable resource in plastic surgical education. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

PubMed

van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

2016-01-01

Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

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

PubMed

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

2014-04-01

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

Repeated Positron Emission Tomography-Computed Tomography and Perfusion-Computed Tomography Imaging in Rectal Cancer: Fluorodeoxyglucose Uptake Corresponds With Tumor Perfusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janssen, Marco H.M., E-mail: marco.janssen@maastro.nl; Aerts, Hugo J.W.L.; Buijsen, Jeroen

2012-02-01

Purpose: The purpose of this study was to analyze both the intratumoral fluorodeoxyglucose (FDG) uptake and perfusion within rectal tumors before and after hypofractionated radiotherapy. Methods and Materials: Rectal cancer patients, referred for preoperative hypofractionated radiotherapy (RT), underwent FDG-positron emission tomography (PET)-computed tomography (CT) and perfusion-CT (pCT) imaging before the start of hypofractionated RT and at the day of the last RT fraction. The pCT-images were analyzed using the extended Kety model, quantifying tumor perfusion with the pharmacokinetic parameters K{sup trans}, v{sub e}, and v{sub p}. The mean and maximum FDG uptake based on the standardized uptake value (SUV) andmore » transfer constant (K{sup trans}) within the tumor were correlated. Also, the tumor was subdivided into eight subregions and for each subregion the mean and maximum SUVs and K{sup trans} values were assessed and correlated. Furthermore, the mean FDG uptake in voxels presenting with the lowest 25% of perfusion was compared with the FDG uptake in the voxels with the 25% highest perfusion. Results: The mean and maximum K{sup trans} values were positively correlated with the corresponding SUVs ({rho} = 0.596, p = 0.001 and {rho} = 0.779, p < 0.001). Also, positive correlations were found for K{sup trans} values and SUVs within the subregions (mean, {rho} = 0.413, p < 0.001; and max, {rho} = 0.540, p < 0.001). The mean FDG uptake in the 25% highest-perfused tumor regions was significantly higher compared with the 25% lowest-perfused regions (10.6% {+-} 5.1%, p = 0.017). During hypofractionated radiotherapy, stable mean (p = 0.379) and maximum (p = 0.280) FDG uptake levels were found, whereas the mean (p = 0.040) and maximum (p = 0.003) K{sup trans} values were found to significantly increase. Conclusion: Highly perfused rectal tumors presented with higher FDG-uptake levels compared with relatively low perfused tumors. Also, intratumor regions with a

Successful prolonged ex vivo lung perfusion for graft preservation in rats.

PubMed

Noda, Kentaro; Shigemura, Norihisa; Tanaka, Yugo; Bhama, Jay K; D'Cunha, Jonathan; Luketich, James D; Bermudez, Christian A

2014-03-01

Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP. The donor heart-lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4 °C. And then, the heart-lung blocks were flushed retrogradely and warmed up to 37 °C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2, 8% CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37 °C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR). R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation. Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.

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

PubMed

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

2014-10-01

Online and non-invasive quantification of critical tissue engineering (TE) construct quality attributes in TE bioreactors is indispensable for the cost-effective up-scaling and automation of cellular construct manufacturing. However, appropriate monitoring techniques for cellular constructs in bioreactors are still lacking. This study presents a generic and robust approach to determine cell number and metabolic activity of cell-based TE constructs in perfusion bioreactors based on single oxygen sensor data in dynamic perfusion conditions. A data-based mechanistic modeling technique was used that is able to correlate the number of cells within the scaffold (R(2)  = 0.80) and the metabolic activity of the cells (R(2)  = 0.82) to the dynamics of the oxygen response to step changes in the perfusion rate. This generic non-destructive measurement technique is effective for a large range of cells, from as low as 1.0 × 10(5) cells to potentially multiple millions of cells, and can open-up new possibilities for effective bioprocess monitoring. © 2014 Wiley Periodicals, Inc.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.

PubMed

Andreasson, Anders S I; Karamanou, Danai M; Gillespie, Colin S; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R; Green, Nicola J; Borthwick, Lee A; Clark, Stephen C; Pauli, Henning; Gould, Kate F; Corris, Paul A; Ali, Simi; Dark, John H; Fisher, Andrew J

2017-03-01

Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

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

PubMed Central

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

2015-01-01

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

Assessment of foot perfusion in patients with a diabetic foot ulcer.

PubMed

Forsythe, Rachael O; Hinchliffe, Robert J

2016-01-01

Assessment of foot perfusion is a vital step in the management of patients with diabetic foot ulceration, in order to understand the risk of amputation and likelihood of wound healing. Underlying peripheral artery disease is a common finding in patients with foot ulceration and is associated with poor outcomes. Assessment of foot perfusion should therefore focus on identifying the presence of peripheral artery disease and to subsequently estimate the effect this may have on wound healing. Assessment of perfusion can be difficult because of the often complex, diffuse and distal nature of peripheral artery disease in patients with diabetes, as well as poor collateralisation and heavy vascular calcification. Conventional methods of assessing tissue perfusion in the peripheral circulation may be unreliable in patients with diabetes, and it may therefore be difficult to determine the extent to which poor perfusion contributes to foot ulceration. Anatomical data obtained on cross-sectional imaging is important but must be combined with measurements of tissue perfusion (such as transcutaneous oxygen tension) in order to understand the global and regional perfusion deficit present in a patient with diabetic foot ulceration. Ankle-brachial pressure index is routinely used to screen for peripheral artery disease, but its use in patients with diabetes is limited in the presence of neuropathy and medial arterial calcification. Toe pressure index may be more useful because of the relative sparing of pedal arteries from medial calcification but may not always be possible in patients with ulceration. Fluorescence angiography is a non-invasive technique that can provide rapid quantitative information about regional tissue perfusion; capillaroscopy, iontophoresis and hyperspectral imaging may also be useful in assessing physiological perfusion but are not widely available. There may be a future role for specialized perfusion imaging of these patients, including magnetic resonance

Correlation of iodine uptake and perfusion parameters between dual-energy CT imaging and first-pass dual-input perfusion CT in lung cancer.

PubMed

Chen, Xiaoliang; Xu, Yanyan; Duan, Jianghui; Li, Chuandong; Sun, Hongliang; Wang, Wu

2017-07-01

To investigate the potential relationship between perfusion parameters from first-pass dual-input perfusion computed tomography (DI-PCT) and iodine uptake levels estimated from dual-energy CT (DE-CT).The pre-experimental part of this study included a dynamic DE-CT protocol in 15 patients to evaluate peak arterial enhancement of lung cancer based on time-attenuation curves, and the scan time of DE-CT was determined. In the prospective part of the study, 28 lung cancer patients underwent whole-volume perfusion CT and single-source DE-CT using 320-row CT. Pulmonary flow (PF, mL/min/100 mL), aortic flow (AF, mL/min/100 mL), and a perfusion index (PI = PF/[PF + AF]) were automatically generated by in-house commercial software using the dual-input maximum slope method for DI-PCT. For the dual-energy CT data, iodine uptake was estimated by the difference (λ) and the slope (λHU). λ was defined as the difference of CT values between 40 and 70 KeV monochromatic images in lung lesions. λHU was calculated by the following equation: λHU = |λ/(70 - 40)|. The DI-PCT and DE-CT parameters were analyzed by Pearson/Spearman correlation analysis, respectively.All subjects were pathologically proved as lung cancer patients (including 16 squamous cell carcinoma, 8 adenocarcinoma, and 4 small cell lung cancer) by surgery or CT-guided biopsy. Interobserver reproducibility in DI-PCT (PF, AF, PI) and DE-CT (λ, λHU) were relatively good to excellent (intraclass correlation coefficient [ICC]Inter = 0.8726-0.9255, ICCInter = 0.8179-0.8842; ICCInter = 0.8881-0.9177, ICCInter = 0.9820-0.9970, ICCInter = 0.9780-0.9971, respectively). Correlation coefficient between λ and AF, and PF were as follows: 0.589 (P < .01) and 0.383 (P < .05). Correlation coefficient between λHU and AF, and PF were as follows: 0.564 (P < .01) and 0.388 (P < .05).Both the single-source DE-CT and dual-input CT perfusion analysis method can be applied to

Validation of an in vitro 3D bone culture model with perfused and mechanically stressed ceramic scaffold.

PubMed

Bouet, G; Cruel, M; Laurent, C; Vico, L; Malaval, L; Marchat, D

2015-05-15

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.

CT perfusion for determination of pharmacologically mediated blood flow changes in an animal tumor model.

PubMed

Hakimé, Antoine; Peddi, Himaja; Hines-Peralta, Andrew U; Wilcox, Carol J; Kruskal, Jonathan; Lin, Shezhang; de Baere, Thierry; Raptopoulos, Vassilios D; Goldberg, S Nahum

2007-06-01

To prospectively compare single- and multisection computed tomographic (CT) perfusion for tumor blood flow determination in an animal model. All animal protocols and experiments were approved by the institutional animal care and use committee before the study was initiated. R3230 mammary adenocarcinoma was implanted in 11 rats. Tumors (18-20 mm) were scanned with dynamic 16-section CT at baseline and after administration of arsenic trioxide, which is known to cause acute reduction in blood flow. The concentration of arsenic was titrated (0-6 mg of arsenic per kilogram of body weight) to achieve a defined blood flow reduction (0%-75%) from baseline levels at 60 minutes, as determined with correlative laser Doppler flowmetry. The mean blood flow was calculated for each of four 5-mm sections that covered the entire tumor, as well as for the entire tumor after multiple sections were processed. Measurements obtained with both methods were correlated with laser Doppler flowmetry measurements. Interobserver agreement was determined for two blinded radiologists, who calculated the percentage of blood flow reduction for the "most representative" single sections at baseline and after arsenic administration. These results were compared with the interobserver variability of the same radiologists obtained by summing blood flow changes for the entire tumor volume. Overall correlations for acute blood flow reduction were demonstrated between laser Doppler flowmetry and the two CT perfusion approaches (single-section CT, r=0.85 and r(2)=0.73; multisection CT, r=0.93 and r(2)=0.87; pooled data, P=.01). CT perfusion disclosed marked heterogeneity of blood flow, with variations of 36% +/- 13 between adjacent 5-mm sections. Given these marked differences, interobserver agreement was much lower for single-section CT (standard deviation, 0.22) than for multisection CT (standard deviation, 0.10; P=.01). Multisection CT perfusion techniques may provide an accurate and more reproducible

Estimation of dynamic time activity curves from dynamic cardiac SPECT imaging

NASA Astrophysics Data System (ADS)

Hossain, J.; Du, Y.; Links, J.; Rahmim, A.; Karakatsanis, N.; Akhbardeh, A.; Lyons, J.; Frey, E. C.

2015-04-01

Whole-heart coronary flow reserve (CFR) may be useful as an early predictor of cardiovascular disease or heart failure. Here we propose a simple method to extract the time-activity curve, an essential component needed for estimating the CFR, for a small number of compartments in the body, such as normal myocardium, blood pool, and ischemic myocardial regions, from SPECT data acquired with conventional cameras using slow rotation. We evaluated the method using a realistic simulation of 99mTc-teboroxime imaging. Uptake of 99mTc-teboroxime based on data from the literature were modeled. Data were simulated using the anatomically-realistic 3D NCAT phantom and an analytic projection code that realistically models attenuation, scatter, and the collimator-detector response. The proposed method was then applied to estimate time activity curves (TACs) for a set of 3D volumes of interest (VOIs) directly from the projections. We evaluated the accuracy and precision of estimated TACs and studied the effects of the presence of perfusion defects that were and were not modeled in the estimation procedure. The method produced good estimates of the myocardial and blood-pool TACS organ VOIs, with average weighted absolute biases of less than 5% for the myocardium and 10% for the blood pool when the true organ boundaries were known and the activity distributions in the organs were uniform. In the presence of unknown perfusion defects, the myocardial TAC was still estimated well (average weighted absolute bias <10%) when the total reduction in myocardial uptake (product of defect extent and severity) was ≤5%. This indicates that the method was robust to modest model mismatch such as the presence of moderate perfusion defects and uptake nonuniformities. With larger defects where the defect VOI was included in the estimation procedure, the estimated normal myocardial and defect TACs were accurate (average weighted absolute bias ≈5% for a defect with 25% extent and 100% severity).

Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

PubMed

Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

2018-05-01

The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

PubMed

Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

2015-06-15

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

Beam hardening correction in CT myocardial perfusion measurement

NASA Astrophysics Data System (ADS)

So, Aaron; Hsieh, Jiang; Li, Jian-Ying; Lee, Ting-Yim

2009-05-01

This paper presents a method for correcting beam hardening (BH) in cardiac CT perfusion imaging. The proposed algorithm works with reconstructed images instead of projection data. It applies thresholds to separate low (soft tissue) and high (bone and contrast) attenuating material in a CT image. The BH error in each projection is estimated by a polynomial function of the forward projection of the segmented image. The error image is reconstructed by back-projection of the estimated errors. A BH-corrected image is then obtained by subtracting a scaled error image from the original image. Phantoms were designed to simulate the BH artifacts encountered in cardiac CT perfusion studies of humans and animals that are most commonly used in cardiac research. These phantoms were used to investigate whether BH artifacts can be reduced with our approach and to determine the optimal settings, which depend upon the anatomy of the scanned subject, of the correction algorithm for patient and animal studies. The correction algorithm was also applied to correct BH in a clinical study to further demonstrate the effectiveness of our technique.

CT Perfusion of the Liver: Principles and Applications in Oncology

PubMed Central

Kim, Se Hyung; Kamaya, Aya

2014-01-01

With the introduction of molecularly targeted chemotherapeutics, there is an increasing need for defining new response criteria for therapeutic success because use of morphologic imaging alone may not fully assess tumor response. Computed tomographic (CT) perfusion imaging of the liver provides functional information about the microcirculation of normal parenchyma and focal liver lesions and is a promising technique for assessing the efficacy of various anticancer treatments. CT perfusion also shows promising results for diagnosing primary or metastatic tumors, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy. Many of the limitations of early CT perfusion studies performed in the liver, such as limited coverage, motion artifacts, and high radiation dose of CT, are being addressed by recent technical advances. These include a wide area detector with or without volumetric spiral or shuttle modes, motion correction algorithms, and new CT reconstruction technologies such as iterative algorithms. Although several issues related to perfusion imaging—such as paucity of large multicenter trials, limited accessibility of perfusion software, and lack of standardization in methods—remain unsolved, CT perfusion has now reached technical maturity, allowing for its use in assessing tumor vascularity in larger-scale prospective clinical trials. In this review, basic principles, current acquisition protocols, and pharmacokinetic models used for CT perfusion imaging of the liver are described. Various oncologic applications of CT perfusion of the liver are discussed and current challenges, as well as possible solutions, for CT perfusion are presented. © RSNA, 2014 Online supplemental material is available for this article. PMID:25058132

Distributed capillary adiabatic tissue homogeneity model in parametric multi-channel blind AIF estimation using DCE-MRI.

PubMed

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

2016-03-01

One of the main challenges in quantitative dynamic contrast-enhanced (DCE) MRI is estimation of the arterial input function (AIF). Usually, the signal from a single artery (ignoring contrast dispersion, partial volume effects and flow artifacts) or a population average of such signals (also ignoring variability between patients) is used. Multi-channel blind deconvolution is an alternative approach avoiding most of these problems. The AIF is estimated directly from the measured tracer concentration curves in several tissues. This contribution extends the published methods of multi-channel blind deconvolution by applying a more realistic model of the impulse residue function, the distributed capillary adiabatic tissue homogeneity model (DCATH). In addition, an alternative AIF model is used and several AIF-scaling methods are tested. The proposed method is evaluated on synthetic data with respect to the number of tissue regions and to the signal-to-noise ratio. Evaluation on clinical data (renal cell carcinoma patients before and after the beginning of the treatment) gave consistent results. An initial evaluation on clinical data indicates more reliable and less noise sensitive perfusion parameter estimates. Blind multi-channel deconvolution using the DCATH model might be a method of choice for AIF estimation in a clinical setup. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2008-02-01

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

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

PubMed Central

Kelleher, Joanne K.; Rouf, Rosanne; Muoio, Deborah M.; Antoniewicz, Maciek R.

2016-01-01

In many forms of cardiomyopathy, alterations in energy substrate metabolism play a key role in disease pathogenesis. Stable isotope tracing in rodent heart perfusion systems can be used to determine cardiac metabolic fluxes, namely those relative fluxes that contribute to pyruvate, the acetyl-CoA pool, and pyruvate anaplerosis, which are critical to cardiac homeostasis. Methods have previously been developed to interrogate these relative fluxes using isotopomer enrichments of measured metabolites and algebraic equations to determine a predefined metabolic flux model. However, this approach is exquisitely sensitive to measurement error, thus precluding accurate relative flux parameter determination. In this study, we applied a novel mathematical approach to determine relative cardiac metabolic fluxes using 13C-metabolic flux analysis (13C-MFA) aided by multiple tracer experiments and integrated data analysis. Using 13C-MFA, we validated a metabolic network model to explain myocardial energy substrate metabolism. Four different 13C-labeled substrates were queried (i.e., glucose, lactate, pyruvate, and oleate) based on a previously published study. We integrated the analysis of the complete set of isotopomer data gathered from these mouse heart perfusion experiments into a single comprehensive network model that delineates substrate contributions to both pyruvate and acetyl-CoA pools at a greater resolution than that offered by traditional methods using algebraic equations. To our knowledge, this is the first rigorous application of 13C-MFA to interrogate data from multiple tracer experiments in the perfused heart. We anticipate that this approach can be used widely to study energy substrate metabolism in this and other similar biological systems. PMID:27496880

Cancer cells growing on perfused 3D collagen model produced higher reactive oxygen species level and were more resistant to cisplatin compared to the 2D model.

PubMed

Liu, Qingxi; Zhang, Zijiang; Liu, Yupeng; Cui, Zhanfeng; Zhang, Tongcun; Li, Zhaohui; Ma, Wenjian

2018-03-01

Three-dimensional (3D) collagen scaffold models, due to their ability to mimic the tissue and organ structure in vivo, have received increasing interest in drug discovery and toxicity evaluation. In this study, we developed a perfused 3D model and studied cellular response to cytotoxic drugs in comparison with traditional 2D cell cultures as evaluated by cancer drug cisplatin. Cancer cells grown in perfused 3D environments showed increased levels of reactive oxygen species (ROS) production compared to the 2D culture. As determined by growth analysis, cells in the 3D culture, after forming a spheroid, were more resistant to the cancer drug cisplatin compared to that of the 2D cell culture. In addition, 3D culturing cells showed elevated level of ROS, indicating a physiological change or the formation of a microenvironment that resembles tumor cells in vivo. These data revealed that cellular response to drugs for cells growing in 3D environments are dramatically different from that of 2D cultured cells. Thus, the perfused 3D collagen scaffold model we report here might be a potentially very useful tool for drug analysis.

Intra-Aortic Balloon Pump Malposition Reduces Visceral Artery Perfusion in an Acute Animal Model.

PubMed

Vondran, Maximilian; Rastan, Ardawan J; Tillmann, Eugen; Seeburger, Jörg; Schröter, Thomas; Dhein, Stefan; Bakhtiary, Farhad; Mohr, Friedrich-Wilhelm

2016-04-01

Visceral artery perfusion can be potentially affected by intra-aortic balloon pump (IABP) catheters. We utilized an animal model to quantify the acute impact of a low balloon position on mesenteric artery perfusion. In six pigs (78 ± 7 kg), a 30-cc IABP was placed in the descending aorta in a transfemoral procedure. The celiac artery (CA) and the cranial mesenteric artery (CMA) were surgically dissected. Transit time blood flow was measured for (i) baseline, (ii) 1:1 augmentation with the balloon proximal to the visceral arteries, and (iii) 1:1 augmentation with the balloon covering the visceral arteries. Blood flow in the CMA and CA was reduced by 17 and 24%, respectively, when the balloon compromised visceral arteries compared with a position above the visceral arteries (flow in mL/min: CMA: (i) 1281 ± 512, (ii) 1389 ± 287, (iii) 1064 ± 276, P < 0.05 for 3 vs. 1 and 3 vs. 2; CA: (i) 885 ± 370, (ii) 819 ± 297, (iii) 673 ± 315; P < 0.05 for 3 vs. 1). The covering of visceral arteries by an IABP balloon causes a significant reduction of visceral artery perfusion; thus, the positioning of this device during implantation is critical for obtaining a satisfactory outcome. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Correlation of quantitative dual-energy computed tomography iodine maps and abdominal computed tomography perfusion measurements: are single-acquisition dual-energy computed tomography iodine maps more than a reduced-dose surrogate of conventional computed tomography perfusion?

PubMed

Stiller, Wolfram; Skornitzke, Stephan; Fritz, Franziska; Klauss, Miriam; Hansen, Jens; Pahn, Gregor; Grenacher, Lars; Kauczor, Hans-Ulrich

2015-10-01

Study objectives were the quantitative evaluation of whether conventional abdominal computed tomography (CT) perfusion measurements mathematically correlate with quantitative single-acquisition dual-energy CT (DECT) iodine concentration maps, the determination of the optimum time of acquisition for achieving maximum correlation, and the estimation of the potential for radiation exposure reduction when replacing conventional CT perfusion by single-acquisition DECT iodine concentration maps. Dual-energy CT perfusion sequences were dynamically acquired over 51 seconds (34 acquisitions every 1.5 seconds) in 24 patients with histologically verified pancreatic carcinoma using dual-source DECT at tube potentials of 80 kVp and 140 kVp. Using software developed in-house, perfusion maps were calculated from 80-kVp image series using the maximum slope model after deformable motion correction. In addition, quantitative iodine maps were calculated for each of the 34 DECT acquisitions per patient. Within a manual segmentation of the pancreas, voxel-by-voxel correlation between the perfusion map and each of the iodine maps was calculated for each patient to determine the optimum time of acquisition topt defined as the acquisition time of the iodine map with the highest correlation coefficient. Subsequently, regions of interest were placed inside the tumor and inside healthy pancreatic tissue, and correlation between mean perfusion values and mean iodine concentrations within these regions of interest at topt was calculated for the patient sample. The mean (SD) topt was 31.7 (5.4) seconds after the start of contrast agent injection. The mean (SD) perfusion values for healthy pancreatic and tumor tissues were 67.8 (26.7) mL per 100 mL/min and 43.7 (32.2) mL per 100 mL/min, respectively. At topt, the mean (SD) iodine concentrations were 2.07 (0.71) mg/mL in healthy pancreatic and 1.69 (0.98) mg/mL in tumor tissue, respectively. Overall, the correlation between perfusion values and

Distribution of perfusion.

PubMed

Glenny, Robb; Robertson, H Thomas

2011-01-01

Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.

Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

NASA Astrophysics Data System (ADS)

Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

2016-10-01

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

Translocation of silver nanoparticles in the ex vivo human placenta perfusion model characterized by single particle ICP-MS.

PubMed

Vidmar, Janja; Loeschner, Katrin; Correia, Manuel; Larsen, Erik H; Manser, Pius; Wichser, Adrian; Boodhia, Kailen; Al-Ahmady, Zahraa S; Ruiz, Jaimé; Astruc, Didier; Buerki-Thurnherr, Tina

2018-06-15

With the extensive use of silver nanoparticles (AgNPs) in various consumer products their potential toxicity is of great concern especially for highly sensitive population groups such as pregnant women and even the developing fetus. To understand if AgNPs are taken up and cross the human placenta, we studied their translocation and accumulation in the human ex vivo placenta perfusion model by single particle ICP-MS (spICP-MS). The impact of different surface modifications on placental transfer was assessed by AgNPs with two different modifications: polyethylene glycol (AgPEG NPs) and sodium carboxylate (AgCOONa NPs). AgNPs and ionic Ag were detected in the fetal circulation in low but not negligible amounts. Slightly higher Ag translocation across the placental barrier for perfusion with AgPEG NPs and higher AgNP accumulation in placental tissue for perfusion with AgCOONa NPs were observed. Since these AgNPs are soluble in water, we tried to distinguish between the translocation of dissolved and particulate Ag. Perfusion with AgNO3 revealed the formation of Ag containing NPs in both circulations over time, of which the amount and their size in the fetal circulation were comparable to those from perfusion experiments with both AgNP types. Although we were not able to clarify whether intact AgNPs and/or Ag precipitates from dissolved Ag cross the placental barrier, our study highlights that uptake of Ag ions and/or dissolution of AgNPs in the tissue followed by re-precipitation in the fetal circulation needs to be considered as an important pathway in studies of AgNP translocation across biological barriers.

Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival.

PubMed

Sevinc, M; Stamp, S; Ling, J; Carter, N; Talbot, D; Sheerin, N

2016-12-01

Ex vivo perfusion is used in our unit for kidneys donated after cardiac death (DCD). Perfusion flow index (PFI), resistance, and perfusate glutathione S-transferase (GST) can be measured to assess graft viability. We assessed whether measurements taken during perfusion could predict long-term outcome after transplantation. All DCD kidney transplants performed from 2002 to 2014 were included in this study. The exclusion criteria were: incomplete data, kidneys not machine perfused, kidneys perfused in continuous mode, and dual transplantation. There were 155 kidney transplantations included in the final analysis. Demographic data, ischemia times, donor hypertension, graft function, survival and machine perfusion parameters after 3 hours were analyzed. Each perfusion parameter was divided into 3 groups as high, medium, and low. Estimated glomerular filtration rate was calculated at 12 months and then yearly after transplantation. There was a significant association between graft survival and PFI and GST (P values, .020 and .022, respectively). PFI was the only independent parameter to predict graft survival. A low PFI during ex vivo hypothermic perfusion is associated with inferior graft survival after DCD kidney transplantation. We propose that PFI is a measure of the health of the graft vasculature and that a low PFI indicates vascular disease and therefore predicts a worse long-term outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model.

PubMed

Tanen, David A; Danish, David C; Clark, Richard F

2003-03-01

saline solution control from time 1 hour to time 8 hours, as determined by means of Kaplan-Meier estimation and the log-rank test (P =.029). FabAV limits the decrease in perfusion pressures in the anterior leg compartment after intramuscular crotaline venom injection in swine compared with saline solution. In addition, FabAV might prevent the development of coagulopathy and increase survival time in this model.

Renal MR angiography and perfusion in the pig using hyperpolarized water.

PubMed

Wigh Lipsø, Kasper; Hansen, Esben Søvsø Szocska; Tougaard, Rasmus Stilling; Laustsen, Christoffer; Ardenkjaer-Larsen, Jan Henrik

2017-09-01

To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. Protons dissolved in deuterium oxide (D 2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. A liquid state polarization of 5.3 ± 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T 1 of 24 ± 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 ± 123 mL/100 mL/min. Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med 78:1131-1135, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Comparison of LDPI to SPECT perfusion imaging using (99m)Tc-sestamibi and (99m)Tc-pyrophosphate in a murine ischemic hind limb model of neovascularization.

PubMed

Hendrikx, Geert; Vries, Mark H; Bauwens, Matthias; De Saint-Hubert, Marijke; Wagenaar, Allard; Guillaume, Joël; Boonen, Levinia; Post, Mark J; Mottaghy, Felix M

2016-12-01

We aimed to determine the accuracy of laser Doppler perfusion imaging (LDPI) in an animal model for hind limb ischemia. We used a murine (C57Bl/6 mice) ischemic hind limb model in which we compared LDPI with the clinically used (99m)Tc-sestamibi SPECT perfusion imaging (n = 7). In addition, we used the SPECT tracer (99m)Tc-pyrophosphate ((99m)Tc-PyP) to image muscular damage (n = 6). LDPI indicated a quick and prominent decrease in perfusion immediately after ligation, subsequently recovering to 21.9 and 25.2 % 14 days later in the (99m)Tc-sestamibi and (99m)Tc-PyP group, respectively. (99m)Tc-sestamibi SPECT scans also showed a quick decrease in perfusion. However, nearly full recovery was reached 7 days post ligation. Muscular damage, indicated by the uptake of (99m)Tc-PyP, was highest at day 3 and recovered to baseline levels at day 14 post ligation. Postmortem histology supported these findings, as a significantly increased collateral diameter was found 7 and 14 days after ligation and peak macrophage infiltration and TUNEL positivity was found on day 3 after ligation. Here, we indicate that LDPI strongly underestimates perfusion recovery in a hind limb model for profound ischemia.

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

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

PubMed

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

2016-10-01

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

Feasibility study on retinal vascular bypass surgery in isolated arterially perfused caprine eye model

PubMed Central

Chen, Y; Wu, W; Zhang, X; Fan, W; Shen, L

2011-01-01

Purpose To investigate the feasibility of bypassing occluded segments of retinal venous main vessels in isolated, arterially perfused caprine eyes via the closed-sky vitrectomy approach using keratoprosthesis. Methods Isolated caprine eyes were used in this study. For each eye, the retinal vessel was perfused by Krebs solution via ophthalmic artery, and pars plana vitrectomy was performed using temporary keratoprosthesis. All retinal micro-vascular maneuvers were performed in a closed-sky eyeball. The main retinal vein was blocked by endodiathermy at the site of the vessel's first branching. Two openings, several millimeters apart, were created by vascular punctures in both the main vein and its branch vein wall straddling the induced occluded segment. Catheterization was achieved using a flexible polyimide tube, with each end inserted into the vessel wall opening. A sealed connection between the vessel and the tube was obtained by endodiathermy. Bypass of the occluded retinal vein segment was thus achieved, and the patency of this vascular bypass was confirmed by intravascular staining. Results Puncturing, catheterization, and endodiathermy were viable by closed-sky approach using keratoprosthesis. Bypassing of the occluded retinal main vein segment was accomplished with the combination of these maneuvers. Good results were obtained in 23 of 38 (60%) caprine eyes. Conclusions This study demonstrated that bypassing the occluded segment of retinal main vein can be successfully performed in a closed-sky eyeball model of isolated, arterially perfused caprine eye. This early work indicated that the more advanced retinal vascular bypass surgery in in vivo eye may be feasible in the future. PMID:21921946

Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

PubMed Central

Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

2016-01-01

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand. PMID:27725720

Finite-element simulation of blood perfusion in muscle tissue during compression and sustained contraction.

PubMed

Vankan, W J; Huyghe, J M; Slaaf, D W; van Donkelaar, C C; Drost, M R; Janssen, J D; Huson, A

1997-09-01

Mechanical interaction between tissue stress and blood perfusion in skeletal muscles plays an important role in blood flow impediment during sustained contraction. The exact mechanism of this interaction is not clear, and experimental investigation of this mechanism is difficult. We developed a finite-element model of the mechanical behavior of blood-perfused muscle tissue, which accounts for mechanical blood-tissue interaction in maximally vasodilated vasculature. Verification of the model was performed by comparing finite-element results of blood pressure and flow with experimental measurements in a muscle that is subject to well-controlled mechanical loading conditions. In addition, we performed simulations of blood perfusion during tetanic, isometric contraction and maximal vasodilation in a simplified, two-dimensional finite-element model of a rat calf muscle. A vascular waterfall in the venous compartment was identified as the main cause for blood flow impediment both in the experiment and in the finite-element simulations. The validated finite-element model offers possibilities for detailed analysis of blood perfusion in three-dimensional muscle models under complicated loading conditions.

DiI Perfusion as a Method for Vascular Visualization in Ambystoma mexicanum.

PubMed

Saltman, Anna J; Barakat, May; Bryant, Donald M; Brodovskaya, Anastasia; Whited, Jessica L

2017-06-16

Perfusion techniques have been used for centuries to visualize the circulation of tissues. Axolotl (Ambystoma mexicanum) is a species of salamander that has emerged as an essential model for regeneration studies. Little is known about how revascularization occurs in the context of regeneration in these animals. Here we report a simple method for visualization of the vasculature in axolotl via perfusion of 1,1'-Dioctadecy-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). DiI is a lipophilic carbocyanine dye that inserts into the plasma membrane of endothelial cells instantaneously. Perfusion is done using a peristaltic pump such that DiI enters the circulation through the aorta. During perfusion, dye flows through the axolotl's blood vessels and incorporates into the lipid bilayer of vascular endothelial cells upon contact. The perfusion procedure takes approximately one hour for an eight-inch axolotl. Immediately after perfusion with DiI, the axolotl can be visualized with a confocal fluorescent microscope. The DiI emits light in the red-orange range when excited with a green fluorescent filter. This DiI perfusion procedure can be used to visualize the vascular structure of axolotls or to demonstrate patterns of revascularization in regenerating tissues.

Myocardial perfusion imaging with PET

PubMed Central

Nakazato, Ryo; Berman, Daniel S; Alexanderson, Erick; Slomka, Piotr

2013-01-01

PET-myocardial perfusion imaging (MPI) allows accurate measurement of myocardial perfusion, absolute myocardial blood flow and function at stress and rest in a single study session performed in approximately 30 min. Various PET tracers are available for MPI, and rubidium-82 or nitrogen-13-ammonia is most commonly used. In addition, a new fluorine-18-based PET-MPI tracer is currently being evaluated. Relative quantification of PET perfusion images shows very high diagnostic accuracy for detection of obstructive coronary artery disease. Dynamic myocardial blood flow analysis has demonstrated additional prognostic value beyond relative perfusion imaging. Patient radiation dose can be reduced and image quality can be improved with latest advances in PET/CT equipment. Simultaneous assessment of both anatomy and perfusion by hybrid PET/CT can result in improved diagnostic accuracy. Compared with SPECT-MPI, PET-MPI provides higher diagnostic accuracy, using lower radiation doses during a shorter examination time period for the detection of coronary artery disease. PMID:23671459

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, T; Boone, J; Kent, M

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

Effects of internal electrode cooling on irreversible electroporation using a perfused organ model.

PubMed

O'Brien, Timothy J; Bonakdar, Mohammad; Bhonsle, Suyashree; Neal, Robert E; Aardema, Charles H; Robertson, John L; Goldberg, S Nahum; Davalos, Rafael V

2018-05-28

This study evaluates the effects of active electrode cooling, via internal fluid circulation, on the irreversible electroporation (IRE) lesion, deployed electric current and temperature changes using a perfused porcine liver model. A bipolar electrode delivered IRE electric pulses with or without activation of internal cooling to nine porcine mechanically perfused livers. Pulse schemes included a constant voltage, and a preconditioned delivery combined with an arc-mitigation algorithm. After treatment, organs were dissected, and treatment zones were stained using triphenyl-tetrazolium chloride (TTC) to demonstrate viability. Thirty-nine treatments were performed with an internally cooled applicator and 21 with a non-cooled applicator. For the constant voltage scenario, the average final electrical current measured was 26.37 and 29.20 A for the cooled and uncooled electrodes respectively ([Formula: see text]). The average final temperature measured was 33.01 and 42.43 °C for the cooled and uncooled electrodes respectively ([Formula: see text]). The average measured ablations (fixed lesion) were 3.88-by-2.08 cm and 3.86-by-2.12 cm for the cooled and uncooled electrode respectively ([Formula: see text], [Formula: see text]). Similarly, the preconditioned/arc-mitigation scenario yielded an average final electrical current measurement of a 41.07 and 47.20 A for the cooled and uncooled electrodes respectively ([Formula: see text]). The average final temperature measured was 34.93 and 44.90 °C for the cooled and uncooled electrodes respectively ([Formula: see text]). The average measured ablations (fixed lesion) were 3.67-by-2.27 cm and 3.58-by-2.09 cm for the cooled and uncooled applicators ([Formula: see text]). The internally-cooled bipolar applicator offers advantages that could improve clinical outcomes. Thermally mitigating internal perfusion technology reduced tissue temperatures and electric current while maintaining similar lesion sizes.

Monitoring peripheral perfusion and microcirculation.

PubMed

Dubin, Arnaldo; Henriquez, Elizabeth; Hernández, Glenn

2018-06-01

Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation. Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time. Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.

Ex-vivo machine perfusion for kidney preservation.

PubMed

Hamar, Matyas; Selzner, Markus

2018-06-01

Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation. Keeping kidney grafts functionally and metabolically active during the preservation period offers a unique chance for viability assessment, reconditioning, and organ repair. Normothermic ex-vivo kidney perfusion has been recently translated into clinical practice. Preclinical results suggest that prolonged warm perfusion appears superior than a brief end-ischemic reconditioning in terms of renal function and injury. An established standardized protocol for continuous warm perfusion is still not available for human grafts. Ex-vivo machine perfusion represents a superior organ preservation method over static cold storage. There is still an urgent need for the optimization of the perfusion fluid and machine technology and to identify the optimal indication in kidney transplantation. Recent research is focusing on graft assessment and therapeutic strategies.

Cochlear perfusion with a viscous fluid.

PubMed

Wang, Yi; Olson, Elizabeth S

2016-07-01

The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawn from basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner's membrane (RM), while in cochleae perfused with 0.125% and 0.25% HA RM was torn. Thus, the CAP threshold elevation was likely due to the broken RM, likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed, perhaps due to the presence and

Cochlear perfusion with a viscous fluid

PubMed Central

Wang, Yi; Olson, Elizabeth S.

2016-01-01

The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawnfrom basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner’s membrane, while in cochleae perfused with 0.125% and 0.25% HA Reissner’s membrane (RM) was torn. Thus, the CAP threshold elevation was likely due to the broken of RM, which likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed

Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liss, Adam L., E-mail: adamliss68@gmail.com; Marsh, Robin B.; Kapadia, Nirav S.

Purpose: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial. Methods and Materials: As part of an institutional review board–approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanningmore » before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy. Results: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001). Conclusions: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective

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

PubMed

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

2008-11-01

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

Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

NASA Astrophysics Data System (ADS)

Ogami, M.; Kulkarni, R.; Wang, H.; Reif, R.; Wang, R. K.

2014-08-01

We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.

Developing a Benchmarking Process in Perfusion: A Report of the Perfusion Downunder Collaboration

PubMed Central

Baker, Robert A.; Newland, Richard F.; Fenton, Carmel; McDonald, Michael; Willcox, Timothy W.; Merry, Alan F.

2012-01-01

Abstract: Improving and understanding clinical practice is an appropriate goal for the perfusion community. The Perfusion Downunder Collaboration has established a multi-center perfusion focused database aimed at achieving these goals through the development of quantitative quality indicators for clinical improvement through benchmarking. Data were collected using the Perfusion Downunder Collaboration database from procedures performed in eight Australian and New Zealand cardiac centers between March 2007 and February 2011. At the Perfusion Downunder Meeting in 2010, it was agreed by consensus, to report quality indicators (QI) for glucose level, arterial outlet temperature, and pCO2 management during cardiopulmonary bypass. The values chosen for each QI were: blood glucose ≥4 mmol/L and ≤10 mmol/L; arterial outlet temperature ≤37°C; and arterial blood gas pCO2 ≥ 35 and ≤45 mmHg. The QI data were used to derive benchmarks using the Achievable Benchmark of Care (ABC™) methodology to identify the incidence of QIs at the best performing centers. Five thousand four hundred and sixty-five procedures were evaluated to derive QI and benchmark data. The incidence of the blood glucose QI ranged from 37–96% of procedures, with a benchmark value of 90%. The arterial outlet temperature QI occurred in 16–98% of procedures with the benchmark of 94%; while the arterial pCO2 QI occurred in 21–91%, with the benchmark value of 80%. We have derived QIs and benchmark calculations for the management of several key aspects of cardiopulmonary bypass to provide a platform for improving the quality of perfusion practice. PMID:22730861

Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model.

PubMed

Hosgood, Sarah A; Moore, Tom; Kleverlaan, Theresa; Adams, Tom; Nicholson, Michael L

2017-10-25

Ex-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system. Porcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit. Pairs of kidneys were randomised to either control (n = 5) or reperfusion with a Cytosorb adsorber (n = 5) integrated into the circuit. Tissue, blood and urine samples were taken for the measurement of inflammation and renal function. Baseline levels of cytokines (IL-6, TNFα, IL-8, IL-10, IL-1β, IL-1α) were similar between groups. Levels of IL-6 and IL-8 in the perfusate significantly increased during reperfusion in the control group but not in the Cytosorb group (P = 0.023, 0.049). Levels of the other cytokines were numerically lower in the Cytosorb group; however, this did not reach statistical significance. The mean renal blood flow (RBF) was significantly higher in the Cytosorb group (162 ± 53 vs. 120 ± 35 mL/min/100 g; P = 0.022). Perfusate levels of prostaglandin E2 were significantly lower in the Cytosorb group (642 ± 762 vs. 3258 ± 980 pg/mL; P = 0.0001). Levels of prostacyclin were significantly lower in the Cytosorb group at 1, 3 and 6 h of reperfusion (P = 0.008, 0.003, 0.0002). Levels of thromboxane were also significantly lower in the Cytosorb group throughout reperfusion (P = 0.005). Haemoadsorption had no effect on creatinine clearance (P = 0.109). Haemoadsorption can reduce the inflammatory response and improve renal blood flow during perfusion. Nonetheless, in this model haemoadsorption had no influence on renal function and this may relate to the broad-spectrum action of the Cytosorb adsorber that also removes potentially important anti

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

PubMed

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

2016-12-01

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

Recombinant antibody production by perfusion cultures of rCHO cells in a depth filter perfusion system.

PubMed

Lee, Joon Chul; Chang, Ho Nam; Oh, Duk Jae

2005-01-01

Recombinant Chinese hamster ovary cells, producing recombinant antibody against the human platelet, were cultivated in a depth filter perfusion system (DFPS). When perfusion cultures with working volume of 1 L were operated at perfusion rates of 5/d and 6/d, volumetric antibody productivities reached values 28 and 34 times higher than that of batch suspension culture in Erlenmeyer flasks and 43 and 53 times higher than that of batch culture in a controlled stirred tank reactor, respectively. Perfusion cultures in the DFPS showed stable antibody production over the whole culture period of up to 20 days. In the DFPS, inoculated cells in suspension were entrapped in a few hours within the depth filter matrix by medium circulation and retained there until the void space of the filter matrix was saturated by the cultured cells. After cells in the depth filter matrix reached saturation, overgrown viable cells at a perfusion rate of 5/d or 6/d were continuously collected into waste medium at a density of 2-4 x 10(5) cells/mL, which resulted in stable operation at high perfusion rates, maintaining values of process parameters such as glucose/lactate concentration, pH, and dissolved oxygen concentration. Because the DFPS overcomes most drawbacks observed with conventional perfusion systems, it is preferable to be used as a key culture system to produce monoclonal antibody stably for a long culture period.

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

PubMed Central

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

2015-01-01

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

NASA Software Cost Estimation Model: An Analogy Based Estimation Model

NASA Technical Reports Server (NTRS)

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

2015-01-01

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

Multiparametric Monitoring of Early Response to Antiangiogenic Therapy: A Sequential Perfusion CT and PET/CT Study in a Rabbit VX2 Tumor Model

PubMed Central

Lee, Hyun-Ju; Lee, Kyung Won; Lee, Hak Jong; Lee, Won Woo

2014-01-01

Objectives. To perform dual analysis of tumor perfusion and glucose metabolism using perfusion CT and FDG-PET/CT for the purpose of monitoring the early response to bevacizumab therapy in rabbit VX2 tumor models and to assess added value of FDG-PET to perfusion CT. Methods. Twenty-four VX2 carcinoma tumors implanted in bilateral back muscles of 12 rabbits were evaluated. Serial concurrent perfusion CT and FDG-PET/CT were performed before and 3, 7, and 14 days after bevacizumab therapy (treatment group) or saline infusion (control group). Perfusion CT was analyzed to calculate blood flow (BF), blood volume (BV), and permeability surface area product (PS); FDG-PET was analyzed to calculate SUVmax, SUVmean, total lesion glycolysis (TLG), entropy, and homogeneity. The flow-metabolic ratio (FMR) was also calculated and immunohistochemical analysis of microvessel density (MVD) was performed. Results. On day 14, BF and BV in the treatment group were significantly lower than in the control group. There were no significant differences in all FDG-PET-derived parameters between both groups. In the treatment group, FMR prominently decreased after therapy and was positively correlated with MVD. Conclusions. In VX2 tumors, FMR could provide further insight into the early antiangiogenic effect reflecting a mismatch in intratumor blood flow and metabolism. PMID:25383376

Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization

PubMed Central

Johnson, Carmen Gacchina; Sharma, Karun V.; Levy, Elliot B.; Woods, David L.; Morris, Aaron H.; Bacher, John D.; Lewis, Andrew L.; Wood, Bradford J.; Dreher, Matthew R.

2015-01-01

Purpose To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Materials and Methods Rabbit Vx2 liver tumors were embolized with 100–300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3–5 per group; 18 total). Results Mean microvascular density was 70 vessels/mm2 ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31+ structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Conclusions Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy. PMID:26321051

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

PubMed

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

2017-09-01

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

Evaluation of Rigid-Body Motion Compensation in Cardiac Perfusion SPECT Employing Polar-Map Quantification

PubMed Central

Pretorius, P. Hendrik; Johnson, Karen L.; King, Michael A.

2016-01-01

We have recently been successful in the development and testing of rigid-body motion tracking, estimation and compensation for cardiac perfusion SPECT based on a visual tracking system (VTS). The goal of this study was to evaluate in patients the effectiveness of our rigid-body motion compensation strategy. Sixty-four patient volunteers were asked to remain motionless or execute some predefined body motion during an additional second stress perfusion acquisition. Acquisitions were performed using the standard clinical protocol with 64 projections acquired through 180 degrees. All data were reconstructed with an ordered-subsets expectation-maximization (OSEM) algorithm using 4 projections per subset and 5 iterations. All physical degradation factors were addressed (attenuation, scatter, and distance dependent resolution), while a 3-dimensional Gaussian rotator was used during reconstruction to correct for six-degree-of-freedom (6-DOF) rigid-body motion estimated by the VTS. Polar map quantification was employed to evaluate compensation techniques. In 54.7% of the uncorrected second stress studies there was a statistically significant difference in the polar maps, and in 45.3% this made a difference in the interpretation of segmental perfusion. Motion correction reduced the impact of motion such that with it 32.8 % of the polar maps were statistically significantly different, and in 14.1% this difference changed the interpretation of segmental perfusion. The improvement shown in polar map quantitation translated to visually improved uniformity of the SPECT slices. PMID:28042170

A historical perspective on the development of modern concepts of tissue perfusion: prehistory to the twentieth century.

PubMed

Ashby, Nathan; Squiers, Joshua

2014-09-01

The historical development of the concept of perfusion is traced, with particular focus on the development of the modern clinical concepts of perfusion through the fields of anatomy, physiology, and biochemistry. This article reviews many of the significant contributors to the changing ideas of perfusion up through the twentieth century that have influenced the modern physiologic circulatory and metabolic models. The developments outlined have provided the modern model of perfusion, linking the cardiopulmonary circulation, tissue oxygen utilization and carbon dioxide production, food intake, tissue waste production and elimination, and ultimately the production and utilization of ATP in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence of ECG changes during adenosine stress and its association with perfusion defect on myocardial perfusion scintigraphy.

PubMed

Taywade, Sameer K; Ramaiah, Vijayaraghavan L; Basavaraja, Harish; Venkatasubramaniam, Parameswaran R; Selvakumar, Job

2017-04-01

Myocardial perfusion scintigraphy (MPS) is a valuable, noninvasive imaging modality in the evaluation of patients with coronary artery disease. Adenosine stress may occasionally be associated with ECG changes. This study evaluated the strength of association between adenosine stress-related ECG changes and perfusion defects on Tc-MPS. 117 (mean age: 61.25±9.27 years; sex: men 87, women 30) patients with known/suspected coronary artery disease underwent adenosine stress MPS. ECG was monitored continuously during adenosine stress for ST-depression. On the basis of the summed difference score, reversible perfusion defects were categorized as follows: normal: less than 4, mild: 4-8, moderate: 9-13, and severe: more than 13. ST-depression was observed in 27/117 (23.1%) and reversible perfusion defects were observed in 18/27 (66.66%) patients. 2/27, 6/27, and 10/27 patients had mild, moderate, and severe ischemia, respectively. 9/27 patients had normal perfusion. ECG changes and perfusion defects showed a moderate strength of association (correlation coefficient r=0.35, P=0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of ECG findings for prediction of ischemia were 35.29, 86.36, 67.67, and 63.33%, respectively. ECG changes during adenosine stress are not uncommon. It shows a moderate strength of association with reversible perfusion defects. ECG changes during adenosine merit critical evaluation of MPS findings.

Job Analysis and Student Assessment Tool: Perfusion Education Clinical Preceptor

PubMed Central

Riley, Jeffrey B.

2007-01-01

Abstract: The perfusion education system centers on the cardiac surgery operating room and the perfusionist teacher who serves as a preceptor for the perfusion student. One method to improve the quality of perfusion education is to create a valid method for perfusion students to give feedback to clinical teachers. The preceptor job analysis consisted of a literature review and interviews with preceptors to list their critical tasks, critical incidents, and cognitive and behavioral competencies. Behaviorally anchored rating traits associated with the preceptors’ tasks were identified. Students voted to validate the instrument items. The perfusion instructor rating instrument with a 0–4, “very weak” to “very strong” Likert rating scale was used. The five preceptor traits for student evaluation of clinical instruction (SECI) are as follows: The clinical instructor (1) encourages self-learning, (2) encourages clinical reasoning, (3) meets student’s learning needs, (4) gives continuous feedback, and (5) represents a good role model. Scores from 430 student–preceptor relationships for 28 students rotating at 24 affiliate institutions with 134 clinical instructors were evaluated. The mean overall good preceptor average (GPA) was 3.45 ± 0.76 and was skewed to the left, ranging from 0.0 to 4.0 (median = 3.8). Only 21 of the SECI relationships earned a GPA <2.0. Analyzing the role of the clinical instructor and performing SECI are methods to provide valid information to improve the quality of a perfusion education program. PMID:17972453

Job analysis and student assessment tool: perfusion education clinical preceptor.

PubMed

Riley, Jeffrey B

2007-09-01

The perfusion education system centers on the cardiac surgery operating room and the perfusionist teacher who serves as a preceptor for the perfusion student. One method to improve the quality of perfusion education is to create a valid method for perfusion students to give feedback to clinical teachers. The preceptor job analysis consisted of a literature review and interviews with preceptors to list their critical tasks, critical incidents, and cognitive and behavioral competencies. Behaviorally anchored rating traits associated with the preceptors' tasks were identified. Students voted to validate the instrument items. The perfusion instructor rating instrument with a 0-4, "very weak" to "very strong" Likert rating scale was used. The five preceptor traits for student evaluation of clinical instruction (SECI) are as follows: The clinical instructor (1) encourages self-learning, (2) encourages clinical reasoning, (3) meets student's learning needs, (4) gives continuous feedback, and (5) represents a good role model. Scores from 430 student-preceptor relationships for 28 students rotating at 24 affiliate institutions with 134 clinical instructors were evaluated. The mean overall good preceptor average (GPA) was 3.45 +/- 0.76 and was skewed to the left, ranging from 0.0 to 4.0 (median = 3.8). Only 21 of the SECI relationships earned a GPA < 2.0. Analyzing the role of the clinical instructor and performing SECI are methods to provide valid information to improve the quality of a perfusion education program.

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

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

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

PubMed

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

2016-12-01

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

Computational fluid model incorporating liver metabolic activities in perfusion bioreactor.

PubMed

Hsu, Myat Noe; Tan, Guo-Dong Sean; Tania, Marshella; Birgersson, Erik; Leo, Hwa Liang

2014-05-01

The importance of in vitro hepatotoxicity testing during early stages of drug development in the pharmaceutical industry demands effective bioreactor models with optimized conditions. While perfusion bioreactors have been proven to enhance mass transfer and liver specific functions over a long period of culture, the flow-induced shear stress has less desirable effects on the hepatocytes liver-specific functions. In this paper, a two-dimensional human liver hepatocellular carcinoma (HepG2) cell culture flow model, under a specified flow rate of 0.03 mL/min, was investigated. Besides computing the distribution of shear stresses acting on the surface of the cell culture, our numerical model also investigated the cell culture metabolic functions such as the oxygen consumption, glucose consumption, glutamine consumption, and ammonia production to provide a fuller analysis of the interaction among the various metabolites within the cell culture. The computed albumin production of our 2D flow model was verified by the experimental HepG2 culture results obtained over 3 days of culture. The results showed good agreement between our experimental data and numerical predictions with corresponding cumulative albumin production of 2.9 × 10(-5) and 3.0 × 10(-5)  mol/m(3) , respectively. The results are of importance in making rational design choices for development of future bioreactors with more complex geometries. © 2013 Wiley Periodicals, Inc.

Time-resolved perfusion imaging at the angiography suite: preclinical comparison of a new flat-detector application to computed tomography perfusion.

PubMed

Jürgens, Julian H W; Schulz, Nadine; Wybranski, Christian; Seidensticker, Max; Streit, Sebastian; Brauner, Jan; Wohlgemuth, Walter A; Deuerling-Zheng, Yu; Ricke, Jens; Dudeck, Oliver

2015-02-01

The objective of this study was to compare the parameter maps of a new flat-panel detector application for time-resolved perfusion imaging in the angiography room (FD-CTP) with computed tomography perfusion (CTP) in an experimental tumor model. Twenty-four VX2 tumors were implanted into the hind legs of 12 rabbits. Three weeks later, FD-CTP (Artis zeego; Siemens) and CTP (SOMATOM Definition AS +; Siemens) were performed. The parameter maps for the FD-CTP were calculated using a prototype software, and those for the CTP were calculated with VPCT-body software on a dedicated syngo MultiModality Workplace. The parameters were compared using Pearson product-moment correlation coefficient and linear regression analysis. The Pearson product-moment correlation coefficient showed good correlation values for both the intratumoral blood volume of 0.848 (P < 0.01) and the blood flow of 0.698 (P < 0.01). The linear regression analysis of the perfusion between FD-CTP and CTP showed for the blood volume a regression equation y = 4.44x + 36.72 (P < 0.01) and for the blood flow y = 0.75x + 14.61 (P < 0.01). This preclinical study provides evidence that FD-CTP allows a time-resolved (dynamic) perfusion imaging of tumors similar to CTP, which provides the basis for clinical applications such as the assessment of tumor response to locoregional therapies directly in the angiography suite.

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

PubMed

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

2005-01-01

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

Extracorporeal Perfusion without Exogenous Anticoagulation: Its Protective Role in Endotoxin Shock.

DTIC Science & Technology

1982-02-19

lethal effects of endotoxin . Group E: Heparinized dogs given endotoxin ; no perfusion. This group served to evaluate the effects of heparin on...recovery from endotoxin shock. Group F: Heparinized dogs perfused 90 minutes; then given endotoxin . This group served to assay the effects of exogenous...stable model and is preperfusion neces- sary to provide protection against the lethal effects of endotoxin ? The first series of experiments (Group B) were

First in vivo magnetic particle imaging of lung perfusion in rats

NASA Astrophysics Data System (ADS)

Zhou, Xinyi Y.; Jeffris, Kenneth E.; Yu, Elaine Y.; Zheng, Bo; Goodwill, Patrick W.; Nahid, Payam; Conolly, Steven M.

2017-05-01

Pulmonary embolism (PE), along with the closely related condition of deep vein thrombosis, affect an estimated 600 000 patients in the US per year. Untreated, PE carries a mortality rate of 30%. Because many patients experience mild or non-specific symptoms, imaging studies are necessary for definitive diagnosis of PE. Iodinated CT pulmonary angiography is recommended for most patients, while nuclear medicine-based ventilation/perfusion (V/Q) scans are reserved for patients in whom the use of iodine is contraindicated. Magnetic particle imaging (MPI) is an emerging tracer imaging modality with high image contrast (no tissue background signal) and sensitivity to superparamagnetic iron oxide (SPIO) tracer. Importantly, unlike CT or nuclear medicine, MPI uses no ionizing radiation. Further, MPI is not derived from magnetic resonance imaging (MRI); MPI directly images SPIO tracers via their strong electronic magnetization, enabling deep imaging of anatomy including within the lungs, which is very challenging with MRI. Here, the first high-contrast in vivo MPI lung perfusion images of rats are shown using a novel lung perfusion agent, MAA-SPIOs.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Pancreas transplants: Evaluation using perfusion scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuni, C.C.; du Cret, R.P.; Boudreau, R.J.

1989-07-01

To determine the value of scintigraphic perfusion studies in evaluating pancreas transplant patients, we reviewed 56 of these studies in 22 patients who had 27 transplants. Seventeen patients underwent two or more studies. The perfusion studies were performed with 20 mCi (740 MBq) of 99mTc-DTPA injected as a bolus followed by eight to 16 serial 2-sec images and a 500,000-count immediate static image. Images were evaluated for (1) the time and intensity of pancreatic peak radioactivity relative to the time and intensity of the iliac arterial peak; (2) relative pancreatic to iliac arterial intensity on the static image; and (3)more » size, homogeneity, and definition of the pancreas. Clinical diagnoses at the time of scintigraphy of normal function (n = 36), rejection (n = 13), pancreatitis (n = 6), or arterial thrombosis (n = 1) were based on insulin requirement, urine amylase, serum glucose, serum amylase, response to therapy, cultures, CT, MR, sonography, scintigraphy with 67Ga or 111In-WBCs, percutaneous drainage results, angiography, surgery, and pathologic examination of resected transplants. Three 99mTc-DTPA perfusion studies showed no pancreatic perfusion, four showed decreasing perfusion on serial studies, and five showed progressive loss of definition of the pancreas on serial studies. Of the three patients with no detectable perfusion, one had a normally functioning transplant, one had arterial thrombosis with transplant infarction, and one had severe rejection with minimal function. Decreasing perfusion was associated with rejection in three patients and pancreatitis in one. Decreasing definition was seen in four patients with rejection and one with pancreatitis. We conclude that perfusion scintigraphy is useful, primarily when performed serially, although nonspecific for evaluating pancreas transplants.« less

Vicarious audiovisual learning in perfusion education.

PubMed

Rath, Thomas E; Holt, David W

2010-12-01

Perfusion technology is a mechanical and visual science traditionally taught with didactic instruction combined with clinical experience. It is difficult to provide perfusion students the opportunity to experience difficult clinical situations, set up complex perfusion equipment, or observe corrective measures taken during catastrophic events because of patient safety concerns. Although high fidelity simulators offer exciting opportunities for future perfusion training, we explore the use of a less costly low fidelity form of simulation instruction, vicarious audiovisual learning. Two low fidelity modes of instruction; description with text and a vicarious, first person audiovisual production depicting the same content were compared. Students (n = 37) sampled from five North American perfusion schools were prospectively randomized to one of two online learning modules, text or video.These modules described the setup and operation of the MAQUET ROTAFLOW stand-alone centrifugal console and pump. Using a 10 question multiple-choice test, students were assessed immediately after viewing the module (test #1) and then again 2 weeks later (test #2) to determine cognition and recall of the module content. In addition, students completed a questionnaire assessing the learning preferences of today's perfusion student. Mean test scores from test #1 for video learners (n = 18) were significantly higher (88.89%) than for text learners (n = 19) (74.74%), (p < .05). The same was true for test #2 where video learners (n = 10) had an average score of 77% while text learners (n = 9) scored 60% (p < .05). Survey results indicated video learners were more satisfied with their learning module than text learners. Vicarious audiovisual learning modules may be an efficacious, low cost means of delivering perfusion training on subjects such as equipment setup and operation. Video learning appears to improve cognition and retention of learned content and may play an important role in how we

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

PubMed

Koning, N J; de Lange, F; van Meurs, M; Jongman, R M; Ahmed, Y; Schwarte, L A; van Nieuw Amerongen, G P; Vonk, A B A; Niessen, H W; Baufreton, C; Boer, C

2018-06-01

Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier

Dynamic CT perfusion imaging of the myocardium: a technical note on improvement of image quality.

PubMed

Muenzel, Daniela; Kabus, Sven; Gramer, Bettina; Leber, Vivian; Vembar, Mani; Schmitt, Holger; Wildgruber, Moritz; Fingerle, Alexander A; Rummeny, Ernst J; Huber, Armin; Noël, Peter B

2013-01-01

To improve image and diagnostic quality in dynamic CT myocardial perfusion imaging (MPI) by using motion compensation and a spatio-temporal filter. Dynamic CT MPI was performed using a 256-slice multidetector computed tomography scanner (MDCT). Data from two different patients-with and without myocardial perfusion defects-were evaluated to illustrate potential improvements for MPI (institutional review board approved). Three datasets for each patient were generated: (i) original data (ii) motion compensated data and (iii) motion compensated data with spatio-temporal filtering performed. In addition to the visual assessment of the tomographic slices, noise and contrast-to-noise-ratio (CNR) were measured for all data. Perfusion analysis was performed using time-density curves with regions-of-interest (ROI) placed in normal and hypoperfused myocardium. Precision in definition of normal and hypoperfused areas was determined in corresponding coloured perfusion maps. The use of motion compensation followed by spatio-temporal filtering resulted in better alignment of the cardiac volumes over time leading to a more consistent perfusion quantification and improved detection of the extend of perfusion defects. Additionally image noise was reduced by 78.5%, with CNR improvements by a factor of 4.7. The average effective radiation dose estimate was 7.1±1.1 mSv. The use of motion compensation and spatio-temporal smoothing will result in improved quantification of dynamic CT MPI using a latest generation CT scanner.

[Activity induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance].

PubMed

Figueroa, Lauro; Díaz, Francisco; Camacho, Abelardo; Díaz, Eliseo; Marvin, Rolando

2009-12-01

Few data exist with respect to the effects of androsterone and their derivatives at cardiovascular level. In addition, the molecular mechanisms and cellular site of action of these androgens are still unclear. An evaluation was conducted on the effects induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance. The effects of both androsterone and hemisuccinate of androsterone on the perfusion pressure and vascular resistance in isolated rat hearts (Langendorff model) were evaluated. The results showed that: (1) the hemisuccinate of androsterone [10(-9) M] increases the perfusion pressure and vascular resistance in comparison with the androsterone [10(-9) M]; (2) the effect of androsterone-derivative [10(-9) M-10(-5) M] on perfusion pressure not was inhibited by indometacin [10(-6) M]; (3) nifedipine [10(-6) M] blocks the effects exerted by hemisuccinate of androsterone [10(-9) M-10(-5) M] on perfusion pressure; and (4) the effect of androsterone-derivative [10(-9) M-10(-5) M] on perfusion pressure in presence of flutamide [10(-6) M] was inhibited. The effects induced by androsterone and hemisuccinate of androsterone on the perfusion pressure and resistance vascular probably involve the interaction of steroid-receptor androgenic and, indirectly, activation of the calcium channel to induce variations in the perfusion pressure.

Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy.

PubMed

Malakasioti, Georgia; Marks, Stephen D; Watson, Tom; Williams, Fariba; Taylor-Allkins, Mariesa; Mamode, Nizam; Morgan, Justin; Hayes, Wesley N

2018-05-11

Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

Hypothermic machine perfusion in kidney transplantation.

PubMed

De Deken, Julie; Kocabayoglu, Peri; Moers, Cyril

2016-06-01

This article summarizes novel developments in hypothermic machine perfusion (HMP) as an organ preservation modality for kidneys recovered from deceased donors. HMP has undergone a renaissance in recent years. This renewed interest has arisen parallel to a shift in paradigms; not only optimal preservation of an often marginal quality graft is required, but also improved graft function and tools to predict the latter are expected from HMP. The focus of attention in this field is currently drawn to the protection of endothelial integrity by means of additives to the perfusion solution, improvement of the HMP solution, choice of temperature, duration of perfusion, and machine settings. HMP may offer the opportunity to assess aspects of graft viability before transplantation, which can potentially aid preselection of grafts based on characteristics such as perfusate biomarkers, as well as measurement of machine perfusion dynamics parameters. HMP has proven to be beneficial as a kidney preservation method for all types of renal grafts, most notably those retrieved from extended criteria donors. Large numbers of variables during HMP, such as duration, machine settings and additives to the perfusion solution are currently being investigated to improve renal function and graft survival. In addition, the search for biomarkers has become a focus of attention to predict graft function posttransplant.

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

PubMed

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

2016-06-01

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

Ex vivo lung perfusion.

PubMed

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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perfusion pressure of a new cannulating fenestrated pedicle screw during cement augmentation.

PubMed

Wang, Zhirong; Zhang, Wen; Xu, Hao; Lu, Aiqing; Yang, Huilin; Luo, Zong-Ping

2018-06-18

Cannulating fenestrated pedicle screws are effective for fixating osteoporotic vertebrae. However, a major limitation is the excessive pressure required to inject a sufficient amount of cement into the vertebral body through the narrow hole of a pedicle screw. We have recently proposed a new cannulating fenestrated pedicle screw with a large hole diameter and a matched inner pin for screw-strength maintenance. Our purpose was to determine whether the new screw can significantly reduce bone-cement perfusion pressure during cement augmentation, METHODS: Two different methods were used to examine perfusion pressure. Hagen-Poisseuille's flow model in a tube was used to calculate pressure drop in the bone-cement channel. Experimentally, both Newtonian silicone oil and bone-cement (polymethyl methacrylate) were tested using a cement pusher through the cannulating screw at a constant rate of 2 ml/min. The internal hollow portion of the screw was the bottleneck of the perfusion, and the new design significantly reduced the perfusion pressure. Specifically, perfusion pressure dropped by 59% (P < 0.05) when diameter size was doubled. The new design effectively improved the application of bone-cement augmentation with the ease of bone-cement perfusion, thereby enhancing operational safety. Copyright © 2018. Published by Elsevier Ltd.

Baseline regional perfusion impacts exercise response to endobronchial valve therapy in advanced pulmonary emphysema.

PubMed

Argula, Rahul G; Strange, Charlie; Ramakrishnan, Viswanathan; Goldin, Jonathan

2013-11-01

Advanced heterogeneous emphysema with hyperinflation impacts exercise tolerance in COPD. Bronchoscopic lung volume reduction using Zephyr endobronchial valves (EBVs) has been shown to improve lung function in patients with heterogeneous emphysema. It is unclear whether the target lobe perfusion of patients receiving EBV therapy impacts exercise tolerance as measured by the 6-min walk test distance (6MWTD). We performed a retrospective analysis on the treatment group of the Endobronchial Valve for Emphysema Palliation Trial (VENT) to evaluate the impact of perfusion, measured by 99mTc-MAA-perfusion scintigraphy, on the 6-month improvement in 6MWTD. A mixed-model analysis was performed for the treatment outcome, adjusting for other variables such as age, target lobe position, fissure integrity, BMI, sex, destruction score, and lobar exclusion. Dichotomized at the median, of the 169 patients who received EBV therapy, 88 had a low target lobe regional perfusion and 81 had high target lobe regional perfusion at baseline. Patients with a low target lobe regional perfusion had a significant improvement in 6MWTD when compared with those with a high baseline target lobe regional perfusion (30.24 m vs 3.72 m, P = .03). Shifts in perfusion after EBV therapy occurred only in patients with high baseline perfusion and did not correlate with improved 6MWTD. Patients having heterogeneous emphysema with a low baseline target lobe regional perfusion benefit from EBV therapy, independent of the degree of target lobe destruction. This effect is attenuated if the EBV therapy is not occlusive. Characterization of baseline perfusion may enhance clinical results of patients with emphysema undergoing EBV therapy. ClinicalTrials.gov; No.: NCT00000606; URL: www.clincialtrials.gov.

Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model.

PubMed

Ahn, Jungho; Cho, Chong-Su; Cho, Seong Woo; Kang, Joo H; Kim, Sung-Yon; Min, Dal-Hee; Song, Joon Myong; Park, Tae-Eun; Jeon, Noo Li

2018-05-25

Vascular networks are the first sites exposed to cationic polymer nanoparticles (NPs) administered intravenously, and thus function as a barrier for NPs reaching the target organ. While cationic polymer NPs have been intensively studied as non-viral delivery systems, their biological effects in human microvessels have been poorly investigated due to a lack of appropriate in vitro systems. Here, we employed a three-dimensional microvessel on a chip, which accurately models in vivo conditions. An open and perfused microvessel surrounded by pericytes was shown to reproduce the important features of living vasculature, including barrier function and biomarkers. Using this microvessel chip, we observed contraction of the microvascular lumen induced by perfused polyethylenimine (PEI)/DNA NPs. We demonstrated that the oxidative stress present when microvessels were exposed to PEI NPs led to rearrangement of microtubules resulting in microvessel contraction. Furthermore, the transcytotic behavior of PEI NPs was analyzed in the microvessel by monitoring the escape of PEI NPs from the microvascular lumen into the perivascular region, which was not possible in two-dimensional culture systems. With our new understanding of the different behaviors of cationic polymer NPs depending on their transcytotic route, we suggest that caveolae-mediated transcytosis is a powerful route for efficient extravascular transport. Microvascular networks are not only biological system constituting largest surface area in the body and but also first site exposed to nanoparticle in vivo. While cationic polymer NPs have been intensively studied as non-viral delivery systems, its biological effects in human microvessel have been poorly investigated due to lack of appropriate in vitro systems. Here, we microengineered an open and perfused 3D pericyte incorporated microvessel model which possesses same morphological characteristic of in vivo. Using the microengineered model, this study represents the

The performance of a reduced-order adaptive controller when used in multi-antenna hyperthermia treatments with nonlinear temperature-dependent perfusion.

PubMed

Cheng, Kung-Shan; Yuan, Yu; Li, Zhen; Stauffer, Paul R; Maccarini, Paolo; Joines, William T; Dewhirst, Mark W; Das, Shiva K

2009-04-07

In large multi-antenna systems, adaptive controllers can aid in steering the heat focus toward the tumor. However, the large number of sources can greatly increase the steering time. Additionally, controller performance can be degraded due to changes in tissue perfusion which vary non-linearly with temperature, as well as with time and spatial position. The current work investigates whether a reduced-order controller with the assumption of piecewise constant perfusion is robust to temperature-dependent perfusion and achieves steering in a shorter time than required by a full-order controller. The reduced-order controller assumes that the optimal heating setting lies in a subspace spanned by the best heating vectors (virtual sources) of an initial, approximate, patient model. An initial, approximate, reduced-order model is iteratively updated by the controller, using feedback thermal images, until convergence of the heat focus to the tumor. Numerical tests were conducted in a patient model with a right lower leg sarcoma, heated in a 10-antenna cylindrical mini-annual phased array applicator operating at 150 MHz. A half-Gaussian model was used to simulate temperature-dependent perfusion. Simulated magnetic resonance temperature images were used as feedback at each iteration step. Robustness was validated for the controller, starting from four approximate initial models: (1) a 'standard' constant perfusion lower leg model ('standard' implies a model that exactly models the patient with the exception that perfusion is considered constant, i.e., not temperature dependent), (2) a model with electrical and thermal tissue properties varied from 50% higher to 50% lower than the standard model, (3) a simplified constant perfusion pure-muscle lower leg model with +/-50% deviated properties and (4) a standard model with the tumor position in the leg shifted by 1.5 cm. Convergence to the desired focus of heating in the tumor was achieved for all four simulated models. The

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

PubMed

Liang, Meng-Ya; Chen, Guang-Xian; Tang, Zhi-Xian; Rong, Jian; Yao, Jian-ping; Wu, Zhong-Kai

2016-03-01

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Quantitative myocardial perfusion from static cardiac and dynamic arterial CT

NASA Astrophysics Data System (ADS)

Bindschadler, Michael; Branch, Kelley R.; Alessio, Adam M.

2018-05-01

Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice ‘bolus tracking’ acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT’s) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative

Organotypic lung culture: A new model for studying ischemia and ex vivo perfusion in lung transplantation.

PubMed

Baste, Jean-Marc; Gay, Arnaud; Smail, Hassiba; Noël, Romain; Bubenheim, Michael; Begueret, Hugues; Morin, Jean-Paul; Litzler, Pierre-Yves

2015-01-01

Donors after cardiac death (DCD) in lung transplantation is considered as a solution for organ shortage. However, it is characterized by warm ischemic period, which could be involved in severe Ischemia-Reperfusion lesion (IR) with early graft dysfunction. We describe a new hybrid model combining in vivo ischemia followed by in vitro reoxygenation using organ-specific culture. A hybrid model using in vivo ischemic period followed by in vitro lung slice reoxygenation was set up in rat to mimic DCD in lung transplantation with in vitro perfusion. Different markers (bioenergetics, oxidant stress assays, and histology) were measured to evaluate the viability of lung tissue after different ischemic times (I-0, I-1, I-2, I-4, I-15 hours) and reoxygenation times (R-0, R-1, R-4, R-24 hours). No differences were found in cell viability, ATP concentrations, extracellular LDH assays or histology, demonstrating extensive viability of up to 4 hours in lung tissue warm ischemia. We found oxidative stress mainly during the ischemic period with no burst at reoxygenation. Cytosolic anti-oxidant system was involved first (I-0,I-1,I-2) followed by mitochondrial anti-oxidant system for extensive ischemia (I-4). Histological features showed differences in this model of ischemia-reoxygenation between bronchial epithelium and lung parenchymal cells, with epithelium regeneration after 2 hours of warm ischemia and 24 hours of perfusion. The results of our hybrid model experiment suggest extensive lung viability of up to 4 hours ischemia. Our model could be an interesting tool to evaluate ex vivo reconditioning techniques after different in vivo lung insults.

Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

PubMed

Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

2016-12-01

Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Myocardial blood flow estimates from dynamic contrast-enhanced magnetic resonance imaging: three quantitative methods

NASA Astrophysics Data System (ADS)

Borrazzo, Cristian; Galea, Nicola; Pacilio, Massimiliano; Altabella, Luisa; Preziosi, Enrico; Carnì, Marco; Ciolina, Federica; Vullo, Francesco; Francone, Marco; Catalano, Carlo; Carbone, Iacopo

2018-02-01

Dynamic contrast-enhanced cardiovascular magnetic resonance imaging can be used to quantitatively assess the myocardial blood flow (MBF), recovering the tissue impulse response function for the transit of a gadolinium bolus through the myocardium. Several deconvolution techniques are available, using various models for the impulse response. The method of choice may influence the results, producing differences that have not been deeply investigated yet. Three methods for quantifying myocardial perfusion have been compared: Fermi function modelling (FFM), the Tofts model (TM) and the gamma function model (GF), with the latter traditionally used in brain perfusion MRI. Thirty human subjects were studied at rest as well as under cold pressor test stress (submerging hands in ice-cold water), and a single bolus of gadolinium weighing 0.1  ±  0.05 mmol kg-1 was injected. Perfusion estimate differences between the methods were analysed by paired comparisons with Student’s t-test, linear regression analysis, and Bland-Altman plots, as well as also using the two-way ANOVA, considering the MBF values of all patients grouped according to two categories: calculation method and rest/stress conditions. Perfusion estimates obtained by various methods in both rest and stress conditions were not significantly different, and were in good agreement with the literature. The results obtained during the first-pass transit time (20 s) yielded p-values in the range 0.20-0.28 for Student’s t-test, linear regression analysis slopes between 0.98-1.03, and R values between 0.92-1.01. From the Bland-Altman plots, the paired comparisons yielded a bias (and a 95% CI)—expressed as ml/min/g—for FFM versus TM, -0.01 (-0.20, 0.17) or 0.02 (-0.49, 0.52) at rest or under stress respectively, for FFM versus GF, -0.05 (-0.29, 0.20) or  -0.07 (-0.55, 0.41) at rest or under stress, and for TM versus GF, -0.03 (-0.30, 0.24) or  -0.09 (-0.43, 0.26) at rest or under stress. With the

Modeling and design of optimal flow perfusion bioreactors for tissue engineering applications.

PubMed

Hidalgo-Bastida, L Araida; Thirunavukkarasu, Sundaramoorthy; Griffiths, Sarah; Cartmell, Sarah H; Naire, Shailesh

2012-04-01

Perfusion bioreactors have been used in different tissue engineering applications because of their consistent distribution of nutrients and flow-induced shear stress within the tissue-engineering scaffold. A widely used configuration uses a scaffold with a circular cross-section enclosed within a cylindrical chamber and inlet and outlet pipes which are connected to the chamber on either side through which media is continuously circulated. However, fluid-flow experiments and simulations have shown that the majority of the flow perfuses through the center. This pattern creates stagnant zones in the peripheral regions as well as in those of high flow rate near the inlet and outlet. This non-uniformity of flow and shear stress, owing to a circular design, results in limited cell proliferation and differentiation in these areas. The focus of this communication is to design an optimized perfusion system using computational fluid dynamics as a mathematical tool to overcome the time-consuming trial and error experimental method. We compared the flow within a circular and a rectangular bioreactor system. Flow simulations within the rectangular bioreactor are shown to overcome the limitations in the circular design. This communication challenges the circular cross-section bioreactor configuration paradigm and provides proof of the advantages of the new design over the existing one. Copyright © 2011 Wiley Periodicals, Inc.

Effects of laser acupuncture on blood perfusion rate

NASA Astrophysics Data System (ADS)

Wang, Xian-ju; Zeng, Chang-chun; Liu, Han-ping; Liu, Song-hao; Liu, Liang-gang

2006-09-01

Based on Pennes equation, the influences of the intensity and the impulse frequency of laser acupuncture on the point tissues' blood flow perfusion rate are discussed. We find that the blood perfusion rate of point tissue increases with the intensity of laser acupuncture increasing. After impulse laser acupuncture the point tissue blood perfusion rate increase little, but after continuum laser acupuncture the point tissues blood perfusion rate increase much.

Simulation of motor unit recruitment and microvascular unit perfusion: spatial considerations.

PubMed

Fuglevand, A J; Segal, S S

1997-10-01

Muscle fiber activity is the principal stimulus for increasing capillary perfusion during exercise. The control elements of perfusion, i.e., microvascular units (MVUs), supply clusters of muscle fibers, whereas the control elements of contraction, i.e., motor units, are composed of fibers widely scattered throughout muscle. The purpose of this study was to examine how the discordant spatial domains of MVUs and motor units could influence the proportion of open capillaries (designated as perfusion) throughout a muscle cross section. A computer model simulated the locations of perfused MVUs in response to the activation of up to 100 motor units in a muscle with 40,000 fibers and a cross-sectional area of 100 mm2. The simulation increased contraction intensity by progressive recruitment of motor units. For each step of motor unit recruitment, the percentage of active fibers and the number of perfused MVUs were determined for several conditions: 1) motor unit fibers widely dispersed and motor unit territories randomly located (which approximates healthy human muscle), 2) regionalized motor unit territories, 3) reversed recruitment order of motor units, 4) densely clustered motor unit fibers, and 5) increased size but decreased number of motor units. The simulations indicated that the widespread dispersion of motor unit fibers facilitates complete capillary (MVU) perfusion of muscle at low levels of activity. The efficacy by which muscle fiber activity induced perfusion was reduced 7- to 14-fold under conditions that decreased the dispersion of active fibers, increased the size of motor units, or reversed the sequence of motor unit recruitment. Such conditions are similar to those that arise in neuromuscular disorders, with aging, or during electrical stimulation of muscle, respectively.

Lung cancer perfusion: can we measure pulmonary and bronchial circulation simultaneously?

PubMed

Yuan, Xiaodong; Zhang, Jing; Ao, Guokun; Quan, Changbin; Tian, Yuan; Li, Hong

2012-08-01

To describe a new CT perfusion technique for assessing the dual blood supply in lung cancer and present the initial results. This study was approved by the institutional review board. A CT protocol was developed, and a dual-input CT perfusion (DI-CTP) analysis model was applied and evaluated regarding the blood flow fractions in lung tumours. The pulmonary trunk and the descending aorta were selected as the input arteries for the pulmonary circulation and the bronchial circulation respectively. Pulmonary flow (PF), bronchial flow (BF), and a perfusion index (PI, = PF/ (PF + BF)) were calculated using the maximum slope method. After written informed consent was obtained, 13 consecutive subjects with primary lung cancer underwent DI-CTP. Perfusion results are as follows: PF, 13.45 ± 10.97 ml/min/100 ml; BF, 48.67 ± 28.87 ml/min/100 ml; PI, 21 % ± 11 %. BF is significantly larger than PF, P < 0.001. There is a negative correlation between the tumour volume and perfusion index (r = 0.671, P = 0.012). The dual-input CT perfusion analysis method can be applied successfully to lung tumours. Initial results demonstrate a dual blood supply in primary lung cancer, in which the systemic circulation is dominant, and that the proportion of the two circulation systems is moderately dependent on tumour size. A new CT perfusion technique can assess lung cancer's dual blood supply. A dual blood supply was confirmed with dominant bronchial circulation in lung cancer. The proportion of the two circulations is moderately dependent on tumour size. This new technique may benefit the management of lung cancer.

Simulating patient-specific heart shape and motion using SPECT perfusion images with the MCAT phantom

NASA Astrophysics Data System (ADS)

Faber, Tracy L.; Garcia, Ernest V.; Lalush, David S.; Segars, W. Paul; Tsui, Benjamin M.

2001-05-01

The spline-based Mathematical Cardiac Torso (MCAT) phantom is a realistic software simulation designed to simulate single photon emission computed tomographic (SPECT) data. It incorporates a heart model of known size and shape; thus, it is invaluable for measuring accuracy of acquisition, reconstruction, and post-processing routines. New functionality has been added by replacing the standard heart model with left ventricular (LV) epicaridal and endocardial surface points detected from actual patient SPECT perfusion studies. LV surfaces detected from standard post-processing quantitation programs are converted through interpolation in space and time into new B-spline models. Perfusion abnormalities are added to the model based on results of standard perfusion quantification. The new LV is translated and rotated to fit within existing atria and right ventricular models, which are scaled based on the size of the LV. Simulations were created for five different patients with myocardial infractions who had undergone SPECT perfusion imaging. Shape, size, and motion of the resulting activity map were compared visually to the original SPECT images. In all cases, size, shape and motion of simulated LVs matched well with the original images. Thus, realistic simulations with known physiologic and functional parameters can be created for evaluating efficacy of processing algorithms.

Engineering of functional, perfusable 3D microvascular networks on a chip.

PubMed

Kim, Sudong; Lee, Hyunjae; Chung, Minhwan; Jeon, Noo Li

2013-04-21

Generating perfusable 3D microvessels in vitro is an important goal for tissue engineering, as well as for reliable modelling of blood vessel function. To date, in vitro blood vessel models have not been able to accurately reproduce the dynamics and responses of endothelial cells to grow perfusable and functional 3D vascular networks. Here we describe a microfluidic-based platform whereby we model natural cellular programs found during normal development and angiogenesis to form perfusable networks of intact 3D microvessels as well as tumor vasculatures based on the spatially controlled co-culture of endothelial cells with stromal fibroblasts, pericytes or cancer cells. The microvessels possess the characteristic morphological and biochemical markers of in vivo blood vessels, and exhibit strong barrier function and long-term stability. An open, unobstructed microvasculature allows the delivery of nutrients, chemical compounds, biomolecules and cell suspensions, as well as flow-induced mechanical stimuli into the luminal space of the endothelium, and exhibits faithful responses to physiological shear stress as demonstrated by cytoskeleton rearrangement and increased nitric oxide synthesis. This simple and versatile platform provides a wide range of applications in vascular physiology studies as well as in developing vascularized organ-on-a-chip and human disease models for pharmaceutical screening.

Comparison of Dextran Perfusion and GSI-B4 Isolectin Staining in a Mouse Model of Oxygen-induced Retinopathy.

PubMed

Huang, Shaofen; Liang, Jiajian; Yam, Gary Hin-Fai; Lu, Zhihao; Pang, Chi Pui; Chen, Haoyu

2015-06-01

Oxygen-induced retinopathy (OIR) is a robust and widely used animal model for the study of retinal neovascularization (NV). Dextran perfusion and Griffonia simplicifolia isolectin B4 (GSI-B4) staining are two common methods for examining the occurrence and extent of OIR. This study provides a quantitative comparison of the two for OIR detection. At postnatal day 7 (PN7), fifteen C57BL/6J mice were exposed to a 75% hyperoxic condition for 5 days and then returned to room air conditions. At PN17, the mice received intravitreal injection of GSI-B4 Alexa Fluor 568 conjugate. After 10 hours, they were infused with FITC-dextran conjugate via the left ventricle. Retinal flat mounts were photographed by confocal microscopy. Areas with fluorescent signals and the total retinal areas were quantified by Image J software. Both GSI-B4 and dextran detected the peripheral neovascular area. The mean hyper fluorescence area was 0.33 ± 0.14% of whole retinal area determined by GSI-B4 staining and 0.25 ± 0.28% determined by dextran perfusion. The difference between the two measures was 0.08% (95% CI:-0.59%, 0.43%). The Pearson correlation coefficient between the two methods was 0.386,P =0.035. The mean coincidence rates were 14.3 ± 13.4% and 24.9 ± 18.5% for GSI-B4 and dextran staining, respectively. Both methods can complement each other in demonstrating and quantitatively evaluating retinal NV. A poor agreement was found between the two methods; GSI-B4 isolectin was more effective than FITC-dextran perfusion in evaluating the extent of retinal NV in a mouse model of OIR.

Perfusion lung imaging in the adult respiratory distress syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pistolesi, M.; Miniati, M.; Di Ricco, G.

1986-07-01

In 29 perfusion lung scans (PLS) of 19 patients with ARDS, 20 of which were obtained within six days from the onset of respiratory symptoms, perfusion abnormalities were the rule. These included focal, nonsegmental defects, mostly peripheral and dorsal, and perfusion redistribution away from the dependent lung zones. PLS were scored for the presence and intensity of perfusion abnormalities and the scores of perfusion redistribution were validated against numerical indices of blood flow distribution per unit lung volume. PLS scores were correlated with arterial blood gas values, hemodynamic parameters, and chest radiographic scores of ARDS. Arterial oxygen tension correlated withmore » the scores of both perfusion defects and redistribution. Perfusion defects correlated better with the radiographic score of ARDS, and perfusion redistribution with PAP and vascular resistance. ARDS patients exhibit peculiar patterns of PLS abnormalities not observed in other disorders. Thus, PLS may help considerably in the detection and evaluation of pulmonary vascular injury in ARDS.« less

3D perfusion mapping in the intact mouse heart after myocardial infarction using myocardial contrast echocardiography

NASA Astrophysics Data System (ADS)

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

2005-04-01

An intact mouse model of surgically-induced myocardial infarction (MI) caused by permanent occlusion of the Left Anterior Descending (LAD) coronary artery was studied. Normal mice with no occlusion were also studied as controls. For each mouse, contrast enhanced ultrasound images of the heart were acquired in parallel cross-sections perpendicular to the sternum at millimeter increments. For accurate 3D reconstruction, ECG gating and a tri-axial adjustable micromanipulator were used for temporal and spatial registration. Ultrasound images at steady-state of blood refilling were color-coded in each slice to show relative perfusion. Myocardial perfusion defects and necrosis were also examined postmortem by staining with Phthalo blue and TTC red dyes. Good correlation (R>0.93) in perfused area size was observed between in vivo measurements and histological staining. A 3D multi-slice model and a 3D rendering of perfusion distribution were created and showed a promising match with postmortem results, lending further credence to its use as a more comprehensive and more reliable tool for in vivo assessment of myocardial perfusion than 2D tomographic analysis.

Use of myocardial perfusion imaging and estimation of associated radiation doses in Germany from 2005 to 2012.

PubMed

Lindner, O; Bengel, F M; Hacker, M; Schäfer, W; Burchert, W

2014-05-01

For several years the Working Group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine has been performing a regular survey to obtain information on technique, utilization and development of myocardial perfusion scintigraphy (MPS). Currently, data of six surveys from 2005 to 2012 are available. The aim of this paper is to deliver a general and comprehensive overview of all surveys documenting the course of patient doses over time and the development of the method. A one-page questionnaire with number of MPS patients, number of stress and rest MPS, referral structure and several technical issues was sent to all centres performing MPS in Germany and evaluated. With the data on protocol utilization, effective MPS patient doses were estimated. MPS per million population (pmp) varied between 2,380 and 2,770. In 2012, MPS pmp showed a slight increase for the first time. From 2005 to 2009 the angiography to MPS ratio increased from 3.4 to 4.4, and the revascularization to MPS ratio decreased from 0.66 to 0.53. In 2012, both indices demonstrated an opposite trend for the first time (4.1 and 0.55). A total of 108 centres participated in all surveys. They showed an increase in MPS patients of 4.0 % over the reporting period. In 2012, more than 50 % of the centres experienced no change or an increase in MPS numbers. The leading single competitor was MRI, followed by angiography and stress echocardiography. (201)Tl studies have decreased since 2005 from 20 to 5 %. (99m)Tc MPS studies showed a mild increase in 2-day protocols. In 2012, the average effective dose per patient was estimated at 7.4 mSv. Due to the decreasing use of (201)Tl, a mild decline over the observation period can be documented. Dynamic exercise stress was the most common stress test and adenosine the leading pharmacological stress agent, with a growing percentage. In 2012, the regadenoson percentage was 9 %. Gated single photon emission computed tomography (SPECT) noted an increasing

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

PubMed Central

Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying

2016-01-01

Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton’s jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC-MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM-DiI-labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Significance Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called “no-option” patients. This study finds that umbilical cord-derived mesenchymal stromal

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia.

PubMed

Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying; Lü, Shuang-Hong; Zhang, Xiao-Zhong

2016-08-01

: Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton's jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC-MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM-DiI-labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called "no-option" patients. This study finds that umbilical cord-derived mesenchymal stromal cells

Robust dynamic myocardial perfusion CT deconvolution using adaptive-weighted tensor total variation regularization

NASA Astrophysics Data System (ADS)

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

2016-03-01

Dynamic myocardial perfusion computed tomography (MPCT) is a promising technique for diagnosis and risk stratification of coronary artery disease by assessing the myocardial perfusion hemodynamic maps (MPHM). Meanwhile, the repeated scanning of the same region results in a relatively large radiation dose to patients potentially. In this work, we present a robust MPCT deconvolution algorithm with adaptive-weighted tensor total variation regularization to estimate residue function accurately under the low-dose context, which is termed `MPD-AwTTV'. More specifically, the AwTTV regularization takes into account the anisotropic edge property of the MPCT images compared with the conventional total variation (TV) regularization, which can mitigate the drawbacks of TV regularization. Subsequently, an effective iterative algorithm was adopted to minimize the associative objective function. Experimental results on a modified XCAT phantom demonstrated that the present MPD-AwTTV algorithm outperforms and is superior to other existing deconvolution algorithms in terms of noise-induced artifacts suppression, edge details preservation and accurate MPHM estimation.

Assessment of hemodynamics in a rat model of liver cirrhosis with precancerous lesions using multislice spiral CT perfusion imaging.

PubMed

Ma, Guolin; Bai, Rongjie; Jiang, Huijie; Hao, Xuejia; Ling, Zaisheng; Li, Kefeng

2013-01-01

To develop an optimal scanning protocol for multislice spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. Male Wistar rats were randomly divided into the control group (n = 80) and the precancerous liver cirrhosis group (n = 40). The control group received saline injection and the liver cirrhosis group received 50 mg/kg DEN i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting the diatrizoate concentration, the flow rate, and the delivery time. The hemodynamics of both groups was further compared using optimized multislice spiral CTP imaging. High-quality CTP images were obtained with following parameters: 150 kV; 150 mAs; 5 mm thickness, 5 mm interval; pitch, 1; matrix, 512 × 512; and FOV, 9.6 cm. Compared to the control group, the liver cirrhosis group had a significantly increased value of the hepatic arterial fraction and the hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal perfusion and mean transit time (P < 0.05). Multislice spiral CTP imaging can be used to evaluate the hemodynamic changes in the rat model of liver cirrhosis with precancerous lesions.

Arterial Perfusion Imaging–Defined Subvolume of Intrahepatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hesheng, E-mail: hesheng@umich.edu; Farjam, Reza; Feng, Mary

2014-05-01

Purpose: To assess whether an increase in a subvolume of intrahepatic tumor with elevated arterial perfusion during radiation therapy (RT) predicts tumor progression after RT. Methods and Materials: Twenty patients with unresectable intrahepatic cancers undergoing RT were enrolled in a prospective, institutional review board–approved study. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed before RT (pre-RT), after delivering ∼60% of the planned dose (mid-RT) and 1 month after completion of RT to quantify hepatic arterial perfusion. The arterial perfusions of the tumors at pre-RT were clustered into low-normal and elevated perfusion by a fuzzy clustering-based method, and the tumor subvolumesmore » with elevated arterial perfusion were extracted from the hepatic arterial perfusion images. The percentage changes in the tumor subvolumes and means of arterial perfusion over the tumors from pre-RT to mid-RT were evaluated for predicting tumor progression post-RT. Results: Of the 24 tumors, 6 tumors in 5 patients progressed 5 to 21 months after RT completion. Neither tumor volumes nor means of tumor arterial perfusion at pre-RT were predictive of treatment outcome. The mean arterial perfusion over the tumors increased significantly at mid-RT in progressive tumors compared with the responsive tumors (P=.006). From pre-RT to mid-RT, the responsive tumors had a decrease in the tumor subvolumes with elevated arterial perfusion (median, −14%; range, −75% to 65%), whereas the progressive tumors had an increase of the subvolumes (median, 57%; range, −7% to 165%) (P=.003). Receiver operating characteristic analysis of the percentage change in the subvolume for predicting tumor progression post-RT had an area under the curve of 0.90. Conclusion: The increase in the subvolume of the intrahepatic tumor with elevated arterial perfusion during RT has the potential to be a predictor for tumor progression post-RT. The tumor subvolume could be a

Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres.

PubMed

Jogiya, Roy; Makowski, Markus; Phinikaridou, Alkystsis; Patel, Ashish S; Jansen, Christian; Zarinabad, Niloufar; Chiribiri, Amedeo; Botnar, Rene; Nagel, Eike; Kozerke, Sebastian; Plein, Sven

2013-07-21

Dynamic first pass contrast-enhanced myocardial perfusion is the standard CMR method for the estimation of myocardial blood flow (MBF) and MBF reserve in man, but it is challenging in rodents because of the high temporal and spatial resolution requirements. Hyperemic first pass myocardial perfusion CMR during vasodilator stress in mice has not been reported. Five C57BL/6 J mice were scanned on a clinical 3.0 Tesla Achieva system (Philips Healthcare, Netherlands). Vasodilator stress was induced via a tail vein catheter with an injection of dipyridamole. Dynamic contrast-enhanced perfusion imaging (Gadobutrol 0.1 mmol/kg) was based on a saturation recovery spoiled gradient echo method with 10-fold k-space and time domain undersampling (k-t PCA). One week later the mice underwent repeat anaesthesia and LV injections of fluorescent microspheres at rest and at stress. Microspheres were analysed using confocal microscopy and fluorescence-activated cell sorting. Mean MBF at rest measured by Fermi-function constrained deconvolution was 4.1 ± 0.5 ml/g/min and increased to 9.6 ± 2.5 ml/g/min during dipyridamole stress (P = 0.005). The myocardial perfusion reserve was 2.4 ± 0.54. The mean count ratio of stress to rest microspheres was 2.4 ± 0.51 using confocal microscopy and 2.6 ± 0.46 using fluorescence. There was good agreement between cardiovascular magnetic resonance CMR and microspheres with no significant difference (P = 0.84). First-pass myocardial stress perfusion CMR in a mouse model is feasible at 3 Tesla. Rest and stress MBF values were consistent with existing literature and perfusion reserve correlated closely to microsphere analysis. Data were acquired on a 3 Tesla scanner using an approach similar to clinical acquisition protocols, potentially facilitating translation of imaging findings between rodent and human studies.

Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety

PubMed Central

Kaczkurkin, Antonia N.; Moore, Tyler M.; Ruparel, Kosha; Ciric, Rastko; Calkins, Monica E.; Shinohara, Russell T.; Elliott, Mark A.; Hopson, Ryan; Roalf, David R.; Vandekar, Simon N.; Gennatas, Efstathios D.; Wolf, Daniel H.; Scott, J. Cobb; Pine, Daniel S.; Leibenluft, Ellen; Detre, John A.; Foa, Edna B.; Gur, Raquel E.; Gur, Ruben C.; Satterthwaite, Theodore D.

2016-01-01

Background Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow (CBF) is one brain phenotype that is known to have marked developmental sex differences. Methods We investigated whether developmental sex differences in CBF mediated sex differences in anxiety and depression symptoms by capitalizing upon a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin labeled MRI at 3T. Perfusion images were related to trait and state anxiety using a general additive model with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty. Results Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for pre-scanner state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in post-pubertal females was mediated by elevated perfusion of the left amygdala. Conclusions Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during the adolescent period may be a critical element of the affective neurobiology underlying sex differences in anxiety and mood symptoms. PMID:27395327

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

PubMed

Eckstein, F S; Scheule, A M; Vogel, U; Schmid, S T; Miller, S; Jurmann, M J; Ziemer, G

1999-05-01

Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would

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

PubMed Central

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

2017-01-01

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

[Design of a pulse oximeter used to low perfusion and low oxygen saturation].

PubMed

Tan, Shuangping; Ai, Zhiguang; Yang, Yuxing; Xie, Qingguo

2013-05-01

This paper presents a new pulse oximeter used to low perfusion at 0.125% and wide oxygen saturation range from 35% to 100%. In order to acquire the best PPG signals, the variable gain amplifier(VGA) is adopted in hardware. The self-developed auto-correlation modeling method is adopted in software and it can extract pulse wave from low perfusion signals and remove motion artifacts partly.

[An automatic system controlled by microcontroller for carotid sinus perfusion].

PubMed

Yi, X L; Wang, M Y; Fan, Z Z; He, R R

2001-08-01

To establish a new method for controlling automatically the carotid perfusion pressure. A cheap practical automatic perfusion unit based on AT89C2051 micro controller was designed. The unit, LDB-M perfusion pump and the carotid sinus of an animal constituted an automatic perfusion system. This system was able to provide ramp and stepwise updown perfusion pattern and has been used in the research of baroreflex. It can insure the precision and reproducibility of perfusion pressure curve, and improve the technical level in corresponding medical field.

Development of an in situ perfused kidney preparation for elasmobranch fish: action of arginine vasotocin.

PubMed

Wells, Alan; Anderson, W Gary; Hazon, Neil

2002-06-01

Acclimation of the European lesser-spotted dogfish Scyliorhinus canicula to reduced environmental salinity [85-70% seawater (SW)] induced a significant diuresis in addition to a significant decrease in plasma osmolality in vivo. The threshold for this diuresis was determined to be 85% SW. Therefore, S. canicula acclimated to 85% SW was selected for further study as a diuretic model in the development of an in situ perfused kidney preparation. The renal role of arginine vasotocin (AVT) in the in situ perfused trunk preparation was investigated. In SW, perfusion of 10(-9) and 10(-10) M AVT resulted in a glomerular antidiuresis and decreases in tubular transport maxima for glucose and perfusate flow. In 85% SW, 10(-10) M AVT had no significant effect on these renal parameters with the exception of transport maxima for glucose and perfusate flow. Tubular parameters remained unchanged by either 10(-9) or 10(-10) M AVT. The results demonstrate that the perfused kidney preparation was a viable tool for the investigation of renal parameters in elasmobranch fish and that AVT induced a glomerular antidiuresis.

Myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification.

PubMed

Kellman, Peter; Hansen, Michael S; Nielles-Vallespin, Sonia; Nickander, Jannike; Themudo, Raquel; Ugander, Martin; Xue, Hui

2017-04-07

�ml/min/g using the BTEX model and 3.4 ± 0.39 and 0.95 ± 0.16 using a Fermi model, for stress and rest, respectively. A dual sequence for myocardial perfusion cardiovascular magnetic resonance and AIF measurement has been optimized for quantification of myocardial blood flow. A validation in phantoms was performed to confirm that the signal conversion to gadolinium concentration was linear. The proposed sequence was integrated with a fully automatic in-line solution for pixel-wise mapping of myocardial blood flow and evaluated in adenosine stress and rest studies on N = 29 normal healthy subjects. Reliable perfusion mapping was demonstrated and produced estimates with low variability.

Optimized retrograde cerebral perfusion reduces ischemic energy depletion.

PubMed

Oda, Teiji; Kimura, Tetsuhiro; Ogata, Yoshitaka; Fujise, Yutaka

2004-01-01

It has been reported that retrograde cerebral perfusion (RCP) provides minimal capillary flow; however, the extent to which RCP can provide aerobic metabolic support is unknown. We evaluated whether perfusate composition optimization for RCP would preserve brain energy metabolism during hypothermic circulatory arrest (HCA) at 20 degrees C in rats. Three types of perfusates were prepared: hemoglobin-free saline, rat red blood cells, and artificial blood substitute (liposome-encapsulated hemoglobin); perfusates were made hypertonic, cooled to 20 degrees C, and oxygenated and CO(2) was administered (pH-stat management). Circulatory arrest was induced in 24 pH-stat-ventilated Wistar rats that had been surface cooled to 20 degrees C; 18 were assigned to the RCP group in which one of the three ( n = 6 each) perfusates was administered via the maxillary vein, and 6 received no perfusion. In two similarly surface-cooled rats (controls), brains were excised when the temperature reached 20 degrees C. After 20 min of RCP or HCA, brains were excised and immediately frozen; brain high-energy phosphates, adenosine, and water content were measured. The liposome-encapsulated hemoglobin perfusate preserved levels of brain tissue adenosine triphosphates and energy charge, but not significantly better than rat red blood cells. Both maintained significantly higher levels than perfusion with oxygenated saline or hypothermic circulatory arrest alone ( P = 0.0419-0.0001), under which regimes high-energy phosphates and energy charge declined to similar low values. RCP with hypertonic solution prevented brain edema. RCP with optimized composition perfusate (pH-stat, hypertonic rat red blood cells or liposome-encapsulated hemoglobin) reduced ischemic energy depletion during 20 min of HCA at 20 degrees C in rats.

Particle size effects on protein and virus-like particle adsorption on perfusion chromatography media.

PubMed

Wu, Yige; Abraham, Dicky; Carta, Giorgio

2015-01-02

The resin structure, chromatographic behavior, and adsorption kinetics of proteins and virus-like-particles (VLPs) are studied for POROS HS 20 and POROS HS 50 (23 and 52 μm mean diameter, respectively) to determine the effects of particle size on perfusion chromatography and to determine the predictive ability of available models. Transmission electron microscopy (TEM) and inverse size-exclusion chromatography (iSEC) show similar structures for the two resins, both containing 200-1000 nm pores that transect a network of much smaller pores. For non-binding conditions, trends of the height equivalent to a theoretical plate (HETP) as a function of reduced velocity are consistent with perfusion. The estimated intraparticle flow fractions for these conditions are 0.0018 and 0.00063 for POROS HS 20 and HS 50, respectively. For strong binding conditions, confocal laser scanning microscopy (CLSM) shows asymmetrical intraparticle concentrations profiles and enhanced rates of IgG adsorption on POROS HS 20 at 1000 cm/h. The corresponding effective diffusivity under flow is 2-3 times larger than for non-flow conditions and much larger than observed for POROS HS 50, consistent with available models. For VLPs, however, adsorption is confined to a thin layer near the particle surface for both resins, suggesting that the bound VLPs block the pores. Copyright © 2014 Elsevier B.V. All rights reserved.

Energy demand of cardioplegically perfused human hearts.

PubMed

Preusse, C J; Winter, J; Schulte, H D; Bircks, W

1985-01-01

Human adult hearts with aortic valve disease (n = 20) and hypertrophic obstructive cardiomyopathy (n = 1) were perfused intraoperatively with cold histidine buffered Bretschneider solution. During a seven minute cardioplegic perfusion the temperature level, the electrolyte level, the resistance of the left (LCA) and right coronary artery (RCA), and myocardial O2 consumption were analysed. Equilibration of K+ was terminated shortly after the start of the perfusion while Na+ equilibration lasted for about 5 minutes. Resistance of RCA did not change significantly, but that of the LCA was diminished significantly (p less than 0.025) within the perfusion period indicating a delayed washout of calcium from the extracellular space. Myocardial O2 consumption was reduced from 2.71 ml/min (1. minute) to 1.51 ml/min (4. minute) to 0.93 ml/min (7. minute) although the temperature had reached a low level after 3 minutes. The difference between 4. to 7. minutes is significant (p less than 0.001). By our results it is concluded that in adult hearts high-volume cardioplegic perfusion at a flow rate of 1 ml/min X gm at a perfusion pressure of 40 to 50 mmHg should be performed for at least 6 to 7 minutes to achieve a sufficient intra-ischemic myocardial protection.

Differential and directional effects of perfusion on electrical and thermal conductivities in liver.

PubMed

Podhajsky, Ronald J; Yi, Ming; Mahajan, Roop L

2009-01-01

Two different measurement probes--an electrical probe and a thermal conductivity probe--were designed, fabricated, calibrated, and used in experimental studies on a pig liver model that was designed to control perfusion rates. These probes were fabricated by photolithography and mounted in 1.5-mm diameter catheters. We measured the local impedance and thermal conductivity, respectively, of the artificially perfused liver at different flow rates and, by rotating the probes, in different directions. The results show that both the local electrical conductivity and the thermal conductivity varied location to location, that thermal conductivity increased with decreased distance to large blood vessels, and that significant directional differences exist in both electrical and thermal conductivities. Measurements at different perfusion rates demonstrated that both the local electrical and local thermal conductivities increased linearly with the square root of perfusion rate. These correlations may be of great value to many energy-based biomedical applications.

Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease.

PubMed

Arrighi, James A; Burg, Matthew; Cohen, Ira S; Soufer, Robert

2003-01-01

Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS

SU-E-I-36: A KWIC and Dirty Look at Dose Savings and Perfusion Metrics in Simulated CT Neuro Perfusion Exams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoffman, J; Martin, T; Young, S

Purpose: CT neuro perfusion scans are one of the highest dose exams. Methods to reduce dose include decreasing the number of projections acquired per gantry rotation, however conventional reconstruction of such scans leads to sampling artifacts. In this study we investigated a projection view-sharing reconstruction algorithm used in dynamic MRI – “K-space Weighted Image Contrast” (KWIC) – applied to simulated perfusion exams and evaluated dose savings and impacts on perfusion metrics. Methods: A FORBILD head phantom containing simulated time-varying objects was developed and a set of parallel-beam CT projection data was created. The simulated scans were 60 seconds long, 1152more » projections per turn, with a rotation time of one second. No noise was simulated. 5mm, 10mm, and 50mm objects were modeled in the brain. A baseline, “full dose” simulation used all projections and reduced dose cases were simulated by downsampling the number of projections per turn from 1152 to 576 (50% dose), 288 (25% dose), and 144 (12.5% dose). KWIC was further evaluated at 72 projections per rotation (6.25%). One image per second was reconstructed using filtered backprojection (FBP) and KWIC. KWIC reconstructions utilized view cores of 36, 72, 144, and 288 views and 16, 8, 4, and 2 subapertures respectively. From the reconstructed images, time-to-peak (TTP), cerebral blood flow (CBF) and the FWHM of the perfusion curve were calculated and compared against reference values from the full-dose FBP data. Results: TTP, CBF, and the FWHM were unaffected by dose reduction (to 12.5%) and reconstruction method, however image quality was improved when using KWIC. Conclusion: This pilot study suggests that KWIC preserves image quality and perfusion metrics when under-sampling projections and that the unique contrast weighting of KWIC could provided substantial dose-savings for perfusion CT scans. Evaluation of KWIC in clinical CT data will be performed in the near future. R01 EB

A continuous perfusion microplate for cell culture.

PubMed

Goral, Vasiliy N; Zhou, Chunfeng; Lai, Fang; Yuen, Po Ki

2013-03-21

We describe a 96-well microplate with fluidically connected wells that enables the continuous fluid perfusion between wells without the need for external pumping. A single unit in such a perfusion microplate consists of three wells: a source well, a sample (cell culture) well in the middle and a waste well. Fluid perfusion is achieved using a combination of the hydrostatic pressure generated by different liquid levels in the wells and the fluid wicking through narrow strips of a cellulose membrane connecting the wells. There is an excellent correspondence between the observed perfusion flow dynamics and the flow simulations based on Darcy's Law. Hepatocytes (C3A cells) cultured for 4 days in the perfusion microplate with no media exchange in the cell culture well had the same viability as hepatocytes exposed to a daily exchange of media. EOC 20 cells that require media conditioned by LADMAC cells were shown to be equally viable in the adjacent cell culture well of the perfusion microplate with LADMAC cells cultured in the source well. Tegafur, a prodrug, when added to primary human hepatocytes in the source well, was metabolized into a cytotoxic metabolite that kills colon cancer cells (HCT 116) cultured in the adjacent cell culture well; no toxicity was observed when only medium was in the source well. These results suggest that the perfusion microplate is a useful tool for a variety of cell culture applications with benefits ranging from labor savings to enabling in vivo-like toxicity studies.

A reappraisal of retrograde cerebral perfusion.

PubMed

Ueda, Yuichi

2013-05-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients.

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

PubMed

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

2015-02-17

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

An alternative method for neonatal cerebro-myocardial perfusion.

PubMed

Luciani, Giovanni Battista; De Rita, Fabrizio; Faggian, Giuseppe; Mazzucco, Alessandro

2012-05-01

Several techniques have already been described for selective cerebral perfusion during repair of aortic arch pathology in children. One method combining cerebral with myocardial perfusion has also been proposed. A novel technique is reported here for selective and independent cerebro-myocardial perfusion for neonatal and infant arch surgery. Technical aspects and potential advantages are discussed.

Goal-directed-perfusion in neonatal aortic arch surgery.

PubMed

Cesnjevar, Robert Anton; Purbojo, Ariawan; Muench, Frank; Juengert, Joerg; Rueffer, André

2016-07-01

Reduction of mortality and morbidity in congenital cardiac surgery has always been and remains a major target for the complete team involved. As operative techniques are more and more standardized and refined, surgical risk and associated complication rates have constantly been reduced to an acceptable level but are both still present. Aortic arch surgery in neonates seems to be of particular interest, because perfusion techniques differ widely among institutions and an ideal form of a so called "total body perfusion (TBP)" is somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory arrest (DHCA), regional cerebral perfusion (RCP/with cardioplegic cardiac arrest or on the perfused beating heart) and TBP exist in parallel and all carry an individual risk for organ damage related to perfusion management, chosen core temperature and time on bypass. Patient safety relies more and more on adequate end organ perfusion on cardiopulmonary bypass, especially sensitive organs like the brain, heart, kidney, liver and the gut, whereby on adequate tissue protection, temperature management and oxygen delivery should be visualized and monitored.

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

PubMed

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

2012-03-01

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

An alternative method for neonatal cerebro-myocardial perfusion

PubMed Central

Luciani, Giovanni Battista; De Rita, Fabrizio; Faggian, Giuseppe; Mazzucco, Alessandro

2012-01-01

Several techniques have already been described for selective cerebral perfusion during repair of aortic arch pathology in children. One method combining cerebral with myocardial perfusion has also been proposed. A novel technique is reported here for selective and independent cerebro-myocardial perfusion for neonatal and infant arch surgery. Technical aspects and potential advantages are discussed. PMID:22307393

Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety.

PubMed

Kaczkurkin, Antonia N; Moore, Tyler M; Ruparel, Kosha; Ciric, Rastko; Calkins, Monica E; Shinohara, Russell T; Elliott, Mark A; Hopson, Ryan; Roalf, David R; Vandekar, Simon N; Gennatas, Efstathios D; Wolf, Daniel H; Scott, J Cobb; Pine, Daniel S; Leibenluft, Ellen; Detre, John A; Foa, Edna B; Gur, Raquel E; Gur, Ruben C; Satterthwaite, Theodore D

2016-11-15

Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences. We investigated whether developmental sex differences in cerebral blood flow mediated sex differences in anxiety and depression symptoms by capitalizing on a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin-labeled magnetic resonance imaging at 3T. Perfusion images were related to trait and state anxiety using general additive models with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty. Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for prescan state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in postpubertal females was mediated by elevated perfusion of the left amygdala. Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during adolescence may be a critical element of the affective neurobiological characteristics underlying sex differences in anxiety and mood symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject. PMID:26721392

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

PubMed

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

2016-09-01

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

Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.

PubMed

van Donkelaar, C C; Huyghe, J M; Vankan, W J; Drost, M R

2001-05-01

The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

PubMed

Halsøy, Kathrine; Kondratiev, Timofey; Tveita, Torkjel; Bjertnaes, Lars J

2016-01-01

Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (P LW ), which was based on body weight (BW) according to the formula: P LW  = 0.0053 BW - 0.48 and presented as Kfc PLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p  < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, Kfc PLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within

Quantification of myocardial blood flow with dynamic perfusion 3.0 Tesla MRI: Validation with (15) O-water PET.

PubMed

Tomiyama, Yuuki; Manabe, Osamu; Oyama-Manabe, Noriko; Naya, Masanao; Sugimori, Hiroyuki; Hirata, Kenji; Mori, Yuki; Tsutsui, Hiroyuki; Kudo, Kohsuke; Tamaki, Nagara; Katoh, Chietsugu

2015-09-01

To develop and validate a method for quantifying myocardial blood flow (MBF) using dynamic perfusion magnetic resonance imaging (MBFMRI ) at 3.0 Tesla (T) and compare the findings with those of (15) O-water positron emission tomography (MBFPET ). Twenty healthy male volunteers underwent magnetic resonance imaging (MRI) and (15) O-water positron emission tomography (PET) at rest and during adenosine triphosphate infusion. The single-tissue compartment model was used to estimate the inflow rate constant (K1). We estimated the extraction fraction of Gd-DTPA using K1 and MBF values obtained from (15) O-water PET for the first 10 subjects. For validation, we calculated MBFMRI values for the remaining 10 subjects and compared them with the MBFPET values. In addition, we compared MBFMRI values of 10 patients with coronary artery disease with those of healthy subjects. The mean resting and stress MBFMRI values were 0.76 ± 0.10 and 3.04 ± 0.82 mL/min/g, respectively, and showed excellent correlation with the mean MBFPET values (r = 0.96, P < 0.01). The mean stress MBFMRI value was significantly lower for the patients (1.92 ± 0.37) than for the healthy subjects (P < 0.001). The use of dynamic perfusion MRI at 3T is useful for estimating MBF and can be applied for patients with coronary artery disease. © 2014 Wiley Periodicals, Inc.

3D ECG- and respiratory-gated non-contrast-enhanced (CE) perfusion MRI for postoperative lung function prediction in non-small-cell lung cancer patients: A comparison with thin-section quantitative computed tomography, dynamic CE-perfusion MRI, and perfusion scan.

PubMed

Ohno, Yoshiharu; Seki, Shinichiro; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Takenaka, Daisuke; Kassai, Yoshimori; Yui, Masao; Sugimura, Kazuro

2015-08-01

To compare predictive capabilities of non-contrast-enhanced (CE)- and dynamic CE-perfusion MRIs, thin-section multidetector computed tomography (CT) (MDCT), and perfusion scan for postoperative lung function in non-small cell lung cancer (NSCLC) patients. Sixty consecutive pathologically diagnosed NSCLC patients were included and prospectively underwent thin-section MDCT, non-CE-, and dynamic CE-perfusion MRIs and perfusion scan, and had their pre- and postoperative forced expiratory volume in one second (FEV1 ) measured. Postoperative percent FEV1 (po%FEV1 ) was then predicted from the fractional lung volume determined on semiquantitatively assessed non-CE- and dynamic CE-perfusion MRIs, from the functional lung volumes determined on quantitative CT, from the number of segments observed on qualitative CT, and from uptakes detected on perfusion scans within total and resected lungs. Predicted po%FEV1 s were then correlated with actual po%FEV1 s, which were %FEV1 s measured postoperatively. The limits of agreement were also determined. All predicted po%FEV1 s showed significant correlation (0.73 ≤ r ≤ 0.93, P < 0.0001) and limits of agreement with actual po%FEV1 (non-CE-perfusion MRI: 0.3 ± 10.0%, dynamic CE-perfusion MRI: 1.0 ± 10.8%, perfusion scan: 2.2 ± 14.1%, quantitative CT: 1.2 ± 9.0%, qualitative CT: 1.5 ± 10.2%). Non-CE-perfusion MRI may be able to predict postoperative lung function more accurately than qualitatively assessed MDCT and perfusion scan. © 2014 Wiley Periodicals, Inc.

Normothermic extracorporeal perfusion of isolated porcine liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Suzuki, Satoshi; Marino, Bruno; Starkey, Graeme K; Chambers, Brenton; Fink, Michael A; Wang, Bao Zhong; Houston, Shane; Eastwood, Glenn; Calzavacca, Paolo; Glassford, Neil; Skene, Alison; Jones, Daryl A; Jones, Robert

2012-09-01

Liver transplantation is a major life-saving procedure, and donation after cardiac death (DCD) has increased the pool of potential liver donors. However, DCD livers are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and, in future, transplant DCD livers. We conducted proof-of-concept experiments using a DCD model in the pig to assess the short-term (4 hours) feasibility and functional efficacy of NELP. Using extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion, and physiological perfusion pressures, we achieved NELP and evidence of function (bile production, paracetamol removal, maintenance of normal ammonia and lactate levels) for 4 hours in pig livers subjected to 15 and 30 minutes of cardiac arrest before explantation. Our experiments justify further investigations of the feasibility and efficacy of human DCD liver preservation by ex-vivo perfusion.

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

PubMed

Strüver, Kay; Friess, Wolfgang; Hedtrich, Sarah

2017-01-01

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

Can dual-energy CT replace perfusion CT for the functional evaluation of advanced hepatocellular carcinoma?

PubMed

Mulé, Sébastien; Pigneur, Frédéric; Quelever, Ronan; Tenenhaus, Arthur; Baranes, Laurence; Richard, Philippe; Tacher, Vania; Herin, Edouard; Pasquier, Hugo; Ronot, Maxime; Rahmouni, Alain; Vilgrain, Valérie; Luciani, Alain

2018-05-01

To determine the degree of relationship between iodine concentrations derived from dual-energy CT (DECT) and perfusion CT parameters in patients with advanced HCC under treatment. In this single-centre IRB approved study, 16 patients with advanced HCC treated with sorafenib or radioembolization who underwent concurrent dynamic perfusion CT and multiphase DECT using a single source, fast kV switching DECT scanner were included. Written informed consent was obtained for all patients. HCC late-arterial and portal iodine concentrations, blood flow (BF)-related and blood volume (BV)-related perfusion parameters maps were calculated. Mixed-effects models of the relationship between iodine concentrations and perfusion parameters were computed. An adjusted p value (Bonferroni method) < 0.05 was considered significant. Mean HCC late-arterial and portal iodine concentrations were 22.7±12.7 mg/mL and 18.7±8.3 mg/mL, respectively. Late-arterial iodine concentration was significantly related to BV (mixed-effects model F statistic (F)=28.52, p<0.0001), arterial BF (aBF, F=17.62, p<0.0001), hepatic perfusion index (F=28.24, p<0.0001), positive enhancement integral (PEI, F=66.75, p<0.0001) and mean slope of increase (F=32.96, p<0.0001), while portal-venous iodine concentration was mainly related to BV (F=29.68, p<0.0001) and PEI (F=66.75, p<0.0001). In advanced HCC lesions, DECT-derived late-arterial iodine concentration is strongly related to both aBF and BV, while portal iodine concentration mainly reflects BV, offering DECT the ability to evaluate both morphological and perfusion changes. • Late-arterial iodine concentration is highly related to arterial BF and BV. • Portal iodine concentration mainly reflects tumour blood volume. • Dual-energy CT offers significantly decreased radiation dose compared with perfusion CT.

Microcirculatory perfusion shift in the gut wall layers induced by extracorporeal circulation.

PubMed

Kalder, Johannes; Ajah, Dieudonne; Keschenau, Paula; Kennes, Lieven N; Tolba, Rene; Kokozidou, Maria; Jacobs, Michael J; Koeppel, Thomas A

2015-02-01

Extracorporeal circulation (ECC) is regularly applied to maintain organ perfusion during major aortic and cardiovascular surgery. During thoracoabdominal aortic repair, ECC-driven selective visceral arterial perfusion (SVP) results in changed microcirculatory perfusion (shift from the muscularis toward the mucosal small intestinal layer) in conjunction with macrohemodynamic hypoperfusion. The underlying mechanism, however, is unclear. Therefore, the aim of this study was to assess in a porcine model whether ECC itself or the hypoperfusion induced by SVP is responsible for the mucosal/muscular shift in the small intestinal wall. A thoracoabdominal aortic approach was performed in 15 healthy pigs divided equally into three groups: group I, control; group II, thoracic aortic cross-clamping with distal aortic perfusion; and group III, thoracic aortic cross-clamping with distal aortic perfusion and SVP. Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurement and fluorescent microspheres. In addition, markers for metabolism and intestinal ischemia-reperfusion injury were determined. ECC with a roller pump induced a significant switch from the muscularis and mucosal layer of the small intestine, even with adequate macrocirculation (mucosal/muscular perfusion ratio: group I vs II, P = .005; group I vs III, P = .0018). Furthermore, the oxygen extraction ratio increased significantly in groups II (>30%) and III (>40%) in the beginning of the ECC compared with the control (group I vs II, P = .0037; group I vs III, P = .0062). Lactate concentrations and pH values did not differ between groups I and II; but group III demonstrated a significant shifting toward a lactate-associated acidosis (lactate: group I vs III, P = .0031; pH: group I vs III, P = .0001). We demonstrated a significant shifting between the small intestinal gut wall layers induced by roller pump-driven ECC. The shift occurs independently of

Meta-Analysis of Stress Myocardial Perfusion Imaging

ClinicalTrials.gov

2017-06-06

Coronary Disease; Echocardiography; Fractional Flow Reserve, Myocardial; Hemodynamics; Humans; Magnetic Resonance Imaging; Myocardial Perfusion Imaging; Perfusion; Predictive Value of Tests; Single Photon Emission Computed Tomography; Positron Emission Tomography; Multidetector Computed Tomography; Echocardiography, Stress; Coronary Angiography

Australian and New Zealand Perfusion Survey: Management and Procedure

PubMed Central

Tuble, Sigrid C.; Willcox, Timothy W.; Baker, Robert A.

2009-01-01

Abstract: In this report, we will discuss management and procedural aspects of perfusion practice. This report allows us to compare and contrast recent trends and changes in perfusion with historic practices. A survey comprised of 233 single-answer and 12 open-ended questions was sent by e-mail to senior perfusionists or individuals in charge of perfusion in 40 hospital groups. The survey encompasses a review of the perfusion practices for the calendar year of 2003, and respondents were required to answer the survey based on the predominant practice in their institutions. Standard management of routine adult cardiopulmonary bypass (CPB) in 2003 consisted of perfusion strategies that achieved a target temperature of 32.0°C (range, 28.0–35.0°C), a flow index of 2.4 L/min/m2 (range, 1.6–3.0 L/min/m2) during normothermia and 1.8 L/min/m2 (range, 1.2–3.0 L/min/m2) during hypothermia, and a pressure during CPB between 50 (range, 30–65 mmHg) and 70 mmHg (range, 60–95 mmHg). Myocardial protection with blood cardioplegia was used in 77% of the 20,688 CPB cases, whereas in 53% cases, cardiotomy blood was never processed. Pre-operatively, 76% of perfusion groups assessed their patients (21% directly with the patient), and 85% responded that perfusionists performed or participated in a formal pre-bypass checklist. The majority of the perfusion groups used a handwritten perfusion record (62%), 12% used an electronic perfusion record, and 26% used both, whereas more than one half of the groups were involved in quality assurance (79%), incident reporting (74%), audits (62%), research (53%), participating in interdisciplinary meetings (53%), and morbidity and mortality meetings (65%). Only 26% conducted formal perfusion team meetings. This report outlines the status of clinical management and procedural performance for perfusion practices in Australia and New Zealand in 2003. Awareness of these trends will allow perfusionists to assess both individual practices and

Perfusion Scintigraphy and Patient Selection for Lung Volume Reduction Surgery

PubMed Central

Chandra, Divay; Lipson, David A.; Hoffman, Eric A.; Hansen-Flaschen, John; Sciurba, Frank C.; DeCamp, Malcolm M.; Reilly, John J.; Washko, George R.

2010-01-01

Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS. Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung. PMID:20538961

Perfusion scintigraphy and patient selection for lung volume reduction surgery.

PubMed

Chandra, Divay; Lipson, David A; Hoffman, Eric A; Hansen-Flaschen, John; Sciurba, Frank C; Decamp, Malcolm M; Reilly, John J; Washko, George R

2010-10-01

It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). To study the role of perfusion scintigraphy in patient selection for LVRS. We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non-high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non-upper lobe-predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Among 284 of 1,045 patients with upper lobe-predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe-predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non-upper lobe-predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe-predominant emphysema when there is low rather than high perfusion to the upper lung.

Vastly accelerated linear least-squares fitting with numerical optimization for dual-input delay-compensated quantitative liver perfusion mapping.

PubMed

Jafari, Ramin; Chhabra, Shalini; Prince, Martin R; Wang, Yi; Spincemaille, Pascal

2018-04-01

To propose an efficient algorithm to perform dual input compartment modeling for generating perfusion maps in the liver. We implemented whole field-of-view linear least squares (LLS) to fit a delay-compensated dual-input single-compartment model to very high temporal resolution (four frames per second) contrast-enhanced 3D liver data, to calculate kinetic parameter maps. Using simulated data and experimental data in healthy subjects and patients, whole-field LLS was compared with the conventional voxel-wise nonlinear least-squares (NLLS) approach in terms of accuracy, performance, and computation time. Simulations showed good agreement between LLS and NLLS for a range of kinetic parameters. The whole-field LLS method allowed generating liver perfusion maps approximately 160-fold faster than voxel-wise NLLS, while obtaining similar perfusion parameters. Delay-compensated dual-input liver perfusion analysis using whole-field LLS allows generating perfusion maps with a considerable speedup compared with conventional voxel-wise NLLS fitting. Magn Reson Med 79:2415-2421, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Perfusion-related stimuli for compensatory lung growth following pneumonectomy

PubMed Central

Dane, D. Merrill; Yilmaz, Cuneyt; Gyawali, Dipendra; Iyer, Roshni; Ravikumar, Priya; Estrera, Aaron S.

2016-01-01

Following pneumonectomy (PNX), two separate mechanical forces act on the remaining lung: parenchymal stress caused by lung expansion, and microvascular distension and shear caused by increased perfusion. We previously showed that parenchymal stress and strain explain approximately one-half of overall compensation; the remainder was presumptively attributed to perfusion-related factors. In this study, we directly tested the hypothesis that perturbation of regional pulmonary perfusion modulates post-PNX lung growth. Adult canines underwent banding of the pulmonary artery (PAB) to the left caudal (LCa) lobe, which caused a reduction in basal perfusion to LCa lobe without preventing the subsequent increase in its perfusion following right PNX while simultaneously exaggerating the post-PNX increase in perfusion to the unbanded lobes, thereby creating differential perfusion changes between banded and unbanded lobes. Control animals underwent sham pulmonary artery banding followed by right PNX. Pulmonary function, regional pulmonary perfusion, and high-resolution computed tomography of the chest were analyzed pre-PNX and 3-mo post-PNX. Terminally, the remaining lobes were fixed for detailed morphometric analysis. Results were compared with corresponding lobes in two control (Sham banding and normal unoperated) groups. PAB impaired the indices of post-PNX extravascular alveolar tissue growth by up to 50% in all remaining lobes. PAB enhanced the expected post-PNX increase in alveolar capillary formation, measured by the prevalence of double-capillary profiles, in both unbanded and banded lobes. We conclude that perfusion distribution provides major stimuli for post-PNX compensatory lung growth independent of the stimuli provided by lung expansion and parenchymal stress and strain. PMID:27150830

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

PubMed

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

2017-07-05

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

Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement.

PubMed

Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

2016-09-01

Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart-lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart-lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart-lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures.

Stability of radiomic features in CT perfusion maps

NASA Astrophysics Data System (ADS)

Bogowicz, M.; Riesterer, O.; Bundschuh, R. A.; Veit-Haibach, P.; Hüllner, M.; Studer, G.; Stieb, S.; Glatz, S.; Pruschy, M.; Guckenberger, M.; Tanadini-Lang, S.

2016-12-01

This study aimed to identify a set of stable radiomic parameters in CT perfusion (CTP) maps with respect to CTP calculation factors and image discretization, as an input for future prognostic models for local tumor response to chemo-radiotherapy. Pre-treatment CTP images of eleven patients with oropharyngeal carcinoma and eleven patients with non-small cell lung cancer (NSCLC) were analyzed. 315 radiomic parameters were studied per perfusion map (blood volume, blood flow and mean transit time). Radiomics robustness was investigated regarding the potentially standardizable (image discretization method, Hounsfield unit (HU) threshold, voxel size and temporal resolution) and non-standardizable (artery contouring and noise threshold) perfusion calculation factors using the intraclass correlation (ICC). To gain added value for our model radiomic parameters correlated with tumor volume, a well-known predictive factor for local tumor response to chemo-radiotherapy, were excluded from the analysis. The remaining stable radiomic parameters were grouped according to inter-parameter Spearman correlations and for each group the parameter with the highest ICC was included in the final set. The acceptance level was 0.9 and 0.7 for the ICC and correlation, respectively. The image discretization method using fixed number of bins or fixed intervals gave a similar number of stable radiomic parameters (around 40%). The potentially standardizable factors introduced more variability into radiomic parameters than the non-standardizable ones with 56-98% and 43-58% instability rates, respectively. The highest variability was observed for voxel size (instability rate  >97% for both patient cohorts). Without standardization of CTP calculation factors none of the studied radiomic parameters were stable. After standardization with respect to non-standardizable factors ten radiomic parameters were stable for both patient cohorts after correction for inter-parameter correlations. Voxel size

Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans.

PubMed

Buck, Amanda K W; Elder, Christopher P; Donahue, Manus J; Damon, Bruce M

2015-08-01

Studying the magnitude and kinetics of blood flow, oxygen extraction, and oxygen consumption at exercise onset and during the recovery from exercise can lead to insights into both the normal control of metabolism and blood flow and the disturbances to these processes in metabolic and cardiovascular diseases. The purpose of this study was to examine the on- and off-kinetics for oxygen delivery, extraction, and consumption as functions of submaximal contraction intensity. Eight healthy subjects performed four 1-min isometric dorsiflexion contractions, with two at 20% MVC and two at 40% MVC. During one contraction at each intensity, relative perfusion changes were measured by using arterial spin labeling, and the deoxyhemoglobin percentage (%HHb) was estimated using the spin- and gradient-echo sequence and a previously published empirical calibration. For the whole group, the mean perfusion did not increase during contraction. The %HHb increased from ∼28 to 38% during contractions of each intensity, with kinetics well described by an exponential function and mean response times (MRTs) of 22.7 and 21.6 s for 20 and 40% MVC, respectively. Following contraction, perfusion increased ∼2.5-fold. The %HHb, oxygen consumption, and perfusion returned to precontraction levels with MRTs of 27.5, 46.4, and 50.0 s, respectively (20% MVC), and 29.2, 75.3, and 86.0 s, respectively (40% MVC). These data demonstrate in human subjects the varied recovery rates of perfusion and oxygen consumption, along with the similar rates of %HHb recovery, across these exercise intensities. Copyright © 2015 the American Physiological Society.

Nuclear cardiology: Myocardial perfusion and function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seldin, D.W.

1991-08-01

Myocardial perfusion studies continue to be a major focus of research, with new investigations of the relationship of exercise-redistribution thallium imaging to diagnosis, prognosis, and case management. The redistribution phenomenon, which seemed to be fairly well understood a few years ago, is now recognized to be much more complex than originally thought, and various strategies have been proposed to clarify the meaning of persistent defects. Pharmacologic intervention with dipyridamole and adenosine has become available as an alternative to exercise, and comparisons with exercise imaging and catheterization results have been described. Thallium itself is no longer the sole single-photon perfusion radiopharmaceutical;more » two new technetium agents are now widely available. In addition to perfusion studies, advances in the study of ventricular function have been made, including reports of studies performed in conjunction with technetium perfusion studies, new insights into cardiac physiology, and the prognostic and case-management information that function studies provide. Finally, work has continued with monoclonal antibodies for the identification of areas of myocyte necrosis. 41 references.« less

A reappraisal of retrograde cerebral perfusion

PubMed Central

2013-01-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

Robust and efficient pharmacokinetic parameter non-linear least squares estimation for dynamic contrast enhanced MRI of the prostate.

PubMed

Kargar, Soudabeh; Borisch, Eric A; Froemming, Adam T; Kawashima, Akira; Mynderse, Lance A; Stinson, Eric G; Trzasko, Joshua D; Riederer, Stephen J

2018-05-01

To describe an efficient numerical optimization technique using non-linear least squares to estimate perfusion parameters for the Tofts and extended Tofts models from dynamic contrast enhanced (DCE) MRI data and apply the technique to prostate cancer. Parameters were estimated by fitting the two Tofts-based perfusion models to the acquired data via non-linear least squares. We apply Variable Projection (VP) to convert the fitting problem from a multi-dimensional to a one-dimensional line search to improve computational efficiency and robustness. Using simulation and DCE-MRI studies in twenty patients with suspected prostate cancer, the VP-based solver was compared against the traditional Levenberg-Marquardt (LM) strategy for accuracy, noise amplification, robustness to converge, and computation time. The simulation demonstrated that VP and LM were both accurate in that the medians closely matched assumed values across typical signal to noise ratio (SNR) levels for both Tofts models. VP and LM showed similar noise sensitivity. Studies using the patient data showed that the VP method reliably converged and matched results from LM with approximate 3× and 2× reductions in computation time for the standard (two-parameter) and extended (three-parameter) Tofts models. While LM failed to converge in 14% of the patient data, VP converged in the ideal 100%. The VP-based method for non-linear least squares estimation of perfusion parameters for prostate MRI is equivalent in accuracy and robustness to noise, while being more reliably (100%) convergent and computationally about 3× (TM) and 2× (ETM) faster than the LM-based method. Copyright © 2017 Elsevier Inc. All rights reserved.

Fully automatic registration and segmentation of first-pass myocardial perfusion MR image sequences.

PubMed

Gupta, Vikas; Hendriks, Emile A; Milles, Julien; van der Geest, Rob J; Jerosch-Herold, Michael; Reiber, Johan H C; Lelieveldt, Boudewijn P F

2010-11-01

Derivation of diagnostically relevant parameters from first-pass myocardial perfusion magnetic resonance images involves the tedious and time-consuming manual segmentation of the myocardium in a large number of images. To reduce the manual interaction and expedite the perfusion analysis, we propose an automatic registration and segmentation method for the derivation of perfusion linked parameters. A complete automation was accomplished by first registering misaligned images using a method based on independent component analysis, and then using the registered data to automatically segment the myocardium with active appearance models. We used 18 perfusion studies (100 images per study) for validation in which the automatically obtained (AO) contours were compared with expert drawn contours on the basis of point-to-curve error, Dice index, and relative perfusion upslope in the myocardium. Visual inspection revealed successful segmentation in 15 out of 18 studies. Comparison of the AO contours with expert drawn contours yielded 2.23 ± 0.53 mm and 0.91 ± 0.02 as point-to-curve error and Dice index, respectively. The average difference between manually and automatically obtained relative upslope parameters was found to be statistically insignificant (P = .37). Moreover, the analysis time per slice was reduced from 20 minutes (manual) to 1.5 minutes (automatic). We proposed an automatic method that significantly reduced the time required for analysis of first-pass cardiac magnetic resonance perfusion images. The robustness and accuracy of the proposed method were demonstrated by the high spatial correspondence and statistically insignificant difference in perfusion parameters, when AO contours were compared with expert drawn contours. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

Enhanced perfusion defect clarity and inhomogeneity in smokers' lungs with deep-inspiratory breath-hold perfusion SPECT images.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Iwanaga, Hideyuki; Hayashi, Norio; Yamashita, Tomio; Matsunaga, Naofumi

2005-09-01

Deep-inspiratory breath-hold (DIBrH) Tc-99m-macroaggregated albumin (MAA) SPECT images were developed to accurately evaluate perfusion impairment in smokers' lungs. DIBrH SPECT was performed in 28 smokers with or without low attenuation areas (LAA) on CT images, using a triple-headed SPECT system and a laser light respiratory tracking device. DIBrH SPECT images were reconstructed from every 4 degrees projection of five adequate 360 degrees projection data sets with almost the same respiratory dimension at 20 sec DIBrH. Perfusion defect clarity was assessed by the lesion (defect)-to-contralateral normal lung count ratios (L/N ratios). Perfusion inhomogeneity was assessed by the coefficient of variation (CV) values of pixel counts and correlated with the diffusing capacity of the lungs for carbon monoxide/alveolar volume (DLCO/VA) ratios. The results were compared with those on conventional images. Five DIBrH projection data sets with minimal dimension differences of 2.9+/-0.6 mm were obtained in all subjects. DIBrH images enhanced perfusion defects compared with conventional images, with significantly higher L/N ratios (P<0.0001), and detected a total of 109 (26.9%) additional detects (513 vs. 404), with excellent inter-observer agreement (kappa value of 0.816). CV values in the smokers' lungs on DIBrH images were also significantly higher compared with those on conventional images (0.31+/-0.10 vs. 0.19+/-0.06, P<0.0001). CV values in smokers on DIBrH images showed a significantly closer correlation with DLCO/VA ratios compared with conventional images (R = 0.872, P<0.0001 vs. R=0.499, P<0.01). By reducing adverse effect of respiratory motion, DIBrH SPECT images enhance perfusion defect clarity and inhomogeneity, and provide more accurate assessment of impaired perfusion in smokers' lungs compared with conventional images.

Computed Tomography Perfusion Imaging for the Diagnosis of Hepatic Alveolar Echinococcosis

PubMed Central

Sade, Recep; Kantarci, Mecit; Genc, Berhan; Ogul, Hayri; Gundogdu, Betul; Yilmaz, Omer

2018-01-01

Objective: Alveolar echinococcosis (AE) is a rare life-threatening parasitic infection. Computed tomography perfusion (CTP) imaging has the potential to provide both quantitative and qualitative information about the tissue perfusion characteristics. The purpose of this study was the examination of the characteristic features and feasibility of CTP in AE liver lesions. Material and Methods: CTP scanning was performed in 25 patients who had a total of 35 lesions identified as AE of the liver. Blood flow (BF), blood volume (BV), portal venous perfusion (PVP), arterial liver perfusion (ALP), and hepatic perfusion indexes (HPI) were computed for background liver parenchyma and each AE lesion. Results: Significant differences were detected between perfusion values of the AE lesions and background liver tissue. The BV, BF, ALP, and PVP values for all components of the AE liver lesions were significantly lower than the normal liver parenchyma (p<0.01). Conclusions: We suggest that perfusion imaging can be used in AE of the liver. Thus, the quantitative knowledge of perfusion parameters are obtained via CT perfusion imaging. PMID:29531482

The effect of the sample size and location on contrast ultrasound measurement of perfusion parameters.

PubMed

Leinonen, Merja R; Raekallio, Marja R; Vainio, Outi M; Ruohoniemi, Mirja O; O'Brien, Robert T

2011-01-01

Contrast-enhanced ultrasound can be used to quantify tissue perfusion based on region of interest (ROI) analysis. The effect of the location and size of the ROI on the obtained perfusion parameters has been described in phantom, ex vivo and in vivo studies. We assessed the effects of location and size of the ROI on perfusion parameters in the renal cortex of 10 healthy, anesthetized cats using Definity contrast-enhanced ultrasound to estimate the importance of the ROI on quantification of tissue perfusion with contrast-enhanced ultrasound. Three separate sets of ROIs were placed in the renal cortex, varying in location, size or depth. There was a significant inverse association between increased depth or increased size of the ROI and peak intensity (P < 0.05). There was no statistically significant difference in the peak intensity between the ROIs placed in a row in the near field cortex. There was no significant difference in the ROIs with regard to arrival time, time to peak intensity and wash-in rate. When comparing two different ROIs in a patient with focal lesions, such as suspected neoplasia or infarction, the ROIs should always be placed at same depth and be as similar in size as possible.

Brain perfusion alterations in tick-borne encephalitis-preliminary report.

PubMed

Tyrakowska-Dadełło, Zuzanna; Tarasów, Eugeniusz; Janusek, Dariusz; Moniuszko-Malinowska, Anna; Zajkowska, Joanna; Pancewicz, Sławomir

2018-03-01

Magnetic resonance imaging (MRI) changes in tick-borne encephalitis (TBE) are non-specific and the pathophysiological mechanisms leading to their formation remain unclear. This study investigated brain perfusion in TBE patients using dynamic susceptibility-weighted contrast-enhanced magnetic resonance perfusion imaging (DSC-MRI perfusion). MRI scans were performed for 12 patients in the acute phase, 3-5days after the diagnosis of TBE. Conventional MRI and DSC-MRI perfusion studies were performed. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) parametric maps were created. The bilateral frontal, parietal, and temporal subcortical regions and thalamus were selected as regions of interest. Perfusion parameters of TBE patients were compared to those of a control group. There was a slight increase in CBF and CBV, with significant prolongation of TTP in subcortical areas in the study subjects, while MTT values were comparable to those of the control group. A significant increase in thalamic CBF (p<0.001) and increased CBV (p<0.05) were observed. Increased TTP and a slight reduction in MTT were also observed within this area. The DSC-MRI perfusion study showed that TBE patients had brain perfusion disturbances, expressed mainly in the thalami. These results suggest that DSC-MRI perfusion may provide important information regarding the areas affected in TBE patients. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2009-05-01

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

Evaluation of pharmacokinetic models for perfusion imaging with dynamic contrast-enhanced magnetic resonance imaging in porcine skeletal muscle using low-molecular-weight contrast agents.

PubMed

Hindel, Stefan; Papanastasiou, Giorgos; Wust, Peter; Maaß, Marc; Söhner, Anika; Lüdemann, Lutz

2018-06-01

Pharmacokinetic models for perfusion quantification with a low-molecular-weight contrast agent (LMCA) in skeletal muscle using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were evaluated. Tissue perfusion was measured in seven regions of interest (ROIs) placed in the total hind leg supplied by the femoral artery in seven female pigs. DCE-MRI was performed using a 3D gradient echo sequence with k-space sharing. The sequence was acquired twice, first after LMCA and then after blood pool contrast agent injection. Blood flow was augmented by continuous infusion of the vasodilator adenosine into the femoral artery, resulting in up to four times increased blood flow. The results obtained with several LMCA models were compared with those of a two-compartment blood pool model (2CBPM) consisting of a capillary and an arteriolar compartment. Measurements performed with a Doppler flow probe placed at the femoral artery served as ground truth. The two-compartment exchange model extended by an arteriolar compartment (E2CXM) showed the highest fit quality of all LMCA models and the most significant correlation with the Doppler measurements, r = 0.78 (P < 0.001). The best correspondence between the capillary perfusion measurements of the LMCA models and those of the 2CBPM was found with the E2CXM (slope of the regression line equal to 1, r = 0.85, P < 0.001). The results for the clinical patient data corresponded very well with the results obtained in the animal experiments. Double-contrast agent DCE-MRI in combination with the E2CXM yields the most reliable results and can be used in clinical routine. Magn Reson Med 79:3154-3162, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Relationship between perfusion index and patent ductus arteriosus in preterm infants.

PubMed

Gomez-Pomar, Enrique; Makhoul, Majd; Westgate, Philip M; Ibonia, Katrina T; Patwardhan, Abhijit; Giannone, Peter J; Bada, Henrietta S; Abu Jawdeh, Elie G

2017-05-01

Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. We obtained 31 echocardiography observations. Mean ΔPI (-0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Over-vibration induced blood perfusion and vascular permeability changes may lead to vocal edema.

PubMed

Wang, Jiajia; Devine, Erin; Fang, Rui; Jiang, Jack J

2017-01-01

To observe blood perfusion and vascular permeability changes under varying vibration frequency exposures. Animal model. Blood perfusion was measured using laser Doppler flowmetry in eight rabbit auricular vessels (four rabbits) under nonvibration, and 62.5-Hz/1-mm, 125-Hz/1-mm, and 250-Hz/0.5-mm vibration frequency/amplitude exposures. Another 12 rabbits were randomly divided into vibration only and vibration with histamine groups. After 3 hours of continuous 125-Hz, 1-mm amplitude vibration of the auricle, vascular permeability was analyzed by absorbance of Evans blue-albumin complex. Significantly lower blood perfusion was observed in the vibration group, compared with no vibration exposure controls. Blood perfusion decreased 29 ± 16% as the vibration frequency was increased from 62.5 Hz to 125 Hz with the vibration amplitude constant at 1 mm. When the frequency was increased from 125 Hz to 250 Hz, while the amplitude was decreased from 1 mm to 0.5 mm, blood flow perfusion further decreased 29 ± 29%, and the decline tendency in blood perfusion showed no significant difference (P = .992). Meanwhile, in the vibration with histamine group, vascular permeability of the vibrated ears increased significantly compared to the nonvibrated ears (P = .005). Overvibration of the vocal folds due to voice overuse or abuse may significantly reduce blood perfusion, and increase vascular permeability in the vocal fold in inflammatory situations, which may lead to the formation of vocal edema. NA Laryngoscope, 127:148-152, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The use of hemoglobin solutions in kidney perfusions.

PubMed

Daniels, F H; McCabe, R E; Leonard, E F

1984-01-01

Solutions of hemoglobin have often been considered for both hypothermic and normothermic perfusion of isolated kidneys. This paper considers basic issues, preparative techniques, and the viscosity of hemoglobin solutions, as well as the demands made by the kidney on a perfusate. The natural system of oxygen transport in higher animals is complex, and its perturbation to produce convenient hemoglobin-based renal perfusates produces numerous problems. The desirable effect of 2,3-diphosphoglycerate is not easily maintained in a perfusate, but its inclusion can be avoided by appropriate choice of species donating hemoglobin. Hemoglobin tetramer in free solution may dissociate and be lost by glomerular filtration. Ferric hemoglobin, the dominant form at redox equilibrium, is useless for oxygen transport; the ferrous form is maintained in the erythrocyte by reducing metabolites and, under normothermic conditions, the ferrous to ferric conversion is slow but significant. Methods for lysis of erythrocytes and removal of their stroma are discussed; reduction of ferric hemoglobin by chemical agents and electrolysis are considered in detail; and means for adjusting concentration and solute background are presented. The need for carbonic anhydrase in hemoglobin solutions used as perfusates is shown and methods for its provision are discussed. A review of viscometric data for hemoglobin solutions is provided to which original data are added. Hemoglobin solutions show a temperature-independent intrinsic viscosity, according to Einstein's theory for a molecule of 23 A radius. The O2 and CO2 transport requirements of renal perfusates are analyzed comprehensively. The normothermic kidney has an unusual respiration pattern, requiring an amount of oxygen that is not fixed but, rather, proportional to the total blood flow rate. In canines the average arterio-venous O2 content difference found by many investigators is 2.14 vol%; the corresponding CO2 value is 2.47 vol%; and the

Regional cardiac wall motion from gated myocardial perfusion SPECT studies

NASA Astrophysics Data System (ADS)

Smith, M. F.; Brigger, P.; Ferrand, S. K.; Dilsizian, V.; Bacharach, S. L.

1999-06-01

A method for estimating regional epicardial and endocardial wall motion from gated myocardial perfusion SPECT studies has been developed. The method uses epicardial and endocardial boundaries determined from four long-axis slices at each gate of the cardiac cycle. The epicardial and endocardial wall position at each time gate is computed with respect to stationary reference ellipsoids, and wall motion is measured along lines normal to these ellipsoids. An initial quantitative evaluation of the method was made using the beating heart from the dynamic mathematical cardiac torso (MCAT) phantom, with and without a 1.5-cm FWHM Gaussian blurring filter. Epicardial wall motion was generally well-estimated within a fraction of a 3.56-mm voxel, although apical motion was overestimated with the Gaussian filter. Endocardial wall motion was underestimated by about two voxels with and without the Gaussian filter. The MCAT heart phantom was modified to model hypokinetic and dyskinetic wall motion. The wall motion analysis method enabled this abnormal motion to be differentiated from normal motion. Regional cardiac wall motion also was analyzed for /sup 201/Tl patient studies. Estimated wall motion was consistent with a nuclear medicine physician's visual assessment of motion from gated long-axis slices for male and female study examples. Additional research is required for a comprehensive evaluation of the applicability of the method to patient studies with normal and abnormal wall motion.

Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry.

PubMed

Fredriksson, Ingemar; Burdakov, Oleg; Larsson, Marcus; Strömberg, Tomas

2013-12-01

The tissue fraction of red blood cells (RBCs) and their oxygenation and speed-resolved perfusion are estimated in absolute units by combining diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF). The DRS spectra (450 to 850 nm) are assessed at two source-detector separations (0.4 and 1.2 mm), allowing for a relative calibration routine, whereas LDF spectra are assessed at 1.2 mm in the same fiber-optic probe. Data are analyzed using nonlinear optimization in an inverse Monte Carlo technique by applying an adaptive multilayered tissue model based on geometrical, scattering, and absorbing properties, as well as RBC flow-speed information. Simulations of 250 tissue-like models including up to 2000 individual blood vessels were used to evaluate the method. The absolute root mean square (RMS) deviation between estimated and true oxygenation was 4.1 percentage units, whereas the relative RMS deviations for the RBC tissue fraction and perfusion were 19% and 23%, respectively. Examples of in vivo measurements on forearm and foot during common provocations are presented. The method offers several advantages such as simultaneous quantification of RBC tissue fraction and oxygenation and perfusion from the same, predictable, sampling volume. The perfusion estimate is speed resolved, absolute (% RBC×mm/s), and more accurate due to the combination with DRS.

Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry

NASA Astrophysics Data System (ADS)

Fredriksson, Ingemar; Burdakov, Oleg; Larsson, Marcus; Strömberg, Tomas

2013-12-01

The tissue fraction of red blood cells (RBCs) and their oxygenation and speed-resolved perfusion are estimated in absolute units by combining diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF). The DRS spectra (450 to 850 nm) are assessed at two source-detector separations (0.4 and 1.2 mm), allowing for a relative calibration routine, whereas LDF spectra are assessed at 1.2 mm in the same fiber-optic probe. Data are analyzed using nonlinear optimization in an inverse Monte Carlo technique by applying an adaptive multilayered tissue model based on geometrical, scattering, and absorbing properties, as well as RBC flow-speed information. Simulations of 250 tissue-like models including up to 2000 individual blood vessels were used to evaluate the method. The absolute root mean square (RMS) deviation between estimated and true oxygenation was 4.1 percentage units, whereas the relative RMS deviations for the RBC tissue fraction and perfusion were 19% and 23%, respectively. Examples of in vivo measurements on forearm and foot during common provocations are presented. The method offers several advantages such as simultaneous quantification of RBC tissue fraction and oxygenation and perfusion from the same, predictable, sampling volume. The perfusion estimate is speed resolved, absolute (% RBC×mm/s), and more accurate due to the combination with DRS.

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

PubMed

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

2015-12-01

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

Oral alprazolam acutely increases nucleus accumbens perfusion

PubMed Central

Wolf, Daniel H.; Pinkham, Amy E.; Satterthwaite, Theodore D.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey; Smith, Mark A.; Detre, John A.; Gur, Ruben C.; Gur, Raquel E.

2014-01-01

Benzodiazepines treat anxiety, but can also produce euphoric effects, contributing to abuse. Using perfusion magnetic resonance imaging, we provide the first direct evidence in humans that alprazolam (Xanax) acutely increases perfusion in the nucleus accumbens, a key reward-processing region linked to addiction. PMID:23070072

Magnetic Particle Imaging for Real-Time Perfusion Imaging in Acute Stroke.

PubMed

Ludewig, Peter; Gdaniec, Nadine; Sedlacik, Jan; Forkert, Nils D; Szwargulski, Patryk; Graeser, Matthias; Adam, Gerhard; Kaul, Michael G; Krishnan, Kannan M; Ferguson, R Matthew; Khandhar, Amit P; Walczak, Piotr; Fiehler, Jens; Thomalla, Götz; Gerloff, Christian; Knopp, Tobias; Magnus, Tim

2017-10-24

The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.

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

PubMed

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

2016-11-21

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

Quantitative Myocardial Perfusion Imaging Versus Visual Analysis in Diagnosing Myocardial Ischemia: A CE-MARC Substudy.

PubMed

Biglands, John D; Ibraheem, Montasir; Magee, Derek R; Radjenovic, Aleksandra; Plein, Sven; Greenwood, John P

2018-05-01

This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial

Pulmonary vascular volume ratio measured by cardiac computed tomography in children and young adults with congenital heart disease: comparison with lung perfusion scintigraphy.

PubMed

Goo, Hyun Woo; Park, Sang Hyub

2017-11-01

Lung perfusion scintigraphy is regarded as the gold standard for evaluating differential lung perfusion ratio in congenital heart disease. To compare cardiac CT with lung perfusion scintigraphy for estimated pulmonary vascular volume ratio in patients with congenital heart disease. We included 52 children and young adults (median age 4 years, range 2 months to 28 years; 31 males) with congenital heart disease who underwent cardiac CT and lung perfusion scintigraphy without an interim surgical or transcatheter intervention and within 1 year. We calculated the right and left pulmonary vascular volumes using threshold-based CT volumetry. Then we compared right pulmonary vascular volume percentages at cardiac CT with right lung perfusion percentages at lung perfusion scintigraphy by using paired t-test and Bland-Altman analysis. The right pulmonary vascular volume percentages at cardiac CT (66.3 ± 14.0%) were significantly smaller than the right lung perfusion percentages at lung perfusion scintigraphy (69.1 ± 15.0%; P=0.001). Bland-Altman analysis showed a mean difference of -2.8 ± 5.8% and 95% limits of agreement (-14.1%, 8.5%) between these two variables. Cardiac CT, in a single examination, can offer pulmonary vascular volume ratio in addition to pulmonary artery anatomy essential for evaluating peripheral pulmonary artery stenosis in patients with congenital heart disease. However there is a wide range of agreement between cardiac CT and lung perfusion scintigraphy.

Evaluation of heart perfusion in patients with acute myocardial infarction using dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Nielsen, Gitte; Fritz-Hansen, Thomas; Dirks, Christina G; Jensen, Gorm B; Larsson, Henrik B W

2004-09-01

To investigate the diagnostic ability of quantitative magnetic resonance imaging (MRI) heart perfusion in acute heart patients, a fast, multislice dynamic contrast-enhanced MRI sequence was applied to patients with acute myocardial infarction. Seven patients with acute transmural myocardial infarction were studied using a Turbo-fast low angle shot (FLASH) MRI sequence to monitor the first pass of an extravascular contrast agent (CA), gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Quantitation of perfusion, expressed as Ki (mL/100 g/minute), in five slices, each having 60 sectors, provided an estimation of the severity and extent of the perfusion deficiency. Reperfusion was assessed both by noninvasive criteria and by coronary angiography (CAG). The Ki maps clearly delineated the infarction in all patients. Thrombolytic treatment was clearly beneficial in one case, but had no effect in the two other cases. Over the time-course of the study, normal perfusion values were not reestablished following thrombolytic treatment in all cases investigated. This study shows that quantitative MRI perfusion values can be obtained from acutely ill patients following acute myocardial infarction. The technique provides information on both the volume and severity of affected myocardial tissue, enabling the power of treatment regimes to be assessed objectively, and this approach should aid individual patient stratification and prognosis. Copyright 2004 Wiley-Liss, Inc.

Magnetic Resonance Imaging of Ventilation and Perfusion in the Lung

NASA Technical Reports Server (NTRS)

Prisk, Gordon Kim (Inventor); Hopkins, Susan Roberta (Inventor); Pereira De Sa, Rui Carlos (Inventor); Theilmann, Rebecca Jean (Inventor); Buxton, Richard Bruce (Inventor); Cronin, Matthew Vincent (Inventor)

2017-01-01

Methods, devices, and systems are disclosed for implementing a fully quantitative non-injectable contrast proton MRI technique to measure spatial ventilation-perfusion (VA/Q) matching and spatial distribution of ventilation and perfusion. In one aspect, a method using MRI to characterize ventilation and perfusion in a lung includes acquiring an MR image of the lung having MR data in a voxel and obtaining a breathing frequency parameter, determining a water density value, a specific ventilation value, and a perfusion value in at least one voxel of the MR image based on the MR data and using the water density value to determine an air content value, and determining a ventilation-perfusion ratio value that is the product of the specific ventilation value, the air content value, the inverse of the perfusion value, and the breathing frequency.

Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion.

PubMed

Iskender, Ilker; Cosgun, Tugba; Arni, Stephan; Trinkwitz, Michael; Fehlings, Stefan; Yamada, Yoshito; Cesarovic, Nikola; Yu, Keke; Frauenfelder, Thomas; Jungraithmayr, Wolfgang; Weder, Walter; Inci, Ilhan

2017-05-20

Ex vivo lung perfusion (EVLP) has improved the process of donor lung management. Cytokine accumulation during EVLP has been shown to correlate with worse outcome after lung transplantation. Our objective in this study was to test the safety and efficacy of cytokine filtration during EVLP in a large animal model. Pig donor lungs were preserved for 24 hours at 4°C, followed by 12 hours of EVLP, according to the Toronto protocol. The perfusate was continuously run through an absorbent device (CytoSorb) via a veno-venous shunt from the reservoir in the filter group. EVLP was performed according to the standard protocol in the control group (n = 5 each). EVLP physiology, lung X-ray, perfusate biochemistry, inflammatory response and microscopic injury were assessed. Cytokine filtration significantly improved airway pressure and dynamic compliance during the 12-hour perfusion period. Lung X-rays acquired at the end of perfusion showed increased consolidation in the control group. Electrolyte imbalance, determined by increased hydrogen, potassium and calcium ion concentrations in the perfusate, was markedly worsened in the control group. Glucose consumption and lactate production were markedly reduced, along with the lactate/pyruvate ratio in the filter group. Cytokine expression profile, tissue myeloperoxidase activity and microscopic lung injury were significantly reduced in the filter group. Continuous perfusate filtration through sorbent beads is effective and safe during prolonged EVLP. Cytokine removal decreased the development of pulmonary edema and electrolyte imbalance through the suppression of anaerobic glycolysis and neutrophil activation in this setting. Further studies are needed to test the beneficial effect of cytokine filtration on post-transplant lung function. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.

PubMed

Ball, Owen; Nguyen, Bao-Ngoc B; Placone, Jesse K; Fisher, John P

2016-12-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

PubMed Central

Ball, Owen; Nguyen, Bao-Ngoc B.; Placone, Jesse K.; Fisher, John P.

2016-01-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID:27272210

Developments in laser Doppler blood perfusion monitoring

NASA Astrophysics Data System (ADS)

Leahy, Martin J.; de Mul, Frits F. M.; Nilsson, Gert E.; Maniewski, Roman; Liebert, Adam

2003-03-01

This paper reviews the development and use of laser Doppler perfusion monitors and imagers. Despite their great success and almost universal applicability in microcirculation research, they have had great difficulty in converting to widespread clinical application. The enormous interest in microvascular blood perfusion coupled with the 'ease of use' of the technique has led to 2000+ publications citing its use. However, useful results can only be achieved with an understanding of the basic principles of the instrumentation and its application in the various clinical disciplines. The basic technical background is explored and definitions of blood perfusion and laser Doppler perfusion are established. The calibration method is then described together with potential routes to standardisation. A guide to the limitations in application of the technique gives the user a clear indication of what can be achieved in new studies as well as possible inadequacy in some published investigations. Finally some clinical applications have found acceptability and these will be explored.

Relationship between dynamic infrared thermal images and blood perfusion rate of the tongue in anaemia patients

NASA Astrophysics Data System (ADS)

Xie, Haiwei; Zhang, Yan

2018-03-01

The relationship between dynamic infrared (IR) thermal images and blood perfusion rate of the tongues of anaemia patients was investigated. Blood perfusion rates at multiple locations on the tongues of 62 anaemia patients and 70 control subjects were measured. For both groups of subjects, dynamic IR thermal images were also recorded within 16 s after the mouth opened. The results showed that the blood perfusion rates at different sites (apex, middle, left side and right side) on the tongues in anaemia patients (3.49, 3.71, 3.85 and 3.77 kg/s m-3) were significantly lower than those at the corresponding sites in control subjects (4.45, 4.66, 4.81 and 4.70 kg/s m-3). After the mouth opened, the tongue temperature decreased more rapidly in anaemia patients than in control subjects. To analyse the heat transfer mechanism, a transient heat transfer model of the tongue was developed. The tongue temperatures in anaemia patients and control subjects were calculated using this model and compared to the tongue temperatures measured by the IR thermal imager. The relationship between the tongue surface temperature and the tongue blood perfusion rate was analysed. The simulation results indicated that the low blood perfusion rate and the correlated changes in anaemia patients can cause faster temperature decreases of the tongue surface.

Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke.

PubMed

Sporns, Peter; Schmidt, Rene; Minnerup, Jens; Dziewas, Rainer; Kemmling, André; Dittrich, Ralf; Zoubi, Tarek; Heermann, Philipp; Cnyrim, Christian; Schwindt, Wolfram; Heindel, Walter; Niederstadt, Thomas; Hanning, Uta

2016-01-01

Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. © 2016 S. Karger AG, Basel.

Permeability estimates in histopathology-proved treatment-induced necrosis using perfusion CT: can these add to other perfusion parameters in differentiating from recurrent/progressive tumors?

PubMed

Jain, R; Narang, J; Schultz, L; Scarpace, L; Saksena, S; Brown, S; Rock, J P; Rosenblum, M; Gutierrez, J; Mikkelsen, T

2011-04-01

Differentiating treatment effects from RPT is a common yet challenging task in a busy neuro-oncologic practice. PS probably represents a different aspect of angiogenesis and vasculature and can provide additional physiologic information about recurrent/progressive enhancing lesions. The purpose of the study was to use PS measured by using PCT to differentiate TIN from RPT in patients with previously irradiated brain tumor who presented with a recurrent/progressive enhancing lesion. Seventy-two patients underwent PCT for assessment of a recurrent/progressive enhancing lesion from January 2006 to November 2009. Thirty-eight patients who underwent surgery and histopathologic diagnosis were included in this analysis. Perfusion parameters such as PS, CBV, CBF, and MTT were obtained from the enhancing lesion as well as from the NAWM. Of 38 patients, 11 were diagnosed with pure TIN and 27 had RPT. Patients with TIN showed significantly lower mean PS values than those with RPT (1.8 ± 0.8 versus 3.6 ± 1.6 mL/100 g/min; P value=.001). The TIN group also showed lower rCBV (1.2 ± 0.3 versus 2.1 ± 0.7; P value<.001), lower rCBF (1.2 ± 0.5 versus 2.6 ± 1.7; P value=.004), and higher rMTT (1.4 ± 0.4 versus 1.0 ± 0.4; P value=.018) compared with the RPT group. PCT and particularly PS can be used in patients with previously treated brain tumors to differentiate TIN from RPT. PS estimates can help increase the accuracy of PCT in differentiating these 2 entities.

Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

PubMed

Kano, M; Coen, S J; Farmer, A D; Aziz, Q; Williams, S C R; Alsop, D C; Fukudo, S; O'Gorman, R L

2014-09-01

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

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

PubMed

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

2015-12-01

The in vitro chondrocyte cell culture for cartilage tissue regeneration in a perfusion bioreactor is a complex process. Mathematical modeling and computational simulation can provide important insights into the culture process, which would be helpful for selecting culture conditions to improve the quality of the developed tissue constructs. However, simulation of the cell culture process is a challenging task due to the complicated interaction between the cells and local fluid flow and nutrient transport inside the complex porous scaffolds. In this study, a mathematical model and computational framework has been developed to simulate the three-dimensional (3D) cell growth in a porous scaffold placed inside a bi-directional flow perfusion bioreactor. The model was developed by taking into account the two-way coupling between the cell growth and local flow field and associated glucose concentration, and then used to perform a resolved-scale simulation based on the lattice Boltzmann method (LBM). The simulation predicts the local shear stress, glucose concentration, and 3D cell growth inside the porous scaffold for a period of 30 days of cell culture. The predicted cell growth rate was in good overall agreement with the experimental results available in the literature. This study demonstrates that the bi-directional flow perfusion culture system can enhance the homogeneity of the cell growth inside the scaffold. The model and computational framework developed is capable of providing significant insight into the culture process, thus providing a powerful tool for the design and optimization of the cell culture process. © 2015 Wiley Periodicals, Inc.

Capacity planning for batch and perfusion bioprocesses across multiple biopharmaceutical facilities.

PubMed

Siganporia, Cyrus C; Ghosh, Soumitra; Daszkowski, Thomas; Papageorgiou, Lazaros G; Farid, Suzanne S

2014-01-01

Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fed-batch or perfusion culture processes such as sequence-dependent changeover times, continuous culture constraints, and decoupled upstream and downstream operations that permit independent scheduling of each. Strategic inventory levels were accounted for by applying cost penalties when they were not met. A rolling time horizon methodology was utilized in conjunction with the MILP model and was shown to obtain solutions with greater optimality in less computational time than the full-scale model. The model was applied to an industrial case study to illustrate how the framework aids decisions regarding outsourcing capacity to third party manufacturers or building new facilities. The impact of variations on key parameters such as demand or titres on the optimal production plans and costs was captured. The analysis identified the critical ratio of in-house to contract manufacturing organization (CMO) manufacturing costs that led the optimization results to favor building a future facility over using a CMO. The tool predicted that if titres were higher than expected then the optimal solution would allocate more production to in-house facilities, where manufacturing costs were lower. Utilization graphs indicated when capacity expansion should be considered. © 2014 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging

PubMed Central

Lin, Wei-Che; Chen, Pei-Chin; Huang, Yung-Cheng; Tsai, Nai-Wen; Chen, Hsiu-Ling; Wang, Hung-Chen; Lin, Tsu-Kung; Chou, Kun-Hsien; Chen, Meng-Hsiang; Chen, Yi-Wen; Lu, Cheng-Hsien

2016-01-01

Abstract Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning. PMID:26844450

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

PubMed

Lin, Wei-Che; Chen, Pei-Chin; Huang, Yung-Cheng; Tsai, Nai-Wen; Chen, Hsiu-Ling; Wang, Hung-Chen; Lin, Tsu-Kung; Chou, Kun-Hsien; Chen, Meng-Hsiang; Chen, Yi-Wen; Lu, Cheng-Hsien

2016-02-01

Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

Localized Spatio-Temporal Constraints for Accelerated CMR Perfusion

PubMed Central

Akçakaya, Mehmet; Basha, Tamer A.; Pflugi, Silvio; Foppa, Murilo; Kissinger, Kraig V.; Hauser, Thomas H.; Nezafat, Reza

2013-01-01

Purpose To develop and evaluate an image reconstruction technique for cardiac MRI (CMR)perfusion that utilizes localized spatio-temporal constraints. Methods CMR perfusion plays an important role in detecting myocardial ischemia in patients with coronary artery disease. Breath-hold k-t based image acceleration techniques are typically used in CMR perfusion for superior spatial/temporal resolution, and improved coverage. In this study, we propose a novel compressed sensing based image reconstruction technique for CMR perfusion, with applicability to free-breathing examinations. This technique uses local spatio-temporal constraints by regularizing image patches across a small number of dynamics. The technique is compared to conventional dynamic-by-dynamic reconstruction, and sparsity regularization using a temporal principal-component (pc) basis, as well as zerofilled data in multi-slice 2D and 3D CMR perfusion. Qualitative image scores are used (1=poor, 4=excellent) to evaluate the technique in 3D perfusion in 10 patients and 5 healthy subjects. On 4 healthy subjects, the proposed technique was also compared to a breath-hold multi-slice 2D acquisition with parallel imaging in terms of signal intensity curves. Results The proposed technique results in images that are superior in terms of spatial and temporal blurring compared to the other techniques, even in free-breathing datasets. The image scores indicate a significant improvement compared to other techniques in 3D perfusion (2.8±0.5 vs. 2.3±0.5 for x-pc regularization, 1.7±0.5 for dynamic-by-dynamic, 1.1±0.2 for zerofilled). Signal intensity curves indicate similar dynamics of uptake between the proposed method with a 3D acquisition and the breath-hold multi-slice 2D acquisition with parallel imaging. Conclusion The proposed reconstruction utilizes sparsity regularization based on localized information in both spatial and temporal domains for highly-accelerated CMR perfusion with potential utility in free

Perfusion MRI: The Five Most Frequently Asked Clinical Questions

PubMed Central

Essig, Marco; Nguyen, Thanh Binh; Shiroishi, Mark S.; Saake, Marc; Provenzale, James M.; Enterline, David S.; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

2013-01-01

OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23971482

[Myokard-Perfusions-SPECT. Myocardial perfusion SPECT - Update S1 guideline].

PubMed

Lindner, Oliver; Bengel, Frank; Burchert, Wolfgang; Dörr, Rolf; Hacker, Marcus; Schäfer, Wolfgang; Schäfers, Michael A; Schmidt, Matthias; Schwaiger, Markus; Vom Dahl, Jürgen; Zimmermann, Rainer

2017-08-14

The S1 guideline for myocardial perfusion SPECT has been published by the Association of the Scientific Medical Societies in Germany (AWMF) and is valid until 2/2022. This paper is a short summary with comments on all chapters and subchapters wich were modified and amended.

Axial oxygen diffusion in the Krogh model: modifications to account for myocardial oxygen tension in isolated perfused rat hearts measured by EPR oximetry.

PubMed

Grinberg, Oleg; Novozhilov, Boris; Grinberg, Stalina; Friedman, Bruce; Swartz, Harold M

2005-01-01

The cylindrical steady-state model developed by Krogh with Erlang has served as the basis of understanding oxygen supply in living tissue for over eighty years. Due to its simplicity and agreement with some observations, it has been extensively used and successfully extended to new fields, especially for situations such as drug diffusion, water transport, and ice formation in tissues. However, the applicability of the model to make even a qualitative prediction of the oxygen level of specific volumes of the tissue is still controversial. We recently have developed an approximate analytical solution of a steady-state diffusion equation for a Krogh cylinder, including oxygen concentration in the capillary. This model was used to explain our previous experimental data on myocardial pO2 in isolated perfused rat hearts measured by EPR oximetry. An acceptable agreement with the experimental data was obtained by assuming that a known limitation of the existing EPR methods--a tendency to over-weight low pO2 values--had resulted in an under-estimate of the pO2. These results are consistent with recent results of others, which stress the importance of taking into account the details of what is measured by various methods.

Effects of dose, flow rate, and bile acid on diclofenac disposition in the perfused rat liver.

PubMed

Uraki, Misato; Kawase, Atsushi; Matsushima, Yuka; Iwaki, Masahiro

2016-06-01

An in situ perfused rat liver system is useful for studying the hepatic disposition of drugs and their metabolites. However, the effects of the perfusion conditions on drug disposition are unclear. We examined the effects of conditions such as flow rate (13 or 26 mL/min) and bile acid on disposition of diclofenac (DF) as a model drug and DF metabolites [diclofenac-1-O-acyl glucuronide (DF-Glu) or 4'-hydroxydiclofenac (DF-4'OH)] in the absence of albumin. DF, DF-Glu, and DF-4'OH concentrations in the perfusate and cumulative amounts of DF-Glu excreted in bile were measured using high-performance liquid chromatography methods. DF in the perfusate was rapidly eliminated as the perfusate flow rate increased. The area under the plasma concentration-time curve from 0 to 60 min (AUC0-60) for DF-Glu and DF-4'OH in a perfusate containing bile acid was lower at a flow rate of 26 and 13 mL/min, respectively. The bile flow rate at 26 mL/min with 24 μM of bile acid in the perfusate was significantly higher (ca. 3.5 times) compared with that at 13 mL/min without bile acid. Cumulative biliary DF-Glu excretion was also dramatically affected by the flow rate and addition of bile acid. This study indicated that the flow rate and bile acid in the perfused rat liver were key factors for bile flow rate and DF, DF-Glu, and DF-4'OH disposition in the absence of albumin.

Coronary Artery Disease: Analysis of Diagnostic Performance of CT Perfusion and MR Perfusion Imaging in Comparison with Quantitative Coronary Angiography and SPECT-Multicenter Prospective Trial.

PubMed

Rief, Matthias; Chen, Marcus Y; Vavere, Andrea L; Kendziora, Benjamin; Miller, Julie M; Bandettini, W Patricia; Cox, Christopher; George, Richard T; Lima, João; Di Carli, Marcelo; Plotkin, Michail; Zimmermann, Elke; Laule, Michael; Schlattmann, Peter; Arai, Andrew E; Dewey, Marc

2018-02-01

Purpose To compare the diagnostic performance of stress myocardial computed tomography (CT) perfusion with that of stress myocardial magnetic resonance (MR) perfusion imaging in the detection of coronary artery disease (CAD). Materials and Methods All patients gave written informed consent prior to inclusion in this institutional review board-approved study. This two-center substudy of the prospective Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) multicenter trial included 92 patients (mean age, 63.1 years ± 8.1 [standard deviation]; 73% male). All patients underwent perfusion CT and perfusion MR imaging with either adenosine or regadenoson stress. The predefined reference standards were combined quantitative coronary angiography (QCA) and single-photon emission CT (SPECT) or QCA alone. Results from coronary CT angiography were not included, and diagnostic performance was evaluated with the Mantel-Haenszel test stratified by disease status. Results The prevalence of CAD was 39% (36 of 92) according to QCA and SPECT and 64% (59 of 92) according to QCA alone. When compared with QCA and SPECT, per-patient diagnostic accuracy of perfusion CT and perfusion MR imaging was 63% (58 of 92) and 75% (69 of 92), respectively (P = .11); sensitivity was 92% (33 of 36) and 83% (30 of 36), respectively (P = .45); and specificity was 45% (25 of 56) and 70% (39 of 56), respectively (P < .01). When compared with QCA alone, diagnostic accuracy of CT perfusion and MR perfusion imaging was 82% (75 of 92) and 74% (68 of 92), respectively (P = .27); sensitivity was 90% (53 of 59) and 69% (41 of 59), respectively (P < .01); and specificity was 67% (22 of 33) and 82% (27 of 33), respectively (P = .27). Conclusion This multicenter study shows that the diagnostic performance of perfusion CT is similar to that of perfusion MR imaging in the detection of CAD. © RSNA, 2017 Online supplemental material is

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

PubMed

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

2017-08-01

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

The effect of modified Blalock-Taussig shunt size and coarctation severity on coronary perfusion after the Norwood operation.

PubMed

Corsini, Chiara; Biglino, Giovanni; Schievano, Silvia; Hsia, Tain-Yen; Migliavacca, Francesco; Pennati, Giancarlo; Taylor, Andrew M

2014-08-01

The size of the modified Blalock-Taussig shunt and the additional presence of aortic coarctation can affect the hemodynamics of the Norwood physiology. Multiscale modeling was used to gather insight into the effects of these variables, in particular on coronary perfusion. A model was reconstructed from cardiac magnetic resonance imaging data of a representative patient, and then simplified with computer-aided design software. Changes were systematically imposed to the semi-idealized three-dimensional model, resulting in a family of nine models (3-, 3.5-, and 4-mm shunt diameter; 0%, 60%, and 90% coarctation severity). Each model was coupled to a lumped parameter network representing the remainder of the circulation to run multiscale simulations. Simulations were repeated including the effect of preserved cerebral perfusion. The concomitant presence of a large shunt and tight coarctation was detrimental in terms of coronary perfusion (13.4% maximal reduction, 1.07 versus 0.927 mL/s) and oxygen delivery (29% maximum reduction, 422 versus 300 mL·min(-1)·m(-2)). A variation in the ratio of pulmonary to systemic blood flow from 0.9 to 1.6 also indicated a "stealing" phenomenon to the detriment of the coronary circulation. A difference could be further appreciated in the computational ventricular pressure-volume loops, with augmented systolic pressures and decreased stroke volumes for tighter coarctation. Accounting for constant cerebral perfusion did not produce substantially different results. Multiscale simulations performed in a parametric fashion revealed a reduction in coronary perfusion in the presence of a large modified Blalock-Taussig shunt and severe coarctation in Norwood patients. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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

USGS Publications Warehouse

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

2003-01-01

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

Ventilation-perfusion distribution in normal subjects.

PubMed

Beck, Kenneth C; Johnson, Bruce D; Olson, Thomas P; Wilson, Theodore A

2012-09-01

Functional values of LogSD of the ventilation distribution (σ(V)) have been reported previously, but functional values of LogSD of the perfusion distribution (σ(q)) and the coefficient of correlation between ventilation and perfusion (ρ) have not been measured in humans. Here, we report values for σ(V), σ(q), and ρ obtained from wash-in data for three gases, helium and two soluble gases, acetylene and dimethyl ether. Normal subjects inspired gas containing the test gases, and the concentrations of the gases at end-expiration during the first 10 breaths were measured with the subjects at rest and at increasing levels of exercise. The regional distribution of ventilation and perfusion was described by a bivariate log-normal distribution with parameters σ(V), σ(q), and ρ, and these parameters were evaluated by matching the values of expired gas concentrations calculated for this distribution to the measured values. Values of cardiac output and LogSD ventilation/perfusion (Va/Q) were obtained. At rest, σ(q) is high (1.08 ± 0.12). With the onset of ventilation, σ(q) decreases to 0.85 ± 0.09 but remains higher than σ(V) (0.43 ± 0.09) at all exercise levels. Rho increases to 0.87 ± 0.07, and the value of LogSD Va/Q for light and moderate exercise is primarily the result of the difference between the magnitudes of σ(q) and σ(V). With known values for the parameters, the bivariate distribution describes the comprehensive distribution of ventilation and perfusion that underlies the distribution of the Va/Q ratio.

Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue

PubMed Central

Lee, Eun Jung; Luo, Jianwen; Duan, Yi; Yeager, Keith; Konofagou, Elisa; Vunjak-Novakovic, Gordana

2012-01-01

Maintenance of normal myocardial function depends intimately on synchronous tissue contraction driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue, but due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation, and unconstrained (i.e., not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate in concert these three key factors. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modeling studies. We then culture cardiac cells obtained from neonatal rats in porous, channeled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After eight days of culture, constructs grown with the simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23±0.10% vs. 0.14±0.05, 0.13±0.08, or 0.09±0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization than either control group. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. PMID:22170772

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy.

PubMed

Austein, Friederike; Riedel, Christian; Kerby, Tina; Meyne, Johannes; Binder, Andreas; Lindner, Thomas; Huhndorf, Monika; Wodarg, Fritz; Jansen, Olav

2016-09-01

Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy. Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke. In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients. Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software. © 2016 American Heart Association, Inc.

Alteration of cerebral perfusion in patients with idiopathic normal pressure hydrocephalus measured by 3D perfusion weighted magnetic resonance imaging.

PubMed

Walter, Christof; Hertel, F; Naumann, E; Mörsdorf, M

2005-12-01

It is controversial whether alteration of cerebral perfusion plays an important role in the pathophysiology of patients with idiopathic normal pressure hydrocephalus (NPH) and can help to predict the outcome after shunt surgery. 28 patients with suspected NPH were examined clinically (Homburg Hydrocephalus Scale, walking test, incontinence protocol) and by 3D dynamic susceptibility based perfusion weighted magnetic resonance imaging (PWI-MRI) before and after cerebrospinal fluid release (spinal tap test, STT). The perfusion parameters (negative integral (NI), time of arrival (T0), time to peak (TTP), mean transit time, and the difference TTP-T0 were analysed. Three different groups of patients were identified preoperatively: In group 1 seven patients showed an increase in the cerebral perfusion and a clinical improvement after STT. The second group (9 patients) also revealed an increase of the cerebral perfusion, but no significant alteration of the clinical assessment could be found. In the third group neither the cerebral perfusion nor the clinical assessment changed. 14 of the 16 patients (group 1 and 2) were examined three months after shunt placement. 11 patients showed a good or excellent result, 2 patients revealed a fair assessment, and only 1 patient had transiently improved. No patient was downgraded after shunting. In the patient group 1 and 2 the NI increased significantly (effect size: 34%), whereas in group 3 no significant alteration of NI was observed. PWI-MRI improves the prediction of outcome after shunt placement in patients with NPH and can offer new insights into the pathophysiology.

Hyperventilation, cerebral perfusion, and syncope.

PubMed

Immink, R V; Pott, F C; Secher, N H; van Lieshout, J J

2014-04-01

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

Renal Cell Carcinoma Perfusion before and after Radiofrequency Ablation Measured with Dynamic Contrast Enhanced MRI: A Pilot Study.

PubMed

Wah, Tze Min; Sourbron, Steven; Wilson, Daniel Jonathan; Magee, Derek; Gregory, Walter Martin; Selby, Peter John; Buckley, David L

2018-01-08

To investigate if the early treatment effects of radiofrequency ablation (RFA) on renal cell carcinoma (RCC) can be detected with dynamic contrast enhanced (DCE)-MRI and to correlate RCC perfusion with RFA treatment time. 20 patients undergoing RFA of their 21 RCCs were evaluated with DCE-MRI before and at one month after RFA treatment. Perfusion was estimated using the maximum slope technique at two independent sittings. Total RCC blood flow was correlated with total RFA treatment time, tumour location, size and histology. DCE-MRI examinations were successfully evaluated for 21 RCCs (size from 1.3 to 4 cm). Perfusion of the RCCs decreased significantly ( p < 0.0001) from a mean of 203 (±80) mL/min/100 mL before RFA to 8.1 (±3.1) mL/min/100 mL after RFA with low intra-observer variability ( r ≥ 0.99, p < 0.0001). There was an excellent correlation ( r = 0.95) between time to complete ablation and pre-treatment total RCC blood flow. Tumours with an exophytic location exhibit the lowest mean RFA treatment time. DCE-MRI can detect early treatment effects by measuring RCC perfusion before and after RFA. Perfusion significantly decreases in the zone of ablation, suggesting that it may be useful for the assessment of treatment efficacy. Pre-RFA RCC blood flow may be used to predict RFA treatment time.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all

Assessment of Tissue Perfusion Following Conventional Liposuction of Perforator-Based Abdominal Flaps

PubMed Central

Saçak, Bülent; Yalçın, Doğuş; Pilancı, Özgür; Tuncer, Fatma Betül; Çelebiler, Özhan

2017-01-01

Background The effect of liposuction on the perforators of the lower abdominal wall has been investigated in several studies. There are controversial results in the literature that have primarily demonstrated the number and patency of the perforators. The aim of this study was to determine the effect of liposuction on the perfusion of perforator-based abdominal flaps using a combined laser–Doppler spectrophotometer (O2C, Oxygen to See, LEA Medizintechnik). Methods Nine female patients undergoing classical abdominoplasty were included in the study. Perforators and the perfusion zones of the deep inferior epigastric artery flap were marked on the patient's abdominal wall. Flap perfusion was quantitatively assessed by measuring blood flow, velocity, capillary oxygen saturation, and relative amount of hemoglobin for each zone preoperatively, after tumescent solution infiltration, following elevation of the flap on a single perforator, and after deep and superficial liposuction, respectively. Results The measurements taken after elevation of the flap were not significantly different than measurements taken after the liposuction procedures. Conclusions The liposuction procedure does not significantly alter the perfusion of perforator-based abdominal flaps in the early period. The abdominal tissue discarded in a classic abdominoplasty operation can be raised as a perforator flap and has been demonstrated to be a unique model for clinical research. PMID:28352599

A high performance biometric signal and image processing method to reveal blood perfusion towards 3D oxygen saturation mapping

NASA Astrophysics Data System (ADS)

Imms, Ryan; Hu, Sijung; Azorin-Peris, Vicente; Trico, Michaël.; Summers, Ron

2014-03-01

Non-contact imaging photoplethysmography (PPG) is a recent development in the field of physiological data acquisition, currently undergoing a large amount of research to characterize and define the range of its capabilities. Contact-based PPG techniques have been broadly used in clinical scenarios for a number of years to obtain direct information about the degree of oxygen saturation for patients. With the advent of imaging techniques, there is strong potential to enable access to additional information such as multi-dimensional blood perfusion and saturation mapping. The further development of effective opto-physiological monitoring techniques is dependent upon novel modelling techniques coupled with improved sensor design and effective signal processing methodologies. The biometric signal and imaging processing platform (bSIPP) provides a comprehensive set of features for extraction and analysis of recorded iPPG data, enabling direct comparison with other biomedical diagnostic tools such as ECG and EEG. Additionally, utilizing information about the nature of tissue structure has enabled the generation of an engineering model describing the behaviour of light during its travel through the biological tissue. This enables the estimation of the relative oxygen saturation and blood perfusion in different layers of the tissue to be calculated, which has the potential to be a useful diagnostic tool.

Compact dual-mode diffuse optical system for blood perfusion monitoring in a porcine model of microvascular tissue flaps

NASA Astrophysics Data System (ADS)

Lee, Seung Yup; Pakela, Julia M.; Helton, Michael C.; Vishwanath, Karthik; Chung, Yooree G.; Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Christian, James F.; O'Reilly, Jameson; Farkas, Dana; Ward, Brent B.; Feinberg, Stephen E.; Mycek, Mary-Ann

2017-12-01

In reconstructive surgery, the ability to detect blood flow interruptions to grafted tissue represents a critical step in preventing postsurgical complications. We have developed and pilot tested a compact, fiber-based device that combines two complimentary modalities-diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy-to quantitatively monitor blood perfusion. We present a proof-of-concept study on an in vivo porcine model (n=8). With a controllable arterial blood flow supply, occlusion studies (n=4) were performed on surgically isolated free flaps while the device simultaneously monitored blood flow through the supplying artery as well as flap perfusion from three orientations: the distal side of the flap and two transdermal channels. Further studies featuring long-term monitoring, arterial failure simulations, and venous failure simulations were performed on flaps that had undergone an anastomosis procedure (n=4). Additionally, benchtop verification of the DCS system was performed on liquid flow phantoms. Data revealed relationships between diffuse optical measures and state of occlusion as well as the ability to detect arterial and venous compromise. The compact construction of the device, along with its noninvasive and quantitative nature, would make this technology suitable for clinical translation.

Evaluation of Microvascular Perfusion and Resuscitation after Severe Injury.

PubMed

Lee, Yann-Leei L; Simmons, Jon D; Gillespie, Mark N; Alvarez, Diego F; Gonzalez, Richard P; Brevard, Sidney B; Frotan, Mohammad A; Schneider, Andrew M; Richards, William O

2015-12-01

Achieving adequate perfusion is a key goal of treatment in severe trauma; however, tissue perfusion has classically been measured by indirect means. Direct visualization of capillary flow has been applied in sepsis, but application of this technology to the trauma population has been limited. The purpose of this investigation was to compare the efficacy of standard indirect measures of perfusion to direct imaging of the sublingual microcirculatory flow during trauma resuscitation. Patients with injury severity scores >15 were serially examined using a handheld sidestream dark-field video microscope. In addition, measurements were also made from healthy volunteers. The De Backer score, a morphometric capillary density score, and total vessel density (TVD) as cumulative vessel area within the image, were calculated using Automated Vascular Analysis (AVA3.0) software. These indices were compared against clinical and laboratory parameters of organ function and systemic metabolic status as well as mortality. Twenty severely injured patients had lower TVD (X = 14.6 ± 0.22 vs 17.66 ± 0.51) and De Backer scores (X = 9.62 ± 0.16 vs 11.55 ± 0.37) compared with healthy controls. These scores best correlated with serum lactate (TVD R(2) = 0.525, De Backer R(2) = 0.576, P < 0.05). Mean arterial pressure, heart rate, oxygen saturation, pH, bicarbonate, base deficit, hematocrit, and coagulation parameters correlated poorly with both TVD and De Backer score. Direct measurement of sublingual microvascular perfusion is technically feasible in trauma patients, and seems to provide real-time assessment of microcirculatory perfusion. This study suggests that in severe trauma, many indirect measurements of perfusion do not correlate with microvascular perfusion. However, visualized perfusion deficiencies do reflect a shift toward anaerobic metabolism.

DRAG REDUCING POLYMER ENCHANCES MICROVASCULAR PERFUSION IN THE TRAUMATIZED BRAIN WITH INTRACRANIAL HYPERTENSION

PubMed Central

Bragin, Denis E.; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V.; Nemoto, Edwin M.

2016-01-01

SUMMARY Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood soluble non-toxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and limb, but have not yet been studied in the brain. Recently, we demonstrated that that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using the in-vivo 2-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow and, as a result, reduced tissue hypoxia in both un-traumatized and traumatized rat brains at high ICP. Our study suggests that DRP could be an effective treatment for improving microvascular flow in brain ischemia caused by high ICP after TBI. PMID:27165871

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

PubMed Central

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

2012-01-01

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

PET Pharmacokinetic Modelling

NASA Astrophysics Data System (ADS)

Müller-Schauenburg, Wolfgang; Reimold, Matthias

Positron Emission Tomography is a well-established technique that allows imaging and quantification of tissue properties in-vivo. The goal of pharmacokinetic modelling is to estimate physiological parameters, e.g. perfusion or receptor density from the measured time course of a radiotracer. After a brief overview of clinical application of PET, we summarize the fundamentals of modelling: distribution volume, Fick's principle of local balancing, extraction and perfusion, and how to calculate equilibrium data from measurements after bolus injection. Three fundamental models are considered: (i) the 1-tissue compartment model, e.g. for regional cerebral blood flow (rCBF) with the short-lived tracer [15O]water, (ii) the 2-tissue compartment model accounting for trapping (one exponential + constant), e.g. for glucose metabolism with [18F]FDG, (iii) the reversible 2-tissue compartment model (two exponentials), e.g. for receptor binding. Arterial blood sampling is required for classical PET modelling, but can often be avoided by comparing regions with specific binding with so called reference regions with negligible specific uptake, e.g. in receptor imaging. To estimate the model parameters, non-linear least square fits are the standard. Various linearizations have been proposed for rapid parameter estimation, e.g. on a pixel-by-pixel basis, for the prize of a bias. Such linear approaches exist for all three models; e.g. the PATLAK-plot for trapping substances like FDG, and the LOGAN-plot to obtain distribution volumes for reversibly binding tracers. The description of receptor modelling is dedicated to the approaches of the subsequent lecture (chapter) of Millet, who works in the tradition of Delforge with multiple-injection investigations.

FABRICA: A Bioreactor Platform for Printing, Perfusing, Observing, & Stimulating 3D Tissues.

PubMed

Smith, Lester J; Li, Ping; Holland, Mark R; Ekser, Burcin

2018-05-15

We are introducing the FABRICA, a bioprinter-agnostic 3D-printed bioreactor platform designed for 3D-bioprinted tissue construct culture, perfusion, observation, and analysis. The computer-designed FABRICA was 3D-printed with biocompatible material and used for two studies: (1) Flow Profile Study: perfused 5 different media through a synthetic 3D-bioprinted construct and ultrasonically analyzed the flow profile at increasing volumetric flow rates (VFR); (2) Construct Perfusion Study: perfused a 3D-bioprinted tissue construct for a week and compared histologically with a non-perfused control. For the flow profile study, construct VFR increased with increasing pump VFR. Water and other media increased VFR significantly while human and pig blood showed shallow increases. For the construct perfusion study, we confirmed more viable cells in perfused 3D-bioprinted tissue compared to control. The FABRICA can be used to visualize constructs during 3D-bioprinting, incubation, and to control and ultrasonically analyze perfusion, aseptically in real-time, making the FABRICA tunable for different tissues.

High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography.

PubMed

Lindsey, Brooks D; Shelton, Sarah E; Martin, K Heath; Ozgun, Kathryn A; Rojas, Juan D; Foster, F Stuart; Dayton, Paul A

2017-04-01

Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.

The impact of age on cerebral perfusion, oxygenation and metabolism during exercise in humans

PubMed Central

Braz, Igor D.

2015-01-01

Abstract Age is one of the most important risk factors for dementia and stroke. Examination of the cerebral circulatory responses to acute exercise in the elderly may help to pinpoint the mechanisms by which exercise training can reduce the risk of brain diseases, inform the optimization of exercise training programmes and assist with the identification of age‐related alterations in cerebral vascular function. During low‐to‐moderate intensity dynamic exercise, enhanced neuronal activity is accompanied by cerebral perfusion increases of ∼10–30%. Beyond ∼60–70% maximal oxygen uptake, cerebral metabolism remains elevated but perfusion in the anterior portion of the circulation returns towards baseline, substantively because of a hyperventilation‐mediated reduction in the partial pressure of arterial carbon dioxide (P aC O2) and cerebral vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest and during incremental dynamic exercise. Nevertheless, the increase in the estimated cerebral metabolic rate for oxygen and the arterial–internal jugular venous differences for glucose and lactate are similar in young and older individuals exercising at the same relative exercise intensities. Correction for the age‐related reduction in P aC O2 during exercise by the provision of supplementary CO2 is suggested to remove ∼50% of the difference in cerebral perfusion between young and older individuals. A multitude of candidates could account for the remaining difference, including cerebral atrophy, and enhanced vasoconstrictor and blunted vasodilatory pathways. In summary, age‐related reductions in cerebral perfusion during exercise are partly associated with a lower P aC O2 in exercising older individuals; nevertheless the cerebral extraction of glucose, lactate and oxygen appear to be preserved. PMID:26435295

New imaging technology: measurement of myocardial perfusion by contrast echocardiography

NASA Technical Reports Server (NTRS)

Rubin, D. N.; Thomas, J. D.

2000-01-01

Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.

Semipermeable Hollow Fiber Phantoms for Development and Validation of Perfusion-Sensitive MR Methods and Signal Models

PubMed Central

Anderson, J.R.; Ackerman, J.J.H.; Garbow, J.R.

2015-01-01

Two semipermeable, hollow fiber phantoms for the validation of perfusion-sensitive magnetic resonance methods and signal models are described. Semipermeable hollow fibers harvested from a standard commercial hemodialysis cartridge serve to mimic tissue capillary function. Flow of aqueous media through the fiber lumen is achieved with a laboratory-grade peristaltic pump. Diffusion of water and solute species (e.g., Gd-based contrast agent) occurs across the fiber wall, allowing exchange between the lumen and the extralumenal space. Phantom design attributes include: i) small physical size, ii) easy and low-cost construction, iii) definable compartment volumes, and iv) experimental control over media content and flow rate. PMID:26167136

Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction

PubMed Central

Barwinska, Daria; Garner, John; Davidson, Darrell D.; Cook, Todd G.; Eckert, George J.; Tholpady, Sunil S.; March, Keith L.; Park, Kinam

2017-01-01

Background: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries. PMID:28894668

Liver perfusion imaging in patients with primary and metastatic liver malignancy: prospective comparison between 99mTc-MAA spect and dynamic CT perfusion.

PubMed

Reiner, Caecilia S; Goetti, Robert; Burger, Irene A; Fischer, Michael A; Frauenfelder, Thomas; Knuth, Alexander; Pfammatter, Thomas; Schaefer, Niklaus; Alkadhi, Hatem

2012-05-01

To prospectively analyze the correlation between parameters of liver perfusion from technetium99m-macroaggregates of albumin (99mTc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy. Twenty-five consecutive patients (11 women, 14 men; mean age 60.9 ± 10.8; range: 32-78 years) with primary (n = 5) or metastatic (n = 20) liver malignancy planned to undergo selective internal radiotherapy underwent dynamic contrast-enhanced CT liver perfusion imaging (four-dimensional spiral mode, scan range 14.8 cm, 15 scans, cycle time 3 seconds) and 99m)Tc-MAA SPECT after intraarterial injection of 180 MBq 99mTc-MAA on the same day. Data were evaluated by two blinded and independent readers for the parameters arterial liver perfusion (ALP), portal venous perfusion (PVP), and total liver perfusion (TLP) from CT, and the 99mTc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT. Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90-0.98, each P < .01) and 99mTc -MAA SPECT (r = 0.91, P < .01). Significant correlation was found between 99mTc-MAA uptake ratio and ALP (r = 0.7, P < .01) in liver tumors. No significant correlation was found between 99mTc-MAA uptake ratio, PVP (r = -0.381, P = .081), and TLP (r = 0.039, P = .862). This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the 99mTc-MAA uptake ratio obtained by SPECT. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Variability and Reproducibility of 3rd-generation dual-source dynamic volume perfusion CT Parameters in Comparison to MR-perfusion Parameters in Rectal Cancer.

PubMed

Sudarski, Sonja; Henzler, Thomas; Floss, Teresa; Gaa, Tanja; Meyer, Mathias; Haubenreisser, Holger; Schoenberg, Stefan O; Attenberger, Ulrike I

2018-05-02

To compare in patients with untreated rectal cancer quantitative perfusion parameters calculated from 3 rd -generation dual-source dynamic volume perfusion CT (dVPCT) with 3-Tesla-MR-perfusion with regard to data variability and tumour differentiation. In MR-perfusion, plasma flow (PF), plasma volume (PV) and mean transit time (MTT) were assessed in two measurements (M1 and M2) by the same reader. In dVPCT, blood flow (BF), blood volume (BV), MTT and permeability (PERM) were assessed respectively. CT dose values were calculated. 20 patients (60 ± 13 years) were analysed. Intra-individual and intra-reader variability of duplicate MR-perfusion measurements was higher compared to duplicate dVPCT measurements. dVPCT-derived BF, BV and PERM could differentiate between tumour and normal rectal wall (significance level for M1 and M2, respectively, regarding BF: p < 0.0001*/0.0001*; BV: p < 0.0001*/0.0001*; MTT: p = 0.93/0.39; PERM: p < 0.0001*/0.0001*), with MR-perfusion this was true for PF and PV (p-values M1/M2 for PF: p = 0.04*/0.01*; PV: p = 0.002*/0.003*; MTT: p = 0.70/0.27*). Mean effective dose of CT-staging incl. dVPCT was 29 ± 6 mSv (20 ± 5 mSv for dVPCT alone). In conclusion, dVPCT has a lower data variability than MR-perfusion while both dVPCT and MR-perfusion could differentiate tumour tissue from normal rectal wall. With 3 rd -generation dual-source CT dVPCT could be included in a standard CT-staging without exceeding national dose reference values.

A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy

NASA Astrophysics Data System (ADS)

Grova, C.; Jannin, P.; Biraben, A.; Buvat, I.; Benali, H.; Bernard, A. M.; Scarabin, J. M.; Gibaud, B.

2003-12-01

Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within

Capacity Planning for Batch and Perfusion Bioprocesses Across Multiple Biopharmaceutical Facilities

PubMed Central

Siganporia, Cyrus C; Ghosh, Soumitra; Daszkowski, Thomas; Papageorgiou, Lazaros G; Farid, Suzanne S

2014-01-01

Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fed-batch or perfusion culture processes such as sequence-dependent changeover times, continuous culture constraints, and decoupled upstream and downstream operations that permit independent scheduling of each. Strategic inventory levels were accounted for by applying cost penalties when they were not met. A rolling time horizon methodology was utilized in conjunction with the MILP model and was shown to obtain solutions with greater optimality in less computational time than the full-scale model. The model was applied to an industrial case study to illustrate how the framework aids decisions regarding outsourcing capacity to third party manufacturers or building new facilities. The impact of variations on key parameters such as demand or titres on the optimal production plans and costs was captured. The analysis identified the critical ratio of in-house to contract manufacturing organization (CMO) manufacturing costs that led the optimization results to favor building a future facility over using a CMO. The tool predicted that if titres were higher than expected then the optimal solution would allocate more production to in-house facilities, where manufacturing costs were lower. Utilization graphs indicated when capacity expansion should be considered. © 2013 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 30:594–606, 2014 PMID:24376262

Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium.

PubMed

Matiukas, Arvydas; Mitrea, Bogdan G; Qin, Maochun; Pertsov, Arkady M; Shvedko, Alexander G; Warren, Mark D; Zaitsev, Alexey V; Wuskell, Joseph P; Wei, Mei-de; Watras, James; Loew, Leslie M

2007-11-01

Styryl voltage-sensitive dyes (e.g., di-4-ANEPPS) have been used successfully for optical mapping in cardiac cells and tissues. However, their utility for probing electrical activity deep inside the myocardial wall and in blood-perfused myocardium has been limited because of light scattering and high absorption by endogenous chromophores and hemoglobin at blue-green excitation wavelengths. The purpose of this study was to characterize two new styryl dyes--di-4-ANBDQPQ (JPW-6003) and di-4-ANBDQBS (JPW-6033)--optimized for blood-perfused tissue and intramural optical mapping. Voltage-dependent spectra were recorded in a model lipid bilayer. Optical mapping experiments were conducted in four species (mouse, rat, guinea pig, and pig). Hearts were Langendorff perfused using Tyrode's solution and blood (pig). Dyes were loaded via bolus injection into perfusate. Transillumination experiments were conducted in isolated coronary-perfused pig right ventricular wall preparations. The optimal excitation wavelength in cardiac tissues (650 nm) was >70 nm beyond the absorption maximum of hemoglobin. Voltage sensitivity of both dyes was approximately 10% to 20%. Signal decay half-life due to dye internalization was 80 to 210 minutes, which is 5 to 7 times slower than for di-4-ANEPPS. In transillumination mode, DeltaF/F was as high as 20%. In blood-perfused tissues, DeltaF/F reached 5.5% (1.8 times higher than for di-4-ANEPPS). We have synthesized and characterized two new near-infrared dyes with excitation/emission wavelengths shifted >100 nm to the red. They provide both high voltage sensitivity and 5 to 7 times slower internalization rate compared to conventional dyes. The dyes are optimized for deeper tissue probing and optical mapping of blood-perfused tissue, but they also can be used for conventional applications.

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

EPA Science Inventory

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

Simultaneous acquisition of perfusion image and dynamic MR angiography using time‐encoded pseudo‐continuous ASL

PubMed Central

Helle, Michael; Koken, Peter; Van Cauteren, Marc; van Osch, Matthias J. P.

2017-01-01

Purpose Both dynamic magnetic resonance angiography (4D‐MRA) and perfusion imaging can be acquired by using arterial spin labeling (ASL). While 4D‐MRA highlights large vessel pathology, such as stenosis or collateral blood flow patterns, perfusion imaging provides information on the microvascular status. Therefore, a complete picture of the cerebral hemodynamic condition could be obtained by combining the two techniques. Here, we propose a novel technique for simultaneous acquisition of 4D‐MRA and perfusion imaging using time‐encoded pseudo‐continuous arterial spin labeling. Methods The time‐encoded pseudo‐continuous arterial spin labeling module consisted of a first subbolus that was optimized for perfusion imaging by using a labeling duration of 1800 ms, whereas the other six subboli of 130 ms were used for encoding the passage of the labeled spins through the arterial system for 4D‐MRA acquisition. After the entire labeling module, a multishot 3D turbo‐field echo‐planar‐imaging readout was executed for the 4D‐MRA acquisition, immediately followed by a single‐shot, multislice echo‐planar‐imaging readout for perfusion imaging. The optimal excitation flip angle for the 3D turbo‐field echo‐planar‐imaging readout was investigated by evaluating the image quality of the 4D‐MRA and perfusion images as well as the accuracy of the estimated cerebral blood flow values. Results When using 36 excitation radiofrequency pulses with flip angles of 5 or 7.5°, the saturation effects of the 3D turbo‐field echo‐planar‐imaging readout on the perfusion images were relatively moderate and after correction, there were no statistically significant differences between the obtained cerebral blood flow values and those from traditional time‐encoded pseudo‐continuous arterial spin labeling. Conclusions This study demonstrated that simultaneous acquisition of 4D‐MRA and perfusion images can be achieved by using time‐encoded pseudo�

Fuel Burn Estimation Model

NASA Technical Reports Server (NTRS)

Chatterji, Gano

2011-01-01

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

Perfusion MRI: The Five Most Frequently Asked Technical Questions

PubMed Central

Essig, Marco; Shiroishi, Mark S.; Nguyen, Thanh Binh; Saake, Marc; Provenzale, James M.; Enterline, David; Anzalone, Nicoletta; Dörfler, Arnd; Rovira, Àlex; Wintermark, Max; Law, Meng

2013-01-01

OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols. PMID:23255738

Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

PubMed

Lindsberg, P J; Sirén, A L; Hallenbeck, J M

1997-01-01

of indices of microvascular perfusion (density, filling) and extravasated plasma constituents in damaged and intact brain areas. In this model, the presence of extravasated plasma constituents the size of proteins did not immediately influence indices of cortical microcirculation. However, microvascular perfusion may be perturbed surrounding such an area of advancing vasogenic edema formation.

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

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Positron emission tomography to assess hypoxia and perfusion in lung cancer

PubMed Central

Verwer, Eline E; Boellaard, Ronald; van der Veldt, Astrid AM

2014-01-01

In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed. PMID:25493221

Effects of aortic tortuosity on left ventricular diastolic parameters derived from gated myocardial perfusion single photon emission computed tomography in patients with normal myocardial perfusion.

PubMed

Kurisu, Satoshi; Nitta, Kazuhiro; Sumimoto, Yoji; Ikenaga, Hiroki; Ishibashi, Ken; Fukuda, Yukihiro; Kihara, Yasuki

2018-06-01

Aortic tortuosity is often found on chest radiograph, especially in aged patients. We tested the hypothesis that aortic tortuosity was associated with LV diastolic parameters derived from gated SPECT in patients with normal myocardial perfusion. One-hundred and twenty-two patients with preserved LV ejection fraction and normal myocardial perfusion were enrolled. Descending aortic deviation was defined as the horizontal distance from the left line of the aortic knob to the most prominent left line of the descending aorta. This parameter was measured for the quantitative assessment of aortic tortuosity. Peak filling rate (PFR) and one-third mean filling rate (1/3 MFR) were obtained from redistribution images as LV diastolic parameters. Descending aortic deviation ranged from 0 to 22 mm with a mean distance of 4.5 ± 6.3 mm. Descending aortic deviation was significantly correlated with age (r = 0.38, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = - 0.21, p = 0.02). Multivariate linear regression analysis revealed that eGFR (β = 0.23, p = 0.02) and descending aortic deviation (β = - 0.23, p = 0.01) were significantly associated with PFR, and that only descending aortic deviation (β = - 0.21, p = 0.03) was significantly associated with 1/3 MFR. Our data suggest that aortic tortuosity is associated with LV diastolic parameters derived from gated SPECT in patients with normal myocardial perfusion.

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

PubMed

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

2017-07-01

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

Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue.

PubMed

Maidhof, Robert; Tandon, Nina; Lee, Eun Jung; Luo, Jianwen; Duan, Yi; Yeager, Keith; Konofagou, Elisa; Vunjak-Novakovic, Gordana

2012-11-01

Maintenance of normal myocardial function depends intimately on synchronous tissue contraction, driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue but, due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation and unconstrained (i.e. not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate these three key factors in concert. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modelling studies. We then cultured cardiac cells obtained from neonatal rats in porous, channelled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After 8 days of culture, constructs grown with simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23 ± 0.10% vs 0.14 ± 0.05%, 0.13 ± 0.08% or 0.09 ± 0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization compared to control groups. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. Copyright © 2011 John Wiley & Sons, Ltd.

Feasibility of high-resolution quantitative perfusion analysis in patients with heart failure.

PubMed

Sammut, Eva; Zarinabad, Niloufar; Wesolowski, Roman; Morton, Geraint; Chen, Zhong; Sohal, Manav; Carr-White, Gerry; Razavi, Reza; Chiribiri, Amedeo

2015-02-12

Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF. A group of 58 patients with heart failure (HF; left ventricular ejection fraction, LVEF ≤ 50%) and 33 patients with normal LVEF (LVEF >50%), referred for suspected coronary artery disease, were studied. All subjects underwent quantitative first-pass stress perfusion imaging using adenosine according to standard acquisition protocols. The feasibility of quantitative perfusion analysis was then assessed using high-resolution, 3 T kt perfusion and voxel-wise Fermi deconvolution. 30/58 (52%) subjects in the HF group had underlying ischaemic aetiology. Perfusion abnormalities were seen amongst patients with ischaemic HF and patients with normal LV function. No regional perfusion defect was observed in the non-ischaemic HF group. Good agreement was found between visual and quantitative analysis across all groups. Absolute stress perfusion rate, myocardial perfusion reserve (MPR) and endocardial-epicardial MPR ratio identified areas with abnormal perfusion in the ischaemic HF group (p = 0.02; p = 0.04; p = 0.02, respectively). In the Normal LV group, MPR and endocardial-epicardial MPR ratio were able to distinguish between normal and abnormal segments (p = 0.04; p = 0.02 respectively). No significant differences of absolute stress perfusion rate or MPR were observed comparing visually normal segments amongst groups. Our results demonstrate the feasibility of high-resolution voxel-wise perfusion assessment in patients with HF.

Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

PubMed

Ward, Andrew; Quinn, Kyle P; Bellas, Evangelia; Georgakoudi, Irene; Kaplan, David L

2013-01-01

The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D) vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF). Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

Correlation between acoustic radiation force impulse (ARFI)-based tissue elasticity measurements and perfusion parameters acquired by perfusion CT in cirrhotic livers: a proof of principle.

PubMed

Esser, Michael; Bitzer, Michael; Kolb, Manuel; Fritz, Jan; Kurucay, Mustafa; Ruff, Christer; Horger, Marius

2018-06-13

To investigate whether liver stiffness measured by acoustic radiation force impulse (ARFI) sonoelastography always correlates with the liver perfusion parameters quantified by perfusion CT in patients with known liver cirrhosis. Sonoelastography and perfusion CT were performed in 50 patients (mean age 65.5; range 45-87 years) with liver cirrhosis, who were classified according to Child-Pugh into class A (30/50, 60%), B (17/50, 34%), and C (3/50, 6%). For standardized ARFI measurements in the left liver lobe at a depth of 4 cm, a convex 6-MHz probe was used. CT examinations were performed using 80 kV, 100 mAs, and 50 ml of iodinated contrast agent injected at 5 ml/s. Using standardized region-of-interest measurements, we quantified arterial, portal venous, and total liver perfusion. There was a significant linear correlation between tissue stiffness and arterial liver perfusion (p = 0.015), and also when limiting the analysis to patients with histology (p = 0.019). In addition, there was a positive correlation between the total blood supply (arterial + portal-venous liver perfusion) to the liver and tissue stiffness (p = 0.001; with histology, p = 0.027). Shear wave velocity increased with higher Child-Pugh stages (p = 0.013). The degree of tissue stiffness in cirrhotic livers correlates expectedly-even if only moderately-with the magnitude of arterial liver perfusion and total liver perfusion. As such, liver elastography remains the leading imaging tool in assessing liver fibrosis.

Perfusion redistribution after a pulmonary-embolism-like event with contrast enhanced EIT.

PubMed

Nguyen, D T; Bhaskaran, A; Chik, W; Barry, M A; Pouliopoulos, J; Kosobrodov, R; Jin, C; Oh, T I; Thiagalingam, A; McEwan, A L

2015-06-01

Recent studies showed that regional pulmonary perfusion can be reliably estimated using electrical impedance tomography (EIT) with the aid of hypertonic saline based contrast enhancement. Building on these successful studies, we studied contrast EIT for pulmonary perfusion defect caused by an artificially induced pulmonary embolism (PE) in a large ovine model (N = 8, 78 ± 7.8 kg). Furthermore, the efficacy of a less invasive contrast bolus of 0.77 ml kg(-1) of NaCl 3% was compared with a more concentrated bolus of 0.13 ml kg(-1) of NaCl 20%. Prior to the injection of each contrast bolus injection, ventilation was turned off to provide a total of 40 to 45 s of apnoea. Each bolus of impedance contrast was injected through a catheter into the right atrium. Pulmonary embolisation was performed by balloon occlusion of part of the right branch of the pulmonary trunk. Four parameters representing the kinetics of the contrast dilution in the lung were evaluated for statistical differences between baseline and PE, including peak value, maximum uptake, maximum washout and area under the curve of the averaged contrast dilution curve in each lung. Furthermore, the right lung to left lung (R2L) ratio of each the aforementioned parameters were assessed. While all of the R2L ratios yielded significantly different means between baseline and PE, it can be concluded that the R2L ratios of area under the curve and peak value of the averaged contrast dilution curve are the most promising and reliable in assessing PE. It was also found that the efficacy of the two types of impedance contrasts were not significantly different in distinguishing PE from baseline in our model.

Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients.

PubMed

Zifan, A; Jiang, Y; Mittal, R K

2017-02-01

The mechanism of esophageal pain in patients with nutcracker esophagus (NE) and other esophageal motor disorders is not known. Our recent study shows that baseline esophageal mucosal perfusion, measured by laser Doppler perfusion monitoring, is lower in NE patients compared to controls. The goal of our current study was to perform a more detailed analysis of esophageal mucosal blood perfusion (EMBP) waveform of NE patients and controls to determine the optimal EMBP biomarkers that combined with suitable statistical learning models produce robust discrimination between the two groups. Laser Doppler recordings of 10 normal subjects (mean age 43 ± 15 years, 8 males) and 10 patients (mean age 47 ± 5.5 years., 8 males) with NE were analyzed. Time and frequency domain features were extracted from the first twenty-minute recordings of the EMBP waveforms, statistically ranked according to four independent evaluation criterions, and analyzed using two statistical learning models, namely, logistic regression (LR) and support vector machines (SVM). The top three ranked predictors between the two groups were the 0.5 and 0.75 perfusion quantile values followed by the surface of the EMBP power spectrum in the frequency domain. ROC curve ranking produced a cross-validated AUC (area under the curve) of 0.93 for SVM and 0.90 for LR. We show that as a group NE patients have lower perfusion values compared to controls, however, there is an overlap between the two groups, suggesting that not all NE patients suffer from low mucosal perfusion levels. © 2016 John Wiley & Sons Ltd.

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

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

Laws of physics help explain capillary non-perfusion in diabetic retinopathy.

PubMed

Stefánsson, E; Chan, Y K; Bek, T; Hardarson, S H; Wong, D; Wilson, D I

2018-02-01

The purpose is to use laws of physics to elucidate the mechanisms behind capillary non-perfusion in diabetic retinopathy. In diabetic retinopathy, loss of pericytes weakens capillary walls and the vessel dilates. A dilated capillary has reduced resistance to flow, therefore increased flow in that vessel and decreased in adjoining capillaries. A preferential shunt vessel is thus formed from the dilated capillary and the adjacent capillaries become non-perfused. We apply the laws of Laplace and Hagen-Poiseuille to better understand the phenomena that lead to capillary non-perfusion. These laws of physics can give a foundation for physical or mathematical models to further elucidate this field of study. The law of Laplace predicts that a weaker vessel wall will dilate, assuming constant transmural pressure. The Hagen-Poiseuille equation for flow and the Ostwald-de Waele relationship for viscosity predict that a dilated vessel will receive a higher portion of the fluid flow than the adjoining capillaries. Viscosity will decrease in the dilated vessel, furthering the imbalance and resulting in a patch of non-perfused capillaries next to the dilated 'preferential' shunt vessel. Physical principles support or inspire novel hypotheses to explain poorly understood phenomena in ophthalmology. This thesis of pericyte death and capillary remodelling, which was first proposed by Cogan and Kuwabara, already agrees with histological and angiographical observations in diabetic retinopathy. We have shown that it is also supported by classical laws of physics.

Cardiac PET perfusion tracers: current status and future directions.

PubMed

Maddahi, Jamshid; Packard, René R S

2014-09-01

PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The availability of these tracers is limited by the need for an onsite ((15)O water and (13)N ammonia) or nearby ((13)N ammonia) cyclotron or commitment to costly generators ((82)Rb). Owing to the short half-lives, such as 76 seconds for (82)Rb, 2.06 minutes for (15)O water, and 9.96 minutes for (13)N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible ((82)Rb and (15)O water) or not practical ((13)N ammonia). Furthermore, the long positron range of (82)Rb makes image resolution suboptimal and its low myocardial extraction limits its defect resolution. In recent years, development of an (18)F-labeled PET perfusion tracer has gathered considerable interest. The longer half-life of (18)F (109 minutes) would make the tracer available as a unit dose from regional cyclotrons and allow use in conjunction with treadmill exercise testing. Furthermore, the short positron range of (18)F would result in better image resolution. Flurpiridaz F 18 is by far the most thoroughly studied in animal models and is the only (18)F-based PET MPI radiotracer currently undergoing clinical evaluation. Preclinical and clinical experience with Flurpiridaz F 18 demonstrated a high myocardial extraction fraction, high image and defect resolution, high myocardial uptake, slow myocardial clearance, and high myocardial-to-background contrast that was stable over time-important properties of an ideal PET MPI radiotracer. Preclinical data from other (18)F-labeled myocardial perfusion tracers are encouraging. Copyright © 2014. Published by Elsevier Inc.

Pulmonary ventilation/perfusion scan

MedlinePlus

... take a ventilation and perfusion scan and then evaluate it with a chest x-ray. All parts ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

Low-Dose Dynamic Cerebral Perfusion Computed Tomography Reconstruction via Kronecker-Basis Representation Tensor Sparsity Regularization

PubMed Central

Zeng, Dong; Xie, Qi; Cao, Wenfei; Lin, Jiahui; Zhang, Hao; Zhang, Shanli; Huang, Jing; Bian, Zhaoying; Meng, Deyu; Xu, Zongben; Liang, Zhengrong; Chen, Wufan

2017-01-01

Dynamic cerebral perfusion computed tomography (DCPCT) has the ability to evaluate the hemodynamic information throughout the brain. However, due to multiple 3-D image volume acquisitions protocol, DCPCT scanning imposes high radiation dose on the patients with growing concerns. To address this issue, in this paper, based on the robust principal component analysis (RPCA, or equivalently the low-rank and sparsity decomposition) model and the DCPCT imaging procedure, we propose a new DCPCT image reconstruction algorithm to improve low dose DCPCT and perfusion maps quality via using a powerful measure, called Kronecker-basis-representation tensor sparsity regularization, for measuring low-rankness extent of a tensor. For simplicity, the first proposed model is termed tensor-based RPCA (T-RPCA). Specifically, the T-RPCA model views the DCPCT sequential images as a mixture of low-rank, sparse, and noise components to describe the maximum temporal coherence of spatial structure among phases in a tensor framework intrinsically. Moreover, the low-rank component corresponds to the “background” part with spatial–temporal correlations, e.g., static anatomical contribution, which is stationary over time about structure, and the sparse component represents the time-varying component with spatial–temporal continuity, e.g., dynamic perfusion enhanced information, which is approximately sparse over time. Furthermore, an improved nonlocal patch-based T-RPCA (NL-T-RPCA) model which describes the 3-D block groups of the “background” in a tensor is also proposed. The NL-T-RPCA model utilizes the intrinsic characteristics underlying the DCPCT images, i.e., nonlocal self-similarity and global correlation. Two efficient algorithms using alternating direction method of multipliers are developed to solve the proposed T-RPCA and NL-T-RPCA models, respectively. Extensive experiments with a digital brain perfusion phantom, preclinical monkey data, and clinical patient data clearly

Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

PubMed

Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

2016-02-01

The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

Right Ventricular Perfusion: Physiology and Clinical Implications.

PubMed

Crystal, George J; Pagel, Paul S

2018-01-01

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular

Blood perfusion construction for infrared face recognition based on bio-heat transfer.

PubMed

Xie, Zhihua; Liu, Guodong

2014-01-01

To improve the performance of infrared face recognition for time-lapse data, a new construction of blood perfusion is proposed based on bio-heat transfer. Firstly, by quantifying the blood perfusion based on Pennes equation, the thermal information is converted into blood perfusion rate, which is stable facial biological feature of face image. Then, the separability discriminant criterion in Discrete Cosine Transform (DCT) domain is applied to extract the discriminative features of blood perfusion information. Experimental results demonstrate that the features of blood perfusion are more concentrative and discriminative for recognition than those of thermal information. The infrared face recognition based on the proposed blood perfusion is robust and can achieve better recognition performance compared with other state-of-the-art approaches.

PREOPERATIVE COMPUTED TOMOGRAPHY VOLUMETRY AND GRAFT WEIGHT ESTIMATION IN ADULT LIVING DONOR LIVER TRANSPLANTATION

PubMed Central

PINHEIRO, Rafael S.; CRUZ-JR, Ruy J.; ANDRAUS, Wellington; DUCATTI, Liliana; MARTINO, Rodrigo B.; NACIF, Lucas S.; ROCHA-SANTOS, Vinicius; ARANTES, Rubens M; LAI, Quirino; IBUKI, Felicia S.; ROCHA, Manoel S.; D´ALBUQUERQUE, Luiz A. C.

2017-01-01

ABSTRACT Background: Computed tomography volumetry (CTV) is a useful tool for predicting graft weights (GW) for living donor liver transplantation (LDLT). Few studies have examined the correlation between CTV and GW in normal liver parenchyma. Aim: To analyze the correlation between CTV and GW in an adult LDLT population and provide a systematic review of the existing mathematical models to calculate partial liver graft weight. Methods: Between January 2009 and January 2013, 28 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. All grafts were perfused with HTK solution. Estimated graft volume was estimated by CTV and these values were compared to the actual graft weight, which was measured after liver harvesting and perfusion. Results: Median actual GW was 782.5 g, averaged 791.43±136 g and ranged from 520-1185 g. Median estimated graft volume was 927.5 ml, averaged 944.86±200.74 ml and ranged from 600-1477 ml. Linear regression of estimated graft volume and actual GW was significantly linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 - 0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients with normal liver parenchyma. A better estimation of graft weight could be reached by multiplying estimated graft volume by 0.82. PMID:28489167

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PubMed

Voskrebenzev, Andreas; Gutberlet, Marcel; Klimeš, Filip; Kaireit, Till F; Schönfeld, Christian; Rotärmel, Alexander; Wacker, Frank; Vogel-Claussen, Jens

2018-04-01

In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement.

PubMed

Tanaka, Akiko; Estrera, Anthony L

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field-and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution.

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement

PubMed Central

Tanaka, Akiko

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field—and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution. PMID:29682460

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl.

PubMed

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal-bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl

PubMed Central

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal–bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER. PMID:29867575

CT perfusion imaging of the liver and the spleen in patients with cirrhosis: Is there a correlation between perfusion and portal venous hypertension?

PubMed

Talakić, Emina; Schaffellner, Silvia; Kniepeiss, Daniela; Mueller, Helmut; Stauber, Rudolf; Quehenberger, Franz; Schoellnast, Helmut

2017-10-01

To correlate hepatic and splenic CT perfusion parameters with hepatic venous pressure gradient (HVPG) measurements in patients with cirrhosis. Twenty-one patients with cirrhosis (males, 17; females, 4; mean ± SD age, 57 ± 7 years) underwent hepatic and splenic perfusion CT on a 320-detector row volume scanner as well as invasive measurement of HVPG. Different CT perfusion algorithms (maximum slope analysis and Patlak plot) were used to measure hepatic arterial flow (HAF), portal venous flow (PVF), hepatic perfusion index (HPI), splenic arterial flow (SAF), splenic blood volume (SBV) and splenic clearance (SCL). Hepatic and splenic perfusion parameters were correlated with HVPG, and sensitivity and specificity for detection of severe portal hypertension (≥12 mmHg) were calculated. The Spearman correlation coefficient was -0.53 (p < 0.05) between SAF and HVPG, and -0.68 (p < 0.01) between HVPG and SCL. Using a cut-off value of 125 ml/min/100 ml for SCL, sensitivity for detection of a HVPG of ≥12 mmHg was 94%, and specificity 100%. There was no significant correlation between hepatic perfusion parameters and HVPG. CT perfusion in patients with cirrhosis showed a strong correlation between SCL and HVPG and may be used for detection of severe portal hypertension. • SAF and SCL are statistically significantly correlated with HVPG • SCL showed stronger correlation with HVPG than SAF • 125 ml/min/100 ml SCL-cut-off yielded 94 % sensitivity, 100 % specificity for severe PH • HAF, PVF and HPI showed no statistically significant correlation with HVPG.

Normothermic machine perfusion of donor livers without the need for human blood products

PubMed Central

Matton, Alix P. M.; Burlage, Laura C.; van Rijn, Rianne; de Vries, Yvonne; Karangwa, Shanice A.; Nijsten, Maarten W.; Gouw, Annette S. H.; Wiersema‐Buist, Janneke; Adelmeijer, Jelle; Westerkamp, Andrie C.; Lisman, Ton

2018-01-01

Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin‐based oxygen carrier (HBOC)‐201. Twenty‐four livers declined for transplantation were transported by using static cold storage. Upon arrival, livers underwent NMP for 6 hours using pressure‐controlled portal and arterial perfusion. A total of 12 livers were perfused using a solution based on RBCs and FFPs (historical cohort), 6 livers with HBOC‐201 and FFPs, and another 6 livers with HBOC‐201 and gelofusine, a gelatin‐based colloid solution. Compared with RBC + FFP perfused livers, livers perfused with HBOC‐201 had significantly higher hepatic adenosine triphosphate content, cumulative bile production, and portal and arterial flows. Biliary secretion of bicarbonate, bilirubin, bile salts, and phospholipids was similar in all 3 groups. The alanine aminotransferase concentration in perfusate was lower in the HBOC‐201–perfused groups. In conclusion, NMP of human donor livers can be performed effectively using HBOC‐201 and gelofusine, eliminating the need for human blood products. Perfusing livers with HBOC‐201 is at least similar to perfusion with RBCs and FFP. Some of the biomarkers of liver function and injury even suggest a possible superiority of an HBOC‐201–based perfusion solution and opens a perspective for further optimization of machine perfusion techniques. Liver Transplantation 24 528–538 2018 AASLD. PMID:29281862

High-frequency Electrocardiogram Analysis in the Ability to Predict Reversible Perfusion Defects during Adenosine Myocardial Perfusion Imaging

NASA Technical Reports Server (NTRS)

Tragardh, Elin; Schlegel, Todd T.; Carlsson, Marcus; Pettersson, Jonas; Nilsson, Klas; Pahlm, Olle

2007-01-01

Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

Estimating Human Trabecular Meshwork Stiffness by Numerical Modeling and Advanced OCT Imaging.

PubMed

Wang, Ke; Johnstone, Murray A; Xin, Chen; Song, Shaozhen; Padilla, Steven; Vranka, Janice A; Acott, Ted S; Zhou, Kai; Schwaner, Stephen A; Wang, Ruikang K; Sulchek, Todd; Ethier, C Ross

2017-09-01

The purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements. Postmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm's canal luminal pressure was directly manipulated. TM stiffness was deduced by an inverse finite element modeling (FEM) approach. A series of AFM forcemaps was acquired along a line traversing the anterior angle on a radially cut flat-mount corneoscleral wedge with TM facing upward. The elastic modulus of normal hTM estimated by inverse FEM was 70 ± 20 kPa (mean ± SD), whereas glaucomatous hTM was slightly stiffer (98 ± 19 kPa). This trend was consistent with TM stiffnesses measured by AFM: normal hTM stiffness = 1.37 ± 0.56 kPa, which was lower than glaucomatous hTM stiffness (2.75 ± 1.19 kPa). None of these differences were statistically significant. TM in HF wedges was softer than that in LF wedges for both normal and glaucomatous eyes based on the inverse FEM approach but not by AFM. Outflow facility was significantly correlated with TM stiffness estimated by FEM in six human eyes (P = 0.018). TM stiffness is higher, but only modestly so, in glaucomatous patients. Outflow facility in both normal and glaucomatous human eyes appears to associate with TM stiffness. This evidence motivates further studies to investigate factors underlying TM biomechanical property regulation.

Tumoricidal responses in spontaneous canine neoplasms after extracorporeal perfusion over immobilized protein A.

PubMed

Terman, D S

1981-01-01

I describe morphologic, histologic, immunohistochemical, and serologic changes in dogs with spontaneous breast adenocarcinoma, squamous cell carcinoma, hemangiopericytoma, and fibrosarcoma after extracorporeal perfusion of plasma over heat-killed and formalin-stabilized Staphylococcus aureus Cowans I (SAC), which was embedded in a membrane filtration system. In 12 dogs with breast adenocarcinoma, tumor necrosis was observed within 12 hours after perfusion; 24 hours after perfusion, multiple visible lesions in 6 of 6 dogs exhibited necrosis, but there was no reaction in uninvolved normal mammary tissue. In 8 dogs, healing of large ulcerated areas of cutaneous tumor was observed within 8 to 18 days after perfusion. Similar tumoricidal responses were observed in dogs with other neoplasms after SAC perfusion. Tumor cell necrosis oserved within 4 hours after extracorporeal perfusion was associated with immunohistochemical deposits of IgG and C'3 and ultrastructural evidence of lytic lesions on tumor cell membranes. No tumoricidal effects were observed after perfusion over Staphylococcus aureus Woods (SAW) (non-protein A bearing) in 3 dogs that previously or subsequently responded to SAC perfusion. No tumoricidal reactions were noted after phlebotomy of up to 50% of plasma volume in 6 tumor-bearing dogs that subsequently responded to SAC perfusion. SAC but not SAW perfusion was followed by increases in circulating tumor associated antibodies (TAA) for up to 48 hours after perfusion. Immune complexes increased after perfusion and remained elevated fo 72 hours. Findings suggest that the acute tumoricial responses are not due to mere removal of circulating immune reactants and may be initiated by TAA that are rendered operational after extracorporeal perfusion over SAC. The rapidity, specificity, and magnitude of the observed tumoricidal effects in various canine neoplastic diseases suggests that this may have potentially broad-based therapeutic and biologic implications

Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

PubMed

Göbel, A; Heldmann, M; Sartorius, A; Göttlich, M; Dirk, A-L; Brabant, G; Münte, T F

2017-01-01

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors. © 2016 British Society for Neuroendocrinology.

An unsupervised approach for measuring myocardial perfusion in MR image sequences

NASA Astrophysics Data System (ADS)

Discher, Antoine; Rougon, Nicolas; Preteux, Francoise

2005-08-01

Quantitatively assessing myocardial perfusion is a key issue for the diagnosis, therapeutic planning and patient follow-up of cardio-vascular diseases. To this end, perfusion MRI (p-MRI) has emerged as a valuable clinical investigation tool thanks to its ability of dynamically imaging the first pass of a contrast bolus in the framework of stress/rest exams. However, reliable techniques for automatically computing regional first pass curves from 2D short-axis cardiac p-MRI sequences remain to be elaborated. We address this problem and develop an unsupervised four-step approach comprising: (i) a coarse spatio-temporal segmentation step, allowing to automatically detect a region of interest for the heart over the whole sequence, and to select a reference frame with maximal myocardium contrast; (ii) a model-based variational segmentation step of the reference frame, yielding a bi-ventricular partition of the heart into left ventricle, right ventricle and myocardium components; (iii) a respiratory/cardiac motion artifacts compensation step using a novel region-driven intensity-based non rigid registration technique, allowing to elastically propagate the reference bi-ventricular segmentation over the whole sequence; (iv) a measurement step, delivering first-pass curves over each region of a segmental model of the myocardium. The performance of this approach is assessed over a database of 15 normal and pathological subjects, and compared with perfusion measurements delivered by a MRI manufacturer software package based on manual delineations by a medical expert.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karki, K; Hugo, G; Ford, J

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 andmore » 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 (250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2

[Intratympanic corticosteroid perfusion in the therapy of Meniere's disease].

PubMed

Sanković-Babić, Snezana; Kosanović, Rade; Ivanković, Zoran; Babac, Snezana; Tatović, Milica

2014-01-01

Over the last two decades the intratympanic perfusion of corticosteroids has been used as a minimally invasive surgical therapy of Meniere's disease. According to experimental studies the antiinflammatory, immunoprotective, antioxidant and neuroprotective role of the locally perfused corticosteroids was noticed in the inner ear structures. The recovery of action potentials in the cells of the Corti organ was confirmed as well as a decreased expression of aquaporine-1, a glycoprotein responsible for labyrinth hydrops and N and K ions derangement. The study showed results of intratympanic perfusion therapy with dexamethasone in patients with retractable Meniere's disease who are resistant to conservative treatment. Single doses of 4 mg/ml dexamethasone were given intratympanically in 19 patients with retractable Meniere's disease. Six single successive doses of dexamethasone were administered in the posteroinferior quadrant of the tympanic membrane. Follow-up of the patients was conducted by using a clinical questionnaire a month after completed perfusion series as well as on every third month up to one year. One month after completed first course of perfusions, in 78% of patients, vertigo problems completely ceased or were markedly reduced. The recovery of hearing function was recorded in 68% and marked tinnitus reduction in 84% of patients. After a year of follow-up, in 63% of patients the reduction of vertigo persisted, while hearing function was satisfactory in 52%. Tinitus reduction was present in 73% of patients. Intratympanic perfusion of dexamethasone in patients with Meniere's disease is a minimally invasive therapeutic method that contributes to the reduction of the intensity of vertigo recurrent attacks, decrease of the intensity of tinnitus and improvement of the average hearing threshold. Patients with chronic diseases and Meniere's disease who are contraindicted for systemic administration of cortocosteroids (hypertension, diabetes, glaucoma, peptic

Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function.

PubMed

Tedesco-Silva, Helio; Mello Offerni, Juliano Chrystian; Ayres Carneiro, Vanessa; Ivani de Paula, Mayara; Neto, Elias David; Brambate Carvalhinho Lemos, Francine; Requião Moura, Lúcio Roberto; Pacheco E Silva Filho, Alvaro; de Morais Cunha, Mirian de Fátima; Francisco da Silva, Erica; Miorin, Luiz Antonio; Demetrio, Daniela Priscila; Luconi, Paulo Sérgio; da Silva Luconi, Waldere Tania; Bobbio, Savina Adriana; Kuschnaroff, Liz Milstein; Noronha, Irene Lourdes; Braga, Sibele Lessa; Barsante, Renata Cristina; Mendes Moreira, João Cezar; Fernandes-Charpiot, Ida Maria Maximina; Abbud-Filho, Mario; Modelli de Andrade, Luis Gustavo; Dalsoglio Garcia, Paula; Tanajura Santamaria Saber, Luciana; Fernandes Laurindo, Alan; Chocair, Pedro Renato; Cuvello Neto, Américo Lourenço; Zanocco, Juliana Aparecida; Duboc de Almeida Soares Filho, Antonio Jose; Ferreira Aguiar, Wilson; Medina Pestana, Jose

2017-05-01

This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF). In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals. Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m 2 vs 49.0 ± 26.9 mL/min per 1.73 m 2 ; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m 2 vs 54.4 ± 28.6 mL/min per 1.73 m 2 ; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed. In this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method.

Perfusion quantification in contrast-enhanced ultrasound (CEUS)--ready for research projects and routine clinical use.

PubMed

Tranquart, F; Mercier, L; Frinking, P; Gaud, E; Arditi, M

2012-07-01

With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers. © Georg Thieme Verlag KG Stuttgart · New York.

Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury

PubMed Central

Mehaffey, J. Hunter; Charles, Eric J.; Sharma, Ashish K.; Salmon, Morgan; Money, Dustin; Schubert, Sarah; Stoler, Mark H; Tribble, Curtis G.; Laubach, Victor E.; Roeser, Mark E.; Kron, Irving L.

2017-01-01

Objective Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation, and may expand the use of marginal organs for transplantation. We hypothesized that four hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury. Methods We utilized a porcine lung injury model using intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response. Two groups (n=4 animals/group) received a 2-hour infusion of LPS via the external jugular vein. Serial blood gases were performed every 30 min until the PO2/FiO2 ratio dropped below 150 on two consecutive readings. Lungs were then randomized to treatment with 4 hours of normothermic EVLP with Steen solution or 4 additional hours of in vivo perfusion (Control). Airway pressures and blood gases were recorded for calculation of dynamic lung compliance and PO2/FiO2 ratios. EVLP was performed according to the NOVEL trial protocol with hourly recruitment maneuvers and oxygen challenge. Results All animals reached a PO2/FiO2 ratio < 150 mmHg within 3 hours after start of LPS infusion. Animals in the Control group had continued decline of oxygenation and compliance during the 4-hour in vivo perfusion period with three of the four animals dying within 4 hours due to severe hypoxia. The EVLP group demonstrated significant improvements in oxygenation and dynamic compliance from hour 1 to hour 4 (365.8±53.0 vs 584.4±21.0 mmHg, p=0.02; 9.0±2.8 vs 15.0±3.6, p=0.02 mL/cmH2O). Conclusions EVLP can successfully rehabilitate LPS-induced lung injury in this preclinical porcine model. Thus EVLP may provide a means to rehabilitate many types of acute lung injury. PMID:28434548

Correlation-based perfusion mapping using time-resolved MR angiography: A feasibility study for patients with suspicions of steno-occlusive craniocervical arteries.

PubMed

Nam, Yoonho; Jang, Jinhee; Park, Sonya Youngju; Choi, Hyun Seok; Jung, So-Lyung; Ahn, Kook-Jin; Kim, Bum-Soo

2018-05-22

To explore the feasibility of using correlation-based time-delay (CTD) maps produced from time-resolved MR angiography (TRMRA) to diagnose perfusion abnormalities in patients suspected to have steno-occlusive lesions in the craniocervical arteries. Twenty-seven patients who were suspected to have steno-occlusive lesions in the craniocervical arteries underwent both TRMRA and brain single-photon emission computed tomography (SPECT). TRMRA was performed on the supra-aortic area after intravenous injection of a 0.03 mmol/kg gadolinium-based contrast agent. Time-to-peak (TTP) maps and CTD maps of the brain were automatically generated from TRMRA data, and their quality was assessed. Detection of perfusion abnormalities was compared between CTD maps and the time-series maximal intensity projection (MIP) images from TRMRA and TTP maps. Correlation coefficients between quantitative changes in SPECT and parametric maps for the abnormal perfusion areas were calculated. The CTD maps were of significantly superior quality than TTP maps (p < 0.01). For perfusion abnormality detection, CTD maps (kappa 0.84, 95% confidence interval [CI] 0.67-1.00) showed better agreement with SPECT than TTP maps (0.66, 0.46-0.85). For perfusion deficit detection, CTD maps showed higher accuracy (85.2%, 95% CI 66.3-95.8) than MIP images (66.7%, 46-83.5), with marginal significance (p = 0.07). In abnormal perfusion areas, correlation coefficients between SPECT and CTD (r = 0.74, 95% CI 0.34-0.91) were higher than those between SPECT and TTP (r = 0.66, 0.20-0.88). CTD maps generated from TRMRA were of high quality and offered good diagnostic performance for detecting perfusion abnormalities associated with steno-occlusive arterial lesions in the craniocervical area. • Generation of perfusion parametric maps from time-resolved MR angiography is clinically useful. • Correlation-based delay maps can be used to detect perfusion abnormalities associated with steno-occlusive craniocervical arteries

Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

PubMed Central

Qi, Qi; Yeung, Timothy Pok Chi; Lee, Ting-Yim; Bauman, Glenn; Crukley, Cathie; Morrison, Laura; Hoffman, Lisa; Yartsev, Slav

2016-01-01

Background Tumor hypoxia is associated with treatment resistance to cancer therapies. Hypoxia can be investigated by immunohistopathologic methods but such procedure is invasive. A non-invasive method to interrogate tumor hypoxia is an attractive option as such method can provide information before, during, and after treatment for personalized therapies. Our study evaluated the correlations between computed tomography (CT) perfusion parameters and immunohistopathologic measurement of tumor hypoxia. Methods Wistar rats, 18 controls and 19 treated with stereotactic radiosurgery (SRS), implanted with the C6 glioma tumor were imaged using CT perfusion on average every five days to monitor tumor growth. A final CT perfusion scan and the brain were obtained on average 14 days (8–22 days) after tumor implantation. Tumor hypoxia was detected immunohistopathologically with pimonidazole. The tumor, necrotic, and pimonidazole-positive areas on histology samples were measured. Percent necrotic area and percent hypoxic areas were calculated. Tumor volume (TV), blood flow (BF), blood volume (BV), and permeability-surface area product (PS) were obtained from the CT perfusion studies. Correlations between CT perfusion parameters and histological parameters were assessed by Spearman’s ρ correlation. A Bonferroni-corrected P value < 0.05 was considered significant. Results BF and BV showed significant correlations with percent hypoxic area ρ = -0.88, P < 0.001 and ρ = -0.81, P < 0.001, respectively, for control animals and ρ = -0.7, P < 0.001 and ρ = -0.6, P = 0.003, respectively, for all animals, while TV and BV were correlated (ρ = -0.64, P = 0.01 and ρ = -0.43, P = 0.043, respectively) with percent necrotic area. PS was not correlated with either percent necrotic or percent hypoxic areas. Conclusions Percent hypoxic area provided significant correlations with BF and BV, suggesting that CT perfusion parameters are potential non-invasive imaging biomarkers of tumor

Normothermic perfusion: a new paradigm for organ preservation.

PubMed

Brockmann, Jens; Reddy, Srikanth; Coussios, Constantin; Pigott, David; Guirriero, Dino; Hughes, David; Morovat, Alireza; Roy, Debabrata; Winter, Lucy; Friend, Peter J

2009-07-01

Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation. We have developed a liver perfusion device that maintains physiological temperature with provision of oxygen and nutrition. Reperfusion experiments suggested that this allows recovery of ischemic damage. In a pig liver transplant model, we compared the outcome following either conventional cold preservation or warm preservation. Preservation periods of 5 and 20 hours and durations of warm ischemia of 40 and 60 minutes were tested. After 20 hours preservation without warm ischemia, post-transplant survival was improved (27%-86%, P = 0.026), with corresponding differences in transaminase levels and histological analysis. With the addition of 40 minutes warm ischemia, the differences were even more marked (cold vs. warm groups 0% vs. 83%, P = 0.001). However, with 60 minutes warm ischemia and 20 hours preservation, there were no survivors. Analysis of hemodynamic and liver function data during perfusion showed several factors to be predictive of posttransplant survival, including bile production, base excess, portal vein flow, and hepatocellular enzymes. Organ preservation by warm perfusion, maintaining physiological pressure and flow parameters, has enabled prolonged preservation and successful transplantation of both normal livers and those with substantial ischemic damage. This technique has the potential to address the shortage of organs for transplantation.

Tissue-Negative Transient Ischemic Attack: Is There a Role for Perfusion MRI?

PubMed

Grams, Raymond W; Kidwell, Chelsea S; Doshi, Amish H; Drake, Kendra; Becker, Jennifer; Coull, Bruce M; Nael, Kambiz

2016-07-01

Approximately 60% of patients with a clinical transient ischemic attack (TIA) do not have DWI evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of perfusion MRI in the evaluation of patients with TIA who have normal DWI findings. The inclusion criteria for this retrospective study were clinical presentation of TIA at admission with a discharge diagnosis of TIA confirmed by a stroke neurologist, MRI including both DWI and perfusion-weighted imaging within 48 hours of symptom onset, and no DWI lesion. Cerebral blood flow (CBF) and time to maximum of the residue function (Tmax) maps were evaluated independently by two observers. Multivariate analysis was used to assess perfusion findings; clinical variables; age, blood pressure, clinical symptoms, diabetes (ABCD2) score; duration of TIA; and time between MRI and onset and resolution of symptoms. Fifty-two patients (33 women, 19 men; age range, 20-95 years) met the inclusion criteria. A regional perfusion abnormality was identified on either Tmax or CBF maps of 12 of 52 (23%) patients. Seven (58%) of the patients with perfusion abnormalities had hypoperfused lesions best detected on Tmax maps; the other five had hyperperfusion best detected on CBF maps. In 11 of 12 (92%) patients with abnormal perfusion MRI findings, the regional perfusion deficit correlated with the initial neurologic deficits. Multivariable analysis revealed no significant difference in demographics, ABCD2 scores, or presentation characteristics between patients with and those without perfusion abnormalities. Perfusion MRI that includes Tmax and CBF parametric maps adds diagnostic value by depicting regions with delayed perfusion or postischemic hyperperfusion in approximately one-fourth of TIA patients who have normal DWI findings.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT

PubMed Central

Okada, David R.; Ghoshhajra, Brian B.; Blankstein, Ron; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Bezerra, Hiram G.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.

2010-01-01

Introduction We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. Methods Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. Results On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall γ = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. Conclusions CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress. PMID:19936863

SU-E-QI-06: Design and Initial Validation of a Precise Capillary Phantom to Test Perfusion Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R; Iacobucci, G; Khobragade, P

2014-06-15

Purpose: To design a precise perfusion phantom mimicking capillaries of the brain vasculature which could be used to test various perfusion protocols and algorithms which generate perfusion maps. Methods: A perfusion phantom was designed in Solidworks and built using additive manufacturing. The phantom was an overall cylindrical shape of diameter and height 20mm and containing capillaries of 200μm or 300μm which were parallel and in contact making up the inside volume where flow was allowed. We created a flow loop using a peristaltic pump and contrast agent was injected manually. Digital Subtraction Angiographic images and low contrast images with conemore » beam CT were acquired after the contrast was injected. These images were analyzed by our own code in LabVIEW software and Time-Density Curve, MTT and TTP was calculated. Results: Perfused area was visible in the cone beam CT images; however, individual capillaries were not distinguishable. The Time-Density Curve acquired was accurate, sensitive and repeatable. The parameters MTT, and TTP offered by the phantom were very sensitive to slight changes in the TDC shape. Conclusion: We have created a robust calibrating model for evaluation of existing perfusion data analysis systems. This approach is extremely sensitive to changes in the flow due to the high temporal resolution and could be used as a golden standard to assist developers in calibrating and testing of imaging perfusion systems and software algorithms. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.« less