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Sample records for adequate tissue perfusion

  1. Adipose Tissue - Adequate, Accessible Regenerative Material

    PubMed Central

    Kolaparthy, Lakshmi Kanth.; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-01-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  2. Monitoring tissue perfusion, oxygenation, and metabolism in critically ill patients.

    PubMed

    Ekbal, Nasirul J; Dyson, Alex; Black, Claire; Singer, Mervyn

    2013-06-01

    Alterations in oxygen transport and use are integral to the development of multiple organ failure; therefore, the ultimate goal of resuscitation is to restore effective tissue oxygenation and cellular metabolism. Hemodynamic monitoring is the cornerstone of management to promptly identify and appropriately manage (impending) organ dysfunction. Prospective randomized trials have confirmed outcome benefit when preemptive or early treatment is directed toward maintaining or restoring adequate tissue perfusion. However, treatment end points remain controversial, in large part because of current difficulties in determining what constitutes "optimal." Information gained from global whole-body monitoring may not detect regional organ perfusion abnormalities until they are well advanced. Conversely, the ideal "canary" organ that is readily accessible for monitoring, yet offers an early and sensitive indicator of tissue "unwellness," remains to be firmly identified. This review describes techniques available for real-time monitoring of tissue perfusion and metabolism and highlights novel developments that may complement or even supersede current tools.

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

    PubMed

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

    1991-01-01

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

  4. 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

  5. Switching off angiogenic signalling: creating channelled constructs for adequate oxygen delivery in tissue engineered constructs.

    PubMed

    Cheema, U; Alekseeva, T; Abou-Neel, E A; Brown, R A

    2010-10-06

    A major question in biomimetic tissue engineering is how much of the structure/function of native vasculature needs to be reproduced for effective tissue perfusion. O2 supplied to cells in 3D scaffolds in vitro is initially dependent upon diffusion through the scaffold and cell consumption. Low O2 (3%) enhances specific cell behaviours, but where O2 is critically low (pathological hypoxia) cell survival becomes compromised. We measured real-time O2 in 3D scaffolds and introduced micro-channelled architecture to controllably increase delivery of O2 to cells and switch off the hypoxic response. Simple static micro-channelling gives adequate perfusion and can be used to control cell generated hypoxia-induced signalling.

  6. Best strategy for cerebral protection in arch surgery - antegrade selective cerebral perfusion and adequate hypothermia

    PubMed Central

    Mohr, Friedrich W.; Etz, Christian D.

    2013-01-01

    Aortic arch surgery remains a complex surgical operation that necessitates specific neuroprotection strategies. Various approaches, such as hypothermic circulatory arrest (HCA), retrograde cerebral perfusion, and antegrade selective cerebral perfusion (aSCP), have each enjoyed periods of popularity. However, while the overall surgical approach tend to favour HCA with aSCP, technical factors, such as perfusion site, perfusate temperature and flow rate and pH management, have not been conclusively elucidated. The optimal extent of hypothermia during circulatory arrest is also unclear, particularly with recent partiality for warmer temperatures. The following perspective details the preferred surgical practice for cerebral protection in aortic arch surgery, based on existing evidence. PMID:23977602

  7. Perfused multiwell plate for 3D liver tissue engineering.

    PubMed

    Domansky, Karel; Inman, Walker; Serdy, James; Dash, Ajit; Lim, Matthew H M; Griffith, Linda G

    2010-01-07

    In vitro models that capture the complexity of in vivo tissue and organ behaviors in a scalable and easy-to-use format are desirable for drug discovery. To address this, we have developed a bioreactor that fosters maintenance of 3D tissue cultures under constant perfusion and we have integrated multiple bioreactors into an array in a multiwell plate format. All bioreactors are fluidically isolated from each other. Each bioreactor in the array contains a scaffold that supports formation of hundreds of 3D microscale tissue units. The tissue units are perfused with cell culture medium circulated within the bioreactor by integrated pneumatic diaphragm micropumps. Electronic controls for the pumps are kept outside the incubator and connected to the perfused multiwell by pneumatic lines. The docking design and open-well bioreactor layout make handling perfused multiwell plates similar to using standard multiwell tissue culture plates. A model of oxygen consumption and transport in the circulating culture medium was used to predict appropriate operating parameters for primary liver cultures. Oxygen concentrations at key locations in the system were then measured as a function of flow rate and time after initiation of culture to determine oxygen consumption rates. After seven days of culture, tissue formed from cells seeded in the perfused multiwell reactor remained functionally viable as assessed by immunostaining for hepatocyte and liver sinusoidal endothelial cell (LSEC) phenotypic markers.

  8. Contactless mapping of rhythmical phenomena in tissue perfusion using PPGI

    NASA Astrophysics Data System (ADS)

    Huelsbusch, Markus; Blazek, Vladimir

    2002-04-01

    This paper presents the experimental setup and preliminary results of a near infrared CCD camera based Photoplethysmography Imaging (PPGI) system, which has been shown to be suitable for contactless and spatially resolved assessment of rhythmical blood volume changes in the skin. To visualize the complex rhythmical patterns in the dermal perfusion the Wavelet Transform is utilized. It is able to jointly assess time and frequency behavior of signals and thus allows to analyze instationary oscillations and variabilities in the different human rhythmics. The presented system is expected to provide new insights into the functional sequences of physiological tissue perfusion as well as of the perfusion status in ulcer formation and wound healing.

  9. Cardiovascular tissue engineering I. Perfusion bioreactors: a review.

    PubMed

    Mironov, Vladimir; Kasyanov, Vladimir A; Yost, Michael J; Visconti, Richard; Twal, Waleed; Trusk, Thomas; Wen, Xuejun; Ozolanta, Iveta; Kadishs, Arnolds; Prestwich, Glenn D; Terracio, Louis; Markwald, Roger R

    2006-01-01

    Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current

  10. Quantitative Analysis of Peripheral Tissue Perfusion Using Spatiotemporal Molecular Dynamics

    PubMed Central

    Lee, Jungsul; Koh, Gou Young; Kwon, Kihwan; Choi, Chulhee

    2009-01-01

    Background Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging. Methodology/Principal Findings We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1. Conclusions/Significance We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis. PMID:19169354

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

    PubMed Central

    Vaughan, J. Thomas

    2009-01-01

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

  12. The Impact of Vasoactive Drugs on Oxygenation and Tissue Perfusion

    DTIC Science & Technology

    1992-01-01

    useful in the management of congestive heart failure, cardiogenic pulmonary edema , mitral or aortic regurgitation and persistent chest pain...administration include refractory cardiac failure, cardiogenic shock, septic shock, post cardiac surgery, and acute renal failure (Opie, 1991; Budnv... cardiogenic , anaphylactic, and septic shock, and cardiac arrest (Zaritsky & Eisenberg, 1986). Affect on Oxygenation and Tissue Perfusion Epinephrine, as with

  13. Review of laser speckle contrast techniques for visualizing tissue perfusion.

    PubMed

    Draijer, Matthijs; Hondebrink, Erwin; van Leeuwen, Ton; Steenbergen, Wiendelt

    2009-07-01

    When a diffuse object is illuminated with coherent laser light, the backscattered light will form an interference pattern on the detector. This pattern of bright and dark areas is called a speckle pattern. When there is movement in the object, the speckle pattern will change over time. Laser speckle contrast techniques use this change in speckle pattern to visualize tissue perfusion. We present and review the contribution of laser speckle contrast techniques to the field of perfusion visualization and discuss the development of the techniques.

  14. In vitro perfusion of engineered heart tissue through endothelialized channels.

    PubMed

    Vollert, Ingra; Seiffert, Moritz; Bachmair, Johanna; Sander, Merle; Eder, Alexandra; Conradi, Lenard; Vogelsang, Alexander; Schulze, Thomas; Uebeler, June; Holnthoner, Wolfgang; Redl, Heinz; Reichenspurner, Hermann; Hansen, Arne; Eschenhagen, Thomas

    2014-02-01

    In engineered heart tissues (EHT), oxygen and nutrient supply via mere diffusion is a likely factor limiting the thickness of cardiac muscle strands. Here, we report on a novel method to in vitro perfuse EHT through tubular channels. Adapting our previously published protocols, we expanded a miniaturized fibrin-based EHT-format to a larger six-well format with six flexible silicone posts holding each EHT (15×25×3 mm³). Thin dry alginate fibers (17×0.04×0.04 mm) were embedded into the cell-fibrin-thrombin mix and, after fibrin polymerization, dissolved by incubation in alginate lyase or sodium citrate. Oxygen concentrations were measured with a microsensor in 14-day-old EHTs (37°C, 21% oxygen) and ranged between 9% at the edges and 2% in the center of the tissue. Perfusion rapidly increased it to 10%-12% in the immediate vicinity of the microchannel. Continuous perfusion (20 μL/h, for 3 weeks) of the tubular lumina (100-500 μm) via hollow posts of the silicone rack increased mean dystrophin-positive cardiomyocyte density (36%±6% vs. 10%±3% of total cell number) and cross sectional area (73±2 vs. 48±1 μm²) in the central part of the tissue compared to nonperfused EHTs. The channels were populated by endothelial cells present in the reconstitution cell mix. In conclusion, we developed a novel approach to generate small tubular structures suitable for perfusion of spontaneously contracting and force-generating EHTs and showed that prolonged perfusion improved cardiac tissue structure.

  15. Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

    PubMed

    Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

    2017-05-01

    Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass.

  16. New vessel formation in the context of cardiomyocyte regeneration--the role and importance of an adequate perfusing vasculature.

    PubMed

    Michelis, Katherine C; Boehm, Manfred; Kovacic, Jason C

    2014-11-01

    The history of revascularization for cardiac ischemia dates back to the early 1960's when the first coronary artery bypass graft procedures were performed in humans. With this 50 year history of providing a new vasculature to ischemic and hibernating myocardium, a profound depth of experience has been amassed in clinical cardiovascular medicine as to what does, and does not work in the context of cardiac revascularization, alleviating ischemia and adequacy of myocardial perfusion. These issues are of central relevance to contemporary cell-based cardiac regenerative approaches. While the cardiovascular cell therapy field is surging forward on many exciting fronts, several well accepted clinical axioms related to the cardiac arterial supply appear to be almost overlooked by some of our current basic conceptual and experimental cell therapy paradigms. We present here information drawn from five decades of the clinical revascularization experience, review relevant new data on vascular formation via cell therapy, and put forward the case that for optimal cell-based cardiac regeneration due attention must be paid to providing an adequate vascular supply.

  17. New vessel formation in the context of cardiomyocyte regeneration – the role and importance of an adequate perfusing vasculature

    PubMed Central

    Michelis, Katherine C.; Boehm, Manfred; Kovacic, Jason C.

    2014-01-01

    The history of revascularization for cardiac ischemia dates back to the early 1960's when the first coronary artery bypass graft procedures were performed in humans. With this 50 year history of providing a new vasculature to ischemic and hibernating myocardium, a profound depth of experience has been amassed in clinical cardiovascular medicine as to what does, and does not work in the context of cardiac revascularization, alleviating ischemia and adequacy of myocardial perfusion. These issues are of central relevance to contemporary cell-based cardiac regenerative approaches. While the cardiovascular cell therapy field is surging forward on many exciting fronts, several well accepted clinical axioms related to the cardiac arterial supply appear to be almost overlooked by some of our current basic conceptual and experimental cell therapy paradigms. We present here information drawn from five decades of the clinical revascularization experience, review relevant new data on vascular formation via cell therapy, and put forward the case that for optimal cell-based cardiac regeneration due attention must be paid to providing an adequate vascular supply. PMID:24841067

  18. Photoplethysmographic sensors for perfusion measurements in spinal cord tissue

    NASA Astrophysics Data System (ADS)

    Phillips, J. P.; Kyriacou, P. A.

    2011-08-01

    Sensors for recording photoplethysmographic signals from the nervous tissue of the spinal cord are described. The purpose of these sensors is to establish whether perfusion is compromised in various states of injury which occur in certain animal models of spinal cord injury, for example compression injury. Various measures of perfusion are applicable such as the amplitude of the photoplethysmograph signal and the oxygen saturation, measured using a dual wavelength configuration. Signals are usually compared to baseline measurements made in uninjured subjects. This paper describes two types of probe, one based on optical fibres, and one in which optotes are placed in direct contact with the tissue surface. Results from a study based on a compression model utilising a fibreoptic sensor are presented.

  19. Dynamic contrast-enhanced MRI as a valuable non-invasive tool to evaluate tissue perfusion of free flaps: Preliminary results.

    PubMed

    Fellner, Claudia; Jung, Ernst M; Prantl, Lukas

    2010-01-01

    Early detection of a compromised circulation of free flaps and an immediate revision may lead to higher rates of flap salvage. The aim of this study was to evaluate the perfusion of the entire flap using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). DCE was performed in 11 patients after flap transplantation using an optimized 3D gradient echo sequence to cover the whole flap. The percentage increase of signal intensity over time was evaluated for the free flap as well as for a reference tissue. Furthermore, normalized signal increase was calculated as the ratio of signal increase within the flaps to the signal increase in the reference tissue. Signal increase in free flaps and reference tissue was compared using the Wilcoxon-test (p < 0.05), normalized signal increase in normally perfused (n = 9) and in flaps with compromised perfusion (n = 2) using Mann-Whitney-test (p < 0.05). Signal increase within normally perfused flaps was similar to the reference tissue. In flaps with compromised perfusion the increase was significantly lower than in reference tissue. Normalized signal increase in adequately perfused flaps and flaps with compromised perfusion also showed a significant difference. DCE MRI may be a valuable non-invasive tool to evaluate tissue perfusion of the complete free flap.

  20. Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering

    PubMed Central

    Li, Siwei; Glynne-Jones, Peter; Andriotis, Orestis G.; Ching, Kuan Y.; Jonnalagadda, Umesh S.; Oreffo, Richard O. C.; Hill, Martyn

    2014-01-01

    Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-built microfluidic perfusion bioreactors with integrated ultrasound standing wave traps. The system employed sweeping acoustic drive frequencies over the range of 890 to 910 kHz and continuous perfusion of the chondrogenic culture medium at a low-shear flow rate to promote the generation of three-dimensional agglomerates of human articular chondrocytes, and enhance cartilage formation by cells of the agglomerates via improved mechanical stimulation and mass transfer rates. Histological examination and assessment of micromechanical properties using indentation-type atomic force microscopy confirmed that the neocartilage grafts were analogous to native hyaline cartilage. Furthermore, in the ex vivo organ culture partial thickness cartilage defect model, implantation of the neocartilage grafts into defects for 16 weeks resulted in the formation of hyaline cartilage-like repair tissue that adhered to the host cartilage and contributed to significant improvements to the tissue architecture within the defects, compared to the empty defects. The study has demonstrated the first successful application of the acoustofluidic perfusion bioreactors to bioengineer scaffold-free neocartilage grafts of human articular chondrocytes that have the potential for subsequent use in second generation autologous chondrocyte implantation procedures for the repair of partial thickness cartilage defects. PMID:25272195

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

    PubMed

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

    2010-11-01

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

  2. Color-Doppler sonographic tissue perfusion measurements reveal significantly diminished renal cortical perfusion in kidneys with vesicoureteral reflux

    PubMed Central

    Scholbach, T. M.; Sachse, C.

    2016-01-01

    Vesicoureteral reflux (VUR) and its sequelae may lead to reduced renal perfusion and loss of renal function. Methods to describe and monitor tissue perfusion are needed. We investigated dynamic tissue perfusion measurement (DTPM) with the PixelFlux-software to measure microvascular changes in the renal cortex in 35 children with VUR and 28 healthy children. DTPM of defined horizontal slices of the renal cortex was carried out. A kidney was assigned to the “low grade reflux”-group if the reflux grade of the voiding cystourethrogram was 1 to 3 and to the “high grade reflux”-group if the reflux grade was 4 to 5. Kidneys with VUR showed a significantly reduced cortical perfusion. Compared to healthy kidneys, this decline reached in low and high grade refluxes within the proximal 50% of the cortex: 3% and 12 %, in the distal 50% of the cortex: 21% and 44 % and in the most distal 20 % of the cortex 41% and 44%. DTPM reveals a perfusion loss in kidneys depending on the degree of VUR, which is most pronounced in the peripheral cortex. Thus, DTPM offers the tool to evaluate microvascular perfusion, to help planning treatment decisions in children with VUR. PMID:27051133

  3. Precise femtosecond laser ablation of dental hard tissue: preliminary investigation on adequate laser parameters

    NASA Astrophysics Data System (ADS)

    Hikov, Todor; Pecheva, Emilia; Montgomery, Paul; Antoni, Frederic; Leong-Hoi, Audrey; Petrov, Todor

    2017-01-01

    This work aims at evaluating the possibility of introducing state-of-the-art commercial femtosecond laser system in restorative dentistry by maintaining well-known benefits of lasers for caries removal, but also in overcoming disadvantages such as thermal damage of irradiated substrate. Femtosecond ablation of dental hard tissue is investigated by changing the irradiation parameters (pulsed laser energy, scanning speed and pulse repetition rate), assessed for enamel and dentin. The femtosecond laser system used in this work may be suitable for cavity preparation in dentin and enamel, due to the expected effective ablation and low temperature increase when using ultra short laser pulses. If adequate laser parameters are selected, this system seems to be promising for promoting a laser-assisted, minimally invasive approach in restorative dentistry.

  4. Impaired Tissue Oxygenation in Metabolic Syndrome Requires Increased Microvascular Perfusion Heterogeneity.

    PubMed

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

    2017-02-01

    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.

  5. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues

    NASA Astrophysics Data System (ADS)

    Miller, Jordan S.; Stevens, Kelly R.; Yang, Michael T.; Baker, Brendon M.; Nguyen, Duc-Huy T.; Cohen, Daniel M.; Toro, Esteban; Chen, Alice A.; Galie, Peter A.; Yu, Xiang; Chaturvedi, Ritika; Bhatia, Sangeeta N.; Chen, Christopher S.

    2012-09-01

    In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture. Here, we printed rigid 3D filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks that could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices, and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core.

  6. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues.

    PubMed

    Miller, Jordan S; Stevens, Kelly R; Yang, Michael T; Baker, Brendon M; Nguyen, Duc-Huy T; Cohen, Daniel M; Toro, Esteban; Chen, Alice A; Galie, Peter A; Yu, Xiang; Chaturvedi, Ritika; Bhatia, Sangeeta N; Chen, Christopher S

    2012-09-01

    In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture. Here, we printed rigid 3D filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks that could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices, and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core.

  7. Rapid casting of patterned vascular networks for perfusable engineered 3D tissues

    PubMed Central

    Miller, Jordan S.; Stevens, Kelly R.; Yang, Michael T.; Baker, Brendon M.; Nguyen, Duc-Huy T.; Cohen, Daniel M.; Toro, Esteban; Chen, Alice A.; Galie, Peter A.; Yu, Xiang; Chaturvedi, Ritika; Bhatia, Sangeeta N.; Chen, Christopher S.

    2012-01-01

    In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core [1]. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture [2–4]. Here, we 3D printed rigid filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks which could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization, and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices (ECMs), and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core. PMID:22751181

  8. Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion

    NASA Astrophysics Data System (ADS)

    Ren, Wenqi; Gan, Qi; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2015-12-01

    Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice.

  9. Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion.

    PubMed

    Ren, Wenqi; Gan, Qi; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2015-12-01

    Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice.

  10. Color Doppler dynamic tissue perfusion measurement: a novel tool in the assessment of renal parenchymal perfusion in children with vesicoureteral reflux

    PubMed Central

    Scholbach, Thomas M.; Scholbach, Jakob; Pawelec, Agata; Nachulewicz, Paweł; Wieczorek, Andrzej P.; Brodzisz, Agnieszka; Zajączkowska, Maria M.; Borzęcka, Halina

    2015-01-01

    Introduction Vesicoureteral reflux (VUR) occurs in 20–50% of children suffering from recurrent urinary tract infections (UTIs) and is associated with an increased risk of renal scarring and impaired renal function. Early detection of renal perfusion deterioration would allow for the implementation of more aggressive treatment and potentially prevent further damage to the renal parenchyma. The aim of the study was to assess renal parenchymal perfusions in children with recurrent UTIs with and without coexisting VUR, and compare the findings with the results of healthy patients. Material and methods Color Doppler sonographic dynamic renal parenchymal perfusion measurements were performed with PixelFlux (Chameleon-Software, Germany) software in 77 children with recurrent UTIs and coexisting VUR and in 30 children with UTIs without VUR. The findings were compared with the results of 53 healthy children. Results Cortical parenchymal perfusion of children suffering from UTIs and VUR was significantly reduced when compared to the control group. Statistically significant differences (p < 0.05) were found in all perfusion parameters (i.e. mean velocity (vmix), mean perfused area (Amix), mean perfusion intensity (Imix), tissue pulsatility index (TPI), and tissue resistance index (TRI)) between the control group and children suffering from UTIs and VUR, particularly VUR grades III and IV. There were no significant differences between the UTI group and the control group. No differences were found between the controls and VUR grade II. Conclusions Renal parenchymal perfusion decreases significantly with higher grades of VUR. PMID:27279857

  11. Dual-mode quantitative imaging of wound tissue oxygenation and perfusion

    NASA Astrophysics Data System (ADS)

    Qin, Ruogu; Huang, Jiwei; Xu, Jeff S.; Ding, Liya; Gnyawali, Surya; Sen, Chandan K.; Huang, Kun; Xu, Ronald X.

    2010-02-01

    Accurate assessment of wound oxygenation and perfusion is important for evaluating wound healing/regression and guiding following therapeutic processes. However, many existing techniques and clinical practices are subjective and qualitative due to background bias, tissue heterogeneity, and inter-patient variation. To overcome these limitations, we developed a dual-modal imaging system for in vivo, non-invasive, real-time quantitative assessment of wound tissue oxygenation and perfusion. The imaging system integrated a broadband light source, a high-resolution CCD camera, a highly sensitive thermal camera, and a liquid crystal tunable filter. A user-friendly interface was developed to control all the components systematically. Advanced algorithms were explored for reliable reconstruction of tissue oxygenation and appropriate co-registration between thermal images and multispectral images. Dual-mode oxygenation and perfusion imaging was demonstrated on both benchtop models and human subjects, and compared with measurements using other methods, such as Laser Doppler and tissue oximeter. The test results suggested that the dual-modal imaging system has the potential for non-contact real-time imaging of wound tissue oxygenation and perfusion.

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

    PubMed

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

    2014-01-01

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

  13. Supportive development of functional tissues for biomedical research using the MINUSHEET® perfusion system

    PubMed Central

    2012-01-01

    Functional tissues generated under in vitro conditions are urgently needed in biomedical research. However, the engineering of tissues is rather difficult, since their development is influenced by numerous parameters. In consequence, a versatile culture system was developed to respond the unmet needs. Optimal adhesion for cells in this system is reached by the selection of individual biomaterials. To protect cells during handling and culture, the biomaterial is mounted onto a MINUSHEET® tissue carrier. While adherence of cells takes place in the static environment of a 24 well culture plate, generation of tissues is accomplished in one of several available perfusion culture containers. In the basic version a continuous flow of always fresh culture medium is provided to the developing tissue. In a gradient perfusion culture container epithelia are exposed to different fluids at the luminal and basal sides. Another special container with a transparent lid and base enables microscopic visualization of ongoing tissue development. A further container exhibits a flexible silicone lid to apply force onto the developing tissue thereby mimicking mechanical load that is required for developing connective and muscular tissue. Finally, stem/progenitor cells are kept at the interface of an artificial polyester interstitium within a perfusion culture container offering for example an optimal environment for the spatial development of renal tubules. The system presented here was evaluated by various research groups. As a result a variety of publications including most interesting applications were published. In the present paper these data were reviewed and analyzed. All of the results point out that the cell biological profile of engineered tissues can be strongly improved, when the introduced perfusion culture technique is applied in combination with specific biomaterials supporting primary adhesion of cells. PMID:23369669

  14. Multimodal tissue perfusion imaging using multi-spectral and thermographic imaging systems applied on clinical data

    NASA Astrophysics Data System (ADS)

    Klaessens, John H. G. M.; Nelisse, Martin; Verdaasdonk, Rudolf M.; Noordmans, Herke Jan

    2013-03-01

    Clinical interventions can cause changes in tissue perfusion, oxygenation or temperature. Real-time imaging of these phenomena could be useful for surgical strategy or understanding of physiological regulation mechanisms. Two noncontact imaging techniques were applied for imaging of large tissue areas: LED based multispectral imaging (MSI, 17 different wavelengths 370 nm-880 nm) and thermal imaging (7.5 to 13.5 μm). Oxygenation concentration changes were calculated using different analyzing methods. The advantages of these methods are presented for stationary and dynamic applications. Concentration calculations of chromophores in tissue require right choices of wavelengths The effects of different wavelength choices for hemoglobin concentration calculations were studied in laboratory conditions and consequently applied in clinical studies. Corrections for interferences during the clinical registrations (ambient light fluctuations, tissue movements) were performed. The wavelength dependency of the algorithms were studied and wavelength sets with the best results will be presented. The multispectral and thermal imaging systems were applied during clinical intervention studies: reperfusion of tissue flap transplantation (ENT), effectiveness of local anesthetic block and during open brain surgery in patients with epileptic seizures. The LED multispectral imaging system successfully imaged the perfusion and oxygenation changes during clinical interventions. The thermal images show local heat distributions over tissue areas as a result of changes in tissue perfusion. Multispectral imaging and thermal imaging provide complementary information and are promising techniques for real-time diagnostics of physiological processes in medicine.

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

    PubMed

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

    2014-05-01

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

  16. 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.

  17. A simple physiologic pulsatile perfusion system for the study of intact vascular tissue.

    PubMed

    Conklin, B S; Surowiec, S M; Lin, P H; Chen, C

    2000-07-01

    Perfusion vascular culture models may provide a useful link between cell culture models and animal culture models by allowing a high level of control over important parameters while maintaining physiologic structure. The purpose of this study was to develop and test a new vascular culture system for pulsatile perfusion culture of intact vascular tissue. The system generates a pulsatile component of flow by means of a cam-driven syringe and a peristaltic pump and compliance chamber. Cams were designed, constructed and tested to simulate canine femoral and common carotid artery flows. The mean pressure was adjusted between 60 and 200 mmHg without significantly affecting flow rate, flow waveform, or the pressure waveform. Porcine common carotid artery segments were cultured in this pulsatile perfusion system. The viability of vascular segments was tested after various culture times with a functional assay that demonstrated both smooth muscle cell and endothelial cell response to vasomotor challenge.

  18. Photoacoustic imaging of blood perfusion in tissue and phantoms

    NASA Astrophysics Data System (ADS)

    Pilatou, Magdalena C.; Kolkman, Roy G. M.; Hondebrink, Erwin; Bolt, Rene A.; de Mul, Frits F. M.

    2001-06-01

    To localize and monitor the blood content in tissue we developed a very sensitive photo-acoustical detector. PVDF has been used as piezo-electric material. In this detector also fibers for the illumination of the sample are integrated. Resolution is about 20 (m in depth and about 50-100 m laterally). We use 532 nm light. We will show how photoacoustics can be used for measuring the thickness of tissue above bone. We will also report measurements on tissue phantoms: e.g. a vessel delta from the epigastric artery branching of a Wistar rat, filled with an artificial blood-resembling absorber. The measurements have been carried out on phantoms containing vessels at several depths. Signal processing was enhanced by Fourier processing of the data.

  19. Doppler optical coherence tomography to monitor the effect of photodynamic therapy on tissue morphology and perfusion

    NASA Astrophysics Data System (ADS)

    Aalders, Maurice C. G.; Triesscheijn, Martijn L.; Ruevekamp, Marjan; de Bruin, Daniel M.; Baas, Paul; Faber, Dirk J.; Stewart, Fiona A.

    2006-07-01

    We investigated the feasibility of using optical coherence tomography (OCT) for noninvasive real-time visualization of the vascular effects of photodynamic therapy (PDT) in normal and tumor tissue in mice. Perfusion control measurements were initially performed after administrating vaso-active drugs or clamping of the subcutaneous tumors. Subsequent measurements were made on tumor-bearing mice before and after PDT using the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). Tumors were illuminated using either a short drug light interval (D-L, 3h), when mTHPC is primarily located in the tumor vasculature or a long D-L interval (48 h), when the drug is distributed throughout the whole tumor. OCT enabled visualization of the different layers of tumor, and overlying skin with a maximal penetration of ≤ 0.5-1 mm. PDT with a short D-L interval resulted in a significant decrease of perfusion in the tumor periphery, to 20% of pre-treatment values at 160 min, whereas perfusion in the skin initially increased by 10% (at 25 min) and subsequently decreased to 60% of pre-treatment values (at 200 min). PDT with a long D-L interval did not induce significant changes in perfusion. The concept of using noninvasive OCT measurements for monitoring early, treatment-related changes in morphology and perfusion may have applications in evaluating effects of anti-angiogenic or antivascular (cancer) therapy.

  20. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    PubMed Central

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  1. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro.

    PubMed

    Killian, Nathaniel J; Vernekar, Varadraj N; Potter, Steve M; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.

  2. Long-term measurement of renal cortical and medullary tissue oxygenation and perfusion in unanesthetized sheep.

    PubMed

    Calzavacca, Paolo; Evans, Roger G; Bailey, Michael; Lankadeva, Yugeesh R; Bellomo, Rinaldo; May, Clive N

    2015-05-15

    The role of renal cortical and medullary hypoxia in the development of acute kidney injury is controversial, partly due to a lack of techniques for the long-term measurement of intrarenal oxygenation and perfusion in conscious animals. We have, therefore, developed a methodology to chronically implant combination probes to chronically measure renal cortical and medullary tissue perfusion and oxygen tension (tPO2) in conscious sheep and evaluated their responsiveness and reliability. A transit-time flow probe and a vascular occluder were surgically implanted on the left renal artery. At the same operation, dual fiber-optic probes, comprising a fluorescence optode to measure tPO2 and a laser-Doppler probe to assess tissue perfusion, were inserted into the renal cortex and medulla. In recovered conscious sheep (n = 8) breathing room air, mean 24-h cortical and medullary tPO2 were similar (31.4 ± 0.6 and 29.7 ± 0.7 mmHg, respectively). In the renal cortex and medulla, a 20% reduction in renal blood flow (RBF) decreased perfusion (14.6 ± 8.6 and 41.2 ± 8.5%, respectively) and oxygenation (48.1 ± 8.5 and 72.4 ± 8.5%, respectively), with greater decreases during a 50% reduction in RBF. At autopsy, minimal fibrosis was observed around the probes. In summary, we have developed a technique to chronically implant fiber-optic probes in the renal cortex and medulla for recording tissue perfusion and oxygenation over many days. In normal resting conscious sheep, cortical and medullary tPO2 were similar. The responses to and recovery from renal artery occlusion, together with the consistent measurements over a 24-h period, demonstrate the responsiveness and stability of the probes.

  3. Limited Accuracy of Colour Doppler Ultrasound Dynamic Tissue Perfusion Measurement in Diabetic Adults

    PubMed Central

    Stoperka, Felix; Karger, Claudia

    2016-01-01

    Dynamic tissue perfusion measurement (DTPM) is a pre-described and available method in pediatric ultrasound to quantify tissue perfusion in renal Doppler ultrasound by particular video analysis software. This study evaluates DTPM during single and between repeated visits after 6 months, calibrates repeated DTPM within different region of interest (ROI) and compares DTPM with kidney function markers in adult patients with early diabetic nephropathy (n = 17). During repeated measurements, no association of readings at the same patients in the same (n = 3 readings) as well as repeated visit (n = 2 visits) could be retrieved. No association between DTPM, MDRD-GFR, albuminuria, age and duration of diabetes was observed. These negative results are presumably related to inconsistency of DTPM due to non-fixed ROI position as could be shown in calibrating series. Further development of the method should be performed to enable reproducible DTPM readings in adults. PMID:28033403

  4. Effects of mechanical stimulation induced by compression and medium perfusion on cardiac tissue engineering.

    PubMed

    Shachar, Michal; Benishti, Nessi; Cohen, Smadar

    2012-01-01

    Cardiac tissue engineering presents a challenge due to the complexity of the muscle tissue and the need for multiple signals to induce tissue regeneration in vitro. We investigated the effects of compression (1 Hz, 15% strain) combined with fluid shear stress (10(-2) -10(-1) dynes/cm(2) ) provided by medium perfusion on the outcome of cardiac tissue engineering. Neonatal rat cardiac cells were seeded in Arginine-Glycine-Aspartate (RGD)-attached alginate scaffolds, and the constructs were cultivated in a compression bioreactor. A daily, short-term (30 min) compression (i.e., "intermittent compression") for 4 days induced the formation of cardiac tissue with typical striation, while in the continuously compressed constructs (i.e., "continuous compression"), the cells remained spherical. By Western blot, on day 4 the expression of the gap junction protein connexin 43 was significantly greater in the "intermittent compression" constructs and the cardiomyocyte markers (α-actinin and N-cadherin) showed a trend of better preservation compared to the noncompressed constructs. This regime of compression had no effect on the proliferation of nonmyocyte cells, which maintained low expression level of proliferating cell nuclear antigen. Elevated secretion levels of basic fibroblast growth factor and transforming growth factor-β in the daily, intermittently compressed constructs likely attributed to tissue formation. Our study thus establishes the formation of an improved cardiac tissue in vitro, when induced by combined mechanical signals of compression and fluid shear stress provided by perfusion.

  5. The use of thermography in early detection of tissue perfusion disorders in rats

    PubMed Central

    Łokaj, Marek; Falkowski, Aleksander; Prowans, Piotr

    2014-01-01

    Introduction Tissue perfusion disorders can be present in various diseases and progress in the form of arterial ischemia or venous stasis with accompanying local changes in temperature. Aim To use of thermography in the diagnostics of early periods of tissue perfusion disorders before the clinical symptoms occur. Material and methods Thirty-two male rats were used. After anesthesia the skin on lower limbs was shaved and femoral vessels of both sides were exposed. In 10 rats the left femoral artery was ligated, in 12 rats the left femoral vein was ligated and in the 10 remaining rats both left femoral vessels were ligated. Thermography of the limbs was performed before the vessels were ligated and after a period of 24 h. The pictures were taken every 5 s during 3 min. Before the measurement, the tissues were cooled down for 20 s with a 5°C water compress. The rate of temperature return to the limbs was evaluated. Results Statistically significant differences were observed after the 24-hour period on the thigh after the ligation of the vein, and on the shank and the foot after ligation of the artery. After the ligature of both vessels, statistically significant differences occurred immediately after their ligature within the thigh and shank and after 24 h on the foot. Conclusions The results show that cameras with an accuracy of 0.05°C can be used to detect tissue perfusion disorders. The special diagnostic value is the ability to detect perfusion disorders before clinical symptoms occur. PMID:25337154

  6. Bio-Pick, Place, and Perfuse: A New Instrument for Three-Dimensional Tissue Engineering

    PubMed Central

    Blakely, Andrew M.; Manning, Kali L.; Tripathi, Anubhav

    2015-01-01

    A grand challenge of tissue engineering is the fabrication of large constructs with a high density of living cells. By adapting the principles of pick-and-place machines used in the high-speed assembly of electronics, we have developed an innovative instrument, the Bio-Pick, Place, and Perfuse (Bio-P3), which picks up large complex multicellular building parts, transports them to a build area, and precisely places the parts at desired locations while perfusing the parts. These assembled parts subsequently fuse to form a larger contiguous tissue construct. Multicellular microtissues were formed by seeding cells into nonadhesive micro-molds, wherein cells self-assembled scaffold-free parts in the shape of spheroids, toroids, and honeycombs. After removal from the molds, the parts were gripped, transported (using an x, y, z controller), and released using the Bio-P3 with little to no effect on cell viability or part structure. As many as 16 toroids were stacked over a 170 μm diameter post where they fused over the course of 48 h to form a single tissue. Larger honeycomb parts were also gripped and stacked onto a build head that, like the gripper head, provided fluid suction to hold and perfuse the parts during assembly. Scaffold-free building parts help to address several of the engineering and biological challenges to large tissue biofabrication, and the Bio-P3 described in this article is a novel instrument for the controlled gripping, placing, stacking, and perfusing of living building parts for solid organ fabrication. PMID:25530515

  7. 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

  8. Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter Engineered Tissue Tubes.

    PubMed

    Schmidt, Jillian B; Tranquillo, Robert T

    2016-05-01

    A cyclic stretch and perfusion bioreactor was designed to culture large diameter engineered tissue tubes for heart valve applications. In this bioreactor, tubular tissues consisting of dermal fibroblasts in a sacrificial fibrin gel scaffold were placed over porated latex support sleeves and mounted in a custom bioreactor. Pulsatile flow of culture medium into the system resulted in cyclic stretching as well as ablumenal, lumenal, and transmural flow (perfusion). In this study, lumenal remodeling, composition, and mechanical strength and stiffness were compared for tissues cyclically stretched in this bioreactor on either the porated latex sleeves or solid latex sleeves, which did not permit lumenal or transmural flow. Tissues cyclically stretched on porated sleeves had regions of increased lumenal remodeling and cellularity that were localized to the columns of pores in the latex sleeve. A CFD model was developed with COMSOL Multiphysics(®) to predict flow of culture medium in and around the tissue, and the predictions suggest that the enhanced lumenal remodeling was likely a result of elevated shear stresses and transmural velocity in these regions. This work highlights the beneficial effects of increased nutrient transport and flow stimulation for accelerating in vitro tissue remodeling.

  9. Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion.

    PubMed

    Schneider, H

    2009-03-01

    In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the

  10. Flap raising on pulsatile perfused cadaveric tissue: a novel method for surgical teaching and exercise.

    PubMed

    Wolff, Klaus-Dietrich; Fichter, Andreas; Braun, Christian; Bauer, Florian; Humbs, Martin

    2014-10-01

    Exercising flap raising procedures on cadavers is considered a prerequisite to prepare for clinical practise. To improve teaching and create conditions as realistic as possible, a perfusion device was developed providing pulsatile flow through the vessels of different donor sites. A plastic bag filled with red stained tab water was placed into a pump, which was driven by an electric motor. The bag was set under rhythmic compression with variable frequency and pressure. The pedicles of the radial forearm, anterolateral thigh, rectus abdominis, fibular and iliac crest flap were cannulated at the origin from their source arteries. Flap raising was performed under pulsatile perfusion in 15 fresh bodies and subsequently in 6 Thiel-embalmed cadavers during a flap raising course. We regularly observed staining of the skin and skin bleeding in fresh bodies and less reliable in embalmed cadavers. All flap pedicles showed pulsatile movements, and the radial pulse became palpable. Most perforators of the anterolateral thigh and osteocutaneous fibular flap could be identified by their pulse. Bleeding from bony tissue and venous return was seldom observed. We conclude that pulsatile perfusion of cadaveric tissue creates more realistic conditions for flap raising and improves teaching for beginners and advanced surgeons.

  11. Tissue to plasma capillary permeability of sup 131 I-albumin in the perfused rabbit ear

    SciTech Connect

    Bent-Hansen, L.; Svendsen, J.H. )

    1991-03-01

    The tissue to plasma transfer of {sup 131}I-albumin was recorded in perfused rabbit ears (n = 6) following equilibration for 24 hr. 125I-fibrinogen served as the plasma marker, and was introduced intravenously 15 min before clamping. The ears were rollerpump perfused with isotonic diluted plasma at a constant rate of (mean {plus minus} SD) 5.1 {plus minus} 1.5 ml (min.100 g)-1. The mean extravascular albumin distribution volume was 12.4 {plus minus} 1.1 ml.100 g-1, and the fibrinogen volume (plasma volume in tissue) was 3.1 {plus minus} 0.4 ml.100 g-1 as determined from biopsies of the contralateral ear. The initial transfer of albumin was marked, and occurred at rates corresponding to a unidirectional clearance (Cl(0)) of 0.068 {plus minus} 0.012 ml (min.100 g)-1. However, with a reduction of mean interstitial albumin tracer content of no more than 4%, net transport decreased to reach slowly declining levels 5 to 10 times lower within 10 min of continued perfusion. The decrease was considered due to rapid exhaustion of a small interstitial pool of tracer immediately adjacent to the exchange vessel membrane, followed by an increasingly retarded outwash from more distant areas. The results suggest a bimodal structural resistance to albumin movement: a relatively low resistance in the capillary membrane, and a considerable restriction to albumin transport located within the interstitial space.

  12. Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects

    SciTech Connect

    Brunken, R.; Schwaiger, M.; Grover-McKay, M.; Phelps, M.E.; Tillisch, J.; Schelbert, H.R.

    1987-09-01

    Positron emission tomography with /sup 13/N-ammonia and /sup 18/F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.

  13. AUGMENTATION OF LIMB PERFUSION AND REVERSAL OF TISSUE ISCHEMIA PRODUCED BY ULTRASOUND-MEDIATED MICROBUBBLE CAVITATION

    PubMed Central

    Belcik, J. Todd; Mott, Brian H.; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J.; Ammi, Azzdine; Linden, Joel M.; Lindner, Jonathan R.

    2015-01-01

    Background Ultrasound can increase tissue blood flow in part through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation, and sought to characterize the biologic mediators. Methods and Results Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in non-ischemic mice after unilateral 10 min exposure to intermittent ultrasound alone (mechanical index [MI] 0.6 or 1.3) or ultrasound with lipid microbubbles (2×108 I.V.). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (p<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3-fold and 10-fold higher than control for MI 0.6 and 1.3, respectively; p<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase (eNOS) attenuated flow augmentation produced by ultrasound and microbubbles by 70% (p<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide (NO) production and muscle phospho-eNOS increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40–50% reduction in flow), ultrasound (MI 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control non-ischemic limb. Conclusions Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of eNOS. PMID:25834183

  14. Optical coherence tomography microangiography for monitoring the response of vascular perfusion to external pressure on human skin tissue

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Hequn; Wang, Ruikang K.

    2014-05-01

    Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT)-based microangiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT microangiography (OMAG) to evaluate changes in blood perfusion in response to externally applied pressure on human skin tissue in vivo. External force is loaded normal to the tissue surface at the nailfold region of a healthy human volunteer. An incremental force is applied step by step and then followed by an immediate release. Skin perfusion events including baseline are continuously imaged by OMAG, allowing for visualization and quantification of the capillary perfusion in the nailfold tissue. The tissue strain maps are simultaneously evaluated through the available OCT structural images to assess the relationship of the microcirculation response to the applied pressure. The results indicate that the perfusion progressively decreases with the constant increase of pressure. Reactive hyperemia occurs right after the removal of the pressure. The perfusion returns to the baseline level after a few minutes. These findings suggest that OMAG may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

  15. Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

    NASA Astrophysics Data System (ADS)

    Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

    2015-03-01

    Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

  16. New methods for monitoring dynamic airway tissue oxygenation and perfusion in experimental and clinical transplantation.

    PubMed

    Khan, Mohammad A; Dhillon, Gundeep; Jiang, Xinguo; Lin, Yu-Chun; Nicolls, Mark R

    2012-11-15

    A dual circulation, supplied by bronchial and pulmonary artery-derived vessels, normally perfuses the airways from the trachea to the terminal bronchioles. This vascular system has been highly conserved through mammalian evolution and is disrupted at the time of lung transplantation. In most transplant centers, this circulation is not restored. The Papworth Hospital Autopsy study has revealed that an additional attrition of periairway vessels is associated with the development of chronic rejection, otherwise known as the bronchiolitis obliterans syndrome (BOS). Experimental studies subsequently demonstrated that airway vessels are subject to alloimmune injury and that the loss of a functional microvascular system identifies allografts that cannot be rescued with immunosuppressive therapy. Therefore, surgical and medical strategies, which preserve the functionality of the existent vasculature in lung transplant patients, may conceivably limit the incidence of BOS. Given these unique anatomic and physiological considerations, there is an emerging rationale to better understand the perfusion and oxygenation status of airways in transplanted lungs. This article describes novel methodologies, some newly developed by our group, for assessing airway tissue oxygenation and perfusion in experimental and clinical transplantation.

  17. Well Plate-Based Perfusion Culture Device for Tissue and Tumor Microenvironment Replication

    PubMed Central

    Zhang, W.; Gu, Y.; Hao, Y.; Sun, Q.; Konior, K.; Wang, H.

    2015-01-01

    There are significant challenges in developing in vitro human tissue and tumor models that can be used to support new drug development and evaluate personalized therapeutics. The challenges include: (1) working with primary cells which are often difficult to maintain ex vivo, (2) mimicking native microenvironments from which primary cells are harvested, and (3) lack of culture devices that can support these microenvironments to evaluate drug responses in a high-throughput manner. Here we report a versatile well plate-based perfusion culture device that was designed, fabricated and used to: (1) ascertain the role of perfusion in facilitating the expansion of human multiple myeloma cells and evaluate drug response of the cells, (2) preserve the physiological phenotype of primary murine osteocytes by reconstructing the 3D cellular network of osteocytes, and (3) circulate primary murine T cells through a layer of primary murine intestine epithelial cells to recapitulate the interaction of the immune cells with the epithelial cells. Through these diverse case studies, we demonstrate the device’s design features to support: (1) the convenient and spatiotemporal placement of cells and biomaterials into the culture wells of the device; (2) the replication of tissues and tumor microenvironments using perfusion, stromal cells, and/or biomaterials; (3) the circulation of non-adherent cells through the culture chambers; and (4) conventional tissue and cell characterization by plate reading, histology, and flow cytometry. Future challenges are identified and discussed from the perspective of manufacturing the device and making its operation for routine and wide use. PMID:26021852

  18. Precise ablation of dental hard tissues with ultra-short pulsed lasers. Preliminary exploratory investigation on adequate laser parameters.

    PubMed

    Bello-Silva, Marina Stella; Wehner, Martin; Eduardo, Carlos de Paula; Lampert, Friedrich; Poprawe, Reinhart; Hermans, Martin; Esteves-Oliveira, Marcella

    2013-01-01

    This study aimed to evaluate the possibility of introducing ultra-short pulsed lasers (USPL) in restorative dentistry by maintaining the well-known benefits of lasers for caries removal, but also overcoming disadvantages, such as thermal damage of irradiated substrate. USPL ablation of dental hard tissues was investigated in two phases. Phase 1--different wavelengths (355, 532, 1,045, and 1,064 nm), pulse durations (picoseconds and femtoseconds) and irradiation parameters (scanning speed, output power, and pulse repetition rate) were assessed for enamel and dentin. Ablation rate was determined, and the temperature increase measured in real time. Phase 2--the most favorable laser parameters were evaluated to correlate temperature increase to ablation rate and ablation efficiency. The influence of cooling methods (air, air-water spray) on ablation process was further analyzed. All parameters tested provided precise and selective tissue ablation. For all lasers, faster scanning speeds resulted in better interaction and reduced temperature increase. The most adequate results were observed for the 1064-nm ps-laser and the 1045-nm fs-laser. Forced cooling caused moderate changes in temperature increase, but reduced ablation, being considered unnecessary during irradiation with USPL. For dentin, the correlation between temperature increase and ablation efficiency was satisfactory for both pulse durations, while for enamel, the best correlation was observed for fs-laser, independently of the power used. USPL may be suitable for cavity preparation in dentin and enamel, since effective ablation and low temperature increase were observed. If adequate laser parameters are selected, this technique seems to be promising for promoting the laser-assisted, minimally invasive approach.

  19. Three dimensional multi-cellular muscle-like tissue engineering in perfusion-based bioreactors.

    PubMed

    Cerino, Giulia; Gaudiello, Emanuele; Grussenmeyer, Thomas; Melly, Ludovic; Massai, Diana; Banfi, Andrea; Martin, Ivan; Eckstein, Friedrich; Grapow, Martin; Marsano, Anna

    2016-01-01

    Conventional tissue engineering strategies often rely on the use of a single progenitor cell source to engineer in vitro biological models; however, multi-cellular environments can better resemble the complexity of native tissues. Previous described co-culture models used skeletal myoblasts, as parenchymal cell source, and mesenchymal or endothelial cells, as stromal component. Here, we propose instead the use of adipose tissue-derived stromal vascular fraction cells, which include both mesenchymal and endothelial cells, to better resemble the native stroma. Percentage of serum supplementation is one of the crucial parameters to steer skeletal myoblasts toward either proliferation (20%) or differentiation (5%) in two-dimensional culture conditions. On the contrary, three-dimensional (3D) skeletal myoblast culture often simply adopts the serum content used in monolayer, without taking into account the new cell environment. When considering 3D cultures of mm-thick engineered tissues, homogeneous and sufficient oxygen supply is paramount to avoid formation of necrotic cores. Perfusion-based bioreactor culture can significantly improve the oxygen access to the cells, enhancing the viability and the contractility of the engineered tissues. In this study, we first investigated the influence of different serum supplementations on the skeletal myoblast ability to proliferate and differentiate during 3D perfusion-based culture. We tested percentages of serum promoting monolayer skeletal myoblast-proliferation (20%) and differentiation (5%) and suitable for stromal cell culture (10%) with a view to identify the most suitable condition for the subsequent co-culture. The 10% serum medium composition resulted in the highest number of mature myotubes and construct functionality. Co-culture with stromal vascular fraction cells at 10% serum also supported the skeletal myoblast differentiation and maturation, hence providing a functional engineered 3D muscle model that resembles

  20. Optical studies of tissue mitochondrial redox in isolated perfused rat lungs

    NASA Astrophysics Data System (ADS)

    Sepehr, R.; Staniszewski, K.; Jacobs, E. R.; Audi, S.; Ranji, M.

    2012-02-01

    Through the monitoring of the auto-fluorescent mitochondrial metabolic coenzymes, NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavoprotein Adenine Dinucleotide), the redox state of metabolism can be probed in real time in many intact organs, but its use has not been fully developed in lungs. The ratio of these fluorophores, (NADH/FAD), referred to as the mitochondrial redox ratio (RR), can be used as a quantitative metabolic marker of tissue. We have designed a fluorometer that can be used to monitor lung surface NADH and FAD fluorescence in isolated perfused lungs. Surface fluorescence NADH and FAD signals were acquired in the absence (control) and presence of pentachlorophenol (PCP), rotenone, and potassium cyanide (KCN). Rotenone, an inhibitor of complex I, increased RR by 18%, predominantly due to an increase in NADH signal. KCN, an inhibitor of complex IV reduced the chain and resulted in an increase of 33% in RR, as a result of 23% increase in NADH and 8% in FAD . PCP, an uncoupler which oxidizes the respiratory chain, decreased RR by 18% as a result of 14% decrease in NADH signal and 4% increase in FAD signal. These results demonstrate the ability of surface fluorometry to detect changes in lung tissue mitochondrial redox state in isolated perfused lungs.

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

    PubMed

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

    2014-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  3. An 'in situ' perfusion system suitable for investigating mammary-tissue metabolism in the lactating rat. Hormonal regulation of acetyl-CoA carboxylase.

    PubMed Central

    Clegg, R A; Calvert, D T

    1988-01-01

    A technique is described for the non-recirculating perfusion of inguinal/abdominal mammary tissue in situ in anaesthetized lactating rats. Tissue viability was maintained, without resort to infusion of vasoactive chemicals which may also be effectors of cellular metabolism, for at least 90 min. Total tissue adenine nucleotides (per mg of DNA) were somewhat decreased in perfused relative to non-perfused mammary tissue. DNA content (per g wet wt. of tissue) was diminished after 90 min of perfusion to approx. 65% of its value in control tissue. Adenylate energy-charge ratios were lower in perfused tissue in the absence of hormones than in control tissue. They were increased to control values by the presence of either insulin or isoprenaline in the perfusate. No changes occurred in flow rate of the perfusate that might account for these increases. In mammary tissue perfused without addition of hormones, acetyl-CoA carboxylase activities were similar to those measured in control tissue samples, although activity-ratio measurements implied some increase in the phosphorylation of this enzyme. Insulin or isoprenaline increased the activity of acetyl-CoA carboxylase, especially when this was measured at low concentrations of citrate. Confirming conclusions from previous experiments with mammary acini and explant preparations, insulin activated acetyl-CoA carboxylase in mammary tissue, but inhibition of its activity was not mediated by cyclic AMP. PMID:2895636

  4. Experimental verification of bioheat transfer theories: measurement of temperature profiles around large artificial vessels in perfused tissue.

    PubMed

    Crezee, J; Lagendijk, J J

    1990-07-01

    The verification of thermal models for use in hyperthermia treatment planning is essential. We investigated the heat transfer between a single vessel and the surrounding vascularised tissue, comparing the conventional bioheat transfer theory and the recently developed keff model using analytical and numerical methods. A plastic tube inserted into the tissue of an isolated perfused organ served as an artificial vessel. This enabled us to vary the blood flow in the vessel and in the tissue independently. The organ used was a bovine kidney, turned into a perfused tissue phantom using an alcohol fixation technique. The temperature profile within the tissue was mapped with constantan-manganin thermocouple wire sensors with a total diameter of 50 microns. The temperature profile relative to the temperature difference between the vessel and organ was measured; increased perfusion caused a reduction of the vessel wall temperature but did not affect the width of the profile. Studying the transient tissue temperature after a step-wise change of the blood temperature in the vessel revealed a faster diffusion of heat at higher perfusion rates. These facts are in accordance with the keff model, but not with the conventional heat-sink theory.

  5. Sensing metabolites for the monitoring of tissue engineered construct cellularity in perfusion bioreactors.

    PubMed

    Simmons, Aaron D; Williams, Cortes; Degoix, Antoine; Sikavitsas, Vassilios I

    2017-04-15

    As the field of tissue engineering progresses ever-further toward realizing clinical implementation of tissue-engineered constructs for wound regeneration, perhaps the most significant hurdle remains the establishment of non-destructive means for real-time in vitro assessment. In order to address this barrier, the study presented herein established the viability of the development of correlations between metabolic rates (specifically oxygen uptake, glucose consumption, and lactate production) and the cellularity of tissue-engineered cultures comprised of rat mesenchymal stem cells dynamically seeded on 85% porous nonwoven spunbonded poly(l-lactic acid) fiber mesh scaffolds. Said scaffolds were cultured for up to 21 days in a flow perfusion bioreactor system wherein α-MEM (supplemented with 10% fetal bovine serum and 1% antibiotic-antimycotic) was perfused directly through each scaffold at low flow rates (~0.15mL/min). Metabolite measurements were obtained intermittently through the use of a fiber-optic probe (for the case of oxygen) and biochemical assays (for glucose and lactate). Such measurements were subsequently correlated with cellularity data obtained utilizing current-standard destructive means. The resulting correlations, all exhibiting high R(2) values, serve as a proof-on-concept for the use of metabolic data for the determination of scaffold cellularity in real-time non-destructively. This study can be easily adapted for use with various cell types, media formulations, and potentially different bioreactor systems. Implementation of more advanced in situ measurement devices could be easily accommodated to allow for true real-time, on-line metabolite monitoring and cellularity estimation.

  6. The Development of a Thin-Filmed, Non-Invasive Tissue Perfusion Sensor to Quantify Capillary Pressure Occlusion of Explanted Organs.

    PubMed

    OBrien, Timothy J; Roghani, Ali R; Jones, Philip A; Aardema, Charles H; Robertson, John L; Diller, Thomas E

    2016-10-05

    A new thin-filmed perfusion sensor was developed using a heat flux gauge, thin-film thermocouple, and a heating element. This sensor, termed "CHFT+", is an enhancement of the previously established CHFT (combined heat flux - temperature) sensor technology predominately used to quantify the severity of burns [1]. The CHFT+ sensor was uniquely designed to measure tissue perfusion on explanted organs destined for transplantation, but could be functionalized and used in a wide variety of other biomedical applications. Exploiting the thin and semi-flexible nature of the new CHFT+ sensor assembly, perfusion measurements can be made from the underside of the organ - providing a quantitative, indirect measure of capillary pressure occlusion. Results from a live tissue test demonstrated, for the first time, the effects of pressure occlusion on an explanted porcine kidney. CHFT+ sensors were placed on top of and underneath 18 kidneys to measure and compare perfusion at perfusate temperatures of 5˚C and 20˚C. The data collected shows greater perfusion on the topside than the underside of the specimen for the length of the experiment. This indicates that pressure occlusion is truly affecting the perfusion and thus, the overall preservation of explanted organs. Moreover, the results demonstrate the effect of preservation temperature on the tissue vasculature. Focusing on the topside perfusion only, the 20˚C perfusion was greater than the 5˚C perfusion, likely due to the vasoconstrictive response at the lower perfusion temperatures.

  7. Biologically Inspired Smart Release System Based on 3D Bioprinted Perfused Scaffold for Vascularized Tissue Regeneration

    PubMed Central

    Cui, Haitao; Zhu, Wei; Holmes, Benjamin

    2016-01-01

    A critical challenge to the development of large‐scale artificial tissue grafts for defect reconstruction is vascularization of the tissue construct. As an emerging tissue/organ manufacturing technique, 3D bioprinting offers great precision in controlling the internal architecture of a scaffold with preferable mechanical strength and printing complicated microstructures comparable to native tissue. However, current bioprinting techniques still exhibit difficulty in achieving biomimetic nano resolution and cooperating with bioactive spatiotemporal signals. In this study, a comprehensive design of engineered vascularized bone construct is presented for the first time by integrating biomimetic 3D bioprinted fluid perfused microstructure with biologically inspired smart release nanocoating, which is regarded as an aspiring concept combining engineering, biological, and material science. In this biologically inspired design, angiogenesis and osteogenesis are successively induced through a matrix metalloprotease 2 regulative mechanism by delivering dual growth factors with sequential release in spatiotemporal coordination. Availability of this system is evaluated in dynamic culture condition, which is similar to fluid surrounding in vivo, as an alternative animal model study. Results, particularly from co‐cultured dynamically samples demonstrate excellent bioactivity and vascularized bone forming potential of nanocoating modified 3D bioprinted scaffolds for human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells. PMID:27818910

  8. Biologically Inspired Smart Release System Based on 3D Bioprinted Perfused Scaffold for Vascularized Tissue Regeneration.

    PubMed

    Cui, Haitao; Zhu, Wei; Holmes, Benjamin; Zhang, Lijie Grace

    2016-08-01

    A critical challenge to the development of large-scale artificial tissue grafts for defect reconstruction is vascularization of the tissue construct. As an emerging tissue/organ manufacturing technique, 3D bioprinting offers great precision in controlling the internal architecture of a scaffold with preferable mechanical strength and printing complicated microstructures comparable to native tissue. However, current bioprinting techniques still exhibit difficulty in achieving biomimetic nano resolution and cooperating with bioactive spatiotemporal signals. In this study, a comprehensive design of engineered vascularized bone construct is presented for the first time by integrating biomimetic 3D bioprinted fluid perfused microstructure with biologically inspired smart release nanocoating, which is regarded as an aspiring concept combining engineering, biological, and material science. In this biologically inspired design, angiogenesis and osteogenesis are successively induced through a matrix metalloprotease 2 regulative mechanism by delivering dual growth factors with sequential release in spatiotemporal coordination. Availability of this system is evaluated in dynamic culture condition, which is similar to fluid surrounding in vivo, as an alternative animal model study. Results, particularly from co-cultured dynamically samples demonstrate excellent bioactivity and vascularized bone forming potential of nanocoating modified 3D bioprinted scaffolds for human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells.

  9. Oxygenation and perfusion monitoring with a hyperspectral camera system for chemical based tissue analysis of skin and organs.

    PubMed

    Holmer, Amadeus; Tetschke, Florian; Marotz, Jörg; Malberg, Hagen; Markgraf, Wenke; Thiele, Christine; Kulcke, Axel

    2016-11-01

    The monitoring of free flaps, free transplants or organs for transplantation still poses a problem in medicine. Available systems for the measurement of perfusion and oxygenation can only perform localized measurements and usually need contact with the tissue. Contact free hyperspectral imaging and near-infrared spectroscopy (NIRS) for the analysis of tissue oxygenation and perfusion have been used in many scientific studies with good results. But up to now the clinical and scientific application of this technology has been hindered by the lack of hyperspectral measurement systems usable in clinical practice. We will introduce the application of a new hyperspectral camera system for the quick and robust recording of remission spectra in the combined VIS and NIR spectral range with high spectral and spatial resolution. This new system can be applied for the clinical monitoring of free flaps and organs providing high quality oxygenation and perfusion images.

  10. Tissue perfusion and oxygenation to monitor fluid responsiveness in critically ill, septic patients after initial resuscitation: a prospective observational study.

    PubMed

    Klijn, Eva; van Velzen, Marit H N; Lima, Alexandre Pinto; Bakker, Jan; van Bommel, Jasper; Groeneveld, A B Johan

    2015-12-01

    Fluid therapy after initial resuscitation in critically ill, septic patients may lead to harmful overloading and should therefore be guided by indicators of an increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to investigate whether tissue perfusion and oxygenation are able to monitor fluid responsiveness, even after initial resuscitation. Thirty-five critically ill, septic patients underwent infusion of 250 mL of colloids, after initial fluid resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual microcirculatory perfusion (SDF: sidestream dark field imaging) and skin perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy) were measured. Fluid responsiveness was defined by a ≥5 or 10% increase in SV upon fluids. In responders to fluids, SDF-derived microcirculatory and skin perfusion and oxygenation increased, but only the increase in cardiac output, mean arterial and pulse pressure, microvascular flow index and relative Hb concentration and oxygen saturation were able to monitor a SV increase. Our proof of principle study demonstrates that non-invasively assessed tissue perfusion and oxygenation is not inferior to invasive hemodynamic measurements in monitoring fluid responsiveness. However skin reflectance spectroscopy may be more helpful than sublingual SDF.

  11. How to choose the therapeutic goals to improve tissue perfusion in septic shock

    PubMed Central

    de Assuncao, Murillo Santucci Cesar; Corrêa, Thiago Domingos; Bravim, Bruno de Arruda; Silva, Eliézer

    2015-01-01

    The early recognition and treatment of severe sepsis and septic shock is the key to a successful outcome. The longer the delay in starting treatment, the worse the prognosis due to persistent tissue hypoperfusion and consequent development and worsening of organ dysfunction. One of the main mechanisms responsible for the development of cellular dysfunction is tissue hypoxia. The adjustments necessary for adequate tissue blood flow and therefore of oxygen supply to metabolic demand according to the assessment of the cardiac index and oxygen extraction rate should be performed during resuscitation period, especially in high complexity patients. New technologies, easily handled at the bedside, and new studies that directly assess the impact of macro-hemodynamic parameter optimization on microcirculation and in the clinical outcome of septic patients, are needed. PMID:26313438

  12. Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation.

    PubMed

    Opacic, Dragan; van Bragt, Kelly A; Nasrallah, Hussein M; Schotten, Ulrich; Verheule, Sander

    2016-04-01

    Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation waves. Far less is known about the role of myocyte metabolism and tissue perfusion in the pathogenesis of AF. However, the rapid rates of electrical activity and contraction during AF must present an enormous challenge to the energy balance of atrial myocytes. This challenge can be met by scaling back energy demand and by increasing energy supply, and there are several indications that both phenomena occur as a result of AF. Still, there is ample evidence that these adaptations fall short of redressing this imbalance, which may represent a driving force for atrial electrical as well as structural remodelling. In addition, several 'metabolic diseases' such as diabetes, obesity, and abnormal thyroid function precipitate some well-known 'culprits' of the AF substrate such as myocyte hypertrophy and fibrosis, while some other AF risk factors, such as heart failure, affect atrial metabolism. This review provides an overview of metabolic and vascular alterations in AF and their involvement in its pathogenesis.

  13. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P < 0.05) over a 13-d period. Total protein synthesis rates could be determined accurately in the bioreactors for up to 30 h and total protein degradation rates could be measured for up to 3 wk. Special fixation and storage conditions necessary for space flight studies were validated as part of the studies. For example, the anabolic autocrine/paracrine skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  14. d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

    PubMed

    Weatherly, Choyce A; Du, Siqi; Parpia, Curran; Santos, Polan T; Hartman, Adam L; Armstrong, Daniel W

    2017-02-16

    The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.

  15. Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

    SciTech Connect

    Boeckner, L.S.; Kies, C.

    1986-03-05

    The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10/sup -6/ was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study.

  16. Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

    PubMed Central

    Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

    2014-01-01

    Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial

  17. Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

    PubMed Central

    Goh, Saik-Kia; Bertera, Suzanne; Olsen, Phillip; Candiello, Joe; Halfter, Willi; Uechi, Guy; Balasubramani, Manimalha; Johnson, Scott; Sicari, Brian; Kollar, Elizabeth; Badylak, Stephen F.; Banerjee, Ipsita

    2013-01-01

    Approximately 285 million people worldwide suffer from diabetes, with insulin supplementation as the most common treatment measure. Regenerative medicine approaches such as a bioengineered pancreas has been proposed as potential therapeutic alternatives. A bioengineered pancreas will benefit from the development of a bioscaffold that supports and enhances cellular function and tissue development. Perfusion-decellularized organs are a likely candidate for use in such scaffolds since they mimic compositional, architectural and biomechanical nature of a native organ. In this study, we investigate perfusion-decellularization of whole pancreas and the feasibility to recellularize the whole pancreas scaffold with pancreatic cell types. Our result demonstrates that perfusion-decellularization of whole pancreas effectively removes cellular and nuclear material while retaining intricate three-dimensional microarchitecture with perfusable vasculature and ductal network and crucial extracellular matrix (ECM) components. To mimic pancreatic cell composition, we recellularized the whole pancreas scaffold with acinar and beta cell lines and cultured up to 5 days. Our result shows successful cellular engraftment within the decellularized pancreas, and the resulting graft gave rise to strong up-regulation of insulin gene expression. These findings support biological utility of whole pancreas ECM as a biomaterials scaffold for supporting and enhancing pancreatic cell functionality and represent a step toward bioengineered pancreas using regenerative medicine approaches. PMID:23787110

  18. Cracking the perfusion code?: Laser-assisted Indocyanine Green angiography and combined laser Doppler spectrophotometry for intraoperative evaluation of tissue perfusion in autologous breast reconstruction with DIEP or ms-TRAM flaps.

    PubMed

    Ludolph, Ingo; Arkudas, Andreas; Schmitz, Marweh; Boos, Anja M; Taeger, Christian D; Rother, Ulrich; Horch, Raymund E; Beier, Justus P

    2016-10-01

    The aim of this prospective study was to assess the correlation of flap perfusion analysis based on laser-assisted Indocyanine Green (ICG) angiography with combined laser Doppler spectrophotometry in autologous breast reconstruction using free DIEP/ms-TRAM flaps. Between February 2014 and July 2015, 35 free DIEP/ms-TRAM flaps were included in this study. Besides the clinical evaluation of flaps, intraoperative perfusion dynamics were assessed by means of laser-assisted ICG angiography and post-capillary oxygen saturation and relative haemoglobin content (rHb) using combined laser Doppler spectrophotometry. Correlation of the aforementioned parameters was analysed, as well as the impact on flap design and postoperative complications. Flap survival rate was 100%. There were no partial flap losses. In three cases, flap design was based on the angiography, contrary to clinical evaluation and spectrophotometry. The final decision on the inclusion of flap areas was based on the angiographic perfusion pattern. Angiography and spectrophotometry showed a correlation in most of the cases regarding tissue perfusion, post-capillary oxygen saturation and relative haemoglobin content. Laser-assisted ICG angiography is a useful tool for intraoperative evaluation of flap perfusion in autologous breast reconstruction with DIEP/ms-TRAM flaps, especially in decision making in cases where flap perfusion is not clearly assessable by clinical signs and exact determination of well-perfused flap margins is difficult to obtain. It provides an objective real-time analysis of flap perfusion, with high sensitivity for the detection of poorly perfused flap areas. Concerning the topographical mapping of well-perfused flap areas, laser-assisted angiography is superior to combined laser Doppler spectrophotometry.

  19. Perfusion pressure-dependent recovery of cortical spreading depression is independent of tissue oxygenation over a wide physiologic range.

    PubMed

    Sukhotinsky, Inna; Yaseen, Mohammad A; Sakadzić, Sava; Ruvinskaya, Svetlana; Sims, John R; Boas, David A; Moskowitz, Michael A; Ayata, Cenk

    2010-06-01

    Spreading depression (SD) is a slowly propagating wave of transient neuronal and glial depolarization that develops after stroke, trauma and subarachnoid hemorrhage. In compromised tissue, repetitive SD-like injury depolarizations reduce tissue viability by worsening the mismatch between blood flow and metabolism. Although the mechanism remains unknown, SDs show delayed electrophysiological recovery within the ischemic penumbra. Here, we tested the hypothesis that the recovery rate of SD can be varied by modulating tissue perfusion pressure and oxygenation. Systemic blood pressure and arterial pO(2) were simultaneously manipulated in anesthetized rats under full physiologic monitoring. We found that arterial hypotension doubled the SD duration, whereas hypertension reduced it by a third compared with normoxic normotensive rats. Hyperoxia failed to shorten the prolonged SD durations in hypotensive rats, despite restoring tissue pO(2). Indeed, varying arterial pO(2) (40 to 400 mm Hg) alone did not significantly influence SD duration, whereas blood pressure (40 to 160 mm Hg) was inversely related to SD duration in compromised tissue. These data suggest that cerebral perfusion pressure is a critical determinant of SD duration independent of tissue oxygenation over a wide range of arterial pO(2) levels, and that hypotension may be detrimental in stroke and subarachnoid hemorrhage, where SD-like injury depolarizations have been observed.

  20. Tissue perfusion measurements: multiple-exposure laser speckle analysis generates laser Doppler-like spectra.

    PubMed

    Thompson, Oliver B; Andrews, Michael K

    2010-01-01

    Variations in skin perfusion are easily detected by laser speckle contrast maps, but a robust interpretation of the information has been lacking. We show that multiple-exposure laser speckle methods produce the same spectral information as laser Doppler methods when applied to targets with embedded moving scatterers. This enables laser speckle measurements to be interpreted more quantitatively. We do this by using computer simulation of speckle data, and by experimental measurements on Brownian motion and skin perfusion using a laser Doppler system and a multiple-exposure laser speckle system. The power spectral density measurements of the light fluctuations derived using both techniques are exactly equivalent. Dermal perfusion can therefore be measured by laser Doppler or laser speckle contrast methods. In particular, multiexposure laser speckle can be rapidly processed to generate a full-field map of the perfusion index proportional to the concentration and mean velocity of red blood cells.

  1. Time-course of cerebral perfusion and tissue oxygenation in the first 6 h after experimental subarachnoid hemorrhage in rats.

    PubMed

    Westermaier, Thomas; Jauss, Alina; Eriskat, Jörg; Kunze, Ekkehard; Roosen, Klaus

    2009-04-01

    Present knowledge about hemodynamic and metabolic changes after subarachnoid hemorrhage (SAH) originates from neuromonitoring usually starting with aneurysm surgery and animal studies that have been focusing on the first 1 to 3 h after SAH. Most patients, however, are referred to treatment several hours after the insult. We examined the course of hemodynamic parameters, cerebral blood flow, and tissue oxygenation (ptiO2) in the first 6 h after experimental SAH. Sixteen Sprague-Dawley rats were subjected to SAH using the endovascular filament model or served as controls (n=8). Bilateral local cortical blood flow, intracranial pressure, cerebral perfusion pressure, and ptiO2 were followed for 6 h after SAH. After induction of SAH, local cortical blood flow rapidly declined to 22% of baseline and returned to 80% after 6 h. The decline of local cortical blood flow markedly exceeded the decline of cerebral perfusion pressure. ptiO2 declined to 57%, recovered after 2 h, and reached > or =140% of baseline after 6 h. Acute vasoconstriction after SAH is indicated by the marked discrepancy of cerebral perfusion pressure and local cortical blood flow. The excess tissue oxygenation several hours after SAH suggests disturbed oxygen utilization and cerebral metabolic depression. Aside from the sudden increase of intracranial pressure at the time of hemorrhage and delayed cerebral vasospasm, the occurrence of acute vasoconstriction and disturbed oxygen utilization may be additional factors contributing to secondary brain damage after SAH.

  2. Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

    SciTech Connect

    Wendler, Johann Jakob; Pech, Maciej; Blaschke, Simon; Porsch, Markus; Janitzky, Andreas; Ulrich, Matthias; Dudeck, Oliver; Ricke, Jens; Liehr, Uwe-Bernd

    2012-04-15

    Purpose: The nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE. Methods: Results of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys. Results: In the dedicated investigation, no acute vascular destruction of the renal parenchyma and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave. Conclusion: The NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.

  3. Management of traumatic brain injury: nursing practice guidelines for cerebral perfusion and brain tissue oxygenation (PbtO2) systems.

    PubMed

    Hession, Diane

    2008-01-01

    Traditional modes of preventing brain cell death in traumatic brain injury (TBI) focus on the enhancement of cerebral perfusion pressure and control of intracranial pressure. Brain tissue oxygenation (PbtO2) monitoring systems are currently available to provide early detection of diminished cerebral oxygenation, and ultimately, ischemia. Research has demonstrated that early detection in PbtO2 is a more delicate measurement of cerebral blood flow and oxygenation. Monitoring PbtO2, in conjunction with cerebral perfusion pressure and intracranial pressure, has been shown to be a better guide to the prevention and treatment of secondary cerebral ischemia. This article reviews TBI, a PbtO2 monitor system description and indications for use, and the importance of nursing practice guidelines and education. With proper guidelines and education, this new technology can be used effectively by bedside clinicians and educators in adult and pediatric intensive care units.

  4. Review of temperature dependence of thermal properties, dielectric properties, and perfusion of biological tissues at hyperthermic and ablation temperatures

    PubMed Central

    Rossmann, Christian; Haemmerich, Dieter

    2016-01-01

    The application of supraphysiological temperatures (>40°C) to biological tissues causes changes at the molecular, cellular, and structural level, with corresponding changes in tissue function and in thermal, mechanical and dielectric tissue properties. This is particularly relevant for image-guided thermal treatments (e.g. hyperthermia and thermal ablation) delivering heat via focused ultrasound (FUS), radiofrequency (RF), microwave (MW), or laser energy; temperature induced changes in tissue properties are of relevance in relation to predicting tissue temperature profile, monitoring during treatment, and evaluation of treatment results. This paper presents a literature survey of temperature dependence of electrical (electrical conductivity, resistivity, permittivity) and thermal tissue properties (thermal conductivity, specific heat, diffusivity). Data of soft tissues (liver, prostate, muscle, kidney, uterus, collagen, myocardium and spleen) for temperatures between 5 to 90°C, and dielectric properties in the frequency range between 460 kHz and 3 GHz are reported. Furthermore, perfusion changes in tumors including carcinomas, sarcomas, rhabdomyosarcoma, adenocarcinoma and ependymoblastoma in response to hyperthmic temperatures up to 46°C are presented. Where appropriate, mathematical models to describe temperature dependence of properties are presented. The presented data is valuable for mathematical models that predict tissue temperature during thermal therapies (e.g. hyperthermia or thermal ablation), as well as for applications related to prediction and monitoring of temperature induced tissue changes. PMID:25955712

  5. 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.

  6. Power modulation contrast enhanced ultrasound for postoperative perfusion monitoring following free tissue transfer in head and neck surgery.

    PubMed

    Sharma, S; Anand, R; Hickman, M; Senior, R; Walji, S; Ramchandani, P L; Culliford, D; Ilankovan, V; Greaves, K

    2010-12-01

    This feasibility study evaluated whether contrast enhanced ultrasound (CEU) was able to assess free flap perfusion following free tissue transfer in the head and neck region. Thirty-six patients underwent standard clinical monitoring (SCM) and CEU postoperatively. The time taken for each technique to detect flap failure was recorded. Qualitative CEU analysis by visual assessment predicted survival in 30/30 (100%) and failure in 5/6 (83%) flaps with sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of 100, 86, 97 and 100%, respectively. Quantitative CEU measurement of blood volume (α) values within healthy perfused flaps was over 60 times higher than in failing flaps (8.25±2.82dB vs. 0.12±0.17dB, respectively, P<0.0001). If a cut-off α value of <1.5dB was used to predict future flap failure, the accuracy of the test was 100% (sensitivity, specificity, PPV, NPV). If a cut-off α value of >1.9dB indicated flap success, the PPV and NPV are 100%. Following surgery, SCM took 76 (±15) h to detect flap failure compared with 18 (±38) h with CEU (P<0.05). CEU is highly accurate in its ability to distinguish between perfused and failing flaps. The technique is quick (<10min) and capable of imaging all flap types.

  7. Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion - A new optical method for microcirculatory assessment.

    PubMed

    Jonasson, Hanna; Fredriksson, Ingemar; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas

    2015-11-01

    We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0-1mm/s, 1-10mm/s and above 10mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20-28years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.

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

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

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

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

    PubMed

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

    2011-04-07

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

  10. Cultivation of human bone-like tissue from pluripotent stem cell-derived osteogenic progenitors in perfusion bioreactors.

    PubMed

    de Peppo, Giuseppe Maria; Vunjak-Novakovic, Gordana; Marolt, Darja

    2014-01-01

    Human pluripotent stem cells represent an unlimited source of skeletal tissue progenitors for studies of bone biology, pathogenesis, and the development of new approaches for bone reconstruction and therapies. In order to construct in vitro models of bone tissue development and to grow functional, clinical-size bone substitutes for transplantation, cell cultivation in three-dimensional environments composed of porous osteoconductive scaffolds and dynamic culture systems-bioreactors-has been studied. Here, we describe a stepwise procedure for the induction of human embryonic and induced pluripotent stem cells (collectively termed PSCs) into mesenchymal-like progenitors, and their subsequent cultivation on decellularized bovine bone scaffolds in perfusion bioreactors, to support the development of viable, stable bone-like tissue in defined geometries.

  11. Development of a Multispectral Tissue Characterization System for Optimization of an Implantable Perfusion Status Monitor for Transplanted Liver

    SciTech Connect

    Baba, Justin S; Letzen, Brian S; Ericson, Milton Nance; Cote, Gerard L.; Xu, Weijian; Wilson, Mark A.

    2009-01-01

    Optimizing wavelength selection for monitoring perfusion during liver transplant requires an in-depth characterization of liver optical properties. With these, the impact of liver absorption and scattering properties can be investigated to select optimal wavelengths for perfusion monitoring. To accomplish this, we are developing a single integrating-sphere-based using a unique spatially resolved diffuse reflectance system for optical properties determination for thick samples. We report early results using a monochromatic source implementation to measure the optical properties of well characterized tissue phantoms made from polystyrene spheres and Trypan blue. The presented results show the promise of using this unique system to measure the optical properties of the tissue phantoms. We are currently in the process of implementing an automated Levenberg Marquardt fitting algorithm to determine the peak location of the diffuse reflectance profile to ensure robust computation of sample optical properties. Future work will focus on the incorporation of multispectral capability to the technique to facilitate development of more realistic liver tissue phantoms.

  12. CONTRAST-ENHANCED ULTRASOUND ASSESSMENT OF IMPAIRED ADIPOSE TISSUE AND MUSCLE PERFUSION IN INSULIN-RESISTANT MICE

    PubMed Central

    Belcik, J. Todd; Davidson, Brian P.; Foster, Ted; Qi, Yue; Zhao, Yan; Peters, Dawn; Lindner, Jonathan R.

    2015-01-01

    Background In diabetes mellitus reduced perfusion and capillary surface area in skeletal muscle, which is a major glucose storage site, contributes to abnormal glucose homeostasis. Using contrast-enhanced ultrasound (CEU) we investigated whether abdominal adipose tissue perfusion is abnormal in insulin resistance (IR) and correlates with glycemic control. Methods and Results Abdominal adipose tissue and skeletal muscle CEU perfusion imaging was performed in obese IR (db/db) mice at 11-12 or 14-16 weeks of age, and in control lean mice. Time-intensity data were analyzed to quantify microvascular blood flow (MBF) and capillary blood volume (CBV). Blood glucose response over one hour was measured after insulin challenge (1 u/Kg, I.P.). Compared to control mice, db/db mice at 11-12 and 14-16 weeks had a higher glucose concentration area-under-the-curve after insulin (11.8±2.8, 20.6±4.3, and 28.4±5.9 mg·min/dL [×1000], respectively, p=0.0002), and also had lower adipose MBF (0.094±0.038, 0.035±0.010, and 0.023±0.01 mL/min/g, p=0.0002) and CBV (1.6±0.6, 1.0±0.3, and 0.5±0.1 mL/100 g, p=0.0017). The glucose area-under-the-curve correlated in a non-linear fashion with both adipose and skeletal muscle MBF and CBV. There were significant linear correlations between adipose and muscle MBF (r=0.81) and CBV (r=0.66). Adipocyte cell volume on histology was 25-fold higher in 14-16 week db/db versus control mice. Conclusions Abnormal adipose MBF and CBV in IR can be detected by CEU and correlates with the degree of impairment in glucose storage. Abnormalities in adipose tissue and muscle appear to be coupled. Impaired adipose tissue perfusion is in part explained by an increase in adipocyte size without proportional vascular response. PMID:25855669

  13. Micro-perfusion for cardiac tissue engineering: development of a bench-top system for the culture of primary cardiac cells.

    PubMed

    Khait, Luda; Hecker, Louise; Radnoti, Desmond; Birla, Ravi K

    2008-05-01

    Tissue-engineered constructs have high metabolic requirements during in vitro culture necessitating the development of micro-perfusion systems to maintain high functional performance. In this study, we describe the design, fabrication, and testing of a novel micro-perfusion system to support the culture of primary cardiac cells. Our system consists of a micro-incubator with independent stages for 35-mm tissue culture plates with inflow/outflow manifolds for fluid delivery and aspiration. A peristaltic pump is utilized for fluid delivery and vacuum for fluid aspiration. Oxygen saturation, pH, and temperature are regulated for the media while temperature is regulated within the micro-incubator, fluid reservoir, and oxygenation chamber. Validation of the perfusion system was carried out using primary cardiac myocytes, isolated from 2- to 3-day-old neonatal rat hearts, plated on collagen-coated tissue culture plates. Two million cells/plate were used and the perfusion system was run for 1 h (without the need for a cell culture incubator) while controls were maintained in a standard cell culture incubator. We evaluated the cell viability, cell adhesion, total protein, total RNA, and changes in the expression of SERCA2 and phospholamban using RT-PCR, with N = 6 for each group. We found that there was no significant change in any variable during the 1-h run in the perfusion system. These studies served to demonstrate the compatibility of the perfusion system to support short-term culture of primary cardiac cells.

  14. Development and validation of a novel bioreactor system for load- and perfusion-controlled tissue engineering of chondrocyte-constructs.

    PubMed

    Schulz, Ronny M; Wüstneck, Nico; van Donkelaar, Corrinus C; Shelton, Julia C; Bader, Augustinus

    2008-11-01

    Osteoarthritis is a severe socio-economical disease, for which a suitable treatment modality does not exist. Tissue engineering of cartilage transplants is the most promising method to treat focal cartilage defects. However, current culturing procedures do not yet meet the requirements for clinical implementation. This article presents a novel bioreactor device for the functional tissue engineering of articular cartilage which enables cyclic mechanical loading combined with medium perfusion over long periods of time, under controlled cultivation and stimulation conditions whilst ensuring system sterility. The closed bioreactor consists of a small, perfused, autoclavable, twin chamber culture device with a contactless actuator for mechanical loading. Uni-axial loading is guided by externally applied magnetic fields with real-time feedback-control from a platform load cell and an inductive proximity sensor. This precise measurement allows the development of the mechanical properties of the cultured tissue to be monitored in real-time. This is an essential step towards clinical implementation, as it allows accounting for differences in the culture procedure induced by patient-variability. This article describes, based on standard agarose hydrogels of 3 mm height and 10 mm diameter, the technical concept, implementation, scalability, reproducibility, precision, and the calibration procedures of the whole bioreactor instrument. Particular attention is given to the contactless loading system by which chondrocyte scaffolds can be compressed at defined loading frequencies and magnitudes, whilst maintaining an aseptic cultivation procedure. In a "proof of principle" experiment, chondrocyte seeded agarose gels were cultured for 21 days in the bioreactor system. Intermittent medium perfusion at a steady flow rate (0.5 mL/min) was applied. Sterility and cell viability (ds-DNA quantification and fluorometric live/dead staining) were preserved in the system. Flow induced shear

  15. A method to expedite data acquisition for multiple spatial-temporal analyses of tissue perfusion by contrast-enhanced ultrasound.

    PubMed

    Hansen, Christian; Hüttebräuker, Nils; Wilkening, Wilko; Ermert, Helmut

    2009-03-01

    For semiquantitative analyses of tissue perfusion using contrast-enhanced ultrasound the acquisition and processing of time intensity curves (TIC) is required. These TICs can be computed for each pixel of an image plane, yielding parametric images of classification numbers like "blood volume" and "flow rate." The expenditure of time for data acquisition and analysis typically limits semiquantitative perfusion imaging to a single image plane in 2-D. 3-D techniques, however, provide a higher diagnostic value since more information (e.g., of an entire lesion) is obtained. Moreover, spatial compounding, being a 2-D-technique where an object is imaged from different viewing angles, is known to improve image quality by reducing artifacts and speckle noise. Both techniques, 3-D and compounding, call for optimized acquisition and processing of TICs in several image planes (3-D) or in several (overlapping) sections of the same image plane (compounding) to decrease the time needed for data acquisition. Here, an approach of interleaved imaging is presented which is applicable, among others, to contrast perfusion imaging using the replenishment method. The total acquisition time is decreased by sequentially scanning image planes twice for short time spans - first, immediately after microbubble destruction to record the initial rise of the TICs, and second, a sufficient time thereafter to assess final values of the TIC. Data from both periods are combined to fit a model function from which parameters are extracted such as perfusion rate and blood volume. This approach was evaluated by in vitro measurements on a perfusion-mimicking phantom for both, individual images such as would be used for volume reconstruction in 3-D and compound images obtained from full angle spatial compounding (FASC, 360 degrees ). An error analysis is conducted to derive the deviation of the extracted parameters of the proposed method compared with the conventional one. These deviations are entailed by

  16. Is there more valuable information in PWI datasets for a voxel-wise acute ischemic stroke tissue outcome prediction than what is represented by typical perfusion maps?

    NASA Astrophysics Data System (ADS)

    Forkert, Nils Daniel; Siemonsen, Susanne; Dalski, Michael; Verleger, Tobias; Kemmling, Andre; Fiehler, Jens

    2014-03-01

    The acute ischemic stroke is a leading cause for death and disability in the industry nations. In case of a present acute ischemic stroke, the prediction of the future tissue outcome is of high interest for the clinicians as it can be used to support therapy decision making. Within this context, it has already been shown that the voxel-wise multi-parametric tissue outcome prediction leads to more promising results compared to single channel perfusion map thresholding. Most previously published multi-parametric predictions employ information from perfusion maps derived from perfusion-weighted MRI together with other image sequences such as diffusion-weighted MRI. However, it remains unclear if the typically calculated perfusion maps used for this purpose really include all valuable information from the PWI dataset for an optimal tissue outcome prediction. To investigate this problem in more detail, two different methods to predict tissue outcome using a k-nearest-neighbor approach were developed in this work and evaluated based on 18 datasets of acute stroke patients with known tissue outcome. The first method integrates apparent diffusion coefficient and perfusion parameter (Tmax, MTT, CBV, CBF) information for the voxel-wise prediction, while the second method employs also apparent diffusion coefficient information but the complete perfusion information in terms of the voxel-wise residue functions instead of the perfusion parameter maps for the voxel-wise prediction. Overall, the comparison of the results of the two prediction methods for the 18 patients using a leave-one-out cross validation revealed no considerable differences. Quantitatively, the parameter-based prediction of tissue outcome led to a mean Dice coefficient of 0.474, while the prediction using the residue functions led to a mean Dice coefficient of 0.461. Thus, it may be concluded from the results of this study that the perfusion parameter maps typically derived from PWI datasets include all

  17. The Effect of Esmolol on Tissue Perfusion and Clinical Prognosis of Patients with Severe Sepsis: A Prospective Cohort Study

    PubMed Central

    Wang, Kaiyu; Xu, Jingqing; Gong, Shurong; Ye, Yong; Chen, Kaihua; Chen, Wei

    2016-01-01

    Purpose. This study was aimed at investigating the effect of esmolol on tissue perfusion and the clinical prognosis of patients with severe sepsis. Materials and Methods. One hundred fifty-one patients with severe sepsis were selected and divided into the esmolol group (n = 75) or the control group (n = 76), who received conventional antiseptic shock treatment. The esmolol group received a continuous infusion of esmolol via a central venous catheter, and their heart rate (HR) was maintained at 70–100 bpm over 72 hours. Results. The HR of all patients reached the target level within 72 hours of treatment for both groups. The effect of esmolol on PvaCO2 was only significant at 48 hours (P < 0.05). ScvO2 increased in the esmolol group and decreased in the control group (P < 0.01). Lac showed a linear downward trend over the treatment time, but the reduction was more significant in the control group at 48 hours (P < 0.05) between the two groups. Kaplan-Meier analysis showed a significantly shorter duration of mechanical ventilation in the esmolol group than in the control group (P < 0.05). Conclusions. Esmolol reduced the duration of mechanical ventilation in patients with severe sepsis, with no significant effect on circulatory function or tissue perfusion. PMID:27652257

  18. Tissue-Muscle Perfusion Scintigraphy of the Lower Limbs in a Patient with Type 2 Diabetes Mellitus and Peripheral Arterial Disease

    PubMed Central

    Manevska, Nevena; Gjorceva, Daniela Pop; Ahmeti, Irfan; Todorovska, Lidija; Stojanoski, Sinisa; Kocovska, Marina Zdraveska

    2016-01-01

    The estimation of tissue perfusion as a hemodynamic consequence of peripheral arterial disease (PAD) in diabetic patients is of great importance in the management of these patients.We present a noninvasive, functional method of 99mTc-MIBI (methoxy-isobutyl-isonitrile) tissue-muscle perfusion scintigraphy (TMPS) of the lower limbs, which assesses tissue perfusion in basal conditions (“rest” study) and exercise conditions (“stress” study). Emphasis is given on perfusion reserve (PR) as an important indicator of preservation of microcirculation and its local autoregulatory mechanisms in PAD. We present a case of a 71-year-old male diabetic patient with skin ulcers of the right foot and an ankle-brachial index >1.2 (0.9-1.1). Dynamic phase TMPS of the lower limbs showed decreased and late arterial vascularization of the right calf (RC) with lower percentage of radioactivity in the 1st minute: RC 66%, left calf (LC) 84%. PR was borderline with a value of 57% for LC and decreased for RC (42%). Functional assessment of hemodynamic consequences of PAD is important in evaluating both advanced and early PAD, especially the asymptomatic form. The method used to determine the TMPS of the lower limbs, can differentiate subtle changes in microcirculation and tissue perfusion. PMID:27299288

  19. Step-by-step protocol to perfuse and dissect the mouse parotid gland and isolation of high-quality RNA from murine and human parotid tissue.

    PubMed

    Watermann, Christoph; Valerius, Klaus Peter; Wagner, Steffen; Wittekindt, Claus; Klussmann, Jens Peter; Baumgart-Vogt, Eveline; Karnati, Srikanth

    2016-04-01

    Macroscopic identification and surgical removal of the mouse parotid gland is demanding because of its anatomic location and size. Moreover, the mouse parotid gland contains high concentrations of RNases, making it difficult to isolate high-quality RNA. So far, appropriate methods for optimal perfusion-fixation and dissection of mouse parotid glands, as well as the isolation of high quality RNA from this tissue, are not available. Here we present a simple, optimized, step-by-step surgical method to perfuse and isolate murine parotid glands. We also compared two common RNA extraction methods (RNeasy Mini Kit versus TRIzol) for their yields of high-quality, intact RNA from human and murine parotid gland tissues that were either snap-frozen or immersed in RNAlater stabilization solution. Mouse parotid tissue that was perfused and immersed in RNAlater and human samples immersed in RNAlater exhibited the best RNA quality, independent of the isolation method.

  20. Temporal and concentration effects of isoflurane anaesthesia on intestinal tissue oxygenation and perfusion in horses.

    PubMed

    Hopster, K; Hopster-Iversen, C; Geburek, F; Rohn, K; Kästner, S B R

    2015-07-01

    The aim of this study was to assess the effect of duration of anaesthesia and concentration of isoflurane on global perfusion as well as intestinal microperfusion and oxygenation. Nine Warmblood horses were premedicated with xylazine; anaesthesia was induced with midazolam and ketamine, and maintained with isoflurane. Horses were ventilated to normocapnia. During 7 h of anaesthesia, mean arterial blood pressures (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration (ETIso) and cardiac output using lithium dilution were measured; cardiac index (CI) was calculated. Intestinal microperfusion and oxygenation were measured using laser Doppler flowmetry and white-light spectrophotometry. Surface probes were placed via median laparotomy on the serosal and mucosal site of the jejunum and the pelvic flexion of the colon. After 3 h of constant ETIso (1.4%), ETIso was increased in 0.2% increments up to 2.4%, followed by a decrease to 1.2% and an increase to 1.4%. The CI and MAP decreased continuously with increasing ETIso to 40 ± 5 mL/kg/min and 52 ± 8 mmHg, respectively. Microperfusion and oxygenation remained unchanged until an ETIso of 2.0% resulted in CI and MAP of 48 ± 5 mL/kg/min and 62 ± 6 mmHg, respectively, and then decreased rapidly. When ETIso decreased back to baseline, CI, MAP, microperfusion and oxygenation recovered to baseline. Isoflurane concentration but not duration of isoflurane anaesthesia influenced central and intestinal oxygenation and perfusion in healthy horses. Under isoflurane, intestinal perfusion appeared to be preserved until a threshold MAP or blood flow was reached.

  1. Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction

    PubMed Central

    Fitzpatrick, J. Raymond; Frederick, John R.; McCormick, Ryan C.; Harris, David A.; Kim, Ah-Young; Muenzer, Jeffrey R.; Gambogi, Alex J.; Liu, Jing Ping; Paulson, E. Carter; Woo, Y. Joseph

    2011-01-01

    Objective Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia. Methods Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure–volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion. Results Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure–volume measurements showed that cardiac function was preserved in these rats. Conclusions Application of a bioengineered 3DFC augments native

  2. Construction of Mesenchymal Stem Cell–Containing Collagen Gel with a Macrochanneled Polycaprolactone Scaffold and the Flow Perfusion Culturing for Bone Tissue Engineering

    PubMed Central

    Yu, Hye-Sun; Won, Jong-Eun; Jin, Guang-Zhen

    2012-01-01

    Abstract A novel bone tissue-engineering construct was developed by using poly(ɛ-caprolactone) (PCL)-macrochanneled scaffolds combined with stem cell-seeded collagen hydrogels and then applying flow perfusion culture. Rat mesenchymal stem cells (MSCs) were loaded into collagen hydrogels, which were then combined with macrochanneled PCL scaffolds. Collagen hydrogels were demonstrated to provide favorable growth environments for MSCs and to foster proliferation. Cell number determination identified retention of substantially fewer (50–60%) cells when they were seeded directly onto macrochanneled PCL than of cells engineered within collagen hydrogels. Additionally, the cells actively proliferated within the combined scaffold for up to 7 days. MSC-loaded collagen–PCL scaffolds were subsequently cultured under flow perfusion to promote proliferation and osteogenic differentiation. Cells proliferated to levels significantly higher in flow perfusion culture than that under static conditions during 21 days. A quantitative polymerase chain reaction (QPCR) assay revealed significant alterations in the transcription of bone-related genes such as osteopontin (OPN), osteocalcin (OCN), and bone sialoprotein (BSP), such as 8-, 2.5-, and 3-fold induction, respectively, after 10 days of flow perfusion relative to those in static culture. OPN and OCN protein levels, as determined by Western blot, increased under flow perfusion. Cellular mineralization was significantly enhanced by the flow perfusion during 21 and 28 days. Analyses of mechanosensitive gene expression induced by flow perfusion shear stress revealed significant upregulation of c-fos and cyclooxygenase-2 (COX-2) during the initial culture period (3–5 days), suggesting that osteogenic stimulation was possible as a result of mechanical force-driven transduction. These results provide valuable information for the design of a new bone tissue-engineering system by combining stem cell-loaded collagen hydrogels with

  3. Effects of different types of hydroxyethyl starch (HES) on microcirculation perfusion and tissue oxygenation in patients undergoing liver surgery.

    PubMed

    Cui, Yinghua; Sun, Bo; Wang, Changsong; Liu, Shujuan; Li, Peng; Shi, Jinghui; Li, Enyou

    2014-01-01

    To compare the effects of hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5, which have different molecular weights and degrees of substitution, on microcirculation perfusion and tissue oxygenation in patients undergoing liver surgery. Thirty patients with an American Society of Anesthesiologists status I/II who were scheduled for liver surgery were randomly divided into two groups: one received an intraoperative HES 130/0.4 infusion equal to the amount of blood loss (HES 130/0.4 group, n=15), and the other received HES 200/0.5 equal to the amount of blood loss (HES 200/0.5 group, n=15). Gastric mucosal perfusion and tissue oxygenation were monitored by measuring the gastric mucosal pH (pHi), which was determined using a carbon dioxide tonometer inserted through a nasogastric tube. Gastric mucosal pHi , hemodynamic parameters, body temperature, and blood gas parameters were recorded upon entering the operating room, before skin incision, one hour and two hours after skin incision, and at the end of surgery. The intraoperative pHi decreased in both groups of patients, but the decline in the HES 130/0.4 group was smaller than that of the HES 200/0.5 group. The pHi of the HES 130/0.4 group was significantly higher than that of the HES 200/0.5 group two hours after skin incision and at the end of surgery (P<0.05). A multivariate analysis showed that the type of colloid used intraoperatively was the only variant that affected pHi (F=0.626, P<0.05). Moreover, there were good correlation between pHi at the end of surgery and the length of postoperative hospital stay (r=-0.536, P<0.05) and the time intervals from surgery to the passage of flatus (r=-0.547, P<0.05). Compared with HES 200/0.5, the use of HES 130/0.4 (with a relatively lower molecular weight and lower degree of substitution) could significantly improve internal organ perfusion and tissue oxygenation in patients undergoing liver surgery with a relatively large amount of blood loss.

  4. Acute Effects of Lateral Thigh Foam Rolling on Arterial Tissue Perfusion Determined by Spectral Doppler and Power Doppler Ultrasound.

    PubMed

    Hotfiel, Thilo; Swoboda, Bernd; Krinner, Sebastian; Grim, Casper; Engelhardt, Martin; Uder, Michael; Heiss, Rafael U

    2017-04-01

    Hotfiel, T, Swoboda, B, Krinner, S, Grim, C, Engelhardt, M, Uder, M, and Heiss, R. Acute effects of lateral thigh foam rolling on arterial tissue perfusion determined by spectral Doppler and power Doppler ultrasound. J Strength Cond Res 31(4): 893-900, 2017-Foam rolling has been developed as a popular intervention in training and rehabilitation. However, evidence on its effects on the cellular and physiological level is lacking. The aim of this study was to assess the effect of foam rolling on arterial blood flow of the lateral thigh. Twenty-one healthy participants (age, 25 ± 2 years; height, 177 ± 9 cm; body weight, 74 ± 9 kg) were recruited from the medical and sports faculty. Arterial tissue perfusion was determined by spectral Doppler and power Doppler ultrasound, represented as peak flow (Vmax), time average velocity maximum (TAMx), time average velocity mean (TAMn), and resistive index (RI), and with semiquantitative grading that was assessed by 4 blindfolded investigators. Measurement values were assessed under resting conditions and twice after foam rolling exercises of the lateral thigh (0 and 30 minutes after intervention). The trochanteric region, mid portion, and distal tibial insertion of the lateral thigh were representative for data analysis. Arterial blood flow of the lateral thigh increased significantly after foam rolling exercises compared with baseline (p ≤ 0.05). We detected a relative increase in Vmax of 73.6% (0 minutes) and 52.7% (30 minutes) (p < 0.001), in TAMx of 53.2% (p < 0.001) and 38.3% (p = 0.002), and in TAMn of 84.4% (p < 0.001) and 68.2% (p < 0.001). Semiquantitative power Doppler scores at all portions revealed increased average grading of 1.96 after intervention and 2.04 after 30 minutes compared with 0.75 at baseline. Our results may contribute to the understanding of local physiological reactions to self-myofascial release.

  5. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    PubMed

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.].

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  7. The isolated perfused kidney: an in vitro test system for evaluation of renal tissue damage induced by high-energy shockwaves sources.

    PubMed

    Bergsdorf, Th; Thüroff, S; Chaussy, Ch

    2005-09-01

    Most of our knowledge of shockwave-induced renal damage is based on animal experiments and clinical observation. We developed a tissue model using isolated porcine kidneys perfused with Berliner Blau dye in physiologic saline using a Ureteromat Perez-Castro peristaltic pump connected to the renal artery. Reproducible results were obtained under a variety of experimental conditions. Further refinements of the model might consist of interposition of tissue layers in the shockwave path or simulation of ventilatory movements.

  8. Monitoring of tissue perfusion during esophagectomies with optical fiber probe spectroscopy

    NASA Astrophysics Data System (ADS)

    Gareau, Dan; Hunter, John; Jacques, Steven

    2010-02-01

    The specific optical spectra of tissues contain information about the biochemical composition. We present a simple optical fiber probe spectrometer design for noninvasive measurement of oxygen saturation in the microvasculature of stomach tissue. In a human Esophagectomy model with 23 patients, we measured the spectrum following surgical ligation of two of the three arterial paths to the stomach tissue that will become the anastamosis. Combining a diffusion model for semi-infinite slab remittance with absorption spectroscopy, we are able to specify the ratio of oxy-hemoglobin to deoxy-hemoglobin present in the tissue. We show a resting state of 0.47 (oxy-hemaglobin/total-hemaglobin) saturation decrease of 29% (p < 0.01) when arterial supply is reduced by artery ligation.

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

    PubMed

    Klein, T J; Sah, R L

    2007-01-01

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

  10. Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study.

    PubMed

    Sánchez-Catasús, Carlos A; Cabrera-Gomez, José; Almaguer Melián, William; Giroud Benítez, José Luis; Rodríguez Rojas, Rafael; Bayard, Jorge Bosch; Galán, Lídice; Sánchez, Reinaldo Galvizu; Fuentes, Nancy Pavón; Valdes-Sosa, Pedro

    2013-01-01

    Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.

  11. Three-dimensional optical micro-angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo

    NASA Astrophysics Data System (ADS)

    Wang, Ruikang K.

    2007-12-01

    Optical micro-angiography (OMAG) is a recently developed method of imaging localized blood perfusion at capillary level resolution within microcirculatory beds. This paper reports that the OMAG is capable of directional blood perfusion mapping in vivo. This is achieved simply by translating the mirror located in the reference arm back and forth while 3D imaging is performed. The mirror which moves toward the incident beam gives the blood perfusion that flows away from the beam direction and vice versa. The approach is experimentally demonstrated by imaging of a flow phantom and then cerebro-vascular perfusion of a live mouse with cranium intact.

  12. Construction and validation of a microprocessor controlled extracorporal circuit in rats for the optimization of isolated limb perfusion.

    PubMed

    Gürtler, Ulrich; Fuchs, Peter; Stangelmayer, Achim; Bernhardt, Günther; Buschauer, Armin; Spruss, Thilo

    2004-12-01

    Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online monitoring of essential perfusion parameters such as temperature (in perfusate, various tissues, and rectum), pH (perfusate), perfusion pressure, and O(2) concentration (in perfusate, tissue), by a tailor-made data acquisition system. This setup permits close supervision of vital parameters during ILP. Various interdependencies, concerning the flow rate and the pressure of perfusate as well as tissue oxygenation were registered. For the measurement of pO(2) values in the perfusate and in different regions of the perfused hind limb, a novel type of microoptode based on quenching of a fluorescent dye was devised. Stable normothermic (37 degrees C) perfusion conditions were maintained at a constant perfusion pressure in the range of 40-60 mm Hg by administration of the spasmo lytic moxaverine (0.5 mg/mL of perfusate as initial dose) at a perfusate flow rate of 0.5 mL/min for 60 min. At the end of an ILP, there were no signs of tissue damage, neither concerning laboratory data (K(+), myoglobin, creatine kinase, lactic dehydrogenase) nor histopathological criteria. The reported ILP model is not only well suited to investigate the effects of hyperthermia but also to assess the efficacy of new antineoplastic approaches, when nude rats, bearing human tumours in the hind limbs, are used.

  13. Vascular Patterns and Perfusion of Mucogingival Tissues and their Relation to Periodontal Flap Design

    DTIC Science & Technology

    1987-05-01

    27 3. Free Gingival Margin (Sulcular aspect) ................... 32 4. Free Gingival Margin ( Oral Aspect).......................41 5...Doppler Readings (Tatoos) ..................... 23 Figure 3 Diagramatic View of Periodontal Ligament and Oral Soft Tissue Vasculature...in the modified Batson No 17 (1% by volume) leaving Mercox as the intermediate (6%) (Lametschwandter et al., 1984)). B. Anatomy of the Oral

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

    PubMed

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

    2017-02-20

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

  15. Goal-directed-perfusion in neonatal aortic arch surgery

    PubMed Central

    Purbojo, Ariawan; Muench, Frank; Juengert, Joerg; Rueffer, André

    2016-01-01

    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. PMID:27709094

  16. Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast-enhanced MRI of soft tissue tumors.

    PubMed

    Marzi, Simona; Stefanetti, Linda; Sperati, Francesca; Anelli, Vincenzo

    2016-01-01

    Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast-enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty-eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion-related diffusion coefficient D* were estimated using a bi-exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3-5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann-Whitney test was used to evaluate the differences between all variables in patients with non-myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non-myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non-myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion-related IVIM parameters and perfusion measured by DCE MRI.

  17. Relationship of brown adipose tissue perfusion and function: a study through β2-adrenoreceptor stimulation.

    PubMed

    Ernande, Laura; Stanford, Kristin I; Thoonen, Robrecht; Zhang, Haihua; Clerte, Maëva; Hirshman, Michael F; Goodyear, Laurie J; Bloch, Kenneth D; Buys, Emmanuel S; Scherrer-Crosbie, Marielle

    2016-04-15

    Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by β2-adrenoreceptor (β2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during β2-AR stimulation using salbutamol infusion in mice (P= 0.003). β2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of β2-AR agonist on brown adipocytes. Finally, β2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively,P= 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.

  18. Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

    PubMed

    Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

    2017-03-01

    Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency.

  19. Visualizing feasible operating ranges within tissue engineering systems using a "windows of operation" approach: a perfusion-scaffold bioreactor case study.

    PubMed

    McCoy, Ryan J; O'Brien, Fergal J

    2012-12-01

    Tissue engineering approaches to developing functional substitutes are often highly complex, multivariate systems where many aspects of the biomaterials, bio-regulatory factors or cell sources may be controlled in an effort to enhance tissue formation. Furthermore, success is based on multiple performance criteria reflecting both the quantity and quality of the tissue produced. Managing the trade-offs between different performance criteria is a challenge. A "windows of operation" tool that graphically represents feasible operating spaces to achieve user-defined levels of performance has previously been described by researchers in the bio-processing industry. This paper demonstrates the value of "windows of operation" to the tissue engineering field using a perfusion-scaffold bioreactor system as a case study. In our laboratory, perfusion bioreactor systems are utilized in the context of bone tissue engineering to enhance the osteogenic differentiation of cell-seeded scaffolds. A key challenge of such perfusion bioreactor systems is to maximize the induction of osteogenesis but minimize cell detachment from the scaffold. Two key operating variables that influence these performance criteria are the mean scaffold pore size and flow-rate. Using cyclooxygenase-2 and osteopontin gene expression levels as surrogate indicators of osteogenesis, we employed the "windows of operation" methodology to rapidly identify feasible operating ranges for the mean scaffold pore size and flow-rate that achieved user-defined levels of performance for cell detachment and differentiation. Incorporation of such tools into the tissue engineer's armory will hopefully yield a greater understanding of the highly complex systems used and help aid decision making in future translation of products from the bench top to the market place.

  20. Temperature-dependent release of ATP from human erythrocytes: mechanism for the control of local tissue perfusion

    PubMed Central

    Kalsi, Kameljit K; González-Alonso, José

    2012-01-01

    Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or ‘bathing solution’ ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r2 = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r2 = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature. PMID:22227202

  1. Temperature-dependent release of ATP from human erythrocytes: mechanism for the control of local tissue perfusion.

    PubMed

    Kalsi, Kameljit K; González-Alonso, José

    2012-03-01

    Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or 'bathing solution' ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r(2) = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r(2) = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature.

  2. 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.

  3. Non-contact tissue perfusion and oxygenation imaging using a LED based multispectral and a thermal imaging system, first results of clinical intervention studies

    NASA Astrophysics Data System (ADS)

    Klaessens, John H. G. M.; Nelisse, Martin; Verdaasdonk, Rudolf M.; Noordmans, Herke Jan

    2013-03-01

    During clinical interventions objective and quantitative information of the tissue perfusion, oxygenation or temperature can be useful for the surgical strategy. Local (point) measurements give limited information and affected areas can easily be missed, therefore imaging large areas is required. In this study a LED based multispectral imaging system (MSI, 17 different wavelengths 370nm-880nm) and a thermo camera were applied during clinical interventions: tissue flap transplantations (ENT), local anesthetic block and during open brain surgery (epileptic seizure). The images covered an area of 20x20 cm, when doing measurements in an (operating) room, they turned out to be more complicated than laboratory experiments due to light fluctuations, movement of the patient and limited angle of view. By constantly measuring the background light and the use of a white reference, light fluctuations and movement were corrected. Oxygenation concentration images could be calculated and combined with the thermal images. The effectively of local anesthesia of a hand could be predicted in an early stage using the thermal camera and the reperfusion of transplanted skin flap could be imaged. During brain surgery, a temporary hyper-perfused area was witnessed which was probably related to an epileptic attack. A LED based multispectral imaging system combined with thermal imaging provide complementary information on perfusion and oxygenation changes and are promising techniques for real-time diagnostics during clinical interventions.

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

    PubMed Central

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

    2016-01-01

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

  5. The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients

    PubMed Central

    Ince, Can

    2010-01-01

    Purpose The clinical use of vasoactive drugs is not only intended to improve systemic hemodynamic variables, but ultimately to attenuate derangements in organ perfusion and oxygenation during shock. This review aims (1) to discuss basic physiology with respect to manipulating vascular tone and its effect on the microcirculation, and (2) to provide an overview of available clinical data on the relation between vasoactive drugs and organ perfusion, with specific attention paid to recent developments that have enabled direct in vivo observation of the microcirculation and concepts that have originated from it. Methods A MedLine search was conducted for clinical articles in the English language over the last 15 years pertainig to shock, sepsis, organ failure, or critically ill patients in combination with vasoactive drugs and specific variables of organ perfusion/oxygenation (e.g., tonometry, indocyanine clearance, laser Doppler, and sidestream dark field imaging). Results Eighty original papers evaluating the specific relationship between organ perfusion/oxygenation and the use of vasoactive drugs were identified and are discussed in light of physiological theory of vasomotor tone. Conclusions Solid clinical data in support of the idea that increasing blood pressure in shock improves microcirculatory perfusion/oxygenation seem to be lacking, and such a concept might not be in line with physiological theory of microcirculation as a low-pressure vascular compartment. In septic shock no beneficial effect on microcirculatory perfusion above a mean arterial pressure of 65 mmHg has been reported, but a wide range in inter-individual effect seems to exist. Whether improvement of microcirculatory perfusion is associated with better patient outcome remains to be elucidated. PMID:20811874

  6. Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures

    PubMed Central

    Ou, Yangguang; Wu, Juanfang; Sandberg, Mats

    2014-01-01

    This review covers recent advances in sampling fluid from the extracellular space of brain tissue by electroosmosis (EO). Two techniques, EO sampling with a single fused-silica capillary and EO push–pull perfusion, have been developed. These tools were used to investigate the function of membrane-bound enzymes with outward-facing active sites, or ectoenzymes, in modulating the activity of the neuropeptides leu-enkephalin and galanin in organotypic-hippocampal-slice cultures (OHSCs). In addition, the approach was used to determine the endogenous concentration of a thiol, cysteamine, in OHSCs. We have also investigated the degradation of coenzyme A in the extracellular space. The approach provides information on ectoenzyme activity, including Michaelis constants, in tissue, which, as far as we are aware, has not been done before. On the basis of computational evidence, EO push–pull perfusion can distinguish ectoenzyme activity with a ~100 µm spatial resolution, which is important for studies of enzyme kinetics in adjacent regions of the rat hippocampus. PMID:25168111

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

    PubMed

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

    2013-09-21

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

  8. A new formalism for the quantification of tissue perfusion by the destruction-replenishment method in contrast ultrasound imaging.

    PubMed

    Arditi, Marcel; Frinking, Peter J A; Zhou, Xiang; Rognin, Nicolas G

    2006-06-01

    A new formalism is presented for the destruction-replenishment perfusion quantification approach at low mechanical index. On the basis of physical considerations, best-fit methods should be applied using perfusion functions with S-shape characteristics. These functions are first described for the case of a geometry with a single flow velocity, then extended to the case of vascular beds with blood vessels having multiple flow velocity values and directions. The principles guiding the analysis are, on one hand, a linearization of video echo signals to overcome the log-compression of the imaging instrument, and, on the other hand, the spatial distribution of the transmit-receive ultrasound beam in the elevation direction. An in vitro model also is described; it was used to confirm experimentally the validity of the approach using a commercial contrast agent. The approach was implemented in the form of a computer program, taking as input a sequence of contrast-specific images, as well as parameters related to the ultrasound imaging equipment used. The generated output is either flow-parameter values computed in regions-of-interest, or parametric flow-images (e.g., mean velocity, mean transit time, mean flow, flow variance, or skewness). This approach thus establishes a base for extracting information about the morphology of vascular beds in vivo, and could allow absolute quantification provided that appropriate instrument calibration is implemented.

  9. The influence of Sildenafil citrate on uterine tissue perfusion and the cardiovascular system during the luteal phase of the ovarian cycle in cows.

    PubMed

    Dzięcioł, Michał; Stańczyk, Ewa; Noszczyk-Nowak, Agnieszka; Michlik, Katarzyna; Kozdrowski, Roland; Niżański, Wojciech; Pasławskab, Urszula; Mrowiec, Jacek; Twardoń, Jan

    2014-03-01

    The aim of the study was to evaluate the influence of the Sildenafil citrate on the blood flow in the uterus of cows during dioestrus. Uterine blood flow was examined in five, healthy, adult cows. Between day 6-8 of the ovarian cycle, each cow received 200mg of sildenafil diluted in 10ml of warm saline into the body of the uterus. Analysis of the blood pressure, ECG and the maximum velocity in m/s (V max) in the aorta was performed and selected parameters of the blood flow (PI, pulsatile index; RI, resistance index; SPV, systolic peak velocity; EDV, end diastolic velocity; FVI, flow velocity integral; SV/DV, systolic peak velocity: end-diastolic velocity ratio) were measured in the uterine artery (Arteria uterine) before and after sildenafil infusion. In addition, Color Doppler examination of the uterine wall perfusion was analyzed. A significant decrease of values of PI and SV/DV ratio as well as an increase of end diastolic velocity and time averaged maximum velocity was noted. With the use of color coded sonography, the increased intensity of the blood flow in the uterine wall was observed. It was concluded that intrauterine administration of sildenafil during dioestrus can increase uterine tissue perfusion.

  10. 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.

  11. Applicability of the Kubelka-Munk theory for the evaluation of reflectance spectra demonstrated for haemoglobin-free perfused heart tissue.

    PubMed

    Hoffmann, J; Lübbers, D W; Heise, H M

    1998-12-01

    Reflectance spectrometry is a useful tool for studying in vivo kinetic changes in the oxygen saturation of haemoglobin and myoglobin as well as the redox state of cytochromes. A method is given which allows the quantification of tissue reflectance spectra using multicomponent analysis. This method utilizes the Kubelka-Munk theory for modelling the measured tissue spectra. To test this approach, reflectance spectra of a haemoglobin-free perfused guinea pig heart were measured by a fast scanning spectrophotometer (100 spectra/s, spectral resolution 1.0 nm) and evaluated using the component absorbance spectra measured separately. A relative mean spectral residual error of 0.15% was achieved by least-squares fitting. Using statistical error propagation, oxygenation of myoglobin is obtained within a relative precision of 1%, and the redox state of cytochromes aa3 and c are determined simultaneously within a margin of 3%; the results for the redox-state of cytochrome b, however, are less precise. Special component error functions are presented to provide a reliability measure for the concentration prediction using this multicomponent assay. The consistency of the theory and the component absorptivity data is tested by regressing the actual concentrations obtained for each of the redox pair components during the various states of tissue oxygenation. A method is described for the recognition and reduction of systematic errors.

  12. Analysis of gravity-induced particle motion and fluid perfusion flow in the NASA-designed rotating zero-head-space tissue culture vessel

    NASA Technical Reports Server (NTRS)

    Wolf, David A.; Schwarz, Ray P.

    1991-01-01

    The gravity induced motions, through the culture media, is calculated of living tissue segments cultured in the NASA rotating zero head space culture vessels. This is then compared with the media perfusion speed which is independent of gravity. The results may be interpreted as a change in the physical environment which will occur by operating the NASA tissue culture systems in actual microgravity (versus unit gravity). The equations governing particle motions which induce flows at the surface of tissues contain g terms. This allows calculation of the fluid flow speed, with respect to a cultured particle, as a function of the external gravitational field strength. The analysis is approached from a flow field perspective. Flow is proportional to the shear exerted on a structure which maintains position within the field. The equations are solved for the deviation of a particle from its original position in a circular streamline as a function of time. The radial deviation is important for defining the operating limits and dimensions of the vessel because of the finite radius at which particles necessarily intercept the wall. This analysis uses a rotating reference frame concept.

  13. The Impact of Hypotensive Epidural Anesthesia on Distal and Proximal Tissue Perfusion in Patients Undergoing Total Hip Arthroplasty.

    PubMed

    Danninger, Thomas; Stundner, Ottokar; Ma, Yan; Bae, James J; Memtsoudis, Stavros G

    2013-11-29

    Little data exists to detail the effect of hypotensive epidural anesthesia on differential tissue oxygenation changes above and below the level of neuraxial blockade. This study was designed to investigate tissue oxygenation in a clinical setting, using non-invasive near-infrared spectroscopy.

  14. Noninvasive, near infrared spectroscopic-measured muscle pH and PO2 indicate tissue perfusion for cardiac surgical patients undergoing cardiopulmonary bypass

    NASA Technical Reports Server (NTRS)

    Soller, Babs R.; Idwasi, Patrick O.; Balaguer, Jorge; Levin, Steven; Simsir, Sinan A.; Vander Salm, Thomas J.; Collette, Helen; Heard, Stephen O.

    2003-01-01

    OBJECTIVE: To determine whether near infrared spectroscopic measurement of tissue pH and Po2 has sufficient accuracy to assess variation in tissue perfusion resulting from changes in blood pressure and metabolic demand during cardiopulmonary bypass. DESIGN: Prospective clinical study. SETTING: Academic medical center. SUBJECTS: Eighteen elective cardiac surgical patients. INTERVENTION: Cardiac surgery under cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: A near infrared spectroscopic fiber optic probe was placed over the hypothenar eminence. Reference Po2 and pH sensors were inserted in the abductor digiti minimi (V). Data were collected every 30 secs during surgery and for 6 hrs following cardiopulmonary bypass. Calibration equations developed from one third of the data were used with the remaining data to investigate sensitivity of the near infrared spectroscopic measurement to physiologic changes resulting from cardiopulmonary bypass. Near infrared spectroscopic and reference pH and Po2 measurements were compared for each subject using standard error of prediction. Near infrared spectroscopic pH and Po2 at baseline were compared with values during cardiopulmonary bypass just before rewarming commenced (hypotensive, hypothermic), after rewarming (hypotensive, normothermic) just before discontinuation of cardiopulmonary bypass, and at 6 hrs following cardiopulmonary bypass (normotensive, normothermic) using mixed-model analysis of variance. Near infrared spectroscopic pH and Po2 were well correlated with the invasive measurement of pH (R2 =.84) and Po2 (R 2 =.66) with an average standard error of prediction of 0.022 +/- 0.008 pH units and 6 +/- 3 mm Hg, respectively. The average difference between the invasive and near infrared spectroscopic measurement was near zero for both the pH and Po2 measurements. Near infrared spectroscopic Po2 significantly decreased 50% on initiation of cardiopulmonary bypass and remained depressed throughout the bypass and

  15. Renal perfusion scintiscan

    MedlinePlus

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  16. Experimental Approach to Evaluate the 11C Perfusion and Diffusion in Small Animal Tissues for HadronPET Applications

    PubMed Central

    Martínez-Rovira, Immaculada; Boisgard, Raphaël; Pottier, Géraldine; Kuhnast, Bertrand; Jan, Sébastien

    2016-01-01

    The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found. PMID:27015269

  17. Possibilities of improving the parameters of hyperthermia in regional isolated limb perfusion using epidural bupivacaine and accurate temperature measurement of the three layers of limb tissue.

    PubMed

    Jastrzebski, Tomasz; Sommer, Anna; Swierblewski, Maciej; Lass, Piotr; Rogowski, Jan; Drucis, Kamil; Kopacz, Andrzej

    2006-06-01

    The present study presents the author's modification of the method, which aims to create proper parameters of the treatment. The selected group consisted of 15 women and eight men, with a mean age of 57.2 years (range from 26 to 72 years). The patients were divided into two groups, depending on whether they were given epidural bupivacaine (group I - 13 patients treated between the years 2001 and 2004) or not [group II (control) - 10 patients treated earlier, between the years 1997 and 2000]. We observed a significant change in the temperature of thigh muscles (P=0.009) and shank muscles (P=0.006). In the control group II, there was a statistically significant difference (P=0.048) in the temperatures between the muscles and subcutaneous tissue on the one hand and the shank skin on the other. That difference was mean 0.67 degrees Celsius (from 0.4 to 0.9) during the perfusion after applying the cytostatic. The temperature of the skin was lower than the temperature of the deeper tissues of the shank and did not exceed 39.9 degrees Celsius. Such a difference in the temperatures was not observed in case of the group I patients who were given bupivacaine into the extrameningeal space before applying the cytostatic. The difference in the temperatures was on average 0.26 degrees Celsius and was not statistically significant (P=0.99), whereas the shank skin temperature was 40.0-40.6 degrees Celsius. The attained results imply that despite the noticeable improvement in the heating of the limb muscles after application of bupivacaine, the improvement in the heating of the skin and subcutaneous tissue is still not satisfactory, although the growing tendency implies such a possibility.

  18. Long term perfusion system supporting adipogenesis

    PubMed Central

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

    2015-01-01

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

  19. Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

    PubMed Central

    Hoven-Gondrie, Miriam L.; Thijssens, Katja M. J.; Van den Dungen, Jan J. A. M.; Loonstra, Jan; van Ginkel, Robert J.

    2007-01-01

    Background Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17–159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50–1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91–1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1–23.9 vs. median, 7.35; range, 4.8–21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0–21.4 vs. median, 10.95; range, 8.0–32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity. PMID:17457649

  20. Left ventricular dyssynchrony assessed by two three-dimensional imaging modalities: phase analysis of gated myocardial perfusion SPECT and tri-plane tissue Doppler imaging

    PubMed Central

    Ajmone Marsan, Nina; Henneman, Maureen M.; Chen, Ji; Ypenburg, Claudia; Dibbets, Petra; Ghio, Stefano; Bleeker, Gabe B.; Stokkel, Marcel P.; van der Wall, Ernst E.; Tavazzi, Luigi; Garcia, Ernest V.

    2007-01-01

    Purpose To compare left ventricular (LV) dyssynchrony assessment by phase analysis from gated myocardial perfusion SPECT (GMPS) with LV dyssynchrony assessment by tri-plane tissue Doppler imaging (TDI). Baseline LV dyssynchrony assessed with standard deviation (SD) of time-to-peak systolic velocity of 12 LV segments (Ts-SD) with TDI has proven to be a powerful predictor of response to CRT. Information on LV dyssynchrony can also be provided by GMPS with phase analysis of regional LV maximal count changes throughout the cardiac cycle. Methods Forty heart failure patients, referred for evaluation of potential eligibility for CRT, underwent both 3D echocardiography, with tri-plane TDI, and resting GMPS. From tri-plane TDI, Ts-SD was used as a validated parameter of LV dyssynchrony and compared with different indices (histogram bandwidth, phase SD, histogram skewness and kurtosis) derived from phase analysis of GMPS. Results Histogram bandwidth and phase SD showed good correlation with Ts-SD (r=0.77 and r=0.74, p<0.0001, respectively). Patients with substantial LV dyssynchrony assessed with tri-plane TDI (Ts-SD ≥33 ms) had also significantly higher values of histogram bandwidth and phase SD. Conclusions The results of this study support the use of phase analysis by GMPS to evaluate LV dyssynchrony. Histogram bandwidth and phase SD showed the best correlation with Ts-SD assessed with tri-plane TDI and appeared the most optimal variables for assessment of LV dyssynchrony with GMPS. PMID:17874098

  1. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  2. Pharmacological optimization of tissue perfusion

    PubMed Central

    Mongardon, N.; Dyson, A.; Singer, M.

    2009-01-01

    After fluid resuscitation, vasoactive drug treatment represents the major cornerstone for correcting any major impairment of the circulation. However, debate still rages as to the choice of agent, dose, timing, targets, and monitoring modalities that should optimally be used to benefit the patient yet, at the same time, minimize harm. This review highlights these areas and some new pharmacological agents that broaden our therapeutic options. PMID:19460775

  3. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    PubMed Central

    Grant, Aaron K.; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E.; Alsop, David C.

    2011-01-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized 13C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic 13C images acquired in rat brain with a balanced steady-state free precession (bSSFP) sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2–4s temporal resolution, 2mm slice thickness, and 700 micron in-plane resolution while retaining adequate signal-to-noise ratio. 13C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4T yield T1=46±4s and T2=0.55±0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the bSSFP image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T2 of roughly 2–4s and a T1 of 43±24s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. PMID:21432901

  4. Intestinal perfusion monitoring using photoplethysmography

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

    In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.

  5. Perfusion decellularization of whole organs.

    PubMed

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

    2014-01-01

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

  6. The effect of head size/shape, miscentering, and bowtie filter on peak patient tissue doses from modern brain perfusion 256-slice CT: How can we minimize the risk for deterministic effects?

    SciTech Connect

    Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Papadakis, Antonios E.; Damilakis, John

    2013-01-15

    Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peak tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of

  7. Engineered Muscle Actuators: Cells and Tissues

    DTIC Science & Technology

    2007-01-10

    platform. Outcomes by milestone: (1) Develop integrated tissue culture bioreactor systems: completed all but bulk perfusion (2) Develop appropriate...tissue culture perfusion bioreactors (B) Second generation cm-scale hybrid swimming robotic platform & control methodologies (C) Guidance of engineered...integrated tissue culture perfusion bioreactors 1. Employ rapid manufacturing techniques for bioreactors 1. accelerate system development 2. increase number

  8. Isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma.

    PubMed

    Wilkinson, Michelle J; Smith, Henry G; Pencavel, Timothy D; Mansfield, David C; Kyula-Currie, Joan; Khan, Aadil A; McEntee, Gráinne; Roulstone, Victoria; Hayes, Andrew J; Harrington, Kevin J

    2016-09-15

    The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes. Previous work in an animal model has demonstrated the efficacy of oncolytic virotherapy when delivered by ILP and, in this study, we report further improvements from combining ILP-delivered oncolytic virotherapy with radiation and surgical resection. In vitro, the combination of radiation with an oncolytic vaccinia virus (GLV-1h68) and melphalan demonstrated increased cytotoxicity in a panel of sarcoma cell lines. The effects were mediated through activation of the intrinsic apoptotic pathway. In vivo, combinations of radiation, oncolytic virotherapy and standard ILP resulted in delayed tumour growth and prolonged survival when compared with standard ILP alone. However, local disease control could only be secured when such treatment was combined with surgical resection, the timing of which was crucial in determining outcome. Combinations of oncolytic virotherapy with surgical resection and radiation have direct clinical relevance in extremity sarcoma and represent an exciting prospect for improving outcomes in this pathology.

  9. Do you mind if I vape? Immediate effects of electronic cigarettes on perfusion in buccal mucosal tissue--a pilot study.

    PubMed

    Reuther, William J; Hale, Beverley; Matharu, Jas; Blythe, John N; Brennan, Peter A

    2016-04-01

    The association between smoking and postoperative complications is compounded in patients who have oral and maxillofacial operations by an additional local effect, and patients often continue to smoke after operation despite advice to stop. Recent studies have suggested that nicotine may reduce inflammation and improve angiogenesis, so topical application may be beneficial for smokers. The electronic cigarette is increasing in popularity and more patients ask whether they can vape after operation. We investigated the effect of electronic cigarettes (of which half contained nicotine and half did not) on blood flow in the buccal mucosa in 10 volunteers immediately after vaping. Smokers were excluded as this was considered an additional variable in a small pilot study and our Trust has a no-smoking policy. After vaping for 5 minutes, capillary blood flow was measured in the buccal mucosa at 5-minute intervals using a laser Doppler probe, and the results were expressed as arbitrary perfusion units. There was a wide variation in results and a small but significant rise (p=0.008) as a result of nicotine vaping, but these fell to the same levels as before within 30 minutes. Electronic cigarettes may have an effect on blood flow to the oral mucosa, although further studies are needed to show whether they improve healing time after operation. Additional work is also needed to compare them with cigarettes.

  10. Reflection imaging of China ink-perfused brain vasculature using confocal laser-scanning microscopy after clarification of brain tissue by the Spalteholz method.

    PubMed

    Gutierre, R C; Vannucci Campos, D; Mortara, R A; Coppi, A A; Arida, R M

    2017-01-05

    Confocal laser-scanning microscopy is a useful tool for visualizing neurons and glia in transparent preparations of brain tissue from laboratory animals. Currently, imaging capillaries and venules in transparent brain tissues requires the use of fluorescent proteins. Here, we show that vessels can be imaged by confocal laser-scanning microscopy in transparent cortical, hippocampal and cerebellar preparations after clarification of China ink-injected specimens by the Spalteholz method. This method may be suitable for global, three-dimensional, quantitative analyses of vessels, including stereological estimations of total volume and length and of surface area of vessels, which constitute indirect approaches to investigate angiogenesis.

  11. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  12. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  13. Metabolism of 7-ethyoxycoumarin by Isolated Perfused Rainbow Trout Livers

    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, vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase leakage, and metabolic clearanc...

  14. Free flap rescue using an extracorporeal perfusion device.

    PubMed

    Fichter, Andreas M; Ritschl, Lucas M; Rau, Andrea; Schwarzer, Claudia; von Bomhard, Achim; Wagenpfeil, Stefan; Wolff, Klaus-Dietrich; Mücke, Thomas

    2016-12-01

    The warm ischaemia time of microvascular free flaps is limited. Incalculable events, such as lack of adequate recipient vessels or intraoperative medical emergencies, can lead to prolonged ischaemia and potentially to flap loss. In this study, critically perfused ischaemic or congested flaps were temporarily perfused with an extracorporeal perfusion system until anastomosis could be commenced. Temporary extracorporeal perfusion was performed in 8 radial forearm flaps for 147 ± 52 (range 77-237) minutes. Flap perfusion was assessed using Indocyanine Green fluorescence angiography and combined laser Doppler flowmetry and remission spectroscopy. Results were compared with those of 30 patients who underwent conventional reconstruction with radial forearm flaps. Flap survival, flap microcirculation, postoperative complications, and hospital stay did not differ between groups. We report successful free flap transfer after short-term extracorporeal perfusion for up to 4 h in 8 patient cases. Temporary extracorporeal free flap perfusion reduces the warm ischaemia time in emergency situations and can help to prevent flap failure in critically perfused or congested flaps. The trial is registered with ClinicalTrials.gov, number NCT02449525.

  15. Abdominal perfusion computed tomography.

    PubMed

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-02-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.

  16. Abdominal Perfusion Computed Tomography

    PubMed Central

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-01-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249

  17. 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

  18. The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system.

    PubMed

    van der Plaats, A; Maathuis, M H J; 'T Hart, N A; Bellekom, A A; Hofker, H S; van der Houwen, E B; Verkerke, G J; Leuvenink, H G D; Verdonck, P; Ploeg, R J; Rakhorst, G

    2006-12-01

    To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion, sufficient oxygenation, a maintained 0-4 degrees C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO(2)) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0-4 degrees C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO(2) was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers. The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.

  19. Lesion area detection using source image correlation coefficient for CT perfusion imaging.

    PubMed

    Fan Zhu; Rodriguez Gonzalez, David; Carpenter, Trevor; Atkinson, Malcolm; Wardlaw, Joanna

    2013-09-01

    Computer tomography (CT) perfusion imaging is widely used to calculate brain hemodynamic quantities such as cerebral blood flow, cerebral blood volume, and mean transit time that aid the diagnosis of acute stroke. Since perfusion source images contain more information than hemodynamic maps, good utilization of the source images can lead to better understanding than the hemodynamic maps alone. Correlation-coefficient tests are used in our approach to measure the similarity between healthy tissue time-concentration curves and unknown curves. This information is then used to differentiate penumbra and dead tissues from healthy tissues. The goal of the segmentation is to fully utilize information in the perfusion source images. Our method directly identifies suspected abnormal areas from perfusion source images and then delivers a suggested segmentation of healthy, penumbra, and dead tissue. This approach is designed to handle CT perfusion images, but it can also be used to detect lesion areas in magnetic resonance perfusion images.

  20. A compact instrument to measure perfusion of vasculature in transplanted maxillofacial free flaps

    NASA Astrophysics Data System (ADS)

    Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Podolsky, Matthew J.; Farkas, Dana; Ward, Brent B.; Vartarian, Mark; Feinberg, Stephen E.; Lee, Seung Yup; Parikh, Urmi; Mycek, Mary-Ann; Christian, James F.

    2016-03-01

    The vascularization and resulting perfusion of transferred tissues are critical to the success of grafts in buried free flap transplantations. To enable long-term clinical monitoring of grafted tissue perfusion during neovascularization and endothelialization, we are developing an implantable instrument for the continuous monitoring of perfusion using diffuse correlation spectroscopy (DCS), and augmented with diffuse reflectance spectroscopy (DRS). This work discusses instrument construction, integration, and preliminary results using a porcine graft model.

  1. 5 CFR 919.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Adequate evidence. 919.900 Section 919.900 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 919.900 Adequate...

  2. A new in vivo magnetic resonance imaging method to noninvasively monitor and quantify the perfusion capacity of three-dimensional biomaterials grown on the chorioallantoic membrane of chick embryos.

    PubMed

    Kivrak Pfiffner, Fatma; Waschkies, Conny; Tian, Yinghua; Woloszyk, Anna; Calcagni, Maurizio; Giovanoli, Pietro; Rudin, Markus; Buschmann, Johanna

    2015-04-01

    Adequate vascularization in biomaterials is essential for tissue regeneration and repair. Current models do not allow easy analysis of vascularization of implants in vivo, leaving it a highly desirable goal. A tool that allows monitoring of perfusion capacity of such biomaterials noninvasively in a cheap, efficient, and reliable in vivo model would hence add great benefit to research in this field. We established, for the first time, an in vivo magnetic resonance imaging (MRI) method to quantify the perfusion capacity of a model biomaterial, DegraPol(®) foam scaffold, placed on the embryonic avian chorioallantoic membrane (CAM) in ovo. Perfusion capacity was assessed through changes in the longitudinal relaxation rate before and after injection of a paramagnetic MRI contrast agent, Gd-DOTA (Dotarem(®); Guerbet S.A.). Relaxation rate changes were compared in three different regions of the scaffold, that is, at the interface to the CAM, in the middle and on the surface of the scaffold (p<0.05). The highest relaxation rate changes, and hence perfusion capacities, were measured in the interface region where the scaffold was attached to the CAM, whereas the surface of the scaffold showed the lowest relaxation rate changes. A strong positive correlation was obtained between relaxation rate changes and histologically determined vessel density (R(2) = 0.983), which corroborates our MRI findings. As a proof-of-principle, we measured the perfusion capacity in different scaffold materials, silk fibroin either with or without human dental pulp stem cells. For these, three to four times larger perfusion capacities were obtained compared to DegraPol; demonstrating that our method is sensitive to reveal such differences. In summary, we present a novel in vivo method for analyzing the perfusion capacity in three-dimensional-biomaterials grown on the CAM, enabling the determination of the perfusion capacity of a large variety of bioengineered materials.

  3. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  4. 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.

  5. [Portable peristaltic perfusion pumps].

    PubMed

    Magallón Pedrera, I; Soto Torres, I

    1999-11-01

    Portable peristaltic perfusion pumps allow one to administer pharmaceuticals in hospitals as well as in primary health care centers and furthermore these pumps present multiple advantages for patients and their families since they make it possible to carry out treatment in a patient's home while at the same time lowering the costs involved. The authors analyze the most out standing aspects of portable peristaltic perfusion pumps along with their characteristics, installation, programming, and how to turn them on; in addition, the authors list the maintenance care which these pumps require.

  6. Noncontact blood perfusion mapping in clinical applications

    NASA Astrophysics Data System (ADS)

    Iakovlev, Dmitry; Dwyer, Vincent; Hu, Sijung; Silberschmidt, Vadim

    2016-04-01

    Non-contact imaging photoplethysmography (iPPG) to detect pulsatile blood microcirculation in tissue has been selected as a successor to low spatial resolution and slow scanning blood perfusion techniques currently employed by clinicians. The proposed iPPG system employs a novel illumination source constructed of multiple high power LEDs with narrow spectral emission, which are temporally modulated and synchronised with a high performance sCMOS sensor. To ensure spectrum stability and prevent thermal wavelength drift due to junction temperature variations, each LED features a custom-designed thermal management system to effectively dissipate generated heat and auto-adjust current flow. The use of a multi-wavelength approach has resulted in simultaneous microvascular perfusion monitoring at various tissue depths, which is an added benefit for specific clinical applications. A synchronous detection algorithm to extract weak photoplethysmographic pulse-waveforms demonstrated robustness and high efficiency when applied to even small regions of 5 mm2. The experimental results showed evidences that the proposed system could achieve noticeable accuracy in blood perfusion monitoring by creating complex amplitude and phase maps for the tissue under examination.

  7. Effects of adenosine perfusion on the metabolism and contractile activity of Rana ridibunda heart.

    PubMed

    Lazou, A; Beis, I

    1987-01-01

    The effects of adenosine were examined on the isolated perfused heart of the frog Rana ridibunda. Adenosine produced negative chronotropic and inotropic effects on frog ventricle in a concentration-dependent manner. The effects of adenosine on cardiac metabolism were also investigated by measuring the tissue content of adenine nucleotides, lactate, pyruvate, adenosine and inorganic phosphate, during adenosine perfusion. Adenosine had no effect on the tissue content of metabolites. No net synthesis of adenine nucleotides was observed during perfusion with increasing concentrations of adenosine. Lactate output from the heart decreased significantly with adenosine perfusion. Correlation of adenosine effects on cardiac muscle with the effects of hypoxia are discussed.

  8. Asynchronicity of facial blood perfusion in migraine.

    PubMed

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A; Kamshilin, Alexei A; Närhi, Matti; Karjalainen, Pasi A; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.

  9. Asynchronicity of Facial Blood Perfusion in Migraine

    PubMed Central

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A.; Kamshilin, Alexei A.; Närhi, Matti; Karjalainen, Pasi A.; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology. PMID:24324592

  10. Regulation of skeletal muscle perfusion during exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Laughlin, M. H.

    1998-01-01

    For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.

  11. In-vivo quantitative evaluation of perfusion zones and perfusion gradient in the deep inferior epigastric artery perforator flap

    NASA Astrophysics Data System (ADS)

    Saint-Cyr, Michel; Lakhiani, Chrisovalantis; Cheng, Angela; Mangum, Michael; Liang, Jinyang; Teotia, Sumeet; Livingston, Edward H.; Zuzak, Karel J.

    2013-03-01

    The selection of well-vascularized tissue during DIEP flap harvest remains controversial. While several studies have elucidated cross-midline perfusion, further characterization of perfusion to the ipsilateral hemiabdomen is necessary for minimizing rates of fat necrosis or partial fat necrosis in bilateral DIEP flaps. Eighteen patients (29 flaps) underwent DIEP flap harvest using a prospectively designed protocol. Perforators were marked and imaged with a novel system for quantitatively measuring tissue oxygenation, the Digital Light Hyperspectral Imager. Images were then analyzed to determine if perforator selection influenced ipsilateral flap perfusion. Flaps based on a single lateral row perforator (SLRP) were found to have a higher level of hemoglobin oxygenation in Zone I (mean %HbO2 = 76.1) compared to single medial row perforator (SMRP) flaps (%HbO2 = 71.6). Perfusion of Zone III relative to Zone I was similar between SLRP and SMRP flaps (97.4% vs. 97.9%, respectively). These differences were not statistically significant (p>0.05). Perfusion to the lateral edge of the flap was slightly greater for SLRP flaps compared SMRP flaps (92.1% vs. 89.5%, respectively). SMRP flaps had superior perfusion travelling inferiorly compared to SLRP flaps (88.8% vs. 83.9%, respectively). Overall, it was observed that flaps were better perfused in the lateral direction than inferiorly. Significant differences in perfusion gradients directed inferiorly or laterally were observed, and perforator selection influenced perfusion in the most distal or inferior aspects of the flap. This suggests broader clinical implications for flap design that merit further investigation.

  12. Asbestos/NESHAP adequately wet guidance

    SciTech Connect

    Shafer, R.; Throwe, S.; Salgado, O.; Garlow, C.; Hoerath, E.

    1990-12-01

    The Asbestos NESHAP requires facility owners and/or operators involved in demolition and renovation activities to control emissions of particulate asbestos to the outside air because no safe concentration of airborne asbestos has ever been established. The primary method used to control asbestos emissions is to adequately wet the Asbestos Containing Material (ACM) with a wetting agent prior to, during and after demolition/renovation activities. The purpose of the document is to provide guidance to asbestos inspectors and the regulated community on how to determine if friable ACM is adequately wet as required by the Asbestos NESHAP.

  13. Monitoring perfusion changes in laser-treated tumors using laser doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Deans, Abby; Hess, Linda; Koss, Michael; Liu, Hong; Chen, Wei R.

    2006-02-01

    Laser Doppler perfusion monitors are effect tools in understanding blood flow in many different types of biological studies. Because the low-intensity lasers used in Doppler perfusion measurements must interact with moving blood cells, the depth of probe-able tissue is limited to the volume of tissue within the hemisphere of radius ~1mm from the probe tip. In addition, heterogeneities in surface perfusion make precise probe placement very important if one is comparing successive measurements. Consequently, useful tissue perfusion measurements have been difficult to obtain, especially in deep tissues. In this study, a new method was developed for monitoring deep-tissue blood perfusion directionally with the Laserflo laser Doppler perfusion probe. The probe was inserted just under the skin superficially to a rat prostatic tumor through the shaft of a 16-gauge needle, which was modified to allow the probe to be exposed without extending beyond the beveled needle tip. Perfusion measurements of the tumor surface or the skin were made by rotating the bevel to face either inside or outside. Using this technique, tumor tissue can be differentiated from either skin or muscle. To study the responses of tumor to light stimulation, an 805nm biomedical treatment laser was used to irradiate the tumor. The perfusion of the tumor surface was shown to decrease slightly with short treatment laser applications (1W for 30 seconds or 1 minute). After a longer treatment session (5 minutes), the perfusion of the tumor tissue increased significantly. However, with an even longer (10 minutes) treatment, the perfusion of the tumor surface was shown to decrease once again. This trend indicates that before laser heating becomes significant, the perfusion decreases for as yet poorly understood reasons. When laser heating becomes significant, after the five-minute session, the perfusion increases dramatically, corresponding to the expected dilation of blood vessels during tissue heating. After

  14. Real-time vascular mechanosensation through ex vivo artery perfusion

    PubMed Central

    2014-01-01

    Background Cell-based perfusion studies have provided great insight into fluid-sensing mechanisms, such as primary cilia in the renal and vascular systems. However, the intrinsic limitations of in vitro cell culture, such as the inability to reflect cellular organization within tissues, has distanced observed paradigms from possible clinical developments. Here we describe a protocol that applies ex vivo artery perfusion and calcium imaging to observe real-time cellular responses to fluid-shear stress. Results Through our ex vivo artery perfusion method, we were able to simulate physiological flow and initiate distinct fluid shear stress mechanosensory responses, as well as induced acetylcholine responses in mouse aortic tissue. The observed calcium profiles confirm results found through previous in vitro cell culture experiments. The overall procedure, including dissection, sample preparation and perfusion, takes around 3 hours to complete. Conclusion Through our unique method, we are able to induce laminar flow within intact mouse aortic tissue and illicit subsequent cellular responses. This method of ex vivo artery perfusion provides the opportunity to bridge the novel findings of in vitro studies with subsequent physiological models of fluid-shear stress mechanosensation in vascular tissues. PMID:24685068

  15. [Myocardial perfusion imaging by digital subtraction angiography].

    PubMed

    Kadowaki, H; Ishikawa, K; Ogai, T; Katori, R

    1986-03-01

    Several methods of digital subtraction angiography (DSA) were compared to determine which could better visualize regional myocardial perfusion using coronary angiography in seven patients with myocardial infarction, two with angina pectoris and five with normal coronary arteries. Satisfactory DSA was judged to be achieved if the shape of the heart on the mask film was identical to that on the live film and if both films were exactly superimposed. To obtain an identical mask film in the shape of each live film, both films were selected from the following three phases of the cardiac cycle; at the R wave of the electrocardiogram, 100 msec before the R wave, and 200 msec before the R wave. The last two were superior for obtaining mask and live films which were similar in shape, because the cardiac motion in these phases was relatively small. Using these mask and live films, DSA was performed either with the continuous image mode (CI mode) or the time interval difference mode (TID mode). The overall perfusion of contrast medium through the artery to the vein was adequately visualized using the CI mode. Passage of contrast medium through the artery, capillary and vein was visualized at each phase using TID mode. Subtracted images were displayed and photographed, and the density of the contrast medium was adequate to display contour lines as in a relief map. Using this DSA, it was found that regional perfusion of the contrast medium was not always uniform in normal subjects, depending on the typography of the coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Funding the Formula Adequately in Oklahoma

    ERIC Educational Resources Information Center

    Hancock, Kenneth

    2015-01-01

    This report is a longevity, simulational study that looks at how the ratio of state support to local support effects the number of school districts that breaks the common school's funding formula which in turns effects the equity of distribution to the common schools. After nearly two decades of adequately supporting the funding formula, Oklahoma…

  17. Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps

    PubMed Central

    Fichter, Andreas M.; Ritschl, Lucas M.; Borgmann, Anna; Humbs, Martin; Luppa, Peter B.; Wolff, Klaus-Dietrich; Mücke, Thomas

    2016-01-01

    Background Extracorporeal perfusion (ECP) might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps. Methods After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood) were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7. Results ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27%) was even lower than after in vivo perfusion (49%), although not statistically significant (P = 0,083). After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%). Angiographic and histological findings confirmed these observations. Conclusions Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies. PMID:26808996

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

    PubMed

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

    2009-09-01

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

  19. Effects of blood perfusion rate on the optimization of RF-capacitive hyperthermia.

    PubMed

    Fujita, S; Tamazawa, M; Kuroda, K

    1998-09-01

    The effects of the blood perfusion rate on the optimization of heating conditions in radio-frequency capacitive hyperthermia were examined using numerical simulations. When the blood perfusion rate in the tumor was smaller than approximately one-half that of normal tissues, optimal selective heating of the tumor was obtained.

  20. Phosphorus nuclear magnetic resonance in isolated perfused rat pancreas

    SciTech Connect

    Matsumoto, Takehisa; Kanno, Tomio; Seo, Yoshiteru; Murakami, Masataka; Watari, Hiroshi National Institute for Physiological Sciences, Okazaki )

    1988-04-01

    Phosphorus nuclear magnetic resonance spectroscopy was applied to measure phosphorus energy metabolites in isolated perfused rat pancreas. The gland was perfused with a modified Krebs-Henseleit solution at room temperature (25{degree}C). {sup 31}P resonances of creatine phosphate (PCr), ATP, ADP, inorganic phosphate (P{sub i}) and phosphomonoesters (PMEs) were observed in all the preparations of pancreas. In different individual preparations, the resonance of PCr varied, but those of ATP were almost the same. The initial levels of PCr and ATP in individual preparations, however, remained almost unchanged during perfusion with the standard solution for 2 h. When the perfusion was stopped, the levels of ATP and PCr decreased, while the levels of PME and P{sub i} increased. At that time, the P{sub i} resonance shfted to a higher magnetic field, indicating that the tissue pH decreased. On reperfusion, the tissue levels of phosphorus compounds and the tissue pH were restored to their initial resting levels. Continuous infusion of 0.1 {mu}M acetylcholine caused marked and sustained increases in the flow of pancreatic juice and protein output. During the stimulation the tissue levels of phosphorus compounds remained unchanged, while the tissue pH was decreased slightly.

  1. Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion.

    PubMed

    Thews, O; Hummel, M; Kelleher, D K; Lecher, B; Vaupel, P

    2002-12-02

    Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca(2+)-channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100-140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 microg min(-1) kg(-1) BW). During constant-pressure isolated limb perfusion, nifedipine can significantly increase perfusion rate (+100%) and RBC flux (+60%) through experimental leg tumours. "Steal phenomena" in favour of the surrounding normal tissue and oedema formation were not observed. Despite the increased oxygen availability (+63%) seen upon application of this calcium channel blocker, nifedipine does not result in a substantial reduction of tumour hypoxia, most probably due to an increase in O(2) uptake with rising O(2) supply to the tumour-bearing hind limb. Nifedipine application during isolated limb perfusion can enhance tumour microcirculation and may therefore promote the delivery (pharmacokinetics) of anti-cancer drugs to the tumour and by this improve the efficacy of pressure-controlled isolated limb perfusion.

  2. 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.

  3. 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.

  4. Proton and fluorine NMR imaging for the assessment of myocardial perfusion

    SciTech Connect

    Horner, B.S.D.

    1985-01-01

    A high field, small bore NMR spectrometer was converted to an imaging system for the detection of fluorine and protons in phantoms and small biological samples. The modified spectrometer system was used to image various phantoms for the assessment of imaging performance. After assessment of the imaging system performance, a water soluble fluorinated compound of relatively low toxicity was investigated for use as an imaging agent for the detection of myocardial perfusion. New Zealand white rabbits were used as the model. Hearts were rapidly extracted and hung via the aorta to a perfusion apparatus which was capable of prolonging heart function throughout the course of the experiment. Perfusion with a standard nutrient solution was followed either by perfusion with a solution to which the fluorinated compound had been added or by ligation of the left coronary artery with subsequent perfusion with the fluorinated compound in perfusate solution. The hearts were then sectioned and imaged. The ligation of the left coronary artery produced a region of impaired perfusion in the left ventricular wall and parts of the septum. The regions of reduced perfusion appeared in the F-19 NMR images as areas of reduced intensity. Proton images of the tissue sections were also obtained for comparison. It was found that infarcted regions may be best visualized by combining the fluorine and proton images. Infarct damage was verified by Gentian violet stain. Relaxation times of fluorine and protons were measured both in perfused tissue and in various concentration solutions.

  5. A perfusion protocol for lizards, including a method for brain removal

    PubMed Central

    Hoops, Daniel

    2015-01-01

    The goal of fixation is to rapidly and uniformly preserve tissue in a life-like state. Perfusion achieves optimal fixation by pumping fixative directly through an animal’s circulatory system. Standard perfusion techniques were developed primarily for application in mammals, which are traditional neuroscience research models. Increasingly, other vertebrate groups are also being used in neuroscience. Following mammalian perfusion protocols for non-mammalian vertebrates often results in failed perfusions. Here, I present a modified perfusion protocol suitable for lizards. Though geared towards standard brain perfusion, this protocol is easily modified for the perfusion of other tissues and for various specialized histological techniques. • The two aortas of the lizard heart, emerging from a single ventricle, mean that care must be taken to place the perfusion needle in the correct aorta, unlike in mammals. • Only the head and neck perfuse – the visceral organs will not decolour, and the body may not twitch. • I also include a method for removing a lizard brain, which differs from mammals due to the incomplete and thicker skull of the lizard. PMID:26150986

  6. Harmonic analysis of perfusion pumps.

    PubMed

    Dougherty, F Carroll; Donovan, F M; Townsley, Mary I

    2003-12-01

    The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.

  7. Measuring perfusion with light (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jansen, Sanne M. A.; de Bruin, Daniel M.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-03-01

    There is no gold standard test for perfusion evaluation in surgery. Optical Imaging techniques are able to image tissue at high resolution and in real-time. Laser Speckle Contrast Imaging, Optical Coherence Tomography, Sidestream Darkfield and Incident Darkfield all use the interaction of light with tissue to create an image. To test their feasibility and explore validity in a controlled setting, we created a phantom with the optical properties of tissue and microvascular channels of 30-400 micrometer. With a Hamilton Syringe Pump we mimicked blood flow velocities of 0-20 mm/sec. Images of all different modalities at different blood flow velocities were compared in terms of imaging depth, resoluation and hemodynamic parameters.

  8. Hydrogels for Engineering of Perfusable Vascular Networks.

    PubMed

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S P; Machens, Hans-Günther; Schilling, Arndt F

    2015-07-14

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation.

  9. Hydrogels for Engineering of Perfusable Vascular Networks

    PubMed Central

    Liu, Juan; Zheng, Huaiyuan; Poh, Patrina S. P.; Machens, Hans-Günther; Schilling, Arndt F.

    2015-01-01

    Hydrogels are commonly used biomaterials for tissue engineering. With their high-water content, good biocompatibility and biodegradability they resemble the natural extracellular environment and have been widely used as scaffolds for 3D cell culture and studies of cell biology. The possible size of such hydrogel constructs with embedded cells is limited by the cellular demand for oxygen and nutrients. For the fabrication of large and complex tissue constructs, vascular structures become necessary within the hydrogels to supply the encapsulated cells. In this review, we discuss the types of hydrogels that are currently used for the fabrication of constructs with embedded vascular networks, the key properties of hydrogels needed for this purpose and current techniques to engineer perfusable vascular structures into these hydrogels. We then discuss directions for future research aimed at engineering of vascularized tissue for implantation. PMID:26184185

  10. Vascular communications between donor and recipient tissues after successful full face transplantation.

    PubMed

    Kumamaru, K K; Sisk, G C; Mitsouras, D; Schultz, K; Steigner, M L; George, E; Enterline, D S; Bueno, E M; Pomahac, B; Rybicki, F J

    2014-03-01

    The vascular reorganization after facial transplantation has important implications on future surgical planning. The purpose of this study was to evaluate blood flow (BF) after full face transplantation using wide area-detector computed tomography (CT) techniques. Three subjects with severe craniofacial injury who underwent full face transplantation were included. All subjects underwent a single anastomosis bilaterally of the artery and vein, and the recipient tongue was preserved. Before and after surgery, dynamic volume CT studies were analyzed for vascular anatomy and blood perfusion. Postsurgical CT showed extensive vascular reorganization for external carotid artery (ECA) angiosome; collateral flows from vertebral, ascending pharyngeal or maxillary arteries supplied the branches from the recipient ECAs distal to the ligation. While allograft tissue was slightly less perfused when the facial artery was the only donor artery when compared to an ECA-ECA anastomosis (4.4 ± 0.4% vs. 5.7 ± 0.7%), allograft perfusion was higher than the recipient normal neck tissue. BF for the recipient tongue was maintained from contralateral/donor arteries when the lingual artery was sacrificed. Venous drainage was adequate for all subjects, even when the recipient internal jugular vein was anastomosed in end-to-end fashion on one side. In conclusion, dynamic CT identified adequate BF for facial allografts via extensive vascular reorganization.

  11. A panel data set on harvest and perfusion decellularization of porcine rectus abdominis

    PubMed Central

    Zhang, Jian; Cheng, Wen Yue; Hu, Zhi Qian; Turner, Neill J.; Zhang, Li; Wang, Qiang; Badylak, Stephen F.

    2016-01-01

    In this dataset, we particularly depicted the harvest and perfusion decellularization of porcine rectus abdominis (RA), accompanied with displaying of the retained vascular trees within the perfusion-decellularized skeletal muscle matrix (pM-ECM) using vascular corrosion casting. In addition, several important tips for successful pM-ECM preparation were emphasized, which including using anatomically isolated skeletal muscle as tissue source with all main feeding and draining vessels perfused, preserving the internal microcirculation availability, aseptic technique and pyrogen free in all steps, sequential perfusion via artery or vein, and longtime washing after decellularization. The data are supplemental to our original research article describing detailed associations of pM-ECM as a clinically relevant scale, three-dimensional scaffold with a vascular network template for tissue-specific regeneration, “Perfusion-decellularized skeletal muscle as a three-dimensional scaffold with a vascular network template” Zhang et al. (2016) [1]. PMID:27158653

  12. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  13. Procedure for decellularization of porcine heart by retrograde coronary perfusion.

    PubMed

    Remlinger, Nathaniel T; Wearden, Peter D; Gilbert, Thomas W

    2012-12-06

    Perfusion-based whole organ decellularization has recently gained interest in the field of tissue engineering as a means to create site-specific extracellular matrix scaffolds, while largely preserving the native architecture of the scaffold. To date, this approach has been utilized in a variety of organ systems, including the heart, lung, and liver (1-5). Previous decellularization methods for tissues without an easily accessible vascular network have relied upon prolonged exposure of tissue to solutions of detergents, acids, or enzymatic treatments as a means to remove the cellular and nuclear components from the surrounding extracellular environment(6-8). However, the effectiveness of these methods hinged upon the ability of the solutions to permeate the tissue via diffusion. In contrast, perfusion of organs through the natural vascular system effectively reduced the diffusion distance and facilitated transport of decellularization agents into the tissue and cellular components out of the tissue. Herein, we describe a method to fully decellularize an intact porcine heart through coronary retrograde perfusion. The protocol yielded a fully decellularized cardiac extracellular matrix (c-ECM) scaffold with the three-dimensional structure of the heart intact. Our method used a series of enzymes, detergents, and acids coupled with hypertonic and hypotonic rinses to aid in the lysis and removal of cells. The protocol used a Trypsin solution to detach cells from the matrix followed by Triton X-100 and sodium deoxycholate solutions to aid in removal of cellular material. The described protocol also uses perfusion speeds of greater than 2 L/min for extended periods of time. The high flow rate, coupled with solution changes allowed transport of agents to the tissue without contamination of cellular debris and ensured effective rinsing of the tissue. The described method removed all nuclear material from native porcine cardiac tissue, creating a site-specific cardiac ECM

  14. 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...

  15. Adenosine thallium 201 myocardial perfusion scintigraphy

    SciTech Connect

    Verani, M.S. )

    1991-07-01

    Pharmacologic coronary vasodilation as an adjunct to myocardial perfusion imaging has become increasingly important in the evaluation of patients with coronary artery disease, in view of the large number of patients who cannot perform an adequate exercise test or in whom contraindications render exercise inappropriate. Adenosine is a very potent coronary vasodilator and when combined with thallium 201 scintigraphy produces images of high quality, with the added advantages of a very short half-life (less than 10 seconds) and the ability to adjust the dose during the infusion, which may enhance safety and curtail the duration of side effects. The reported sensitivity and specificity of adenosine thallium 201 scintigraphy for the detection of coronary artery disease are high and at least comparable with imaging after exercise or dipyridamole administration. 23 refs.

  16. Cerebral-Body Perfusion Model

    DTIC Science & Technology

    1990-07-01

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

  17. Serum thyroglobulin reference intervals in regions with adequate and more than adequate iodine intake.

    PubMed

    Wang, Zhaojun; Zhang, Hanyi; Zhang, Xiaowen; Sun, Jie; Han, Cheng; Li, Chenyan; Li, Yongze; Teng, Xiaochun; Fan, Chenling; Liu, Aihua; Shan, Zhongyan; Liu, Chao; Weng, Jianping; Teng, Weiping

    2016-11-01

    The purpose of this study was to establish normal thyroglobulin (Tg) reference intervals (RIs) in regions with adequate and more than adequate iodine intake according to the National Academy of Clinical Biochemistry (NACB) guidelines and to investigate the relationships between Tg and other factors.A total of 1317 thyroid disease-free adult subjects (578 men, 739 nonpregnant women) from 2 cities (Guangzhou and Nanjing) were enrolled in this retrospective, observational study. Each subject completed a questionnaire and underwent physical and ultrasonic examination. Serum Tg, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), Tg antibody (TgAb), and urinary iodine concentration (UIC) were measured. Reference groups were established on the basis of TSH levels: 0.5 to 2.0 and 0.27 to 4.2 mIU/L.The Tg RIs for Guangzhou and Nanjing were 1.6 to 30.0 and 1.9 to 25.8 ng/mL, respectively. No significant differences in Tg were found between genders or among different reference groups. Stepwise linear regression analyses showed that TgAb, thyroid volume, goiter, gender, age, and TSH levels were correlated with Tg.In adults from regions with adequate and more than adequate iodine intake, we found that Tg may be a suitable marker of iodine status; gender-specific Tg RI was unnecessary; there was no difference between Tg RIs in regions with adequate and more than adequate iodine intake; and the TSH criterion for selecting the Tg reference population could follow the local TSH reference rather than 0.5 to 2.0 mIU/L.

  18. Serum thyroglobulin reference intervals in regions with adequate and more than adequate iodine intake

    PubMed Central

    Wang, Zhaojun; Zhang, Hanyi; Zhang, Xiaowen; Sun, Jie; Han, Cheng; Li, Chenyan; Li, Yongze; Teng, Xiaochun; Fan, Chenling; Liu, Aihua; Shan, Zhongyan; Liu, Chao; Weng, Jianping; Teng, Weiping

    2016-01-01

    Abstract The purpose of this study was to establish normal thyroglobulin (Tg) reference intervals (RIs) in regions with adequate and more than adequate iodine intake according to the National Academy of Clinical Biochemistry (NACB) guidelines and to investigate the relationships between Tg and other factors. A total of 1317 thyroid disease-free adult subjects (578 men, 739 nonpregnant women) from 2 cities (Guangzhou and Nanjing) were enrolled in this retrospective, observational study. Each subject completed a questionnaire and underwent physical and ultrasonic examination. Serum Tg, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), Tg antibody (TgAb), and urinary iodine concentration (UIC) were measured. Reference groups were established on the basis of TSH levels: 0.5 to 2.0 and 0.27 to 4.2 mIU/L. The Tg RIs for Guangzhou and Nanjing were 1.6 to 30.0 and 1.9 to 25.8 ng/mL, respectively. No significant differences in Tg were found between genders or among different reference groups. Stepwise linear regression analyses showed that TgAb, thyroid volume, goiter, gender, age, and TSH levels were correlated with Tg. In adults from regions with adequate and more than adequate iodine intake, we found that Tg may be a suitable marker of iodine status; gender-specific Tg RI was unnecessary; there was no difference between Tg RIs in regions with adequate and more than adequate iodine intake; and the TSH criterion for selecting the Tg reference population could follow the local TSH reference rather than 0.5 to 2.0 mIU/L. PMID:27902589

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

    PubMed

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

    1983-10-31

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

  20. Blue laser light increases perfusion of a skin flap via release of nitric oxide from hemoglobin.

    PubMed

    Mittermayr, Rainer; Osipov, Anatoly; Piskernik, Christina; Haindl, Susanne; Dungel, Peter; Weber, Carina; Vladimirov, Yuri A; Redl, Heinz; Kozlov, Andrey V

    2007-01-01

    It has recently been shown that nitrosyl complexes of hemoglobin (NO-Hb) are sensitive to low-level blue laser irradiation, suggesting that laser irradiation can facilitate the release of biologically active nitric oxide (NO), which can affect tissue perfusion. The aim of this study was to evaluate the therapeutic value of blue laser irradiation for local tissue perfusion after surgical intervention. Blood was withdrawn from a rat, exposed to NO and infused back to the same rat or used for in vitro experiments. In vitro, an increase of NO-Hb levels (electron paramagnetic resonance spectroscopy) up to 15 microM in rat blood did not result in the release of detectable amounts of NO (NO selective electrode). Blue laser irradiation of NO-Hb in blood caused decomposition of NO-Hb complexes and release of free NO. Systemic infusion of NO-Hb in rats affected neither systemic circulation (mean arterial pressure) nor local tissue perfusion (Doppler blood flow imaging system). In contrast, a clear enhancement of local tissue perfusion was observed in epigastric flap when elevated NO-Hb levels in blood were combined with local He-Cd laser irradiation focused on the left epigastric artery. The enhancement of regional tissue perfusion was not accompanied by any detectable changes in systemic circulation. This study demonstrates that blue laser irradiation improves local tissue perfusion in a controlled manner stimulating NO release from NO-Hb complexes.

  1. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... JavaScript. A pulmonary ventilation/perfusion scan involves two nuclear scan tests to measure breathing (ventilation) and circulation ( ... In: Mettler FA, Guiberteau MJ, eds. Essentials of Nuclear Medicine Imaging . 6th ed. Philadelphia, PA: Elsevier Saunders; ...

  2. Modelling Brain Temperature and Perfusion for Cerebral Cooling

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  3. Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times.

    PubMed

    Farnebo, Simon; Thorfinn, Johan; Henricson, Joakim; Tesselaar, Erik

    2010-12-01

    Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r=0.80; RBC concentration: r=0.94). This correlation increases with longer occlusion durations (1, 5 and 10min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2)=0.59; RBC concentration: r(2)=0.78) and the recovery times (perfusion: r(2)=0.62; RBC concentration: r(2)=0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.

  4. Parametric perfusion imaging based on low-cost ultrasound platform.

    PubMed

    Gu, Xiaolin; Zhong, Hui; Wan, Mingxi; Hu, Xiaowen; Lv, Dan; Shen, Liang; Zhang, Xiaomei

    2010-01-01

    In this study, we attempted to implement parametric perfusion imaging to quantify blood perfusion based on modified low-cost ultrasound platform. A novel ultrasound contrast-specific imaging method called pulse-inversion harmonic sum-squared-differences (PIHSSD) was proposed for improving the sensitivity for detecting contrast agents and the accuracy of parametric perfusion imaging, which combined pulse-inversion harmonic (PIH) with pulse-inversion sum-squared-differences (PISSD) threshold-based decision. PIHSSD method just involved simple operations including addition and multiplication and was easy to realize. The sequences of contrast images without logarithmic compression were used to acquire time intensity curves (TICs) from numerous equal-sized regions-of-interest (ROI) covering the entire image plane. Parametric perfusion images were obtained based on the parameters extracted from the TICs, including peak value (PV), area under curve (AUC), mean transit time (MTT), peak value time (PVT), peak width (PW) and climbing rate (CR). Flow phantom was used for validation and the results suggested that PIHSSD method provided 9.6 to 20.3 dB higher contrast-to-tissue ratio (CTR) than PIH method. The results of the experiments of rabbit kidney also showed that the CTR of PIHSSD images was higher than that of PIH images, and the parametric perfusion images based on PIHSSD method provided more accurate quantification of blood perfusion compared with those based on PIH and PISSD methods. It demonstrated that the parametric perfusion imaging achieved good performance though implemented on low-cost ultrasound platform. (E-mail: mxwan@mail.xjtu.edu.cn).

  5. 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

  6. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  7. Modelling of temperature and perfusion during scalp cooling.

    PubMed

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

    2005-09-07

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

  8. 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.

  9. Adequate mathematical modelling of environmental processes

    NASA Astrophysics Data System (ADS)

    Chashechkin, Yu. D.

    2012-04-01

    In environmental observations and laboratory visualization both large scale flow components like currents, jets, vortices, waves and a fine structure are registered (different examples are given). The conventional mathematical modeling both analytical and numerical is directed mostly on description of energetically important flow components. The role of a fine structures is still remains obscured. A variety of existing models makes it difficult to choose the most adequate and to estimate mutual assessment of their degree of correspondence. The goal of the talk is to give scrutiny analysis of kinematics and dynamics of flows. A difference between the concept of "motion" as transformation of vector space into itself with a distance conservation and the concept of "flow" as displacement and rotation of deformable "fluid particles" is underlined. Basic physical quantities of the flow that are density, momentum, energy (entropy) and admixture concentration are selected as physical parameters defined by the fundamental set which includes differential D'Alembert, Navier-Stokes, Fourier's and/or Fick's equations and closing equation of state. All of them are observable and independent. Calculations of continuous Lie groups shown that only the fundamental set is characterized by the ten-parametric Galilelian groups reflecting based principles of mechanics. Presented analysis demonstrates that conventionally used approximations dramatically change the symmetries of the governing equations sets which leads to their incompatibility or even degeneration. The fundamental set is analyzed taking into account condition of compatibility. A high order of the set indicated on complex structure of complete solutions corresponding to physical structure of real flows. Analytical solutions of a number problems including flows induced by diffusion on topography, generation of the periodic internal waves a compact sources in week-dissipative media as well as numerical solutions of the same

  10. Rate of change in central corneal thickness: a viability indicator for conventional drainage tissues in organ culture.

    PubMed

    Wan, Z; Brigatti, L; Ranger-Moore, J; Ethier, C R; Stamer, W D

    2006-06-01

    Organ culture of human anterior segments is a powerful tool for understanding trabecular meshwork biology. However, data from a significant percentage of cultured anterior segments are unusable because tissues fail to meet quality control requirements, such as having adequate trabecular meshwork histology. The purpose of the present study was to evaluate a novel, real time method for assessing the viability of conventional drainage tissues in the human anterior segment perfusion model. Twenty-two human anterior segments were perfusion cultured using standard techniques for one week while measuring outflow facility and central corneal thickness (CCT). After perfusion-fixation, toludine blue-stained histological sections of drainage tissues from all four quadrants of each anterior segment were graded and endothelial cell nuclei from cornea centers were stained with 4',6-diamidino-2-phenylindole and counted. We found that most anterior segments with a stable outflow facility had a CCT that decreased over time, while anterior segments with an unstable outflow facility had CCT measurements that failed to decrease over time (P<0.01). When comparing CCT measurements to histological appearance of outflow tissues, we found that in 11/11 cases, anterior segments with an acceptable histological score had a negative CCT slope (P<0.01). Conversely in 3/4 instances, anterior segments with an unacceptable histological score had a positive CCT slope. Lastly, we observed a significant relationship between CCT measurements and corneal endothelial density (P<0.01). Thus, the simple procedure of measuring CCT during anterior segment perfusion provides a second useful measure to assess the viability of the anterior segment during the perfusion process.

  11. Use of the new preservation solution Custodiol-N supplemented with dextran for hypothermic machine perfusion of the kidney.

    PubMed

    Gallinat, Anja; Lüer, Bastian; Swoboda, Sandra; Rauen, Ursula; Paul, Andreas; Minor, Thomas

    2013-04-01

    Custodiol-N is a new preservation solution specifically designed to prevent free radical-induced tissue alterations and to protect vascular integrity of the graft. Thus, Custodiol-N appears particularly suitable as base solution for oxygenated machine preservation and its putative benefit for renal preservation by hypothermic machine perfusion (HMP) was investigated using a porcine in vitro model. Kidneys were retrieved from German Landrace pigs and preserved for 20 h by pulsatile oxygenated HMP on a Lifeport kidney transporter (syst. pressure 30 mmHg, 30cycles/min). Each graft was randomly assigned to the use of one of the following preservation solutions: Custodiol-N solution supplemented with 50 g/l dextran 40 (CND) or kidney perfusion solution 1 (KPS-1). Renal viability was evaluated upon reperfusion in vitro with diluted autologous blood from the donor for 120 min at 37°C. After 2h of postischemic reperfusion CND-preserved kidneys exhibited significantly higher renal blood flow and urine production. Oxygen consumption was also higher in the CND group than in KPS-1 kidneys. Clearance of creatinine increased during reperfusion of CND kidneys but declined in KPS-1 grafts ending in significantly higher values in CND kidneys. No differences between the groups were seen for enzyme release or fractional excretion of sodium. In conclusion the data presented provide first experimental evidence for adequate organ protective potential of CND in HMP as compared to the gold standard KPS-KPS-11.

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

    PubMed Central

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

    2016-01-01

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

  13. Dynamic CT head phantom for perfusion and angiography studies

    NASA Astrophysics Data System (ADS)

    Russell, K.; Blazeski, A.; Dannecker, K.; Lee, Q. Y.; Holscher, C.; Donahue, C.; van Kampen, W.

    2010-03-01

    Contrast imaging is a compelling enhancement for the portable, flat panel-based brain CT scanner currently under development at Xoran. Due to the relative low temporal resolution of flat panel detectors, enabling tomographic imaging on such platform requires optimizing the imaging and injection protocols. A dynamic CT head phantom was designed to facilitate this task. The Dynamic Perfusion and Angiography Model (PAM), mimics tissue attenuation in CT images, provides physiological timing for angiography and perfusion studies, and moves fluid with properties similar to those of blood. The design consists of an arterial system, which contains bifurcating vessels that feed into perfusion chambers, mimicking blood flow through capillaries and smaller vessels, and a venous system, which is symmetrical to the arterial side and drains the perfusion chambers. The variation of geometry and flow rate in the phantom provides the physiological total time that fluid spends in the head, and the difference in material densities correlates to CT numbers for biological tissues. This paper discusses the design of Dynamic PAM and shows experimental results demonstrating its ability to realistically simulate blood flow. Results of dynamic imaging studies of the phantom are also presented.

  14. Measuring blood delivery to solitary pulmonary nodules using perfusion magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Wang, Zhifeng; Shen, Li; Gao, Ling; Ford, James C.; Makedon, Fillia S.; Pearlman, Justin D.

    2006-03-01

    With perfusion magnetic resonance imaging (pMRI), perfusion describes the amount of blood passing through a block of tissue in a certain period of time. In pMRI, the tissue having more blood passing through will show higher intensity value as more contrast-labeled blood arrives. Perfusion reflects the delivery of essential nutrients to a block of tissue, and is an important parameter for the tissue status. Considering solitary pulmonary nodules (SPN), perfusion differences between malignant and benign nodules have been studied by different techniques. Much effort has been put into its characterization. In this paper, we proposed and implemented extraction of the SPN time intensity profile to measure blood delivery to solitary pulmonary nodules, describing their perfusion effects. In this method, a SPN time intensity profile is created based on intensity values of the solitary pulmonary nodule in lung pMRI images over time. This method has two steps: nodule tracking and profile clustering. Nodule tracking aligns the solitary pulmonary nodule in pMRI images taken at different time points, dealing with nodule movement resulted from breathing and body movement. Profile clustering implements segmentation of the nodule region and extraction of the time intensity profile of a solitary pulmonary nodule. SPN time intensity profiles reflect patterns of blood delivery to solitary pulmonary nodules, giving us a description of perfusion effect and indirect evidence of tumor angiogenesis. Analysis on SPN time intensity profiles will help the diagnosis of malignant nodules for early lung cancer detection.

  15. Evaluation of Feline Renal Perfusion with Contrast-Enhanced Ultrasonography and Scintigraphy

    PubMed Central

    Vanderperren, Katrien; Bosmans, Tim; Dobbeleir, André; Duchateau, Luc; Hesta, Myriam; Lybaert, Lien; Peremans, Kathelijne; Vandermeulen, Eva; Saunders, Jimmy

    2016-01-01

    Contrast-enhanced ultrasound (CEUS) is an emerging technique to evaluate tissue perfusion. Promising results have been obtained in the evaluation of renal perfusion in health and disease, both in human and veterinary medicine. Renal scintigraphy using 99mTc-Mercaptoacetyltriglycine (MAG3) is another non-invasive technique that can be used to evaluate renal perfusion. However, no data are available on the ability of CEUS or 99mTc- MAG3 scintigraphy to detect small changes in renal perfusion in cats. Therefore, both techniques were applied in a normal feline population to evaluate detection possibilities of perfusion changes by angiotensin II (AT II). Contrast-enhanced ultrasound using a bolus injection of commercially available contrast agent and renal scintigraphy using 99mTc-MAG3 were performed in 11 healthy cats after infusion of 0,9% NaCl (control) and AT II. Angiotensin II induced changes were noticed on several CEUS parameters. Mean peak enhancement, wash-in perfusion index and wash-out rate for the entire kidney decreased significantly after AT II infusion. Moreover, a tendency towards a lower wash-in area-under-the curve was present. Renal scintigraphy could not detect perfusion changes induced by AT II. This study shows that CEUS is able to detect changes in feline renal perfusion induced by AT II infusion. PMID:27736928

  16. Viable neurons with luxury perfusion in hydrocephalus.

    PubMed

    Wong, C Y; Luciano, M G; MacIntyre, W J; Brunken, R C; Hahn, J F; Go, R T

    1997-09-01

    A woman with hydrocephalus due to aqueductal stenosis had functional imaging of cerebral perfusion and metabolism to demonstrate the effects of endoscopic third ventriculostomy--a new form of internal surgical shunting. Technetium-99m-ECD SPECT and 18F-FDG PET showed regional luxury perfusion at the left frontal region. Three months after a successful third ventriculostomy, a repeated imaging of cerebral perfusion and metabolism showed resolution of luxury perfusion and global improvement of both perfusion and metabolism. This concurred with postoperative clinical improvement. The paired imaging of cerebral perfusion and metabolism provides more information than just imaging perfusion or metabolism. Thus, the detection of perfusion and metabolism mismatch may open a new window of opportunity for surgical intervention.

  17. A New Apparatus and Surgical Technique for the Dual Perfusion of Human Tumor Xenografts in Situ in Nude Rats

    PubMed Central

    Dauchy, Robert T; Dauchy, Erin M; Mao, Lulu; Belancio, Victoria P; Hill, Steven M; Blask, David E

    2012-01-01

    We present a new perfusion system and surgical technique for simultaneous perfusion of 2 tissue-isolated human cancer xenografts in nude rats by using donor blood that preserves a continuous flow. Adult, athymic nude rats (Hsd:RH-Foxn1rnu) were implanted with HeLa human cervical or HT29 colon adenocarcinomas and grown as tissue-isolated xenografts. When tumors reached an estimated weight of 5 to 6 g, rats were prepared for perfusion with donor blood and arteriovenous measurements. The surgical procedure required approximately 20 min to complete for each tumor, and tumors were perfused for a period of 150 min. Results showed that tumor venous blood flow, glucose uptake, lactic acid release, O2 uptake and CO2 production, uptake of total fatty acid and linoleic acid and conversion to the mitogen 13-HODE, cAMP levels, and activation of several marker kinases were all well within the normal physiologic, metabolic, and signaling parameters characteristic of individually perfused xenografts. This new perfusion system and technique reduced procedure time by more than 50%. These findings demonstrate that 2 human tumors can be perfused simultaneously in situ or ex vivo by using either rodent or human blood and suggest that the system may also be adapted for use in the dual perfusion of other organs. Advantages of this dual perfusion technique include decreased anesthesia time, decreased surgical manipulation, and increased efficiency, thereby potentially reducing the numbers of laboratory animals required for scientific investigations. PMID:22546915

  18. Framework for cognitive analysis of dynamic perfusion computed tomography with visualization of large volumetric data

    NASA Astrophysics Data System (ADS)

    Hachaj, Tomasz; Ogiela, Marek R.

    2012-10-01

    The proposed framework for cognitive analysis of perfusion computed tomography images is a fusion of image processing, pattern recognition, and image analysis procedures. The output data of the algorithm consists of: regions of perfusion abnormalities, anatomy atlas description of brain tissues, measures of perfusion parameters, and prognosis for infracted tissues. That information is superimposed onto volumetric computed tomography data and displayed to radiologists. Our rendering algorithm enables rendering large volumes on off-the-shelf hardware. This portability of rendering solution is very important because our framework can be run without using expensive dedicated hardware. The other important factors are theoretically unlimited size of rendered volume and possibility of trading of image quality for rendering speed. Such rendered, high quality visualizations may be further used for intelligent brain perfusion abnormality identification, and computer aided-diagnosis of selected types of pathologies.

  19. Understanding the pelvic pain mechanism is key to find an adequate therapeutic approach.

    PubMed

    Van Kerrebroeck, Philip

    2016-06-25

    Pain is a natural mechanism to actual or potential tissue damage and involves both a sensory and an emotional experience. In chronic pelvic pain, localisation of pain can be widespread and can cause considerable distress. A multidisciplinary approach is needed in order to fully understand the pelvic pain mechanism and to identify an adequate therapeutic approach.

  20. Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin

    NASA Astrophysics Data System (ADS)

    Chin, Michael S.; Freniere, Brian B.; Lo, Yuan-Chyuan; Saleeby, Jonathan H.; Baker, Stephen P.; Strom, Heather M.; Ignotz, Ronald A.; Lalikos, Janice F.; Fitzgerald, Thomas J.

    2012-02-01

    Studies examining acute oxygenation and perfusion changes in irradiated skin are limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance spectroscopy, provides noninvasive, quantified measurements of cutaneous oxygenation and perfusion. This study examines whether HSI can assess acute changes in oxygenation and perfusion following irradiation. Skin on both flanks of nude mice (n=20) was exposed to 50 Gy of beta radiation from a strontium-90 source. Hyperspectral images were obtained before irradiation and on selected days for three weeks. Skin reaction assessment was performed concurrently with HSI. Desquamative injury formed in all irradiated areas. Skin reactions were first seen on day 7, with peak formation on day 14, and resolution beginning by day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous changes were observed (p<0.001). Further increases over baseline were seen on day 14, but returned to baseline levels by day 21. For perfusion, similar increases were seen on days 1 and 14. Unlike tissue oxygenation, perfusion was decreased below baseline on day 21 (p<0.002). HSI allows for complete visualization and quantification of tissue oxygenation and perfusion changes in irradiated skin, and may also allow prediction of acute skin reactions based on early changes seen after irradiation.

  1. Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin.

    PubMed

    Chin, Michael S; Freniere, Brian B; Lo, Yuan-Chyuan; Saleeby, Jonathan H; Baker, Stephen P; Strom, Heather M; Ignotz, Ronald A; Lalikos, Janice F; Fitzgerald, Thomas J

    2012-02-01

    Studies examining acute oxygenation and perfusion changes in irradiated skin are limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance spectroscopy, provides noninvasive, quantified measurements of cutaneous oxygenation and perfusion. This study examines whether HSI can assess acute changes in oxygenation and perfusion following irradiation. Skin on both flanks of nude mice (n=20) was exposed to 50 Gy of beta radiation from a strontium-90 source. Hyperspectral images were obtained before irradiation and on selected days for three weeks. Skin reaction assessment was performed concurrently with HSI. Desquamative injury formed in all irradiated areas. Skin reactions were first seen on day 7, with peak formation on day 14, and resolution beginning by day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous changes were observed (p<0.001). Further increases over baseline were seen on day 14, but returned to baseline levels by day 21. For perfusion, similar increases were seen on days 1 and 14. Unlike tissue oxygenation, perfusion was decreased below baseline on day 21 (p<0.002). HSI allows for complete visualization and quantification of tissue oxygenation and perfusion changes in irradiated skin, and may also allow prediction of acute skin reactions based on early changes seen after irradiation.

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

    PubMed

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

    2012-06-01

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

  3. Molecular and Cellular Basis of Microvascular Perfusion Deficits Induced by Clostridium perfringens and Clostridium septicum

    PubMed Central

    Hickey, Michael J.; Kwan, Rain Y. Q.; Awad, Milena M.; Kennedy, Catherine L.; Young, Lauren F.; Hall, Pam; Cordner, Leanne M.; Lyras, Dena; Emmins, John J.; Rood, Julian I.

    2008-01-01

    Reduced tissue perfusion leading to tissue ischemia is a central component of the pathogenesis of myonecrosis caused by Clostridium perfringens. The C. perfringens α-toxin has been shown capable of inducing these changes, but its potential synergy with perfringolysin O (θ-toxin) is less well understood. Similarly, Clostridium septicum is a highly virulent causative agent of spontaneous gas gangrene, but its effect on the microcirculation has not been examined. Therefore, the aim of this study was to use intravital microscopy to examine the effects of C. perfringens and C. septicum on the functional microcirculation, coupled with the use of isogenic toxin mutants to elucidate the role of particular toxins in the resultant microvascular perfusion deficits. This study represents the first time this integrated approach has been used in the analysis of the pathological response to clostridial toxins. Culture supernatants from wild-type C. perfringens induced extensive cell death within 30 min, as assessed by in vivo uptake of propidium iodide. Furthermore, significant reductions in capillary perfusion were observed within 60 min. Depletion of either platelets or neutrophils reduced the alteration in perfusion, consistent with a role for these blood-borne cells in obstructing perfusion. In addition, mutation of either the α-toxin or perfringolysin O structural genes attenuated the reduction in perfusion, a process that was reversed by genetic complementation. C. septicum also induced a marked reduction in perfusion, with the degree of microvascular compromise correlating with the level of the C. septicum α-toxin. Together, these data indicate that as a result of its ability to produce α-toxin and perfringolysin O, C. perfringens rapidly induces irreversible cellular injury and a marked reduction in microvascular perfusion. Since C. septicum induces a similar reduction in microvascular perfusion, it is postulated that this function is central to the pathogenesis of

  4. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

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

    PubMed Central

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

    2016-01-01

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

  6. 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.

  7. Intrahemispheric Perfusion in Chronic Stroke-Induced Aphasia

    PubMed Central

    Walenski, Matthew; Chen, YuFen; Caplan, David; Rapp, Brenda; Grunewald, Kristin; Nunez, Mia; Zinbarg, Richard; Parrish, Todd B.

    2017-01-01

    Stroke-induced alterations in cerebral blood flow (perfusion) may contribute to functional language impairments and recovery in chronic aphasia. Using MRI, we examined perfusion in the right and left hemispheres of 35 aphasic and 16 healthy control participants. Across 76 regions (38 per hemisphere), no significant between-subjects differences were found in the left, whereas blood flow in the right was increased in the aphasic compared to the control participants. Region-of-interest (ROI) analyses showed a varied pattern of hypo- and hyperperfused regions across hemispheres in the aphasic participants; however, there were no significant correlations between perfusion values and language abilities in these regions. These patterns may reflect autoregulatory changes in blood flow following stroke and/or increases in general cognitive effort, rather than maladaptive language processing. We also examined blood flow in perilesional tissue, finding the greatest hypoperfusion close to the lesion (within 0–6 mm), with greater hypoperfusion in this region compared to more distal regions. In addition, hypoperfusion in this region was significantly correlated with language impairment. These findings underscore the need to consider cerebral perfusion as a factor contributing to language deficits in chronic aphasia as well as recovery of language function. PMID:28357141

  8. 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.

  9. Integration of hollow fiber membranes improves nutrient supply in three-dimensional tissue constructs.

    PubMed

    Bettahalli, N M S; Vicente, J; Moroni, L; Higuera, G A; van Blitterswijk, C A; Wessling, M; Stamatialis, D F

    2011-09-01

    Sufficient nutrient and oxygen transport is a potent modulator of cell proliferation in in vitro tissue-engineered constructs. The lack of oxygen and culture medium can create a potentially lethal environment and limit cellular metabolic activity and growth. Diffusion through scaffold and multi-cellular tissue typically limits transport in vitro, leading to potential hypoxic regions and reduction in the viable tissue thickness. For the in vitro generation of clinically relevant tissue-engineered grafts, current nutrient diffusion limitations should be addressed. Major approaches to overcoming these include culture with bioreactors, scaffolds with artificial microvasculature, oxygen carriers and pre-vascularization of the engineered tissues. This study focuses on the development and utilization of a new perfusion culture system to provide adequate nutrient delivery to cells within large three-dimensional (3D) scaffolds. Perfusion of oxygenated culture medium through porous hollow fiber (HF) integrated within 3D free form fabricated (FFF) scaffolds is proposed. Mouse pre-myoblast (C2C12) cells cultured on scaffolds of poly(ethylene-oxide-terephthalate)-poly(butylene-terephthalate) block copolymer (300PEOT55PBT45) integrated with porous HF membranes of modified poly(ether-sulfone) (mPES, Gambro GmbH) is used as a model system. Various parameters such as fiber transport properties, fiber spacing within a scaffold and medium flow conditions are optimized. The results show that four HF membranes integrated with the scaffold significantly improve the cell density and cell distribution. This study provides a basis for the development of a new HF perfusion culture methodology to overcome the limitations of nutrient diffusion in the culture of large 3D tissue constructs.

  10. Drug effects on functional structures in isolated perfused pig heart

    NASA Astrophysics Data System (ADS)

    Trinks, Tobias; Rauh, Robert; Hiller, Michael; Kessler, Manfred D.

    2002-06-01

    Until today monitoring of immediate drug tissue interaction in living organs is an unsolved problem. However, for the development of new drugs and the improvement of medical therapy outcome it would be helpful to get new tools to visualize drug effects on tissue directly. With the EMPHO II SSK and a 3D-scanning device we detected changes of functional structures in an isolated perfused pig heart model after adding commonly used drugs like verapamil, nitroglycerin and salviae miltiorrhizae (Chinese herbal drug). In the paper the results are presented.

  11. 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.

  12. Early Support of Intracranial Perfusion

    DTIC Science & Technology

    2013-10-01

    automated real-time vital signs monitoring data” was funded by USAF (MSA); UM PI: Deborah Stein  The project, titled “Noninvasive intracranial pressure ...scoring of cerebral perfusion pressure and intracranial pressure provides a Brain Trauma Index that predicts outcome in patients with severe TBI... intracranial pressure dose index: Dynamic 3-D scoring in the assessment of Traumatic Brain Injury Proceedings of American Association for the Surgery of

  13. 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

  14. 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.

  15. Whole-organ perfusion of the pancreas using dynamic volume CT in patients with primary pancreas carcinoma: acquisition technique, post-processing and initial results.

    PubMed

    Kandel, Sonja; Kloeters, Christian; Meyer, Henning; Hein, Patrick; Hilbig, Andreas; Rogalla, Patrik

    2009-11-01

    The purpose of this study was to evaluate a whole-organ perfusion protocol of the pancreas in patients with primary pancreas carcinoma and to analyse perfusion differences between normal and diseased pancreatic tissue. Thirty patients with primary pancreatic malignancy were imaged on a 320-slice CT unit. Twenty-nine cancers were histologically proven. CT data acquisition was started manually after contrast-material injection (8 ml/s, 350 mg iodine/ml) and dynamic density measurements in the right ventricle. After image registration, perfusion was determined with the gradient-relationship technique and volume regions-of-interest were defined for perfusion measurements. Contrast time-density curves and perfusion maps were generated. Statistical analysis was performed using the Kolmogorov-Smirnov test for analysis of normal distribution and Kruskal-Wallis test (nonparametric ANOVA) with Bonferroni correction for multiple stacked comparisons. In all 30 patients the entire pancreas was imaged, and registration could be completed in all cases. Perfusion of pancreatic carcinomas was significantly lower than of normal pancreatic tissue (P < 0.001) and could be visualized on colored perfusion maps. The 320-slice CT allows complete dynamic visualization of the pancreas and enables calculation of whole-organ perfusion maps. Perfusion imaging carries the potential to improve detection of pancreatic cancers due to the perfusion differences.

  16. Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations

    SciTech Connect

    Hirayama, H.; Xu, X.; Pang, K.S. )

    1989-08-01

    Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid ({sup 14}C)glucose absorption against a concentration gradient and a lack of ({sup 3}H)-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.

  17. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Adequate file search. 716.25 Section 716.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of...

  18. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Adequate file search. 716.25 Section 716.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of...

  19. "Something Adequate"? In Memoriam Seamus Heaney, Sister Quinlan, Nirbhaya

    ERIC Educational Resources Information Center

    Parker, Jan

    2014-01-01

    Seamus Heaney talked of poetry's responsibility to represent the "bloody miracle", the "terrible beauty" of atrocity; to create "something adequate". This article asks, what is adequate to the burning and eating of a nun and the murderous gang rape and evisceration of a medical student? It considers Njabulo Ndebele's…

  20. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  1. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  2. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  3. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  4. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  5. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  6. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  7. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  8. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  9. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  10. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  11. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

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

    PubMed

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

    2011-10-01

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

  13. Perfusion measurements by micro-CT using prior image constrained compressed sensing (PICCS): initial phantom results.

    PubMed

    Nett, Brian E; Brauweiler, Robert; Kalender, Willi; Rowley, Howard; Chen, Guang-Hong

    2010-04-21

    Micro-CT scanning has become an accepted standard for anatomical imaging in small animal disease and genome mutation models. Concurrently, perfusion imaging via tracking contrast dynamics after injection of an iodinated contrast agent is a well-established tool for clinical CT scanners. However, perfusion imaging is not yet commercially available on the micro-CT platform due to limitations in both radiation dose and temporal resolution. Recent hardware developments in micro-CT scanners enable continuous imaging of a given volume through the use of a slip-ring gantry. Now that dynamic CT imaging is feasible, data may be acquired to measure tissue perfusion using a micro-CT scanner (CT Imaging, Erlangen, Germany). However, rapid imaging using micro-CT scanners leads to high image noise in individual time frames. Using the standard filtered backprojection (FBP) image reconstruction, images are prohibitively noisy for calculation of voxel-by-voxel perfusion maps. In this study, we apply prior image constrained compressed sensing (PICCS) to reconstruct images with significantly lower noise variance. In perfusion phantom experiments performed on a micro-CT scanner, the PICCS reconstruction enabled a reduction to 1/16 of the noise variance of standard FBP reconstruction, without compromising the spatial or temporal resolution. This enables a significant increase in dose efficiency, and thus, significantly less exposure time is needed to acquire images amenable to perfusion processing. This reduction in required irradiation time enables voxel-by-voxel perfusion maps to be generated on micro-CT scanners. Sample perfusion maps using a deconvolution-based perfusion analysis are included to demonstrate the improvement in image quality using the PICCS algorithm.

  14. Advanced Techniques in Musculoskeletal Oncology: Perfusion, Diffusion, and Spectroscopy.

    PubMed

    Teixeira, Pedro A Gondim; Beaumont, Marine; Gabriela, Hossu; Bailiang, Chen; Verhaeghe, Jean-luc; Sirveaux, François; Blum, Alain

    2015-12-01

    The imaging characterization of musculoskeletal tumors can be challenging, and a significant number of lesions remain indeterminate when conventional imaging protocols are used. In recent years, clinical availability of functional imaging methods has increased. Functional imaging has the potential to improve tumor detection, characterization, and follow-up. The most frequently used functional methods are perfusion imaging, diffusion-weighted imaging (DWI), and MR proton spectroscopy (MRS). Each of these techniques has specific protocol requirements and diagnostic pitfalls that need to be acknowledged to avoid misdiagnoses. Additionally, the application of functional methods in the MSK system has various technical issues that need to be addressed to ensure data quality and comparability. In this article, the application of contrast-enhanced perfusion imaging, DWI, and MRS for the evaluation of bone and soft tissue tumors is discussed, with emphasis on acquisition protocols, technical difficulties, and current clinical indications.

  15. Scalable Approach for Extrusion and Perfusion of Tubular, Heterotypic Biomaterials

    NASA Astrophysics Data System (ADS)

    Jeronimo, Mark David

    Soft material tubes are critical in the vasculature of mammalian tissues, forming networks of blood vessels and airways. Homogeneous and heterogeneous hydrogel tubes were extruded in a one-step process using a three layer microfluidic device. Co-axial cylindrical flow of crosslinking solutions and an alginate matrix is generated by a radial arrangement of microfluidic channels at the device's vertical extrusion outlet. The flow is confined and begins a sol-gel transition immediately as it extrudes at velocities upwards of 4 mm/s. This approach allows for predictive control over the dimensions of the rapidly formed tubular structures for outer diameters from 600 microm to 3 mm. A second microfluidic device hosts tube segments for controlled perfusion and pressurization using a reversible vacuum seal. On-chip tube deflection is observed and modeled as a measure of material compliance and circumferential elasticity. I anticipate applications of these devices for perfusion cell culture of cell-laden hydrogel tubes.

  16. ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

    PubMed Central

    Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

    2012-01-01

    Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

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

    SciTech Connect

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

    2013-01-01

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

  18. Region 9: Arizona Adequate Letter (10/14/2003)

    EPA Pesticide Factsheets

    This is a letter from Jack P. Broadben,. Director, to Nancy Wrona and Dennis Smith informing them that Maricopa County's motor vehicle emissions budgets in the 2003 MAGCO Maintenance Plan are adequate for transportation conformity purposes.

  19. Region 6: Texas Adequate Letter (4/16/2010)

    EPA Pesticide Factsheets

    This letter from EPA to Texas Commission on Environmental Quality determined 2021 motor vehicle emission budgets for nitrogen oxides (NOx) and volatile organic compounds (VOCs) for Beaumont/Port Arthur area adequate for transportation conformity purposes

  20. Region 2: New Jersey Adequate Letter (5/23/2002)

    EPA Pesticide Factsheets

    This April 22, 2002 letter from EPA to the New Jersey Department of Environmental Protection determined 2007 and 2014 Carbon Monoxide (CO) Mobile Source Emissions Budgets adequate for transportation conformity purposes and will be announced in the Federal

  1. Region 8: Colorado Adequate Letter (10/29/2001)

    EPA Pesticide Factsheets

    This letter from EPA to Colorado Department of Public Health and Environment determined Denvers' particulate matter (PM10) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes.

  2. Region 1: New Hampshire Adequate Letter (8/12/2008)

    EPA Pesticide Factsheets

    This July 9, 2008 letter from EPA to the New Hampshire Department of Environmental Services, determined the 2009 Motor Vehicle Emissions Budgets (MVEBs) are adequate for transportation conformity purposes and will be announced in the Federal Register (FR).

  3. Region 8: Colorado Adequate Letter (1/20/2004)

    EPA Pesticide Factsheets

    This letter from EPA to Colorado Department of Public Health and Environment determined Greeleys' Carbon Monoxide (CO) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes and will be announced in the FR.

  4. Region 8: Utah Adequate Letter (6/10/2005)

    EPA Pesticide Factsheets

    This letter from EPA to Utah Department of Environmental Quality determined Salt Lake Citys' and Ogdens' Carbon Monoxide (CO) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes.

  5. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  6. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  7. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  8. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  9. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  10. Region 6: New Mexico Adequate Letter (8/21/2003)

    EPA Pesticide Factsheets

    This is a letter from Carl Edlund, Director, to Alfredo Santistevan regarding MVEB's contained in the latest revision to the Albuquerque Carbon Monoxide State Implementation Plan (SIP) are adequate for transportation conformity purposes.

  11. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  12. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... require access to and use of records contained in a system of records are adequately trained to protect... with the appropriate security software, in accordance with regulations of the Archivist of the...

  13. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  14. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... require access to and use of records contained in a system of records are adequately trained to protect... with the appropriate security software, in accordance with regulations of the Archivist of the...

  15. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  16. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  17. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... require access to and use of records contained in a system of records are adequately trained to protect... with the appropriate security software, in accordance with regulations of the Archivist of the...

  18. Region 9: Nevada Adequate Letter (3/30/2006)

    EPA Pesticide Factsheets

    This is a letter from Deborah Jordan, Director, to Leo M. Drozdoff regarding Nevada's motor vehicle emissions budgets in the 2005 Truckee Meadows CO Redesignation Request and Maintenance Plan are adequate for transportation conformity decisions.

  19. Effect of dietary selenium on biotransformation and excretion of mutagenic metabolites of N-nitrosodimethylamine and 1,1-dimethylhydrazine in the liver perfusion/cell culture system.

    PubMed

    Beije, B; Olsson, U; Onfelt, A

    1987-01-01

    The mutagenicity of N-nitrosodimethylamine (NDMA) and 1,1-dimethylhydrazine (UDMH) has been studied in an isolated liver perfusion/cell culture system. The liver donors, male Wistar rats, were either selenium (Se)-deficient or had a physiologically adequate Se status (Se-supplemented). Mutagenicity was measured in perfusate and bile with Chinese hamster V79 cells as the genetic target. Se deficiency increased the mutagenic effect of NDMA in the perfusate, whereas no mutagenicity was detected in the bile of either Se-deficient or Se-supplemented livers. No significant increase in the mutagenicity of UDMH was seen in the perfusate with Se deficiency, but the bile became mutagenic. Se deficiency thus increased the mutagenicity of both NDMA and UDMH: with NDMA, the effect was observed in the perfusate, and with UDMH, in the bile.

  20. 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.

  1. The measurement of diffusion and perfusion in biological systems using magnetic resonance imaging.

    PubMed

    Thomas, D L; Lythgoe, M F; Pell, G S; Calamante, F; Ordidge, R J

    2000-08-01

    The aim of this review is to describe two recent developments in the use of magnetic resonance imaging (MRI) in the study of biological systems: diffusion and perfusion MRI. Diffusion MRI measures the molecular mobility of water in tissue, while perfusion MRI measures the rate at which blood is delivered to tissue. Therefore, both these techniques measure quantities which have direct physiological relevance. It is shown that diffusion in biological systems is a complex phenomenon, influenced directly by tissue microstructure, and that its measurement can provide a large amount of information about the organization of this structure in normal and diseased tissue. Perfusion reflects the delivery of essential nutrients to tissue, and so is directly related to its status. The concepts behind the techniques are explained, and the theoretical models that are used to convert MRI data to quantitative physical parameters are outlined. Examples of current applications of diffusion and perfusion MRI are given. In particular, the use of the techniques to study the pathophysiology of cerebral ischaemia/stroke is described. It is hoped that the biophysical insights provided by this approach will help to define the mechanisms of cell damage and allow evaluation of therapies aimed at reducing this damage.

  2. [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.

  3. Technetium myocardial perfusion agents: an introduction

    SciTech Connect

    English, R.J.; Kozlowski, J.; Tumeh, S.S.; Holman, B.L.

    1987-09-01

    This is the third in a series of four Continuing Education articles on developing radiopharmaceuticals. After reading this article, the reader should be able to: 1) understand the basic concepts of myocardial perfusion imaging; and 2) discuss the advantages of the technetium myocardial perfusion complexes over thallium-201.

  4. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  5. Excorporeal Normothermic Machine Perfusion Resuscitates Pig DCD Livers with Extended Warm Ischemia

    PubMed Central

    Xu, Hongzhi; Berendsen, Tim; Kim, Karen; Soto-Gutiérrez, Alejandro; Bertheium, Francios; Yarmush, Martin L.; Hertl, Martin

    2013-01-01

    Background The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system. Methods Livers from 12 Yorkshire pigs (20–30 kg) were subjected to either 0 min (WI-0 group, n = 6) or 60 min (WI-60 group, n = 6) of warm ischemia and 2 h of cold storage in UW solution, followed by 4 h of oxygenated sanguineous normothermic machine perfusion. Liver viability and metabolic function were analyzed hourly. Results Warm ischemic livers showed elevated transaminase levels and reduced ATP concentration. After the start of machine perfusion, transaminase levels stabilized and there was recovery of tissue ATP, coinciding with an increase in bile production. These parameters reached comparable levels to the control group after 1 h of machine perfusion. Histology and gross morphology confirmed recovery of the ischemic allografts. Conclusion Our data demonstrate that metabolic and functional parameters of livers with extended warm ischemic time (60 min) can be significantly improved using normothermic machine perfusion. We hereby compound the existing body of evidence that machine perfusion is a viable solution for reconditioning marginal organs. PMID:22099594

  6. Kinetic assessment of manganese using magnetic resonance imaging in the dually perfused human placenta in vitro

    SciTech Connect

    Miller, R.K.; Mattison, D.R.; Panigel, M.; Ceckler, T.; Bryant, R.; Thomford, P.

    1987-10-01

    The transfer and distribution of paramagnetic manganese was investigated in the dually perfused human placenta in vitro (using 10, 20, 100 ..mu..M Mn with and without /sup 54/Mn) using magnetic resonance imaging (MRI) and conventional radiochemical techniques. The human placenta concentrated /sup 54/Mn rapidly during the first 15 min of perfusion and by 4 hr was four times greater than the concentrations of Mn in the maternal perfusate, while the concentration of Mn in the fetal perfusate was 25% of the maternal perfusate levels. Within placentae, 45% of the /sup 54/Mn was free in the 100,000g supernatant, with 45% in the 1000g pellet. The magnetic field dependence of proton nuclear spin-lattice relaxation time (T/sub 1/) in placental tissue supports this Mn binding. Mn primarily affected the MRI partial saturation rather than spin-echo images of the human placenta, which provided for the separation of perfusate contributions from those produced by Mn. The washout of the Mn from the placenta was slow compared with its uptake, as determined by MRI. Thus, Mn was concentrated by the human placenta, but transfer of Mn across the placenta was limited in either direction. These studies also illustrate the opportunity for studies of human placental function using magnetic resonance imaging as a noninvasive biomarker.

  7. Perfusion Magnetic Resonance Imaging: A Comprehensive Update on Principles and Techniques

    PubMed Central

    Li, Ka-Loh; Ostergaard, Leif; Calamante, Fernando

    2014-01-01

    Perfusion is a fundamental biological function that refers to the delivery of oxygen and nutrients to tissue by means of blood flow. Perfusion MRI is sensitive to microvasculature and has been applied in a wide variety of clinical applications, including the classification of tumors, identification of stroke regions, and characterization of other diseases. Perfusion MRI techniques are classified with or without using an exogenous contrast agent. Bolus methods, with injections of a contrast agent, provide better sensitivity with higher spatial resolution, and are therefore more widely used in clinical applications. However, arterial spin-labeling methods provide a unique opportunity to measure cerebral blood flow without requiring an exogenous contrast agent and have better accuracy for quantification. Importantly, MRI-based perfusion measurements are minimally invasive overall, and do not use any radiation and radioisotopes. In this review, we describe the principles and techniques of perfusion MRI. This review summarizes comprehensive updated knowledge on the physical principles and techniques of perfusion MRI. PMID:25246817

  8. Kidney transplantation after oxygenated machine perfusion preservation with Custodiol-N solution.

    PubMed

    Minor, Thomas; Paul, Andreas; Efferz, Patrik; Wohlschlaeger, Jeremias; Rauen, Ursula; Gallinat, Anja

    2015-09-01

    Custodiol-N, a new preservation solution, has been shown particularly suitable for hypothermic machine perfusion preservation (HMP) in isolated porcine kidneys. These preliminary results should be confirmed in an actual transplant model in vivo. Kidney function after 21 h of HMP was studied in an autotransplant model using Landrace pigs (25-30 kg; n = 6 per group). Perfusion was performed with oxygenated perfusate, using either Custodiol-N solution including 50 g/l dextran 40 (CND) or kidney perfusion solution 1 (KPS-1) as gold standard. Viability of the grafts was followed for 1 week after bilateral nephrectomy in the recipient pigs. HMP with CND resulted in less acute tubular injury, evaluated by levels of fatty acid-binding protein and better clearance function during the first 24 h after Tx than with KPS-1 (P < 0.05, resp.). Serum creatinine tended to be lower in the CND group during the whole observation period. Histological tissue scores one week after Tx were similar in both groups. Expression of endothelin-1 as well as of Toll-like receptor 4 15 min after reperfusion was lower in the CND group (P < 0.05), suggesting less endothelial stress response. The data provide first in vivo evidence for the suitability of Custodiol-N as an effective perfusate for renal machine perfusion.

  9. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    PubMed

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P < 0.01). The diagnostic results of CEUS and MRI perfusion quantitative analysis were not significantly different (P > 0.05). However, the quantitative parameter of them were significantly positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis can both dynamically monitor the liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

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

    SciTech Connect

    Mullani, N.A.

    1984-11-01

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

  11. Sequential assembly of 3D perfusable microfluidic hydrogels.

    PubMed

    He, Jiankang; Zhu, Lin; Liu, Yaxiong; Li, Dichen; Jin, Zhongmin

    2014-11-01

    Bottom-up tissue engineering provides a promising way to recreate complex structural organizations of native organs in artificial constructs by assembling functional repeating modules. However, it is challenging for current bottom-up strategies to simultaneously produce a controllable and immediately perfusable microfluidic network in modularly assembled 3D constructs. Here we presented a bottom-up strategy to produce perfusable microchannels in 3D hydrogels by sequentially assembling microfluidic modules. The effects of agarose-collagen composition on microchannel replication and 3D assembly of hydrogel modules were investigated. The unique property of predefined microchannels in transporting fluids within 3D assemblies was evaluated. Endothelial cells were incorporated into the microfluidic network of 3D hydrogels for dynamic culture in a house-made bioreactor system. The results indicated that the sequential assembly method could produce interconnected 3D predefined microfluidic networks in optimized agarose-collagen hydrogels, which were fully perfusable and successfully functioned as fluid pathways to facilitate the spreading of endothelial cells. We envision that the presented method could be potentially used to engineer 3D vascularized parenchymal constructs by encapsulating primary cells in bulk hydrogels and incorporating endothelial cells in predefined microchannels.

  12. Ventilation and perfusion magnetic resonance imaging of the lung

    PubMed Central

    Bauman, Grzegorz; Eichinger, Monika

    2012-01-01

    Summary A close interaction between the respiratory pump, pulmonary parenchyma and blood circulation is essential for a normal lung function. Many pulmonary diseases present, especially in their initial phase, a variable regional impairment of ventilation and perfusion. In the last decades various techniques have been established to measure the lung function. Besides the global pulmonary function tests (PFTs) imaging techniques gained increasing importance to detect local variations in lung function, especially for ventilation and perfusion assessment. Imaging modalities allow for a deeper regional insight into pathophysiological processes and enable improved planning of invasive procedures. In contrast to computed tomography (CT) and the nuclear medicine techniques, magnetic resonance imaging (MRI), as a radiation free imaging modality gained increasing importance since the early 1990 for the assessment of pulmonary function. The major inherent problems of lung tissue, namely the low proton density and the pulmonary and cardiac motion, were overcome in the last years by a constant progress in MR technology. Some MR techniques are still under development, a process which is driven by scientific questions regarding the physiology and pathophysiology of pulmonary diseases, as well as by the need for fast and robust clinically applicable imaging techniques as safe therapy monitoring tools. MRI can be considered a promising ionizing-free alternative to techniques like CT or nuclear medicine techniques for the evaluation of lung function. The goal of this article is to provide an overview on selected MRI techniques for the assessment of pulmonary ventilation and perfusion. PMID:22802864

  13. 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.

  14. [Compromized myocardial perfusion in arrhythmias (author's transl)].

    PubMed

    Simon, H; Neumann, G; Felix, R; Hedde, H; Schaede, A; Thurn, P; Winkler, C

    1977-09-15

    In 7 patients with arrhythmias of various origin the myocardial scintigram displayed either a diffuse or circumscript defect of the perfusion. The coronary arteriogram was normal in all patients. The localized defect of the perfusion in 2 patients was in the region of the upper part of the interventricular septum. Both had a left bundle brunch block. A correlation between the perfusion defect and the electrophysiological abnormality seems probable. The perfusion defect in one of the patients is most probably caused by a previous myocarditis followed by fibrous changes. In the other 6 patients the cause for the perfusion defect is not obvious. A history of myocarditis is missing. The presence of "small vessel disease" in those patients has however to be considered. Our results point to the relation between an abnormality of the microcirculation and arrhythmias in younger patients.

  15. Effect of graded hypoxia on retention of technetium-99m-nitroheterocycle in perfused rat heart

    SciTech Connect

    Rumsey, W.L.; Patel, B.; Linder, K.E.

    1995-04-01

    The purpose of this investigation was to determine the effects of graded hypoxia on the retention of a {sup 99m}Tc-labeled nitroimidazole. Rat hearts were perfused retrogradely with Krebs-Henseleit buffer at 37{degrees}C and paced at 5 Hz. After a 20-min stabilization period, coronary flow was maintained at 8 ml/min/g wet wt and the hearts were perfused with media equilibrated with gas mixtures containing 5% CO{sub 2} and various levels of O{sub 2}, from 544 to 29 Torr. Technetium-99m-O(PnAO-1-(2-nitroimidazole)), BMS-181321, was infused for 20 min into a side port of the aortic cannula. Perfusion continued for an additional 40 min to allow for compound clearance. Each decrease of perfusate PO{sub 2} brought about an increase in the retention of BMS-181321, resulting in a good correlation between its retention and perfusate PO{sub 2} (r=0.97). Myocardial oxygen consumption was independent of oxygen delivery when the perfusate oxygen pressure was greater than 350 Torr. Below this value, oxygen consumption declined markedly as influent PO{sub 2}. A good correlation was obtained between retention of the nitroheterocycle and the cytosolic lactate/pyruvate ratio (r=0.98). When glucose was omitted from the perfusate (PO{sub 2}=27 Torr), retention of the nitroheterocycle was increased by about 25% as compared to hearts perfused in the presence of this substrate. These results indicate that myocardial retention of BMS-181321 is coupled to the level of tissue oxygenation and that hypoxic retention may be affected by substrate input. 24 refs., 3 figs., 1 tab.

  16. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  17. Quantification of brain perfusion with tracers retained by the brain

    SciTech Connect

    Pupi, A.; Bacciottini, L.; De Cristofaro, M.T.R.; Formiconi, A.R.; Castagnoli, A.

    1991-12-31

    Almost a decade ago, tracers, labelled with {sup 123}I and {sup 99m}Tc, that are retained by the brain, started to be used for studies of regional brain perfusion (regional cerebral blood flow, rCBF). To date, these tracers have been used for brain perfusion imaging with SPECT in brain disorders as well as for physiological activation protocols. Only seldom, however, have they been used in protocols that quantitatively measure rCBF. Nevertheless, comparative studies with perfusion reference tracers have repeatedly demonstrated that the brain uptake of these brain-retained tracers is correlated to perfusion, the major determinant of the distribution of these tracers in the brain. The brain kinetics of {sup 99m}Tc HMPAO, which is the tracer most commonly used, was described with a two-compartment tissue model. The theoretical approach, which is, in itself, sufficient for modeling quantitative measurements with {sup 99m}Tc HMPAO, initially suggested the possibility of empirically narrowing the distance between the brain`s regional uptake of the tracer and rCBF with a linearization algorithm which uses the cerebellum as the reference region. The value of this empirical method is hampered by the fact that the cerebellum can be involved in cerebrovascular disease (i.e. cerebellar diaschisis) as well as in several other brain disorders (e.g. anxiety, and dementia of the Alzheimer type). It also was proposed that different reference regions (occipital, whole slice, or whole brain) should be selected in relation to the brain disorder under study. However, this approach does not solve the main problem because it does not equip us with a reliable tool to evaluate rCBF with a high predictive value, and, at the same time, to reduce intersubject variability. The solution would be to measure a quantitative parameter which directly reflects rCBF, such as the unidirectional influx constant of the freely diffusible flow-limited tracers. 45 refs., 3 figs., 1 tab.

  18. Chromium absorption in the vascularly perfused rat intestine

    SciTech Connect

    Dowling, H.J.; Offenbacher, E.G.; Pi-Sunyer, F.X.

    1986-03-01

    The mechanism of chromium (Cr) absorption by the rat small intestine was investigated using a double perfusion technique wherein the luman of the small intestine and the vasculature supplying it were separately perfused. The intestinal perfusate (IP) was a nutrient-rich tissue culture medium (TCM) with added inorganic Cr and /sup 51/Cr. The vascular perfusate (VP) was a Krebs-Ringer bicarbonate solution (KRB) containing 4.7% dextran, 0.1% glucose and 5% human serum. Cr absorption was calculated by the amount of /sup 51/Cr detected in the VP. To determine the transport mechanism for Cr, its absorption into the VP was measured at various Cr concentrations of the IP ranging from 10-400 ppb CrCl/sub 3/. The amount of Cr absorbed into the blood rose linearly with the intestinal Cr concentration suggesting a process of simple diffusion. Manipulations of the VP and IP constituents were made to investigate their effects on Cr absorption. When serum was omitted from the VP, Cr adsorption was suppressed, suggesting that serum component(s) are necessary for optimal Cr absorption. When either of 2 plasma transport proteins (apo-transferrin, albumin) were added to the serum-free VP at physiological levels, Cr absorption returned to, but did not exceed, control levels. When the TCM was replaced with a KRB solution; Cr absorption was suppressed indicating that there are nutrient(s) of the TCM which facilitate Cr absorption. Further suppression occurred when a Cr concentration gradient opposing Cr absorption was created (IP at 100 ppb Cr, VP at 400 ppb Cr).

  19. Ultrasound Shear Wave Elasticity Imaging Quantifies Coronary Perfusion Pressure Effect on Cardiac Compliance

    PubMed Central

    Nagle, Matt; Trahey, Gregg E.; Wolf, Patrick D.

    2016-01-01

    Diastolic heart failure (DHF) is a major source of cardiac related morbidity and mortality in the world today. A major contributor to, or indicator of DHF is a change in cardiac compliance. Currently, there is no accepted clinical method to evaluate the compliance of cardiac tissue in diastolic dysfunction. Shear wave elasticity imaging (SWEI) is a novel ultrasound-based elastography technique that provides a measure of tissue stiffness. Coronary perfusion pressure affects cardiac stiffness during diastole; we sought to characterize the relationship between these two parameters using the SWEI technique. In this work, we demonstrate how changes in coronary perfusion pressure are reflected in a local SWEI measurement of stiffness during diastole. Eight Langendorff perfused isolated rabbit hearts were used in this study. Coronary perfusion pressure was changed in a randomized order (0–90 mmHg range) and SWEI measurements were recorded during diastole with each change. Coronary perfusion pressure and the SWEI measurement of stiffness had a positive linear correlation with the 95% confidence interval (CI) for the slope of 0.009–0.011 m/s/mmHg (R2 = 0.88). Furthermore, shear modulus was linearly correlated to the coronary perfusion pressure with the 95% CI of this slope of 0.035–0.042 kPa/mmHg (R2 = 0.83). In conclusion, diastolic SWEI measurements of stiffness can be used to characterize factors affecting cardiac compliance specifically the mechanical interaction (cross-talk) between perfusion pressure in the coronary vasculature and cardiac muscle. This relationship was found to be linear over the range of pressures tested. PMID:25291788

  20. Comparative studies on the toxicity of mercury, cadmium, and copper toward the isolated perfused rat liver.

    PubMed

    Strubelt, O; Kremer, J; Tilse, A; Keogh, J; Pentz, R; Younes, M

    1996-02-23

    The toxic effects of cadmium, mercury, and copper were compared over the over range 0.01, 0.03, and 0.1 mM using the isolated perfused rat liver preparation. All metals caused similar changes in various parameters used to describe general toxicity. Thus reductions in oxygen consumption, perfusion flow, and biliary secretion were found, while lactate dehydrogenase release into the perfusate, as well as liver weight, increased also in a dose-dependent fashion. Each metal caused similar magnitudes of changes and exerted similar potency. Measurement of other parameters indicating more specific injury revealed a number of differences. Although all metals reduced hepatic ATP concentration, mercury and cadmium were more potent than copper in this respect. Cadmium was the most potent at decreasing reduced glutathione levels. Mercury was most effective at increasing tissue calcium content, while copper was less so, and cadmium ineffective. Only copper significantly increased tissue malondialdehyde (MDA) content, while all metals increased its release into perfusate. Furthermore, whereas cadmium seemed the most potent metal in increasing MDA release, it was least efficacious, while copper was the most. Antioxidants such as superoxide dismutase, catalase, and Trolox C only reduced cadmium's influence on MDA in perfusate; however, they did not affect cadmium's ability to alter most other parameters of vitality. Albumin reversed the toxic effects of copper and mercury, but not cadmium. While metal-induced reductions in perfusion flow accounted for some of the toxic effects of the metals investigated, the results as a whole supported the suggestion that all metals exerted toxicity at the mitochondria, since ATP levels were reduced in a manner that could not be reproduced by perfusion flow reduction alone. Lipid peroxidation appears to play little role in determining toxicity induced by any of these metals. Furthermore, albumin may play an important physiological role in

  1. SIMPLE MACHINE PERFUSION SIGNIFICANTLY ENHANCES HEPATOCYTE YIELDS OF ISCHEMIC AND FRESH RAT LIVERS.

    PubMed

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3 hour room temperature (20±2°C) machine perfusion protocol to treat non-premedicated livers exposed to 1 hour of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers, and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Further, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized.

  2. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

    PubMed Central

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E.; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3-h room temperature (20 ± 2°C) machine perfusion protocol to treat nonpremedicated livers exposed to 1 h of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated, and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Furthermore, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized. PMID:25431743

  3. Activated neutrophils injure the isolated, perfused rat liver by an oxygen radical-dependent mechanism.

    PubMed Central

    Dahm, L. J.; Schultze, A. E.; Roth, R. A.

    1991-01-01

    Under certain circumstances, segmented neutrophils (PMNs) injure extrahepatic tissue by releasing toxic oxygen species and degradative enzymes. The authors used an isolated, perfused rat liver preparation to determine whether PMNs might injure the liver. Livers from fasted rats were perfused with Krebs-Ringer bicarbonate buffer (pH 7.4) containing 3% bovine serum albumin (BSA) in a recirculating system. Rat peritoneal PMNs (4 x 10(8] or vehicle (Hank's balanced salt solution [HBSS], pH 7.35) were added, and liver injury was assessed 90 minutes later by release of alanine aminotransferase (ALT) into the perfusion medium and histopathologic analysis of liver sections. Perfusion of livers receiving only HBSS for 90 minutes resulted in a small increase in ALT activity in the perfusion medium but did not significantly alter histologic features of liver sections. Addition of unstimulated PMNs did not increase further the ALT activity and, with the exception of vascular neutrophilia, did not significantly change the histomorphology compared with controls. When PMNs activated with a combination of phorbol myristate acetate (PMA, 31 ng/ml) and lithocholate (100 mumol/l [micromolar]) were added to the perfusion system, however, livers released greater amounts of ALT than those perfused with PMA, lithocholate, and HBSS. Activated PMNs caused a transient reduction in flow of perfusion medium that lasted approximately 5 to 15 minutes. Liver sections had multifocal to coalescing foci of moderate to severe, acute hepatocellular necrosis associated with the areas of intense sinusoidal neutrophilia. In addition a second type of lesion was observed and was characterized by triangular foci of necrosis located adjacent to periportal regions of sinusoids or portal veins containing neutrophilic thrombi. These lesions were void of PMNs and were consistent with infarcts. A combination of superoxide dismutase and catalase added to the perfusion medium (500 U/ml each) prevented the

  4. Perfusion imaging with non-contrast ultrasound

    NASA Astrophysics Data System (ADS)

    Tierney, Jaime E.; Dumont, Douglas M.; Byram, Brett C.

    2016-04-01

    A Doppler ultrasound clutter filter that enables estimation of low velocity blood flow could considerably improve ultrasound as a tool for clinical diagnosis and monitoring, including for the evaluation of vascular diseases and tumor perfusion. Conventional Doppler ultrasound is currently used for visualizing and estimating blood flow. However, conventional Doppler is limited by frame rate and tissue clutter caused by involuntary movement of the patient or sonographer. Spectral broadening of the clutter due to tissue motion limits ultrasound's ability to detect blood flow less than about 5mm/s at an 8MHz center frequency. We propose a clutter filtering technique that may increase the sensitivity of Doppler measurements to at least as low as 0.41mm/s. The proposed filter uses an adaptive demodulation scheme that decreases the bandwidth of the clutter. To test the performance of the adaptive demodulation method at removing sonographer hand motion, six volunteer subjects acquired data from a basic quality assurance phantom. Additionally, to test initial in vivo feasibility, an arterial occlusion reactive hyperemia study was performed to assess the efficiency of the proposed filter at preserving signals from blood velocities 2mm/s or greater. The hand motion study resulted in initial average bandwidths of 577Hz (28.5mm/s), which were decreased to 7.28Hz (0.36mm/s) at -60 dB at 3cm using our approach. The in vivo power Doppler study resulted in 15.2dB and 0.15dB dynamic ranges between the lowest and highest blood flow time points for the proposed filter and conventional 50Hz high pass filter, respectively.

  5. Perfusion deconvolution in DSC-MRI with dispersion-compliant bases.

    PubMed

    Pizzolato, Marco; Boutelier, Timothé; Deriche, Rachid

    2017-02-01

    Perfusion imaging of the brain via Dynamic Susceptibility Contrast MRI (DSC-MRI) allows tissue perfusion characterization by recovering the tissue impulse response function and scalar parameters such as the cerebral blood flow (CBF), blood volume (CBV), and mean transit time (MTT). However, the presence of bolus dispersion causes the data to reflect macrovascular properties, in addition to tissue perfusion. In this case, when performing deconvolution of the measured arterial and tissue concentration time-curves it is only possible to recover the effective, i.e. dispersed, response function and parameters. We introduce Dispersion-Compliant Bases (DCB) to represent the response function in the presence and absence of dispersion. We perform in silico and in vivo experiments, and show that DCB deconvolution outperforms oSVD and the state-of-the-art CPI+VTF techniques in the estimation of effective perfusion parameters, regardless of the presence and amount of dispersion. We also show that DCB deconvolution can be used as a pre-processing step to improve the estimation of dispersion-free parameters computed with CPI+VTF, which employs a model of the vascular transport function to characterize dispersion. Indeed, in silico results show a reduction of relative errors up to 50% for dispersion-free CBF and MTT. Moreover, the DCB method recovers effective response functions that comply with healthy and pathological scenarios, and offers the advantage of making no assumptions about the presence, amount, and nature of dispersion.

  6. Chondrogenesis in perfusion bioreactors using porous silk scaffolds and hESC-derived MSCs.

    PubMed

    Tiğli, R Seda; Cannizaro, Chris; Gümüşderelioğlu, Menemşe; Kaplan, David L

    2011-01-01

    Tissue engineered cartilage can be grown in vitro with the use of cell-scaffold constructs and bioreactors. The present study was designed to investigate the effects of perfusion bioreactors on the chondrogenic potential of engineered constructs prepared from porous silk fibroin scaffolds seeded with human embryonic stem cell (hESC)-derived mesencyhmal stem cells (MSCs). After four weeks of incubation, constructs cultured in perfusion bioreactors showed significantly higher amounts of glycosaminoglycans (GAGs) (p < 0.001), DNA (p < 0.001), total collagen (p < 0.01), and collagen II (p < 0.01) in comparison to static culture. Mechanical stiffness of constructs increased 3.7-fold under dynamic culture conditions and RT-PCR results concluded that cells cultured in perfusion bioreactors highly expressed (p < 0.001) cartilage-related genes when compared with static culture. Distinct differences were noted in tissue morphology, including polygonal extracellular matrix structure of engineered constructs in thin superficial zones and an inner zone under static and dynamic conditions, respectively. The results suggest that the utility of perfusion bioreactors to modulate the growth of tissue-engineered cartilage and enhance tissue growth in vitro.

  7. Regulatory requirements for providing adequate veterinary care to research animals.

    PubMed

    Pinson, David M

    2013-09-01

    Provision of adequate veterinary care is a required component of animal care and use programs in the United States. Program participants other than veterinarians, including non-medically trained research personnel and technicians, also provide veterinary care to animals, and administrators are responsible for assuring compliance with federal mandates regarding adequate veterinary care. All program participants therefore should understand the regulatory requirements for providing such care. The author provides a training primer on the US regulatory requirements for the provision of veterinary care to research animals. Understanding the legal basis and conditions of a program of veterinary care will help program participants to meet the requirements advanced in the laws and policies.

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

    PubMed Central

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

    2013-01-01

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

  9. Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities: case report

    PubMed Central

    2007-01-01

    Background It has recently become evident that circulating thyroid antibodies are found in excess among patients suffering from mood disorders. Moreover, a manic episode associated with Hashimoto's thyroiditis has recently been reported as the first case of bipolar disorder due to Hashimoto's encephalopathy. We report a case in which Hashimoto's thyroiditis was suspected to be involved in the deteriorating course of mood disorder and discuss potential pathogenic mechanisms linking thyroid autoimmunity with psychopathology. Case presentation A 43-year-old woman, with a history of recurrent depression since the age of 31, developed manic, psychotic, and soft neurological symptoms across the last three years in concomitance with her first diagnosis of Hashimoto's thyroiditis. The patient underwent a thorough medical and neurological workup. Circulating thyroperoxidase antibodies were highly elevated but thyroid function was adequately maintained with L-thyroxine substitution. EEG was normal and no other signs of current CNS inflammation were evidenced. However, brain magnetic resonance imaging evidenced several non-active lesions in the white matter from both hemispheres, suggestive of a non-specific past vasculitis. Brain single-photon emission computed tomography showed cortical perfusion asymmetry particularly between frontal lobes. Conclusion We hypothesize that abnormalities in cortical perfusion might represent a pathogenic link between thyroid autoimmunity and mood disorders, and that the rare cases of severe Hashimoto's encephalopathy presenting with mood disorder might be only the tip of an iceberg. PMID:18096026

  10. Chondrogenic phenotype of articular chondrocytes in monoculture and co-culture with mesenchymal stem cells in flow perfusion.

    PubMed

    Dahlin, Rebecca L; Meretoja, Ville V; Ni, Mengwei; Kasper, F Kurtis; Mikos, Antonios G

    2014-11-01

    This work investigated the effect of flow perfusion bioreactor culture with and without transforming growth factor-β3 (TGF-β3) supplementation on the proliferation, extracellular matrix (ECM) production, and chondrogenic gene expression of chondrocytes both in monoculture and in co-culture with bone marrow-derived mesenchymal stem cells (MSCs). Both cell populations were cultured on electrospun poly(ɛ-caprolactone) scaffolds for 2 weeks in static or flow perfusion culture with and without TGF-β3. Overall, it was observed that without growth factors, flow perfusion culture resulted in increased cell proliferation and ECM with a more cartilage-like composition. While with TGF-β3 induction, flow perfusion constructs generally had lower chondrogenic gene expression than the corresponding static cultures, the growth factor still had an inductive effect on the cells with enhanced gene expression compared with the corresponding noninduced cultures. In addition, while flow perfusion cultures generally had reduced overall ECM content, the ECM distribution was more homogenous compared with the corresponding static cultures. These results are significant in that they indicate that while flow perfusion culture has some beneficial effects on the chondrogenic phenotype of articular chondrocytes, flow perfusion alone is not sufficient to maintain the chondrogenic phenotype of chondrocytes in either monoculture or co-culture, thus demonstrating the advantages of using exogenously added growth factors in flow perfusion culture. Furthermore, the results demonstrate the advantages of flow perfusion culture for the creation of large tissue engineered constructs and the potential of co-cultures of articular chondrocytes and MSCs to be used in flow perfusion culture.

  11. The Mouse Isolated Perfused Kidney Technique.

    PubMed

    Czogalla, Jan; Schweda, Frank; Loffing, Johannes

    2016-11-17

    The mouse isolated perfused kidney (MIPK) is a technique for keeping a mouse kidney under ex vivo conditions perfused and functional for 1 hr. This is a prerequisite for studying the physiology of the isolated organ and for many innovative applications that may be possible in the future, including perfusion decellularization for kidney bioengineering or the administration of anti-rejection or genome-editing drugs in high doses to prime the kidney for transplantation. During the time of the perfusion, the kidney can be manipulated, renal function can be assessed, and various pharmaceuticals administered. After the procedure, the kidney can be transplanted or processed for molecular biology, biochemical analysis, or microscopy. This paper describes the perfusate and the surgical technique needed for the ex vivo perfusion of mouse kidneys. Details of the perfusion apparatus are given and data are presented showing the viability of the kidney's preparation: renal blood flow, vascular resistance, and urine data as functional, transmission electron micrographs of different nephron segments as morphological readouts, and western blots of transport proteins of different nephron segments as molecular readout.

  12. The placental pursuit for an adequate oxidant balance between the mother and the fetus

    PubMed Central

    Herrera, Emilio A.; Krause, Bernardo; Ebensperger, German; Reyes, Roberto V.; Casanello, Paola; Parra-Cordero, Mauro; Llanos, Anibal J.

    2014-01-01

    The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled. PMID:25009498

  13. Comparability and Reliability Considerations of Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Maier, Kimberly S.; Maiti, Tapabrata; Dass, Sarat C.; Lim, Chae Young

    2012-01-01

    The purpose of this study is to develop an estimate of Adequate Yearly Progress (AYP) that will allow for reliable and valid comparisons among student subgroups, schools, and districts. A shrinkage-type estimator of AYP using the Bayesian framework is described. Using simulated data, the performance of the Bayes estimator will be compared to…

  14. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... operate actively in accordance with your Articles and within the context of your business plan, as... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL...

  15. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... operate actively in accordance with your Articles and within the context of your business plan, as... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL...

  16. Is the Stock of VET Skills Adequate? Assessment Methodologies.

    ERIC Educational Resources Information Center

    Blandy, Richard; Freeland, Brett

    In Australia and elsewhere, four approaches have been used to determine whether stocks of vocational education and training (VET) skills are adequate to meet industry needs. The four methods are as follows: (1) the manpower requirements approach; (2) the international, national, and industry comparisons approach; (3) the labor market analysis…

  17. Do Beginning Teachers Receive Adequate Support from Their Headteachers?

    ERIC Educational Resources Information Center

    Menon, Maria Eliophotou

    2012-01-01

    The article examines the problems faced by beginning teachers in Cyprus and the extent to which headteachers are considered to provide adequate guidance and support to them. Data were collected through interviews with 25 school teachers in Cyprus, who had recently entered teaching (within 1-5 years) in public primary schools. According to the…

  18. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  19. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  20. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  1. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  2. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  3. Understanding Your Adequate Yearly Progress (AYP), 2011-2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation…

  4. 34 CFR 200.13 - Adequate yearly progress in general.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Adequate yearly progress in general. 200.13 Section 200.13 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE...

  5. 34 CFR 200.13 - Adequate yearly progress in general.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Adequate yearly progress in general. 200.13 Section 200.13 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE...

  6. Region 9: Arizona Adequate Letter (11/1/2001)

    EPA Pesticide Factsheets

    This is a letter from Jack P. Broadbent, Director, Air Division to Nancy Wrona and James Bourney informing them of the adequacy of Revised MAG 1999 Serious Area Carbon Monoxide Plan and that the MAG CO Plan is adequate for Maricopa County.

  7. Ventilation-perfusion imaging in pulmonary papillomatosis

    SciTech Connect

    Espinola, D.; Rupani, H.; Camargo, E.E.; Wagner, H.N. Jr.

    1981-11-01

    Three children with laryngeal papillomas involving the lungs had serial ventilation-perfusion scintigrams to assess results of therapy designed to reduce the bronchial involvement. Different imaging patterns were observed depending on size, number, and location of lesions. In early parenchymal involvement a ventilation-perfusion mismatch was seen. The initial and follow-up studies correlated well with clinical and radiographic findings. This noninvasive procedure is helpful in evaluating ventilatory and perfusion impairment in these patients as well as their response to treatment.

  8. 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

  9. Ipragliflozin effectively reduced visceral fat in Japanese patients with type 2 diabetes under adequate diet therapy.

    PubMed

    Yamamoto, Chiho; Miyoshi, Hideaki; Ono, Kota; Sugawara, Hajime; Kameda, Reina; Ichiyama, Mei; Yamamoto, Kohei; Nomoto, Hiroshi; Nakamura, Akinobu; Atsumi, Tatsuya

    2016-06-30

    To investigate if ipragliflozin, a novel sodium-glucose co-transporter 2 inhibitor, alters body composition and to identify variables associated with reductions in visceral adipose tissue in Japanese patients with type 2 diabetes mellitus. This prospective observational study enrolled Japanese participants with type 2 diabetes mellitus. Subjects were administered ipragliflozin (50 mg/day) once daily for 16 weeks. Body composition, visceral adipose tissue volume and plasma variables were measured at 0, 8, and 16-weeks. The subjects' lifestyle habits including diet and exercise were evaluated at baseline and 16 weeks. The primary endpoint was defined as the decrease of visceral adipose tissue mass. Twenty-four of 26 enrolled participants completed the study. The visceral adipose tissue decreased significantly (110 ± 33 to 101 ± 36 cm(2), p = 0.005) as well as other parameters for metabolic insufficiency including hemoglobin A1c. Seventy-one % of the total body weight reduction (-2.49 kg) was estimated by a decrease in fat mass (-1.77 kg), and the remaining reduction (22%) by water volume (-0.55 kg). A minor but significant reduction in the skeletal muscle index was also observed. Correlation analyses were performed to identify variables associated with changes in visceral adipose tissue and the only significant variable identified was diet therapy (Spearman's r = -0.416, p = 0.043). Ipragliflozin significantly decreased visceral adipose tissue, and improved parametres for metabolic dysfunction. Adequate diet therapy would be necessary to induce and enhance the therapeutic merit.

  10. An Examination of Ultrasound Measured Tissue Perfusion on Breast Cancer

    DTIC Science & Technology

    1998-12-01

    anesthetized with xylazine (Rompun) (10 mg/kg s.c.) and ketamine (50 mg/kg i.m.). Supplemental doses of ketamine were administered i.v. through an ear vein ...Tucson, AZ) was administered through the ear vein catheter, either as a 10 ul/kg bolus (approximately 106 bubbles/kg) or diluted to 4% (volYvol.) in...115, ImaRx Pharmaceuticals Corp., Tucson AZ) was administered through the ear vein catheter, either as a 10 ul/kg bolus (approximately 106 bubbles

  11. Evolution of pulmonary perfusion defects demonstrated with contrast-enhanced dynamic MR perfusion imaging.

    PubMed

    Howarth, N R; Beziat, C; Berthezène, Y

    1999-01-01

    Pulmonary perfusion defects can be demonstrated with contrast-enhanced dynamic MR perfusion imaging. We present the case of a patient with a pulmonary artery sarcoma who presented with a post-operative pulmonary embolus and was followed in the post-operative period with dynamic contrast-enhanced MR perfusion imaging. This technique allows rapid imaging of the first passage of contrast material through the lung after bolus injection in a peripheral vein. To our knowledge, this case report is the first to describe the use of this MR technique in showing the evolution of peripheral pulmonary perfusion defects associated with pulmonary emboli.

  12. Technical Pitfalls of Signal Truncation in Perfusion MRI of Glioblastoma.

    PubMed

    Wong, Kelvin K; Fung, Steve H; New, Pamela Z; Wong, Stephen T C

    2016-01-01

    Dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) is widely used in clinical settings for the radiological diagnosis of brain tumor. The signal change in brain tissue in gradient echo-based DSC PWI is much higher than in spin echo-based DSC PWI. Due to its exquisite sensitivity, gradient echo-based sequence is the preferred method for imaging of all tumors except those near the base of the skull. However, high sensitivity also comes with a dynamic range problem. It is not unusual for blood volume to increase in gene-mediated cytotoxic immunotherapy-treated glioblastoma patients. The increase of fractional blood volume sometimes saturates the MRI signal during first-pass contrast bolus arrival and presents signal truncation artifacts of various degrees in the tumor when a significant amount of blood exists in the image pixels. It presents a hidden challenge in PWI, as this signal floor can be either close to noise level or just above and can go no lower. This signal truncation in the signal intensity time course is a significant issue that deserves attention in DSC PWI. In this paper, we demonstrate that relative cerebral blood volume and relative cerebral blood flow (rCBF) are underestimated due to signal truncation in DSC perfusion, in glioblastoma patients. We propose the use of second-pass tissue residue function in rCBF calculation using least-absolute-deviation deconvolution to avoid the underestimation problem.

  13. Deiodination of thyroid hormones by the perfused rat liver

    PubMed Central

    Hillier, A. P.

    1972-01-01

    1. An investigation has been made into the deiodination of thyroid hormones by the perfused rat liver. The hormones were labelled with 125I in the phenolic ring and the rate of deiodination was estimated by measuring the release of radio-iodide into the perfusate. 2. At tracer concentrations, 0·98% of the liver thyroxine is deiodinated/5 min. The deiodination of tri-iodothyronine is considerably faster, 3·3%/5 min. 3. Deiodination is very sensitive to changes in temperature. 4. The reaction shows saturation kinetics typical of many enzymes, the reciprocal of the rate of deiodination being proportional to the reciprocal of the hormone concentration in the tissue. The maximum rate of deiodination of each hormone is about 1·5 μg/min for a whole liver preparation weighing 16 g. 5. Tri-iodothyronine inhibits thyroxine deiodination and vice versa, suggesting that a single enzyme is responsible for both reactions. 6. Propyl thiouracil (PTU) at high concentrations inhibits the deiodination of both hormones. 7. An abnormally high rate of deiodination is associated with the actual injection of hormone into the preparation. This suggests that only the free (unbound) hormone in the tissue is directly available to the deiodinating enzyme. 8. About half of the whole body deiodination of thyroxine is relatively insensitive to PTU. It is suggested that most of this type of deiodination is performed in the liver and that the process is one of inactivation. PMID:5033472

  14. Technical Pitfalls of Signal Truncation in Perfusion MRI of Glioblastoma

    PubMed Central

    Wong, Kelvin K.; Fung, Steve H.; New, Pamela Z.; Wong, Stephen T. C.

    2016-01-01

    Dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) is widely used in clinical settings for the radiological diagnosis of brain tumor. The signal change in brain tissue in gradient echo-based DSC PWI is much higher than in spin echo-based DSC PWI. Due to its exquisite sensitivity, gradient echo-based sequence is the preferred method for imaging of all tumors except those near the base of the skull. However, high sensitivity also comes with a dynamic range problem. It is not unusual for blood volume to increase in gene-mediated cytotoxic immunotherapy-treated glioblastoma patients. The increase of fractional blood volume sometimes saturates the MRI signal during first-pass contrast bolus arrival and presents signal truncation artifacts of various degrees in the tumor when a significant amount of blood exists in the image pixels. It presents a hidden challenge in PWI, as this signal floor can be either close to noise level or just above and can go no lower. This signal truncation in the signal intensity time course is a significant issue that deserves attention in DSC PWI. In this paper, we demonstrate that relative cerebral blood volume and relative cerebral blood flow (rCBF) are underestimated due to signal truncation in DSC perfusion, in glioblastoma patients. We propose the use of second-pass tissue residue function in rCBF calculation using least-absolute-deviation deconvolution to avoid the underestimation problem. PMID:27531989

  15. Positron emission tomography in ischaemic stroke: cerebral perfusion and metabolism after stroke onset.

    PubMed

    Yasaka, M; Read, S J; O'Keefe, G J; Egan, G F; Pointon, O; McKay, W J; Donnan, G A

    1998-10-01

    PET studies were performed in 37 patients up to 1 month after ischaemic stroke to observe the relationships between cerebral blood flow (CBF), rate of cerebral oxygen metabolism (CMRO(2)) and oxygen extraction fraction (OEF) with time. PET findings were classified as misery perfusion (two patients), luxury perfusion (15 patients), matched hypoperfusion-hypometabolism (17 patients) or normal (nine patients). Misery perfusion was seen up to 3 days post-stroke, suggesting an extended time window during which at least some tissue may be salvageable. Luxury perfusion, an indication of non-nutritional flow, was seen as early as 30 h and as late as 23 days, but more commonly between 3 and 7 days. A matched reduction of CBF and CMRO(2) was seen during all time periods, but as early as 27 hours. Since this was associated with severely impaired CBF, presumably from the onset of stroke, it can be assumed that the duration of cerebral tissue survival is less than 27 h under these conditions. We inferred that, for maximal tissue recovery, therapy will need to be introduced within 27 h after stroke, but that at least some potential for recovery exists up to 3 days.

  16. 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

  17. Improved exercise myocardial perfusion during lidoflazine therapy

    SciTech Connect

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-11-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

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

    NASA Astrophysics Data System (ADS)

    Abeykoon, Sumeda B.

    The quantitative assessment of perfusion is important for early recognition of a variety of heart diseases, determination of disease severity and their cure. In conventional approach of measuring cardiac perfusion by arterial spin labeling, the relative difference in the apparent T1 relaxation times in response to selective and non-selective inversion of blood entering the region of interest is related to perfusion via a two-compartment tissue model. But accurate determination of T1 in small animal hearts is difficult and prone to errors due to long scan times. The purpose of this study is to develop a fast, robust and simple method to quantitatively assess myocardial perfusion using arterial spin labeling. The proposed method is based on signal intensities (SI) of inversion recovery slice-select, non-select and steady-state images. Especially in this method data are acquired at a single inversion time and at short repetition times. This study began by investigating the accuracy of assessment of perfusion using a two compartment system. First, determination of perfusion by T1 and SI were implemented to a simple, two-compartment phantom model. Mathematical model developed for full spin exchange models (in-vivo experiments) by solving a modified Bloch equation was modified to develop mathematical models (T1 and SI) for a phantom (zero spin exchange). The phantom result at different flow rates shows remarkable evidence of accuracy of the two-compartment model and SI, T1 methods: the SI method has less propagation error and less scan time. Next, twelve healthy C57BL/6 mice were scanned for quantitative perfusion assessment and three of them were repeatedly scanned at three different time points for a reproducibility test. The myocardial perfusion of healthy mice obtained by the SI-method, 5.7+/-1.6 ml/g/min, was similar (p=0.38) to that obtained by the conventional T1 method, 5.6+/- 2.3 ml/g/min. The reproducibility of the SI method shows acceptable results: the

  19. Visualization of myocardial perfusion after percutaneous myocardial septal ablation for hypertrophic cardiomyopathy using superharmonic imaging.

    PubMed

    Ten Cate, Folkert J; Bouakaz, Ayache; Krenning, Boudewijn; Vletter, Wim; de Jong, Nico

    2003-04-01

    Harmonic imaging is used for detection of ultrasound contrast agents in myocardial perfusion studies. However, harmonic imaging has limitations because of the presence of tissue harmonics, which results in less specificity and sensitivity, thus, lower contrast-to-tissue ratio. We describe a clinical example using superharmonic imaging. This technique detects the third, fourth, and fifth harmonics. These harmonics are not created in tissue, resulting, hence, in a high contrast-to-tissue ratio. After myocardial alcohol ablation for hypertrophic cardiomyopathy areas of nontreated and treated myocardium, normal and low flow could be visualized with superharmonic imaging.

  20. Correction for partial volume effects in brain perfusion ECT imaging

    NASA Astrophysics Data System (ADS)

    Koole, Michel; Staelens, Steven; Van de Walle, Rik; Lemahieu, Ignace L.

    2003-05-01

    The accurate quantification of brain perfusion for emission computed tomography data (PET-SPECT) is limited by partial volume effects (PVE). This study presents a new approach to estimate accurately the true tissue tracer activity within the grey matter tissue compartment. The methodology is based on the availability of additional anatomical side information and on the assumption that activity concentration within the white matter tissue compartment is constant. Starting from an initial estimate for the white matter grey matter activity, the true tracer activity within the grey matter tissue compartment is estimated by an alternating ML-EM-algorithm. During the updating step the constant activity concentration within the white matter compartment is modelled in the forward projection in order to reconstruct the true activity distribution within the grey matter tissue compartment, hence reducing partial volume averaging. Consequently the estimate for the constant activity in the white matter tissue compartment is updated based on the new estimated activity distribution in the grey matter tissue compartment. We have tested this methodology by means of computer simulations. A T1-weighted MR brainscan of a patient was segmented into white matter, grey matter and cerebrospinal fluid, using the segmentation package of the SPM-software (Statistical Parametric Mapping). The segmented grey and white matter were used to simulate a SPECT acquisition, modelling the noise and the distance dependant detector response. Scatter and attenuation were ignored. Following the above described strategy, simulations have shown it is possible to reconstruct the true activity distribution for the grey matter tissue compartment (activity/tissue volume), assuming constant activity in the white matter tissue compartment.

  1. Army General Fund Adjustments Not Adequately Documented or Supported

    DTIC Science & Technology

    2016-07-26

    statements were unreliable and lacked an adequate audit trail. Furthermore, DoD and Army managers could not rely on the data in their accounting...risk that AGF financial statements will be materially misstated and the Army will not achieve audit readiness by the congressionally mandated...and $6.5 trillion in yearend adjustments made to Army General Fund data during FY 2015 financial statement compilation. We conducted this audit in

  2. Perfusion visualization and analysis for pulmonary embolism

    NASA Astrophysics Data System (ADS)

    Vaz, Michael S.; Kiraly, Atilla P.; Naidich, David P.; Novak, Carol L.

    2005-04-01

    Given the nature of pulmonary embolism (PE), timely and accurate diagnosis is critical. Contrast enhanced high-resolution CT images allow physicians to accurately identify segmental and sub-segmental emboli. However, it is also important to assess the effect of such emboli on the blood flow in the lungs. Expanding upon previous research, we propose a method for 3D visualization of lung perfusion. The proposed method allows users to examine perfusion throughout the entire lung volume at a single glance, with areas of diminished perfusion highlighted so that they are visible independent of the viewing location. This may be particularly valuable for better accuracy in assessing the extent of hemodynamic alterations resulting from pulmonary emboli. The method also facilitates user interaction and may help identify small peripheral sub-segmental emboli otherwise overlooked. 19 patients referred for possible PE were evaluated by CT following the administration of IV contrast media. An experienced thoracic radiologist assessed the 19 datasets with 17 diagnosed as being positive for PE with multiple emboli. Since anomalies in lung perfusion due to PE can alter the distribution of parenchymal densities, we analyzed features collected from histograms of the computed perfusion maps and demonstrate their potential usefulness as a preliminary test to suggest the presence of PE. These histogram features also offer the possibility of distinguishing distinct patterns associated with chronic PE and may even be useful for further characterization of changes in perfusion or overall density resulting from associated conditions such as pneumonia or diffuse lung disease.

  3. Brain/language relationships identified with diffusion and perfusion MRI: Clinical applications in neurology and neurosurgery.

    PubMed

    Hillis, Argye E

    2005-12-01

    Diffusion and perfusion MRI have contributed to stroke management by identifying patients with tissue "at risk" for further damage in acute stroke. However, the potential usefulness of these imaging modalities, along with diffusion tensor imaging, can be expanded by using these imaging techniques with concurrent assessment of language and other cognitive skills to identify the specific cognitive deficits that are associated with diffusion and perfusion abnormalities in particular brain regions. This paper illustrates how this combined behavioral and imaging methodology can yield information that is useful for predicting specific positive effects of intervention to restore blood flow in hypoperfused regions of brain identified with perfusion MRI, and for predicting negative effects of resection of particular brain regions or fiber bundles. Such data allow decisions about neurological and neurosurgical interventions to be based on specific risks and benefits in terms of functional consequences.

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

    PubMed

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

    2013-02-01

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

  5. 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.

  6. 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.

  7. Patient directed perfusion pressure on bypass, an analogy from electrical engineering--a new concept.

    PubMed

    Warwick, Richard; Poole, Robert; Palmer, Kenneth; Johnson, Ian; Poullis, Michael

    2010-03-01

    Organ ischemia, particularly mesenteric and renal, can occur despite a seemingly adequate perfusion flow and pressure during a period of cardiopulmonary bypass. The blood pressure to run bypass at remains a contentious issue. We present the concept that perfusion pressure during cardiopulmonary bypass should be patient specific, depending on an individual's resting pre-procedural blood pressure. Four simulated arterial traces with variable morphology, but identical systolic and diastolic blood pressures, were analyzed to calculate the medical mean, arithmetic mean, and root mean square of the blood pressure tracing. Using the standard medical formula for calculation of mean blood pressure, you can potentially underestimate perfusion pressure by 12 mmHg in a normotensive subject. The root mean square pressure calculates the equivalent non pulsatile pressure that will deliver the same hydraulic power to the circulation as its pulsatile equivalent. Patient specific perfusion pressures, calculated via root mean square may potentially help reduce the incidence of organ ischemia during cardiopulmonary bypass. Clinical trials are needed to confirm or refute this concept.

  8. Dipyridamole-thallium-201 tomography documenting improved myocardial perfusion with therapy in Kawasaki disease

    SciTech Connect

    Nienaber, C.A.; Spielmann, R.P.; Hausdorf, G.

    1988-12-01

    Thallium-201 tomographic perfusion studies after pharmacologic vasodilation were performed in seven children (aged 2 years 8 months to 8 years 7 months), 3 to 20 months after the acute stage of the disease. In all patients coronary aneurysms were seen on cross-sectional echocardiograms. The scintigrams of six children showed no significant regional reduction of myocardial thallium-201 uptake. These children had remained asymptomatic in the follow-up period after the acute inflammatory stage of Kawasaki disease. Persistent and transient thallium defects were present in one child with acute posterolateral myocardial infarction; obstruction of two coronary vessels supplying the defect zones was confirmed by contrast angiography. After 8 months of treatment a follow-up nuclear scan showed marked reduction in the size of the defect and almost complete abolishment of the ischemic reaction. Thus tomographic thallium-201 perfusion scintigraphy in conjunction with vasodilation stress is useful to assess myocardial perfusion in children with Kawasaki disease and demonstrates marked improvement in regional perfusion after adequate medical therapy.

  9. Patient Directed Perfusion Pressure on Bypass, an Analogy from Electrical Engineering—A New Concept

    PubMed Central

    Warwick, Richard; Poole, Robert; Palmer, Kenneth; Johnson, Ian; Poullis, Michael

    2010-01-01

    Abstract: Organ ischemia, particularly mesenteric and renal, can occur despite a seemingly adequate perfusion flow and pressure during a period of cardiopulmonary bypass. The blood pressure to run bypass at remains a contentious issue. We present the concept that perfusion pressure during cardiopulmonary bypass should be patient specific, depending on an individual’s resting pre-procedural blood pressure. Four simulated arterial traces with variable morphology, but identical systolic and diastolic blood pressures, were analyzed to calculate the medical mean, arithmetic mean, and root mean square of the blood pressure tracing. Using the standard medical formula for calculation of mean blood pressure, you can potentially underestimate perfusion pressure by 12 mmHg in a normotensive subject. The root mean square pressure calculates the equivalent non pulsatile pressure that will deliver the same hydraulic power to the circulation as its pulsatile equivalent. Patient specific perfusion pressures, calculated via root mean square may potentially help reduce the incidence of organ ischemia during cardiopulmonary bypass. Clinical trials are needed to confirm or refute this concept. PMID:20437793

  10. [99mTc-ECD dynamic SPECT in "luxury perfusion" of subacute stroke].

    PubMed

    Ogasawara, K; Fujiwara, S; Yoshimoto, T

    1995-11-01

    To evaluate the cerebral pharmacokinetics of 99mTc-ethyl cysteinate dimer (99mTc-ECD) at blood flow levels beyond the normal range, we investigated "luxury perfusion" in subacute stroke, ictal hyperperfusion in epilepsy and post-decompressive hyperemia in head trauma. All 7 patients showed a hyperactive area on SPECT studies using 99mTc-HM-PAO. 99mTc-ECD static image demonstrated a hyperactive area in both epilepsy and head trauma, and a hypoactive area in "luxury perfusion." On the dynamic SPECT of 99mTc-ECD in both epilepsy and head trauma, brain distribution of the tracer was determined within 2 min. postinjection and remained stable for up to 1 hour; however, "luxury perfusion" area showed a change from initial hyperactivity to late hypoactivity with the passage of time. The time activity curve in "luxury perfusion" area demonstrated a steep decrease of counts/pixel for up to 4-5 minutes postinjection, and a moderate decrease in the following phase. The early wash-out mechanism of 99mTc-ECD from "luxury perfusion" area can be described by a biexponential function including an initial steep decrease representing the rapid loss of the lipophilic complexes which were not metabolized in injured brain tissue.

  11. ULTRASTRUCTURAL ALTERATIONS PRODUCED IN MAMMALIAN MYOCARDIUM BY VARIATION IN PERFUSATE IONIC COMPOSITION

    PubMed Central

    Legato, Marianne J.; Spiro, David; Langer, Glenn A.

    1968-01-01

    This study describes the changes produced in the subcellular morphology of mammalian myocardium when perfusate sodium, calcium, and chloride concentrations are varied. By means of a recently developed perfusion technique, functioning dog papillary muscles were perfused with isotonic solutions of varying ionic compositions. Examination of the tissue in the electron microscope revealed that control muscles showed satisfactory preservation of ultrastructure, demonstrating that the protocol itself did not create significant morphological artefact. Low sodium chloride perfusion produced dilatation of both transverse tubules and longitudinal sarcoplasmic reticulum elements. Low sodium or high calcium concentrations produced dilation of tubular elements of the longitudinal sarcoplasmic reticulum while leaving transverse tubules intact. High calcium perfusion produced mitochondrial swelling and vacuolization. Mitochondrial precipitate, both crystalline and amorphous in form, was observed and presumed to be calcium phosphate, either alone or mixed with calcium carbonate. The possibility that the morphological changes observed might indicate subcellular loci of specific ion permeability is discussed. A correlation of the known kinetic behavior of sodium and calcium ions in mammalian myocardium with the ultrastructural alterations produced is suggested. PMID:5650905

  12. A 4D CT digital phantom of an individual human brain for perfusion analysis

    PubMed Central

    Brune, Christoph; van Ginneken, Bram; Prokop, Mathias

    2016-01-01

    Brain perfusion is of key importance to assess brain function. Modern CT scanners can acquire perfusion maps of the cerebral parenchyma in vivo at submillimeter resolution. These perfusion maps give insights into the hemodynamics of the cerebral parenchyma and are critical for example for treatment decisions in acute stroke. However, the relations between acquisition parameters, tissue attenuation curves, and perfusion values are still poorly understood and cannot be unraveled by studies involving humans because of ethical concerns. We present a 4D CT digital phantom specific for an individual human brain to analyze these relations in a bottom-up fashion. Validation of the signal and noise components was based on 1,000 phantom simulations of 20 patient imaging data. This framework was applied to quantitatively assess the relation between radiation dose and perfusion values, and to quantify the signal-to-noise ratios of penumbra regions with decreasing sizes in white and gray matter. This is the first 4D CT digital phantom that enables to address clinical questions without having to expose the patient to additional radiation dose. PMID:27917312

  13. Comparative studies on the toxicity of mercury, cadmium, and copper toward the isolated perfused rat liver

    SciTech Connect

    Strubelt, O.; Kremer, J.; Tilse, A.; Keogh, J.; Pentz, K.R.; Younes, M.

    1996-02-01

    The toxic effects of cadmium, mercury, and copper were compared over the range 0.01, 0.03, and 0.1 mM using the isolated perfused rat liver preparation. All metals caused similar changes in various parameters used to describe general toxicity. Reductions in oxygen consumption, perfusion flow, and biliary secretion were found, while lactate dehydrogenase release , as well as liver weight, increased in a dose-dependent fashion. Each metal caused similar magnitudes of changes and exerted similar potency. Measurement of other parameters revealed a number of differences. Although all metals reduced hepatic ATP concentration, mercury and cadmium were more potent than copper. Cadmium was the most potent at decreasing reduced glutathione levels. Mercury was most effective at increasing tissue calcium content, while copper was less so, and cadmium ineffective. Only copper significantly increased tissue malondialdehyde (MDA) content, while all metals increased its release into perfusate, cadmium seemed the most potent metal in increasing MDA release, but it was least efficacious, while copper was the most. Antioxidants such as superoxide dismutase, catalase, and Trolox C only reduced cadmium`s influence on MDA in perfusate; but did not affect cadmium`s ability to alter most other parameters of vitality. Albumin reversed the toxic effects of copper and mercury, but not cadmium. While metal-induced reductions in perfusion flow accounted for some of the toxic effects of the metals, the results as a whole supported the suggestion that all metals exerted toxicity at the mitochondria, since ATP levels were reduced in a manner that could not be reproduced by perfusion flow reduction alone. Lipid peroxidation appears to play little role in determining toxicity induced by any of these metals. Furthermore, albumin may play an important physiological role in preventing hepatic injury that might otherwise be induced through acute metal intoxication. 40 refs., 4 figs., 2 tabs.

  14. A micro-perfusion bioreactor for on line investigation of ECM remodeling under hydrodynamic and biochemical stimulation.

    PubMed

    Garziano, A; Urciuolo, F; Imparato, G; Martorina, F; Corrado, B; Netti, P

    2016-03-07

    Tissue-on-chip (TOC) systems aim at replicating complex biological dynamics in vitro with the potential either to improve the understanding of human biology or to develop more accurate therapeutic strategies. To replicate faithfully the intricate interrelationships between cells and their surrounding microenvironment, the three-dimensional (3D) tissue model must possess a responsive extracellular matrix (ECM). ECM remodeling plays a pivotal role in guiding cells and tissues functions and such aspect is somewhat denied during in vitro studies. For this purpose, we fabricated a micro-perfusion bioreactor capable to sustain the viability of 3D engineered tissue models recapitulating the process of the native ECM deposition and assembly. Engineered human dermis micro-tissue precursors (HD-μTP) were used as building blocks to generate a final tissue. HD-μTP were loaded in the perfusion space of the micro-perfusion bioreactor and, under the superimposition of different fluid dynamic regimes and biochemical stimulation, they synthesized new collagen proteins that were, then, assembled in the perfusion space forming a continuum of cells embedded in their own ECM. The micro-perfusion bioreactor was fabricated to allow the on-line monitoring of the oxygen consumption and the assembly of the newly formed collagen network via real time acquisition of the second harmonic generation (SHG) signal. The possibility to detect the collagen reorganization due to both fluid dynamic and biochemical stimulation, let us to define the optimal perfusion configuration in order to obtain a TOC system based on an endogenous and responsive ECM.

  15. Multiple-indicator dilution technique for characterization of normal and retrograde flow in once-through rat liver perfusions

    SciTech Connect

    St-Pierre, M.V.; Schwab, A.J.; Goresky, C.A.; Lee, W.F.; Pang, K.S.

    1989-02-01

    The technique of normal and retrograde rat liver perfusion has been widely used to probe zonal differences in drug-metabolizing activities. The validity of this approach mandates the same tissue spaces being accessed by substrates during both normal and retrograde perfusions. Using the multiple-indicator dilution technique, we presently examine the extent to which retrograde perfusion alters the spaces accessible to noneliminated references. A bolus dose of 51Cr-labeled red blood cells, 125I-albumin, 14C-sucrose and 3H2O was injected into the portal (normal) or hepatic (retrograde) vein of rat livers perfused at 10 ml per min per liver. The outflow perfusate was serially collected over 220 sec to characterize the transit times and the distribution spaces of the labels. During retrograde perfusion, red blood cells, albumin and sucrose profiles peaked later and lower than during normal perfusion, whereas the water curves were similar. The transit times of red blood cells, albumin and sucrose were longer (p less than 0.005), whereas those for water did not change. Consequently, retrograde flow resulted in significantly larger sinusoidal blood volumes (45%), albumin Disse space (42%) and sucrose Disse space (25%) than during normal flow, whereas the distribution spaces for total and intracellular water remained unaltered. The distension of the vascular tree was confirmed by electron microscopy, by which occasional isolated foci of widened intercellular recesses and spaces of Disse were observed. Cellular ultrastructure was otherwise unchanged, and there was no difference found between normal and retrograde perfusion for bile flow rates, AST release, perfusion pressure, oxygen consumption and metabolic removal of ethanol, a substrate with flow-limited distribution, which equilibrates rapidly with cell water (hepatic extraction ratios were virtually identical: normal vs. retrograde, 0.50 vs. 0.48 at 6 to 7.4 mM input concentration).

  16. Indocyanine green-enhanced fluorescence for assessing parathyroid perfusion during thyroidectomy

    PubMed Central

    Liu, Xiaoli; Wu, Chewei; Anuwong, Angkoon; Kim, Hoon Yub; Liu, Renbin; Randolph, Gregory W.; Inversini, Davide; Boni, Luigi; Rausei, Stefano; Frattini, Francesco; Dionigi, Gianlorenzo

    2016-01-01

    Identification of the parathyroid glands during thyroid surgery may prevent their inadvertent surgical removal and thus provide a better postoperative quality of life. Nevertheless, the most common “technique” for intraoperative evaluation of perfusion of parathyroid gland tissues during thyroid surgery is visual inspection of the physical condition of tissues, e.g., their color and bleeding edges. Another technique is measurement of intact parathyroid hormone. Recently, indocyanine green-enhanced fluorescence has been used in various surgical techniques, particularly laparoscopic surgery, to improve visualization and to provide detailed anatomical information. Fluorescent optical guidance helps surgeons to avoid inadvertent tissue injury while enhancing procedural efficiency. This technique has potential use for evaluating perfusion of the parathyroid gland in real-time intraoperative angiography. PMID:27867866

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

    NASA Astrophysics Data System (ADS)

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

    2003-05-01

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

  18. Modulation of perfusion and oxygenation by red blood cell oxygen affinity during acute anemia.

    PubMed

    Cabrales, Pedro; Tsai, Amy G; Intaglietta, Marcos

    2008-03-01

    Responses to exchange transfusion using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen (O(2)) affinity were studied in the hamster window chamber model during acute anemia to determine its role on microvascular perfusion and tissue oxygenation. Allosteric effectors were introduced in the RBCs by electroporation. Inositol hexaphosphate (IHP) and 5-hydroxymethyl-2-furfural (5HMF) were used to decrease and increase Hb-O(2) affinity. In vitro P50s (partial pressure of O(2) at 50% Hb saturation) were modified to 10, 25, 45, and 50 mm Hg (normal P50 is 32 mm Hg). Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kD to 18% hematocrit (Hct). Modified RBCs (at 18% Hct in 5% albumin solution) were infused by exchange transfusion of 35% of blood volume. Systemic parameters, microvascular perfusion, capillary perfusion (functional capillary density, FCD), and microvascular Po(2) levels were measured. RBcs with P50 of 45 mm Hg increased tissue Po(2) and decreased O(2) delivery (Do(2)) and extraction (Vo(2)) and RBCs with P50 of 60 mmHg reduced FCD, microvascular flow, tissue Po(2), Do(2) and Vo(2). Erythrocytes with increased Hb-O(2) affinity maintained hemodynamic conditions, Do(2) and decreased tissue Po(2). This study shows that in an anemic condition, maximal tissue Po(2) does not correspond to maximal Do(2) and Vo(2).

  19. Distal limb perfusion: Achilles' heel in peripheral venoarterial extracorporeal membrane oxygenation.

    PubMed

    Mohite, Prashant N; Fatullayev, Javid; Maunz, Olaf; Kaul, Sundip; Sabashnikov, Anton; Weymann, Alexander; Saez, Diana G; Patil, Nikhil P; Zych, Bartlomiej; Popov, Aron F; DeRobertis, Fabio; Bahrami, Toufan; Amrani, Mohamed; Simon, Andre R

    2014-11-01

    Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory assist method that offers circulatory as well as respiratory support efficiently via peripheral access; however, it is liable to complications. Limb ischemia is one of the notorious complications of ECMO but can be avoided utilizing a proper distal limb perfusion method. A retrospective study of patients undergoing peripheral venoarterial (VA) ECMO for various reasons between June 2010 and December 2012 was performed. All patients were evaluated by our multidisciplinary team for suitability as candidates for ECMO. A peripheral VA-ECMO circuit was implanted via groin: inflow cannula in the femoral vein, an outflow cannula and distal-perfusion cannula, or an introducer sheath in the femoral artery. During the study period, 83 patients underwent various types of ECMO; 45 received peripheral VA-ECMO. Distal limb perfusion was achieved with an introducer sheath (6-8 Fr) in 13 cases and with a distal-perfusion cannula (10-12 Fr) in 32 cases. Nine (20%) patients developed signs of ischemia; five (11.2%) were treated conservatively, while four (8.8%) required surgical intervention. One patient required a below-knee amputation. The incidences of limb ischemia and limb ischemia requiring surgical intervention were significantly higher for the introducer sheath compared with the cannula (30.6 vs. 15.6% and 15.4 vs. 6.25%, respectively). Moreover, the patients supported on ECMO with a distal-perfusion cannula spent a significantly longer time on ECMO compared with the ones in whom an introducer sheath was used (11.9 ± 9.1 vs. 7.7 ± 4.3 days). The mean cannula size was significantly greater than the mean introducer sheath size (11.1 ± 1.3 vs. 7.0 ± 1.1 Fr). Use of a distal-perfusion cannula is a most reliable method of limb perfusion in peripheral VA-ECMO. The cannula can ensure adequate and smooth perfusion of the limb owing to its large caliber, its less turbulent flow, the ability it

  20. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-07

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

  1. Genetic modification of preimplantation embryos: toward adequate human research policies.

    PubMed

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects.

  2. Elements for adequate informed consent in the surgical context.

    PubMed

    Abaunza, Hernando; Romero, Klaus

    2014-07-01

    Given a history of atrocities and violations of ethical principles, several documents and regulations have been issued by a wide variety of organizations. They aim at ensuring that health care and clinical research adhere to defined ethical principles. A fundamental component was devised to ensure that the individual has been provided the necessary information to make an informed decision regarding health care or participation in clinical research. This article summarizes the history and regulations for informed consent and discusses suggested components for adequate consent forms for daily clinical practice in surgery as well as clinical research.

  3. Is correction necessary when clinically determining quantitative cerebral perfusion parameters from multi-slice dynamic susceptibility contrast MR studies?

    PubMed

    Salluzzi, M; Frayne, R; Smith, M R

    2006-01-21

    Several groups have modified the standard singular value decomposition (SVD) algorithm to produce delay-insensitive cerebral blood flow (CBF) estimates from dynamic susceptibility contrast (DSC) perfusion studies. However, new dependences of CBF estimates on bolus arrival times and slice position in multi-slice studies have been recently recognized. These conflicting findings can be reconciled by accounting for several experimental and algorithmic factors. Using simulation and clinical studies, the non-simultaneous measurement of arterial and tissue concentration curves (relative slice position) in a multi-slice study is shown to affect time-related perfusion parameters, e.g. arterial-tissue-delay measurements. However, the current clinical impact of relative slice position on amplitude-related perfusion parameters, e.g. CBF, can be expected to be small unless any of the following conditions are present individually or in combination: (a) high concentration curve signal-to-noise ratios, (b) small tissue mean transit times, (c) narrow arterial input functions or (d) low temporal resolution of the DSC image sequence. Recent improvements in magnetic resonance (MR) technology can easily be expected to lead to scenarios where these effects become increasingly important sources of inaccuracy for all perfusion parameter estimates. We show that using Fourier interpolated (high temporal resolution) residue functions reduces the systematic error of the perfusion parameters obtained from multi-slice studies.

  4. Perfusion culture-induced template-assisted assembling of cell-laden microcarriers is a promising route for fabricating macrotissues.

    PubMed

    Wang, Xiu; Jiao, Qingling; Zhang, Songjie; Ye, Zhaoyang; Zhou, Yan; Tan, Wen-Song

    2014-11-01

    Mass transfer limitation in conventional top-down tissue engineering makes it impossible to fabricate large size viable tissue replacements. In the present study, we aimed at performing a systemic investigation of the assembling process in perfusion culture for fabricating centimeter-scale macrotissues from cell-laden microcarriers following a bottom-up modular approach. Cells (human fibroblasts, human mesenchymal stem cells, or HepG2 cells) were seeded onto microcarriers (Cytopore-2 or CultiSpher S) in spinner flasks and cultured for 14 days and subsequently transferred to a perfusion chamber for assembling. It was found that growth of different cells on different microcarriers varied and aggregation of cell-laden microcarriers was favored with CultiSpher S. After perfusion culture for 14 days, while all microtissues could assemble into integral macrotissues, macrotissues of HepG2 cells were structurally most inferior and the assembling of cell-laden CultiSpher S led to a significant shrinkage. By designing perfusion chamber and using agar-based templates, tubular, disc, and alphabetic letter-shaped macrotissues could be easily fabricated, suggesting template-assisted assembling. Importantly, it was revealed that there existed both optimal perfusion culture time (21 days) and packing condition (1/4 compression) for the assembling of microtissues. This study lays a solid foundation for future applications of this microtissue assembling technique in tissue engineering.

  5. Effects of pressure on the shear modulus, mass and thickness of the perfused porcine kidney.

    PubMed

    Helfenstein, C; Gennisson, J-L; Tanter, M; Beillas, P

    2015-01-02

    Eleven fresh ex vivo porcine kidneys were perfused in the artery, vein and ureter with degassed Dulbecco׳s Modified Eagle Medium (DMEM). The effect of perfusion pressure was evaluated using ten different pressures combinations. The shear modulus of the tissues was estimated during perfusion using shear wave elastography. The organ weight change was measured by a digital scale and cameras were used to follow the changes of the dimensions after each pressure combination. The effect of perfusion on the weight and the thickness was non-reversible, whereas the effect on the shear modulus was reversible. Pressure was found to increase the average shear modulus in the cortex by as much as 73%. A pressure of 80 mmHg was needed to observe tissues shear modulus in the same range as in vivo tests (Gcortex=9.1 kPa, Gmedulla=8.5 kPa ex vivo versus Gcortex=9.1 kPa, Gmedulla=8.7 kPa in vivo in Gennisson et al., 2012).

  6. Quantifying dose to the reconstructed breast: Can we adequately treat?

    SciTech Connect

    Chung, Eugene; Marsh, Robin B.; Griffith, Kent A.; Moran, Jean M.; Pierce, Lori J.

    2013-04-01

    To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V{sub 20}. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

  7. Synthesis of Essential Amino Acids from Their α-Keto Analogues by Perfused Rat Liver and Muscle

    PubMed Central

    Walser, Mackenzie; Lund, Patricia; Ruderman, Neil B.; Coulter, A. W.

    1973-01-01

    Most essential amino acids can be replaced by their α-keto-analogues in the diet. These ketoacids have therefore been proposed as substitutes for dietary protein. In order to determine their fate in tissues of normal animals, isolated rat liver and hindquarter (muscle) preparations were perfused with keto-analogues of valine, leucine, isoleucine, methionine, or phenylalanine. When perfused at 1.5-2.0 mM, all five compounds were utilized rapidly by the liver of 48-h starved rats, at rates varying from 49 to 155 μmol/h per 200g rat. The corresponding amino acids appeared in the medium in significantly increased concentrations. Perfusion with phenylpyruvate also led to the appearance of tyrosine. Urea release was unaltered. Measurement of metabolite concentrations in freeze-clamped liver revealed two abnormalities, particularly at ketoacid concentrations of 5 mM or above: a large increase in α-ketoglutarate, and a moderate to marked decrease in tissue glutamine. This decrease was quantitatively sufficient to account for nitrogen appearing in newly synthesized amino acids. Isolated hindquarters of fed rats were perfused with the same ketoacids at concentrations of 1.3-8.0 mM. All were utilized at rates varying from 1.4 to 7.0 μmol/h per g muscle perfused. The corresponding amino acids were released at greatly increased rates. Alanine and glutamate levels fell in some perfusions, but the principal nitrogen donor in muscle was not identified; the content of glutamine in tissue, and its rate of release into the perfusate remained constant. PMID:4748513

  8. Development and validation of a segmentation-free polyenergetic algorithm for dynamic perfusion computed tomography.

    PubMed

    Lin, Yuan; Samei, Ehsan

    2016-07-01

    Dynamic perfusion imaging can provide the morphologic details of the scanned organs as well as the dynamic information of blood perfusion. However, due to the polyenergetic property of the x-ray spectra, beam hardening effect results in undesirable artifacts and inaccurate CT values. To address this problem, this study proposes a segmentation-free polyenergetic dynamic perfusion imaging algorithm (pDP) to provide superior perfusion imaging. Dynamic perfusion usually is composed of two phases, i.e., a precontrast phase and a postcontrast phase. In the precontrast phase, the attenuation properties of diverse base materials (e.g., in a thorax perfusion exam, base materials can include lung, fat, breast, soft tissue, bone, and metal implants) can be incorporated to reconstruct artifact-free precontrast images. If patient motions are negligible or can be corrected by registration, the precontrast images can then be employed as a priori information to derive linearized iodine projections from the postcontrast images. With the linearized iodine projections, iodine perfusion maps can be reconstructed directly without the influence of various influential factors, such as iodine location, patient size, x-ray spectrum, and background tissue type. A series of simulations were conducted on a dynamic iodine calibration phantom and a dynamic anthropomorphic thorax phantom to validate the proposed algorithm. The simulations with the dynamic iodine calibration phantom showed that the proposed algorithm could effectively eliminate the beam hardening effect and enable quantitative iodine map reconstruction across various influential factors. The error range of the iodine concentration factors ([Formula: see text]) was reduced from [Formula: see text] for filtered back-projection (FBP) to [Formula: see text] for pDP. The quantitative results of the simulations with the dynamic anthropomorphic thorax phantom indicated that the maximum error of iodine concentrations can be reduced from

  9. Comparison of the effects of adenine-ribose with adenosine for maintenance of ATP concentrations in 5-day hypothermically perfused dog kidneys.

    PubMed

    McAnulty, J F; Southard, J H; Belzer, F O

    1988-10-01

    The quality of preservation of kidneys is dependent upon a number of factors, one of which may be the concentration of adenine nucleotides in the tissue during long-term perfusion preservation. In this study we have investigated how adenine (5 mM) and ribose (5 mM) in combination affect the concentration of adenine nucleotides in dog kidney cortical tissue after 5 days of continuous hypothermic perfusion preservation. These results were compared to kidneys perfused with adenosine and without any added purine precursors of adenine nucleotide synthesis. Additionally, we investigated how these conditions affected renal tissue slice function after 5 days of preservation and how adenine plus ribose affected renal function after autotransplantation in the dog. Adenosine is nearly completely degraded during 5 days of perfusion but there was little loss of adenine (10%). The adenosine triphosphate concentration in kidney cortical tissue was higher in adenine/ribose-perfused kidneys (1.41 +/- 0.19 mumol/g) than in adenosine-perfused kidneys (0.71 +/- 0.1 mumol/g) after 5 days of preservation. Tissue slices prepared from kidneys preserved in the presence of adenine plus ribose were metabolically more functional (slice volume control and electrolyte pump activity) than slices from adenosine-perfused kidneys. Adenine plus ribose had no detrimental effects on kidneys preserved for 3 days as tested in the autotransplant model but did not yield successful 5-day preservation. Because of some potentially detrimental factors in using adenosine as an adenine nucleotide synthesis precursor, we have now switched to the combination of adenine and ribose for perfusion preservation of kidneys both in the laboratory and in the clinic.

  10. Multimodal imaging of cutaneous wound tissue

    NASA Astrophysics Data System (ADS)

    Zhang, Shiwu; Gnyawali, Surya; Huang, Jiwei; Ren, Wenqi; Gordillo, Gayle; Sen, Chandan K.; Xu, Ronald

    2015-01-01

    Quantitative assessment of wound tissue ischemia, perfusion, and inflammation provides critical information for appropriate detection, staging, and treatment of chronic wounds. However, few methods are available for simultaneous assessment of these tissue parameters in a noninvasive and quantitative fashion. We integrated hyperspectral, laser speckle, and thermographic imaging modalities in a single-experimental setup for multimodal assessment of tissue oxygenation, perfusion, and inflammation characteristics. Algorithms were developed for appropriate coregistration between wound images acquired by different imaging modalities at different times. The multimodal wound imaging system was validated in an occlusion experiment, where oxygenation and perfusion maps of a healthy subject's upper extremity were continuously monitored during a postocclusive reactive hyperemia procedure and compared with standard measurements. The system was also tested in a clinical trial where a wound of three millimeters in diameter was introduced on a healthy subject's lower extremity and the healing process was continuously monitored. Our in vivo experiments demonstrated the clinical feasibility of multimodal cutaneous wound imaging.

  11. Computed tomography perfusion imaging denoising using Gaussian process regression

    NASA Astrophysics Data System (ADS)

    Zhu, Fan; Carpenter, Trevor; Rodriguez Gonzalez, David; Atkinson, Malcolm; Wardlaw, Joanna

    2012-06-01

    Brain perfusion weighted images acquired using dynamic contrast studies have an important clinical role in acute stroke diagnosis and treatment decisions. However, computed tomography (CT) images suffer from low contrast-to-noise ratios (CNR) as a consequence of the limitation of the exposure to radiation of the patient. As a consequence, the developments of methods for improving the CNR are valuable. The majority of existing approaches for denoising CT images are optimized for 3D (spatial) information, including spatial decimation (spatially weighted mean filters) and techniques based on wavelet and curvelet transforms. However, perfusion imaging data is 4D as it also contains temporal information. Our approach using Gaussian process regression (GPR), which takes advantage of the temporal information, to reduce the noise level. Over the entire image, GPR gains a 99% CNR improvement over the raw images and also improves the quality of haemodynamic maps allowing a better identification of edges and detailed information. At the level of individual voxel, GPR provides a stable baseline, helps us to identify key parameters from tissue time-concentration curves and reduces the oscillations in the curve. GPR is superior to the comparable techniques used in this study.

  12. Ocular perfusion pressure and ocular blood flow in glaucoma

    PubMed Central

    Cherecheanu, A Popa; Garhofer, G; Schmidl, D; Werkmeister, R; Schmetterer, L

    2013-01-01

    Glaucoma is a progressive optic neuropathy of unknown origin. It has been hypothesized that a vascular component is involved in glaucoma pathophysiology. This hypothesis has gained support from studies showing that reduced ocular perfusion pressure is a risk factor for the disease. The exact nature of the involvement is, however, still a matter of debate. Based on recent evidence we propose a model including primary and secondary insults in glaucoma. The primary insult appears to happen at the optic nerve head. Increased intraocular pressure and ischemia at the post-laminar optic nerve head affects retinal ganglion cell axons. Modulating factors are the biomechanical properties of the tissues and cerebrospinal fluid pressure. After this primary insult retinal ganglion cells function at a reduced energy level and are sensitive to secondary insults. These secondary insults may happen if ocular perfusion pressure falls below the lower limit of autoregulation or if neurovascular coupling fails. Evidence for both faulty autoregulation and reduced hyperemic response to neuronal stimulation has been provided in glaucoma patients. The mechanisms appear to involve vascular endothelial dysfunction and impaired astrocyte-vessel signaling. A more detailed understanding of these pathways is required to direct neuroprotective strategies via the neurovascular pathway. PMID:23009741

  13. Endoscopic ICG perfusion imaging for flap transplants: technical development

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Schachenmayr, Hilmar; Ehrhardt, André; Göbel, Werner; Zhorzel, Sven; Betz, Christian Stephan

    2010-02-01

    Objective: Following tumour surgery in the head and neck region, skin flap transplants are usually required to cover the resection area. The purpose of the development was to provide a simple and reliable means to assess whether the transplanted flap is sufficiently perfused. Methods: Fluorescence of intravenously injected Indocyanine green (ICG) was detected with a slightly modified 3-chip CCD camera. Appropriately coated optical filters allow for excitation of ICG with NIR light and detection of NIR ICGfluorescence with the blue channel of the camera. In addition, low intensities of white light can be transmitted to allow for simultaneous display of a remission image in the green and red channels of the camera. Further processing was performed with a LabVIEW program. Results: A satisfactory white light image (red, green and blue display (RGB)) could be calculated from the remission images recorded with the green and red channels of the camera via a look-up table. The look-up table was programmed to provide an optimized blue intensity value for each combination of red and green values. This was generated using a reference image. Implementation of image tracking and intensity measurements in regions of interest (ROIs) in the images is useful to reliably monitor perfusion kinetics of flap and adjacent normal tissue.

  14. Myocardial perfusion scintigraphy: the evidence

    PubMed Central

    Anagnostopoulos, C.; Cerqueira, M.; Ell, P. J.; Flint, E. J.; Harbinson, M.; Kelion, A. D.; Al-Mohammad, A.; Prvulovich, E. M.; Shaw, L. J.; Tweddel, A. C.

    2003-01-01

    This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by

  15. Perfusion-diffusion mismatch: does it identify who will benefit from reperfusion therapy?

    PubMed

    Powers, William J

    2012-06-01

    A method to determine which patients would benefit from reperfusion therapies after 4.5 h would greatly add to our ability to reduce the disability caused by stroke. The goal of magnetic resonance perfusion-diffusion imaging in hyperacute ischemic stroke is to identify regions of the brain that will die if untreated and will live and regain function if quickly reperfused. The clinical value of perfusion-diffusion imaging in hyperacute ischemic stroke can be proven only by demonstrating empirically in a randomized controlled trial (RCT) that there is an improvement in patient outcome that depends on the use of the neuroimaging modality to guide therapy. To date, there have been only a few RCTs that have evaluated whether perfusion-diffusion imaging can identify a subgroup of patients with ischemic stroke more than 4.5 h from onset in whom the overall benefit from reperfusion therapy outweighs the risk. None have met the rigorous design requirements of the three-group study necessary to adequately test this hypothesis, and none have even met their own criteria for demonstrating a clinical benefit. While studies are not sufficient to conclusively disprove the hypothesis there are no RCT data to support it, and thus, the clinical value of MRI perfusion-diffusion imaging in this setting remains unproven. It is worthy of further investigation in rigorously designed RCTs. However, the risks of symptomatic intracerebral hemorrhage with reperfusion therapies in acute ischemic stroke are proven. Unless RCT data are forthcoming to demonstrate that MRI perfusion-diffusion mismatch improves clinical outcome, it should not be used to guide delayed reperfusion therapy.

  16. Prostate cancer between prognosis and adequate/proper therapy

    PubMed Central

    Grozescu, T; Popa, F

    2017-01-01

    Knowing the indolent, non-invasive nature of most types of prostate cancer, as well as the simple fact that the disease seems more likely to be associated with age rather than with other factors (50% of men at the age of 50 and 80% at the age of 80 have it [1], with or without presenting any symptom), the big challenge of this clinical entity was to determine severity indicators (so far insufficient) to guide the physician towards an adequate attitude in the clinical setting. The risk of over-diagnosing and over-treating many prostate cancer cases (indicated by all the major European and American studies) is real and poses many question marks. The present paper was meant to deliver new research data and to reset the clinical approach in prostate cancer cases. PMID:28255369

  17. The cerebellopontine angle: does the translabyrinthine approach give adequate access?

    PubMed

    Fagan, P A; Sheehy, J P; Chang, P; Doust, B D; Coakley, D; Atlas, M D

    1998-05-01

    A long-standing but unfounded criticism of the translabyrinthine approach is the misperception that this approach does not give adequate access to the cerebellopontine angle. Because of what is perceived as limited visualization and operating space within the cerebellopontine angle, some surgeons still believe that the translabyrinthine approach is inappropriate for large acoustic tumors. In this study, the surgical access to the cerebellopontine angle by virtue of the translabyrinthine approach is measured and analyzed. The parameters are compared with those measured for the retrosigmoid approach. This series objectively confirms that the translabyrinthine approach offers the neurotologic surgeon a shorter operative depth to the tumor, via a similar-sized craniotomy. This permits superior visualization by virtue of a wider angle of surgical access. Such access is achieved with the merit of minimal cerebellar retraction.

  18. Barriers to adequate prenatal care utilization in American Samoa

    PubMed Central

    Hawley, Nicola L; Brown, Carolyn; Nu’usolia, Ofeira; Ah-Ching, John; Muasau-Howard, Bethel; McGarvey, Stephen T

    2013-01-01

    Objective To describe the utilization of prenatal care in American Samoan women and to identify socio-demographic predictors of inadequate prenatal care utilization. Methods Using data from prenatal clinic records, women (n=692) were categorized according to the Adequacy of Prenatal Care Utilization Index as having received adequate plus, adequate, intermediate or inadequate prenatal care during their pregnancy. Categorical socio-demographic predictors of the timing of initiation of prenatal care (week of gestation) and the adequacy of received services were identified using one way Analysis of Variance (ANOVA) and independent samples t-tests. Results Between 2001 and 2008 85.4% of women received inadequate prenatal care. Parity (P=0.02), maternal unemployment (P=0.03), and both parents being unemployed (P=0.03) were negatively associated with the timing of prenatal care initation. Giving birth in 2007–2008, after a prenatal care incentive scheme had been introduced in the major hospital, was associated with earlier initiation of prenatal care (20.75 versus 25.12 weeks; P<0.01) and improved adequacy of received services (95.04% versus 83.8%; P=0.02). Conclusion The poor prenatal care utilization in American Samoa is a major concern. Improving healthcare accessibility will be key in encouraging women to attend prenatal care. The significant improvements in the adequacy of prenatal care seen in 2007–2008 suggest that the prenatal care incentive program implemented in 2006 may be a very positive step toward addressing issues of prenatal care utilization in this population. PMID:24045912

  19. Imaging of myocardial perfusion with magnetic resonance.

    PubMed

    Barkhausen, Jörg; Hunold, Peter; Jochims, Markus; Debatin, Jörg F

    2004-06-01

    Coronary artery disease (CAD) is currently the leading cause of death in developed nations. Reflecting the complexity of cardiac function and morphology, noninvasive diagnosis of CAD represents a major challenge for medical imaging. Although coronary artery stenoses can be depicted with magnetic resonance (MR) and computed tomography (CT) techniques, its functional or hemodynamic impact frequently remains elusive. Therefore, there is growing interest in other, target organ-specific parameters such as myocardial function at stress and first-pass myocardial perfusion imaging to assess myocardial blood flow. This review explores the pathophysiologic background, recent technical developments, and current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

  20. CT Mapping of the Distribution of Saline During Radiofrequency Ablation with Perfusion Electrodes

    SciTech Connect

    Gillams, A.R. Lees, W.R.

    2005-05-15

    Purpose. During radiofrequency (RF) ablation, adjunctive saline increases the size of the ablation zone and therefore electrodes that simultaneously deliver current and saline have been developed, but the addition of saline also results in an irregular ablation zone. Our aim was to study the distribution of saline during RF ablation. Methods. Four patients were treated: 3 with liver metastases and 1 with hepatocellular carcinoma (HCC). Two different perfusion electrodes were used: a high-perfusion-rate, straight electrode (Berchtold, Germany) and a low-perfusion-rate, expandable electrode (RITA Medical Systems, USA). The saline perfusate was doped with non-ionic contrast medium to render it visible on CT and the electrical conductivity was measured. CT scans were obtained of each electrode position prior to ablation and repeated after ablation. Contrast-enhanced CT was performed 18-24 hr later to demonstrate the ablation zone. All treatments were carried out according to the manufacturer's recommended protocol. Results. The addition of a small quantity of non-ionic contrast did not alter the electrical conductivity of the saline. Contrast-doped saline extravasated beyond the tumor in all 3 patients with metastases but was limited in the patient with HCC. In some areas where saline had extravasated there was reduced enhancement on contrast-enhanced CT consistent with tissue ablation. One patient treated with the high-perfusion-rate system sustained a jejunal perforation requiring surgery. Conclusion. Saline can extravasate beyond the tumor and with the high-perfusion-rate system this resulted in an undesirable extension of the ablation zone and a complication.

  1. The mesenterially perfused rat small intestine: A versatile approach for pharmacological testings.

    PubMed

    Schreiber, Dominik; Klotz, Markus; Laures, Kerstin; Clasohm, Jasmin; Bischof, Michael; Schäfer, Karl-Herbert

    2014-05-01

    Pharmaceutical compounds enter the body via several major natural gateways; i.e. the lung, the skin and the gastrointestinal tract. Drug application during surgical operations can lead to severe impairment of gastrointestinal motility, which can contribute to a paralytic ileus. Here we investigated an ex vivo perfused small intestine model that allows us to ascertain the influence of pharmaceuticals upon the gut. Corresponding segments from the proximal jejunum of adult rats were used. Their mesenteric arteries and veins were cannulated and the jejunal segment excised. The individual segments were placed in a custom designed perfusion chamber and perfusion performed through the intestinal lumen as well as the mesenteric superior artery. Three test drugs, which are commonly used in anesthesiology; i.e. pentobarbital, propofol and ketamine were administered via the blood vessels. Their effects upon gastrointestinal motility patterns were evaluated by optical measurements. Longitudinal and pendular movements were distinguishable and separately analyzed. Pharmacological effects of the individual substances could be investigated. Propofol (50-200 μg/ml) was found to decrease intestinal motility, especially longitudinal movements in a dose dependent manner. Pentobarbital decreased intestinal motility only at high concentrations, above 2.5 mg/ml. A dose of 2.5 mg/ml lead to an increase in longitudinal- and pendular movements in comparison to control, while ketamine (2.5-10 mg/ml) did not alter intestinal motility at all. Histological examination of the perfused segments revealed only minor changes in tissue morphology after perfusion. The perfusion approach shown here allows for the identification of compounds which interfere with gut motility in a highly sophisticated way. It is suitable for characterization of drug and dose specific changes in motility patterns and can be used in drug development and preclinical studies.

  2. Reproducibility and variability of very low dose hepatic perfusion CT in metastatic liver disease

    PubMed Central

    Topcuoğlu, Osman Melih; Karçaaltıncaba, Muşturay; Akata, Deniz; Özmen, Mustafa Nasuh

    2016-01-01

    PURPOSE We aimed to determine the intra- and interobserver agreement on the software analysis of very low dose hepatic perfusion CT (pCT). METHODS A total of 53 pCT examinations were obtained from 21 patients (16 men, 5 women; mean age, 60.4 years) with proven liver metastasis from various primary cancers. The pCT examinations were analyzed by two readers independently and perfusion parameters were noted for whole liver, whole metastasis, metastasis wall, and normal-looking liver (liver tissue without metastasis) in regions of interest (ROIs). Readers repeated the analysis after an interval of one month. Intra- and interobserver agreements were assessed with intraclass correlation coefficients (ICC) and Bland-Altman statistics. RESULTS The mean ICCs of all ROIs between readers were 0.91, 0.93, 0.86, 0.45, 0.53, and 0.66 for blood flow (BF), blood volume (BV), permeability, arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI), respectively. The mean ICCs of all ROIs between readings were 0.86, 0.91, 0.81, 0.53, 0.56, and 0.71 for BF, BV, permeability, ALP, PVP, and HPI, respectively. There was greater agreement on the parameters measured for the whole metastasis than on the parameters measured for the metastasis wall. The effective dose of all perfusion CT studies was 2.9 mSv. CONCLUSION There is greater intra- and interobserver agreement for BF and BV than for permeability, ALP, PVP, and HPI at very low dose hepatic pCT. Permeability, ALP, PVP, and HPI parameters cannot be used in clinical practice for hepatic pCT with an effective dose of 2.9 mSv. PMID:27759566

  3. A novel portable perfused manometric system for recording of small intestinal motility.

    PubMed

    Samsom, M; Smout, A J; Hebbard, G; Fraser, R; Omari, T; Horowitz, M; Dent, J

    1998-04-01

    -channel silicone rubber manometric assembly with a portable perfusion system is a feasible technique which is relatively inexpensive. Computer-assisted data processing allows for adequate elimination of artefacts and automated numerical analysis.

  4. Selective cerebro-myocardial perfusion in complex congenital aortic arch pathology: a novel technique.

    PubMed

    De Rita, Fabrizio; Lucchese, Gianluca; Barozzi, Luca; Menon, Tiziano; Faggian, Giuseppe; Mazzucco, Alessandro; Luciani, Giovanni Battista

    2011-11-01

    . Renal function proved satisfactory in all, while liver function was adequate in all but one. The present experience suggests that selective and independent cerebro-myocardial perfusion is feasible in patients with complex or recurrent aortic arch disease, starting from premature newborn less than 2.0 kg of body weight to adults. The technique is as safe as previously reported methods of cerebro-myocardial perfusion and possibly more versatile.

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

    PubMed

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

    2014-09-01

    estimation is feasible, and provides a promising tool for decoupling perfusion and tissue volume.

  6. 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

  7. Role of hypothermic machine perfusion in liver transplantation.

    PubMed

    Schlegel, Andrea; Dutkowski, Philipp

    2015-06-01

    Machine liver perfusion has significantly evolved during the last ten years to optimize extended criteria liver grafts and to address the worldwide organ shortage. This review gives an overview on available ex vivo and in vivo data on hypothermic machine liver perfusion. We discuss also possible protective pathways and show most recent clinical applications of hypothermic machine liver perfusion in human.

  8. Imaging considerations for a technetium-99m myocardial perfusion agent

    SciTech Connect

    English, R.J.; Jones, A.G.; Davison, A.; Lister-James, J.; Campbell, S.; Holman, B.L.

    1986-03-01

    Myocardial perfusion imaging with /sup 201/Tl chloride suffers from a number of physical, geometric, and dosimetric constraints that could be diminished if an agent labeled with /sup 99m/Tc were available. The cationic complex /sup 99m/Tc hexakis-(t-butylisonitrile)technetium(I) ((/sup 99m/Tc)TBI) has been shown to concentrate in the myocardial tissue of both animals and humans, with preliminary clinical studies demonstrating a number of technical attributes not possible with /sup 201/Tl. Technetium-99m-TBI is a promising myocardial imaging agent that may permit high quality planar, gated, and tomographic imaging of both myocardial ischemia and infarction with reduced imaging times and improved resolution.

  9. Persufflation (gaseous oxygen perfusion) as a method of heart preservation

    PubMed Central

    2013-01-01

    Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed. PMID:23607734

  10. CAD system for automatic analysis of CT perfusion maps

    NASA Astrophysics Data System (ADS)

    Hachaj, T.; Ogiela, M. R.

    2011-03-01

    In this article, authors present novel algorithms developed for the computer-assisted diagnosis (CAD) system for analysis of dynamic brain perfusion, computer tomography (CT) maps, cerebral blood flow (CBF), and cerebral blood volume (CBV). Those methods perform both quantitative analysis [detection and measurement and description with brain anatomy atlas (AA) of potential asymmetries/lesions] and qualitative analysis (semantic interpretation of visualized symptoms). The semantic interpretation (decision about type of lesion: ischemic/hemorrhagic, is the brain tissue at risk of infraction or not) of visualized symptoms is done by, so-called, cognitive inference processes allowing for reasoning on character of pathological regions based on specialist image knowledge. The whole system is implemented in.NET platform (C# programming language) and can be used on any standard PC computer with.NET framework installed.

  11. Suivi in situ de cultures tridimensionnelles en bioreacteur a perfusion grace a la tomographie d'emission par positrons

    NASA Astrophysics Data System (ADS)

    Chouinard, Julie

    The continuous assessment of developing tissue substitutes is crucial to understand their evolution over time. However, this represents quite a challenge when thick samples must be evaluated with standard microscopy techniques. Common characterization methods are time consuming and usually result in the destruction of the culture. Real-time, in situ, non-invasive and non-destructives methods are needed to monitor the growth of large non-transparent constructs in tissue engineering. Medical imaging modalities, which can provide information on the structure and function of internal organs and tissues in living organisms, have the potential of allowing repetitive monitoring of these 3D cultures in vitro. The working hypothesis of this thesis was to establish standard noninvasive and nondestructive real-time bioreactor imaging protocols for in situ monitoring of the viability and metabolism of endothelial cells when grown in perfused 3D fibrin gel scaffolds. To achieve this goal, a culture chamber with hollow fibers was designed and a pulsatile perfusion bioreactor system, able to promote cell survival and proliferation, was constructed and validated. Standard imaging protocols in Positron Emission Tomography (PET) are not adapted to image bioreactor systems. A suitable method had to be devised using the well-known radiotracer 18F-fluorodeoxyglucose ( 18FDG), a marker of glucose metabolism. Optimal uptake conditions were determined using cell monolayers and the best parameters were then applied on perfused 3D cultures to evaluate perfusion, cell viability and emerging cell structures. After only 12 hours of culture, the cell density could be estimated and cell structures were localized within the fibrin gels after 1-2 weeks of culture. PET is a promising tool for tissue engineering with many specific tracers available that might eventually be able to reveal new information on tissue development. Key words: Endothelial cells, Perfusion bioreactor, Positron Emission

  12. Rheology of perfusates and fluid dynamical effects during whole organ decellularization: a perspective to individualize decellularization protocols for single organs.

    PubMed

    Hülsmann, Jörn; Aubin, Hug; Bandesha, Shahbaz T; Kranz, Alexander; Stoldt, Volker R; Lichtenberg, Artur; Akhyari, Payam

    2015-09-03

    The approach of whole organ decellularization is rapidly becoming more widespread within the tissue engineering community. Today it is well known that the effects of decellularization protocols may vary with the particular type of treated tissue. However, there are no methods known to individualize decellularization protocols while automatically ensuring a standard level of quality to minimize adverse effects on the resulting extracellular matrix. Here we follow this idea by introducing two novel components into the current practice. First, a non-invasive method for online monitoring of resulting fluid dynamical characteristics of the coronary system is demonstrated for application during the perfusion decellularization of whole hearts. Second, the observation of the underlying rheological characteristics of the perfusates is employed to detect ongoing progress and maturation of the decellularization process. Measured data were contrasted to the respective release of specific cellular components. We demonstrate rheological measurements to be capable of detecting cellular debris along with a discriminative capture of DNA and protein ratios. We demonstrate that this perfusate biomass is well correlated to the biomass loss in the extracellular matrix produced by decellularization. The appearance of biomass components in the perfusates could specifically reflect the appearance of fluid dynamical characteristics that we monitored during the decellularization process. As rheological measuring of perfusate samples can be done within minutes, without any time-consuming preparation steps, we predict this to be a promising novel analytic strategy to control decellularization protocols, in time, by the actual conditions of the processed organ.

  13. Lung Perfusion Scanning in Hepatic Cirrhosis

    PubMed Central

    Stanley, N. N.; Ackrill, P.; Wood, J.

    1972-01-01

    Abnormal lung perfusion scans using radioactive particles were found in five out of six cases of hepatic cirrhosis with arterial hypoxaemia. None had clinical evidence of cardiopulmonary disease or signs of pulmonary embolism on arteriography. The scan defects are probably caused by a disorder of the pulmonary microvasculature, which may show regional variation in severity. ImagesFIG. 1FIG. 2 PMID:4645896

  14. Coupling between resting cerebral perfusion and EEG.

    PubMed

    O'Gorman, R L; Poil, S-S; Brandeis, D; Klaver, P; Bollmann, S; Ghisleni, C; Lüchinger, R; Martin, E; Shankaranarayanan, A; Alsop, D C; Michels, L

    2013-07-01

    While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

  15. Nuclear cardiology: Myocardial perfusion and function

    SciTech Connect

    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; 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.

  16. 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

  17. Direct 3D bioprinting of perfusable vascular constructs using a blend bioink

    PubMed Central

    Jia, Weitao; Gungor-Ozkerim, P. Selcan; Zhang, Yu Shrike; Yue, Kan; Zhu, Kai; Liu, Wanjun; Pi, Qingment; Byambaa, Batzaya; Dokmeci, Mehmet Remzi; Shin, Su Ryon; Khademhosseini, Ali

    2017-01-01

    Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(-ethylene glycol)-tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also

  18. Leukotriene C4 action and metabolism in the isolated perfused bullfrog heart.

    PubMed

    Herman, R P; Heller, R S; Canavan, C M; Herman, C A

    1988-08-01

    The effects of leukotrienes (LTs) have been widely studied in the isolated perfused mammalian heart; however, little is known about the effect or metabolism of LTs in the isolated bullfrog heart. Isolated perfused bullfrog hearts were administered randomized doses of LTC4, LTD4, or LTE4. The cardiac parameters of heart rate, developed tension, and its first derivative (dT/dt) were recorded. LTC4 was the most potent of the leukotrienes tested in eliciting positive inotropic effects. LTD4 and LTE4 were equally effective but about one order of magnitude less potent than LTC4. None of the LTs showed any chronotropic effects in this preparation. A series of [3H]LTC4 metabolism experiments were carried out using whole perfused hearts and minced bullfrog heart tissue. Isolated perfused bullfrog hearts administered [3H]LTC4 converted significant amounts to [3H]LTD4, and to a lesser degree, [3H]LTE4, during the 6-min course of collection. Both minced atrial and ventricular tissue converted [3H]LTC4 to radioactive metabolites that co-migrated with authentic LTD4 and LTE4 standards. In both tissues, the major product was [3H]LTD4, with smaller amounts of [3H]LTE4 produced. The atrium converted significantly more [3H]LTC4 to its metabolites than did the ventricle. The metabolism of [3H]LTC4 to [3H]LTD4 by both tissues was virtually abolished in the presence of serine borate. Cysteine had no effect on [3H]LTE4 production. The data in this study demonstrate that leukotrienes have the opposite inotropic effect on the heart when compared with mammals. Also in contrast to mammals, frogs metabolize LTC4 to a less potent compound and may use the LTC4 to LTD4 conversion as a mechanism of LTC4 inactivation.

  19. Systemic Crisis of Civilization: In Search for Adequate Solution

    NASA Astrophysics Data System (ADS)

    Khozin, Grigori

    In December 1972 a jumbo jet crashed in the Florida Everglades with the loss of 101 lives. The pilot, distracted by a minor malfunction, failed to note until too late the warning signal that - correctly - indicated an impending disaster. His sudden, astonished cry of Hey, what happening here? were his last words 1. Three decades after this tragic episode, as the Humankind approaches the threshold of the third Millennium, the problem of adequate reaction to warning signals of different nature and of distinguishing minor malfunctions in everyday life of society, in economy and technology as well as in evolution of biosphere from grave threats to the world community and the phenomenon of life on our planet remains crucial to human survival and the future of Civilization. Rational use of knowledge and technology available to the world community remains in this context the corner stone of discussions on the destiny of the intelligent life both on the planet Earth and in the Universe (the fact of intelligent life in the Universe is to be detected by the Humankind)…

  20. ENSURING ADEQUATE SAFETY WHEN USING HYDROGEN AS A FUEL

    SciTech Connect

    Coutts, D

    2007-01-22

    Demonstration projects using hydrogen as a fuel are becoming very common. Often these projects rely on project-specific risk evaluations to support project safety decisions. This is necessary because regulations, codes, and standards (hereafter referred to as standards) are just being developed. This paper will review some of the approaches being used in these evolving standards, and techniques which demonstration projects can implement to bridge the gap between current requirements and stakeholder desires. Many of the evolving standards for hydrogen-fuel use performance-based language, which establishes minimum performance and safety objectives, as compared with prescriptive-based language that prescribes specific design solutions. This is being done for several reasons including: (1) concern that establishing specific design solutions too early will stifle invention, (2) sparse performance data necessary to support selection of design approaches, and (3) a risk-adverse public which is unwilling to accept losses that were incurred in developing previous prescriptive design standards. The evolving standards often contain words such as: ''The manufacturer shall implement the measures and provide the information necessary to minimize the risk of endangering a person's safety or health''. This typically implies that the manufacturer or project manager must produce and document an acceptable level of risk. If accomplished using comprehensive and systematic process the demonstration project risk assessment can ease the transition to widespread commercialization. An approach to adequately evaluate and document the safety risk will be presented.

  1. DARHT -- an adequate EIS: A NEPA case study

    SciTech Connect

    Webb, M.D.

    1997-08-01

    In April 1996 the US District Court in Albuquerque ruled that the Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility Environmental Impact Statement (EIS), prepared by the Los Alamos Area Office, US Department of Energy (DOE), was adequate. The DARHT EIS had been prepared in the face of a lawsuit in only 10 months, a third of the time usually allotted for a DOE EIS, and for only a small fraction of the cost of a typical DOE EIS, and for only a small fraction of the cost of a typical DOE EIS. It subject was the first major facility to be built in decades for the DOE nuclear weapons stockpile stewardship program. It was the first EIS to be prepared for a proposal at DOE`s Los Alamos National Laboratory since 1979, and the first ever prepared by the Los Alamos Area Office. Much of the subject matter was classified. The facility had been specially designed to minimize impacts to a nearby prehistoric Native American ruin, and extensive consultation with American Indian Pueblos was required. The week that the draft EIS was published Laboratory biologists identified a previously unknown pair of Mexican spotted owls in the immediate vicinity of the project, bringing into play the consultation requirements of the Endangered Species Act. In spite of these obstacles, the resultant DARHT EIS was reviewed by the court and found to meet all statutory and regulatory requirements; the court praised the treatment of the classified material which served as a basis for the environmental analysis.

  2. Dose Limits for Man do not Adequately Protect the Ecosystem

    SciTech Connect

    Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

    2004-08-01

    It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words, if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.

  3. Cardiac catecholamines in rats fed copper deficient or copper adequate diets containing fructose or starch

    SciTech Connect

    Scholfield, D.J.; Fields, M.; Beal, T.; Lewis, C.G.; Behall, K.M. )

    1989-02-09

    The symptoms of copper (Cu) deficiency are known to be more severe when rats are fed a diet with fructose (F) as the principal carbohydrate. Mortality, in males, due to cardiac abnormalities usually occurs after five weeks of a 62% F, 0.6 ppm Cu deficient diet. These effects are not observed if cornstarch (CS) is the carbohydrate (CHO) source. Studies with F containing diets have shown increased catecholamine (C) turnover rates while diets deficient in Cu result in decreased norepinephrine (N) levels in tissues. Dopamine B-hydroxylase (EC 1.14.17.1) is a Cu dependent enzyme which catalyzes the conversion of dopamine (D) to N. An experiment was designed to investigate the effects of CHO and dietary Cu on levels of three C in cardiac tissue. Thirty-two male and female Sprague-Dawley rats were fed Cu deficient or adequate diets with 60% of calories from F or CS for 6 weeks. N, epinephrine (E) and D were measured by HPLC. Statistical analysis indicates that Cu deficiency tends to decrease N levels, while having the reverse effect on E. D did not appear to change. These findings indicate that Cu deficiency but not dietary CHO can affect the concentration of N and E in rat cardiac tissue.

  4. Spectral imaging technique for retinal perfusion detection using confocal scanning laser ophthalmoscopy.

    PubMed

    Rasta, Seyed Hossein; Manivannan, Ayyakkannu; Sharp, Peter F

    2012-11-01

    To evaluate retinal perfusion in the human eye, a dual-wavelength confocal scanning laser ophthalmoscope (cSLO) was developed that provides spectral imaging of the fundus using a combination of red (670 nm) and near-infrared (810 nm) wavelengths. The image of the ocular fundus was analyzed to find out if quantitative measurements of the reflectivity of tissue permit assessment of the oxygen perfusion of tissue. We explored problems that affect the reproducibility of patient measurements such as non-uniformity errors on the image. For the first time, an image processing technique was designed and used to minimize the errors of oxygen saturation measurements by illumination correction in retina wide field by increasing SNR. Retinal images were taken from healthy and diabetic retinopathy eyes using the cSLO with a confocal aperture of 100 μm. The ratio image (RI) of red/IR, as oxygen saturation (SO2) index, was calculated for normal eyes. The image correction technique improved the reproducibility of the measurements. Average RI intensity variation of healthy retina tissue was determined within a range of about 5.5%. The capability of the new technique to discriminate oxygenation levels of retinal artery and vein was successfully demonstrated and showed good promise in the diagnosis of the perfused retina.

  5. Spectral imaging technique for retinal perfusion detection using confocal scanning laser ophthalmoscopy

    NASA Astrophysics Data System (ADS)

    Rasta, Seyed Hossein; Manivannan, Ayyakkannu; Sharp, Peter F.

    2012-11-01

    To evaluate retinal perfusion in the human eye, a dual-wavelength confocal scanning laser ophthalmoscope (cSLO) was developed that provides spectral imaging of the fundus using a combination of red (670 nm) and near-infrared (810 nm) wavelengths. The image of the ocular fundus was analyzed to find out if quantitative measurements of the reflectivity of tissue permit assessment of the oxygen perfusion of tissue. We explored problems that affect the reproducibility of patient measurements such as non-uniformity errors on the image. For the first time, an image processing technique was designed and used to minimize the errors of oxygen saturation measurements by illumination correction in retina wide field by increasing SNR. Retinal images were taken from healthy and diabetic retinopathy eyes using the cSLO with a confocal aperture of 100 μm. The ratio image (RI) of red/IR, as oxygen saturation (SO2) index, was calculated for normal eyes. The image correction technique improved the reproducibility of the measurements. Average RI intensity variation of healthy retina tissue was determined within a range of about 5.5%. The capability of the new technique to discriminate oxygenation levels of retinal artery and vein was successfully demonstrated and showed good promise in the diagnosis of the perfused retina.

  6. Automated scoring of regional lung perfusion in children from contrast enhanced 3D MRI

    NASA Astrophysics Data System (ADS)

    Heimann, Tobias; Eichinger, Monika; Bauman, Grzegorz; Bischoff, Arved; Puderbach, Michael; Meinzer, Hans-Peter

    2012-03-01

    MRI perfusion images give information about regional lung function and can be used to detect pulmonary pathologies in cystic fibrosis (CF) children. However, manual assessment of the percentage of pathologic tissue in defined lung subvolumes features large inter- and intra-observer variation, making it difficult to determine disease progression consistently. We present an automated method to calculate a regional score for this purpose. First, lungs are located based on thresholding and morphological operations. Second, statistical shape models of left and right children's lungs are initialized at the determined locations and used to precisely segment morphological images. Segmentation results are transferred to perfusion maps and employed as masks to calculate perfusion statistics. An automated threshold to determine pathologic tissue is calculated and used to determine accurate regional scores. We evaluated the method on 10 MRI images and achieved an average surface distance of less than 1.5 mm compared to manual reference segmentations. Pathologic tissue was detected correctly in 9 cases. The approach seems suitable for detecting early signs of CF and monitoring response to therapy.

  7. 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.

  8. The Cadaveric Perfusion and Angiography as a Teaching Tool: Imaging the Intracranial Vasculature in Cadavers

    PubMed Central

    Turkoglu, Erhan; Seckin, Hakan; Gurer, Bora; Ahmed, Azam; Uluc, Kutluay; Pulfer, Kari; Arat, Anıl; Niemann, David; Baskaya, Mustafa K.

    2014-01-01

    Background and Study Aim To enhance the visualization of the intracranial vasculature of cadavers under gross examination with a combination of imaging modalities. Material and Methods A total of 20 cadaver heads were used to test two different perfusion techniques. First, fixed cadaver heads were perfused with water; second, fresh cadavers were perfused with saline and 10% formalin. Subsequently, brains were removed and fixed. The compounds used were silicone rubber, silicone rubber mixed with powdered barium sulfate, and silicone rubber mixed with tantalum dioxide prepared by the first perfusion technique and gelatin mixed with liquid barium prepared with the second technique. Conventional X-ray imaging, computed tomography (CT), dynamic computed tomography (dCT), and postprocessing three-dimensional (3D) images were used to evaluate all the heads. Results Gelatinized barium was better visualized when compared with tantalum dioxide in conventional X-ray images. The blood vessels injected with either tantalum dioxide or gelatinized barium demonstrated a higher enhancement than the surrounding soft tissues with CT or dCT. The quality of the 3D reconstruction of the intracranial vasculature was significantly better in the CT images obtained from the gelatinized barium group. Conclusions Radiologic examinations of the heads injected with gelatinized barium facilitates the 3D understanding of cerebrovascular anatomy as an important tool for neuroanatomy training. PMID:25452903

  9. Initial testing of a 3D printed perfusion phantom using digital subtraction angiography

    PubMed Central

    Khobragade, Parag; Ying, Leslie; Snyder, Kenneth; Wack, David; Bednarek, Daniel R.; Rudin, Stephen; Ionita, Ciprian N.

    2015-01-01

    Perfusion imaging is the most applied modality for the assessment of acute stroke. Parameters such as Cerebral Blood Flow (CBF), Cerebral Blood volume (CBV) and Mean Transit Time (MTT) are used to distinguish the tissue infarct core and ischemic penumbra. Due to lack of standardization these parameters vary significantly between vendors and software even when provided with the same data set. There is a critical need to standardize the systems and make them more reliable. We have designed a uniform phantom to test and verify the perfusion systems. We implemented a flow loop with different flow rates (250, 300, 350 ml/min) and injected the same amount of contrast. The images of the phantom were acquired using a Digital Angiographic system. Since this phantom is uniform, projection images obtained using DSA is sufficient for initial validation. To validate the phantom we measured the contrast concentration at three regions of interest (arterial input, venous output, perfused area) and derived time density curves (TDC). We then calculated the maximum slope, area under the TDCs and flow. The maximum slope calculations were linearly increasing with increase in flow rate, the area under the curve decreases with increase in flow rate. There was 25% error between the calculated flow and measured flow. The derived TDCs were clinically relevant and the calculated flow, maximum slope and areas under the curve were sensitive to the measured flow. We have created a systematic way to calibrate existing perfusion systems and assess their reliability. PMID:26633914

  10. In vitro performance of a perfusion and oxygenation optical sensor using a unique liver phantom

    NASA Astrophysics Data System (ADS)

    Akl, Tony J.; King, Travis J.; Long, Ruiqi; Ericson, M. N.; Wilson, Mark A.; McShane, Michael J.; Coté, Gerard L.

    2012-03-01

    Between the years 1999 and 2008, on average 2,052 people died per year on the waiting list for liver transplants. Monitoring perfusion and oxygenation in transplanted organs in the 7 to 14 days period post-transplant can enhance graft and patient survival rates, and resultantly increase the availability of organs. In this work, we present in vitro results using a unique liver phantom that support the ability of our sensor to detect perfusion changes in the portal vein at low levels (50 mL/min . 4.5% of normal level). Our sensor measures diffuse reflection from three wavelengths (735, 805 and 940 nm) around the hemoglobin isobestic point (805 nm) to determine perfusion and oxygenation separately. To assess the sensitivity of our sensor to flow changes in the low range, we used two peristaltic pumps to pump a dye solution mimicking the optical properties of oxygenated blood, at various rates, through a PDMS based phantom mimicking the optical properties of liver tissue. The collected pulsatile signal increased by 120% (2.2X) for every 100 mL/min flow rise for all three wavelengths in the range 50 to 500 mL/min. In addition, we used different dye mixtures to mimic oxygenation changes at constant perfusion/flow levels. The optical properties of the dye mixtures mimic oxygen saturations ranging between 0 and 100%. The sensor was shown to be sensitive to changes in oxygen saturations above 50%.

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  12. Initial testing of a 3D printed perfusion phantom using digital subtraction angiography

    NASA Astrophysics Data System (ADS)

    Wood, Rachel P.; Khobragade, Parag; Ying, Leslie; Snyder, Kenneth; Wack, David; Bednarek, Daniel R.; Rudin, Stephen; Ionita, Ciprian N.

    2015-03-01

    Perfusion imaging is the most applied modality for the assessment of acute stroke. Parameters such as Cerebral Blood Flow (CBF), Cerebral Blood volume (CBV) and Mean Transit Time (MTT) are used to distinguish the tissue infarct core and ischemic penumbra. Due to lack of standardization these parameters vary significantly between vendors and software even when provided with the same data set. There is a critical need to standardize the systems and make them more reliable. We have designed a uniform phantom to test and verify the perfusion systems. We implemented a flow loop with different flow rates (250, 300, 350 ml/min) and injected the same amount of contrast. The images of the phantom were acquired using a Digital Angiographic system. Since this phantom is uniform, projection images obtained using DSA is sufficient for initial validation. To validate the phantom we measured the contrast concentration at three regions of interest (arterial input, venous output, perfused area) and derived time density curves (TDC). We then calculated the maximum slope, area under the TDCs and flow. The maximum slope calculations were linearly increasing with increase in flow rate, the area under the curve decreases with increase in flow rate. There was 25% error between the calculated flow and measured flow. The derived TDCs were clinically relevant and the calculated flow, maximum slope and areas under the curve were sensitive to the measured flow. We have created a systematic way to calibrate existing perfusion systems and assess their reliability.

  13. The culture of human embryonic stem cells in microchannel perfusion bioreactors

    NASA Astrophysics Data System (ADS)

    Korin, Natanel; Bransky, Avishay; Dinnar, Uri; Levenberg, Shulamit

    2007-12-01

    The culture of human Embryonic Stem (ES) cells in microchannel bioreactors can be highly beneficial for ES cell biology studies and ES tissue engineering applications. In the present study we examine the use of Human Foreskin Fibroblasts (HFF) cells as feeder cells for human ES culture in a microchannel perfusion bioreactor. PDMS microchannels (depth:130 micron) were fabricated using conventional soft-lithography techniques. The channels were sterilized, coated with a human fibronectin solution and seeded with cells. Following a period of static incubation, culture medium was perfused through the channels at various flow rates and cell growth was monitored throughout the culture process. Mass transport and fluid mechanics models were used to evaluate the culture conditions (shear stress, oxygen levels within the micro-bioreactor as a function of the medium flow rate. The conditions for successful long-term culture (>7 days) of HFF under flow were established. Experiments with human embryonic stem cells cultured in microchannels show that the conditions essential to co-culture human ES cell on HFF cells under perfusion differ from the conditions necessary for HFF cell culture. Human ES cells were found to be highly sensitive to flow and culture conditions and did not grow under flow rates which were suitable for HFF long-term culture. Successful culture of undifferentiated human ES cell colonies in a perfusion micro-bioreactor is a basic step towards utilizing microfluidic techniques to explore stem cell biology.

  14. Assessment of Skeletal Muscle Perfusion using Contrast-Enhanced Ultrasonography: Technical Note

    PubMed Central

    Qureshi, Adnan I.; Saleem, Muhammad A.; Aytac, Emrah; Wallery, Shawn S.

    2017-01-01

    Background Intravenous contrast-enhanced ultrasonography is a recently developed technique for assessment of tissue perfusion, but has not been used for assessment of skeletal muscle perfusion. Methods We studied a 42-year-old woman in whom myonecrosis was suspected due to systemic vasculitis and ischemia. The biceps brachii (right) and quadriceps femoris (vastus medialis) on right-hand side and subsequently left-hand side were imaged. Intravenous bolus of activated perflutren lipid microspheres was injected and B-Flow color mode (brown color) was used within a selected region of interest to image the passage of contrast through muscle parenchyma throughout three cardiac cycles. Results Visual interpretation of muscle perfusion was performed based on the maximal intensity of contrast in the muscle, and the speed of contrast replenishment. No deficits were noted in the perfusion pattern. The arterial phase demonstrated stellate vascularity, centrifugal filling, and homogeneous hypervascularity at peak enhancement. Conclusions The bolus of contrast resulted in good signal persistence and satisfactory imaging for multiple muscle groups. PMID:28243350

  15. Influence of red blood cell aggregation on perfusion of an artificial microvascular network.

    PubMed

    Reinhart, Walter H; Piety, Nathaniel Z; Shevkoplyas, Sergey S

    2016-09-19

    Red blood cells (RBCs) suspended in plasma form multicellular aggregates under low flow conditions, increasing apparent blood viscosity at low shear rates. It has previously been unclear, however, if RBC aggregation affects microvascular perfusion. Here we analyzed the impact of RBC aggregation on perfusion and 'capillary' hematocrit in an artificial microvascular network (AMVN) at driving pressures ranging from 5 to 60 cmH2 O to determine if aggregation could improve tissue oxygenation. RBCs were suspended at 30% hematocrit in either 46.5 g/L dextran 40 (D40, non-aggregating medium) or 35 g/L dextran 70 (D70, aggregating medium) solutions with equal viscosity. Aggregation was readily observed in the AMVN for RBCs suspended in D70 at driving pressures ≤ 40 cmH2 O. The AMVN perfusion rate was the same for RBCs suspended in aggregating and non-aggregating medium, at both 'venular' and 'capillary' level. Estimated 'capillary' hematocrit was higher for D70 suspensions than for D40 suspensions at intermediate driving pressures (5 - 40 cm H2 O). We conclude that although RBC aggregation did not affect the AMVN perfusion rate independently of the driving pressure, a higher hematocrit in the 'capillaries' of the network for D70 suspensions suggested a better oxygen transport capacity in the presence of RBC aggregation. This article is protected by copyright. All rights reserved.

  16. MRI can determine the adequate area for debridement in the case of Fournier's gangrene.

    PubMed

    Yoneda, Akira; Fujita, Fumihiko; Tokai, Hirotaka; Ito, Yuichiro; Haraguchi, Masashi; Tajima, Yoshitsugu; Kanematsu, Takashi

    2010-01-01

    A 57-year-old man was transferred to our hospital because of gluteal pain. His right buttock had flare and swelling. Complete blood count showed leukocytosis, and renal failure was evident. Pelvic computed tomography (CT) revealed that the abscess, including gas, was widespread into the hypodermal tissue of the right buttock. Fournier's gangrene had been suspected, and immediate drainage was performed on the right buttock. The symptom and the condition improved rapidly, but on the day after the operation, the patient became drowsy and fell into endotoxic shock. Magnetic resonance imaging (MRI) revealed strong inflammation along the entire fascia of the right femur and necrotizing fasciitis. MRI was very useful for identification of the necrotic range. Immediately, an emergency operation was performed; 3 wide incisions were made on the right thigh and crus for drainage. The patient was cared for intensively under a sedated condition, and irrigation and debridement were repeated every day. Culture of the pus revealed mixed infection of Escherichia coli and anaerobic bacteria, and a large quantity of antimicrobial drug was used. The inflammatory reaction decreased, and the patient's general condition tentatively improved. With Fournier's gangrene, initiating adequate surgical and medical treatment is essential. Therefore, MRI should be used in the early exact diagnosis of this disease to obtain knowledge of the extent of necrosis and to determine the adequate area for debridement.

  17. On Adequate Comparisons of Antenna Phase Center Variations

    NASA Astrophysics Data System (ADS)

    Schoen, S.; Kersten, T.

    2013-12-01

    One important part for ensuring the high quality of the International GNSS Service's (IGS) products is the collection and publication of receiver - and satellite antenna phase center variations (PCV). The PCV are crucial for global and regional networks, since they introduce a global scale factor of up to 16ppb or changes in the height component with an amount of up to 10cm, respectively. Furthermore, antenna phase center variations are also important for precise orbit determination, navigation and positioning of mobile platforms, like e.g. the GOCE and GRACE gravity missions, or for the accurate Precise Point Positioning (PPP) processing. Using the EUREF Permanent Network (EPN), Baire et al. (2012) showed that individual PCV values have a significant impact on the geodetic positioning. The statements are further supported by studies of Steigenberger et al. (2013) where the impact of PCV for local-ties are analysed. Currently, there are five calibration institutions including the Institut für Erdmessung (IfE) contributing to the IGS PCV file. Different approaches like field calibrations and anechoic chamber measurements are in use. Additionally, the computation and parameterization of the PCV are completely different within the methods. Therefore, every new approach has to pass a benchmark test in order to ensure that variations of PCV values of an identical antenna obtained from different methods are as consistent as possible. Since the number of approaches to obtain these PCV values rises with the number of calibration institutions, there is the necessity for an adequate comparison concept, taking into account not only the numerical values but also stochastic information and computational issues of the determined PCVs. This is of special importance, since the majority of calibrated receiver antennas published by the IGS origin from absolute field calibrations based on the Hannover Concept, Wübbena et al. (2000). In this contribution, a concept for the adequate

  18. Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

    PubMed Central

    Youn, Gilmer; Jones, Brenda; Jelliffe, Roger W.; Drusano, George L.; Rodvold, Keith A.; Lodise, Thomas P.

    2014-01-01

    The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter. PMID:24165176

  19. Is clinical measurement of anatomic axis of the femur adequate?

    PubMed

    Wu, Chi-Chuan

    2017-03-23

    Background and purpose - The accuracy of using clinical measurement from the anterior superior iliac spine (ASIS) to the center of the knee to determine an anatomic axis of the femur has rarely been studied. A radiographic technique with a full-length standing scanogram (FLSS) was used to assess the adequacy of the clinical measurement. Patients and methods - 100 consecutive young adult patients (mean age 34 (20-40) years) with chronic unilateral lower extremity injuries were studied. The pelvis and intact contralateral lower extremity images in the FLSS were selected for study. The angles between the tibial axis and the femoral shaft anatomic axis (S-AA), the piriformis anatomic axis (P-AA), the clinical anatomic axis (C-AA), and the mechanical axis (MA) were compared between sexes. Results - Only the S-AA and C-AA angles were statistically significantly different in the 100 patients (3.6° vs. 2.8°; p = 0.03). There was a strong correlation between S-AA, P-AA, and C-AA angles (r > 0.9). The average intersecting angle between MA and S-AA in the femur in the 100 patients was 5.5°, and it was 4.8° between MA and C-AA. Interpretation - Clinical measurement of an anatomic axis from the ASIS to the center of the knee may be an adequate and acceptable method to determine lower extremity alignment. The optimal inlet for antegrade femoral intramedullary nailing may be the lateral edge of the piriformis fossa.

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

    PubMed Central

    Tang, Gilbert H. L.

    2013-01-01

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

  1. Plasmid pVAX1-NH36 purification by membrane and bead perfusion chromatography.

    PubMed

    Franco-Medrano, Diana Ivonne; Guerrero-Germán, Patricia; Montesinos-Cisneros, Rosa María; Ortega-López, Jaime; Tejeda-Mansir, Armando

    2017-03-01

    The demand for plasmid DNA (pDNA) has increased in response to the rapid advances in vaccines applications to prevent and treat infectious diseases caused by virus, bacteria or parasites, such as Leishmania species. The immunization protocols require large amounts of supercoiled plasmid DNA (sc-pDNA) challenging the development of efficient and profitable processes for capturing and purified pDNA molecules from large volumes of lysates. A typical bioprocess involves four steps: fermentation, primary recovery, intermediate recovery and final purification. Ion-exchange chromatography is one of the key operations in the purification schemes of pDNA owing the chemical structure of these macromolecules. The goal of this research was to compare the performance of the final purification step of pDNA using ion-exchange chromatography on columns packed with Mustang Q membranes or perfusive beads POROS 50 HQ. The experimental results showed that both matrixes could separate the plasmid pVAX1-NH36 (3936 bp) from impurities in clarified Escherichia coli lysates with an adequate resolution. In addition, a 24- and 21-fold global purification factor was obtained. An 88 and 63% plasmid recuperation was achieved with ion-exchange membranes and perfusion beads, respectively. A better understanding of perfusion-based matrices for the purification of pDNA was developed in this research.

  2. The effect of muscle contusion on cortical bone and muscle perfusion following reamed, intramedullary nailing: a novel canine tibia fracture model

    PubMed Central

    2010-01-01

    Background Management of tibial fractures associated with soft tissue injury remains controversial. Previous studies have assessed perfusion of the fractured tibia and surrounding soft tissues in the setting of a normal soft tissue envelope. The purpose of this study was to determine the effects of muscle contusion on blood flow to the tibial cortex and muscle during reamed, intramedullary nailing of a tibial fracture. Methods Eleven adult canines were distributed into two groups, Contusion or No-Contusion. The left tibia of each canine underwent segmental osteotomy followed by limited reaming and locked intramedullary nailing. Six of the 11 canines had the anterior muscle compartment contused in a standardized fashion. Laser doppler flowmetry was used to measure cortical bone and muscle perfusion during the index procedure and at 11 weeks post-operatively. Results Following a standardized contusion, muscle perfusion in the Contusion group was higher compared to the No-Contusion group at post-osteotomy and post-reaming (p < 0.05). Bone perfusion decreased to a larger extent in the Contusion group compared to the No-Contusion group following osteotomy (p < 0.05), and the difference in bone perfusion between the two groups remained significant throughout the entire procedure (p < 0.05). At 11 weeks, muscle perfusion was similar in both groups (p > 0.05). There was a sustained decrease in overall bone perfusion in the Contusion group at 11 weeks, compared to the No-Contusion group (p < 0.05). Conclusions Injury to the soft tissue envelope may have some deleterious effects on intraosseous circulation. This could have some influence on the fixation method for tibia fractures linked with significant soft tissue injury. PMID:21118566

  3. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    SciTech Connect

    Dowdle, S.C.; Human, D.G.; Mann, M.D. )

    1990-08-01

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

  4. Evaluation of decellularization protocols for production of tubular small intestine submucosa scaffolds for use in oesophageal tissue engineering.

    PubMed

    Syed, Omaer; Walters, Nick J; Day, Richard M; Kim, Hae-Won; Knowles, Jonathan C

    2014-12-01

    Small intestine submucosa (SIS) has emerged as one of a number of naturally derived extracellular matrix (ECM) biomaterials currently in clinical use. In addition to clinical applications, ECM materials form the basis for a variety of approaches within tissue engineering research. In our preliminary work it was found that SIS can be consistently and reliably made into tubular scaffolds which confer certain potential advantages. Given that decellularization protocols for SIS are applied to sheet-form SIS, it was hypothesized that a tubular-form SIS would behave differently to pre-existing protocols. In this work, tubular SIS was produced and decellularized by the conventional peracetic acid-agitation method, peracetic acid under perfusion along with two commonly used detergent-perfusion protocols. The aim of this was to produce a tubular SIS that was both adequately decellularized and possessing the mechanical properties which would make it a suitable scaffold for oesophageal tissue engineering, which was one of the goals of this work. Analysis was carried out via mechanical tensile testing, DNA quantification, scanning electron and light microscopy, and a metabolic assay, which was used to give an indication of the biocompatibility of each decellularization method. Both peracetic acid protocols were shown to be unsuitable methods with the agitation-protocol-produced SIS, which was poorly decellularized, and the perfusion protocol resulted in poor mechanical properties. Both detergent-based protocols produced well-decellularized SIS, with no adverse mechanical effects; however, one protocol emerged, SDS/Triton X-100, which proved superior in both respects. However, this SIS showed reduced metabolic activity, and this cytotoxic effect was attributed to residual reagents. Consequently, the use of SIS produced using the detergent SD as the decellularization agent was deemed to be the most suitable, although the elimination of the DNase enzyme would give further

  5. Perfusion-Decellularization of Porcine Lung and Trachea for Respiratory Bioengineering.

    PubMed

    Weymann, Alexander; Patil, Nikhil Prakash; Sabashnikov, Anton; Korkmaz, Sevil; Li, Shiliang; Soos, Pal; Ishtok, Roland; Chaimow, Nicole; Pätzold, Ines; Czerny, Natalie; Schmack, Bastian; Popov, Aron-Frederik; Simon, Andre Rüdiger; Karck, Matthias; Szabo, Gabor

    2015-12-01

    Decellularization of native organs may provide an acellular tissue platform for organ regeneration. However, decellularization involves a trade-off between removal of immunogenic cellular elements and preservation of biomechanical integrity. We sought to develop a bioartificial scaffold for respiratory tissue engineering by decellularization of porcine lungs and trachea while preserving organ architecture and vasculature. Lung-trachea preparations from 25 German Landrace pigs were perfused in a modified Langendorff circuit and decellularized by an SDC (sodium deoxycholate)-based perfusion protocol. Decellularization was evaluated by histology and fluorescence microscopy, and residual DNA quantified spectrophotometrically and compared with controls. Airway compliance was evaluated by endotracheal intubation and mechanical ventilation to simulate physiological breathing-induced stretch. Structural integrity was evaluated by bronchoscopy and biomechanical stress/strain analysis by measuring passive tensile strength, all compared with controls. Decellularized lungs and trachea lacked intracellular components but retained specific collagen fibers and elastin. Quantitative DNA analysis demonstrated a significant reduction of DNA compared with controls (32.8 ± 12.4 μg DNA/mg tissue vs. 179.7 ± 35.8 μg DNA/mg tissue, P < 0.05). Lungs and trachea decellularized by our perfusion protocol demonstrated increased airway compliance but preserved biomechanical integrity as compared with native tissue. Whole porcine lungs-tracheae can be successfully decellularized to create an acellular scaffold that preserves extracellular matrix and retains structral integrity and three-dimensional architecture to provide a bioartifical platform for respiratory tissue engineering.

  6. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats

    PubMed Central

    Opie, L. H.; Mansford, K. R. L.; Owen, Patricia

    1971-01-01

    1. In the isolated perfused rat heart, the contractile activity and the oxygen uptake were varied by altering the aortic perfusion pressure, or by the atrial perfusion technique (`working heart'). 2. The maximum increase in the contractile activity brought about an eightfold increase in the oxygen uptake. The rate of glycolytic flux rose, while tissue contents of hexose monophosphates, citrate, ATP and creatine phosphate decreased, and contents of ADP and AMP rose. 3. The changes in tissue contents of adenine nucleotides during increased heart work were time-dependent. The ATP content fell temporarily (30s and 2min) after the start of left-atrial perfusion; at 5 and 10min values were normal; and at 30 and 60min values were decreased. ADP and AMP values were increased in the first 15min, but were at control values 30 or 60min after the onset of increased heart work. 4. During increased heart work changes in the tissue contents of adenine nucleotide and of citrate appeared to play a role in altered regulation of glycolysis at the level of phosphofructokinase activity. 5. In recirculation experiments increased heart work for 30min was associated with increased entry of [14C]glucose (11.1mm) and glycogen into glycolysis and a comparable increase in formation of products of glycolysis (lactate, pyruvate and 14CO2). There was no major accumulation of intermediates. Glycogen was not a major fuel for respiration. 6. Increased glycolytic flux in Langendorff perfused and working hearts was obtained by the addition of insulin to the perfusion medium. The concomitant increases in the tissue values of hexose phosphates and of citrate contrasted with the decreased values of hexose monophosphates and of citrate during increased glycolytic flux obtained by increased heart work. 7. Decreased glycolytic flux in Langendorff perfused hearts was obtained by using acute alloxan-diabetic and chronic streptozotocin-diabetic rats; in the latter condition there were decreased tissue

  7. Early Time Points Perfusion Imaging

    PubMed Central

    Kwong, Kenneth K.; Reese, Timothy G.; Nelissen, Koen; Wu, Ona; Chan, Suk-Tak; Benner, Thomas; Mandeville, Joseph B.; Foley, Mary; Vanduffel, Wim; Chesler, David A.

    2010-01-01

    The aim was to investigate the feasibility of making relative cerebral blood flow (rCBF) maps from MR images acquired with short TR by measuring the initial arrival amount of Gd-DTPA evaluated within a time window before any contrast agent has a chance to leave the tissue. We named this rCBF measurement technique utilizing the early data points of the Gd-DTPA bolus the “early time points” method (ET), based on the hypothesis that early time point signals were proportional to rCBF. Simulation data were used successfully to examine the ideal behavior of ET while monkey’s MRI results offered encouraging support to the utility of ET for rCBF calculation. A better brain coverage for ET could be obtained by applying the Simultaneous Echo Refocusing (SER) EPI technique. A recipe to run ET was presented, with attention paid to the noise problem around the time of arrival (TOA) of the contrast agent. PMID:20851196

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

    PubMed Central

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

    2011-01-01

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

  9. The blood perfusion and NADH/FAD content combined analysis in patients with diabetes foot

    NASA Astrophysics Data System (ADS)

    Dremin, Victor V.; Sidorov, Victor V.; Krupatkin, Alexander I.; Galstyan, Gagik R.; Novikova, Irina N.; Zherebtsova, Angelina I.; Zherebtsov, Evgeny A.; Dunaev, Andrey V.; Abdulvapova, Zera N.; Litvinova, Karina S.; Rafailov, Ilya E.; Sokolovski, Sergei G.; Rafailov, Edik U.

    2016-03-01

    Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients.

  10. Imaging of drug effects in perfused liver

    NASA Astrophysics Data System (ADS)

    Dammann, Marc; Mahlke, Christine; Kessler, Manfred D.

    2002-06-01

    Various medications affect the systemic circulation and organ oxygenation causing dilatation or constriction of blood vessels. Imminent liver failure can be generated by reduced perfusion of different origins. In this case hepatic vasodilatation would be a therapeutical approach for improving patient's condition. Our examinations have been performed in perfused rat liver using spectrometric methods. Two defined areas of the liver were measured punctually. We compared the influence of Tetramethylpyrazine and Glyceroltrinitrate on hemoglobin oxygenation (HbO2) and concentration (Hb-conc.) in rat liver after application of Norepinephrine, which caused a mid decrease in hemoglobin oxygenation of 47,9 %. Both increased the HbO2, but differed from each other in manner of time and extent. Tetramethylpyrazine indicated a longer effect than Glyceroltrinitrate. Furthermore, HbO2 and Hb-conc. showed a conversed relation. From the shape of the absorption spectra it is possible to derive the oxygenation of hemoglobin.

  11. Effect of cardiac dysrhythmia on cerebral perfusion.

    PubMed

    Sand, B J; Rose, H B; Barker, W F

    1976-07-01

    Extracranial carotid arterial obstructive disease has been the entity most commonly associated with transient cerebrovascular insufficiency. A nonobstructive, frequently overlooked cause of cerebral ischemia is cardiac dysrhythmia. We have explored this by observations of experimental animals and of man. Blood flow and pressure in the carotid arteries of dogs were shown to be decreased by mechnically induced premature ventricular contractions. The significance of the cardiogenic contribution to altered cerebrovascular perfusion was studied by ocular and brachial plethysmography in 210 patients suspected by history of having carotid arterial insufficiency. Of the 210 patients, 62 demonstrated abnormal ocular plethysmographic recordings, and of those, nine had dysrhythmias associated with significant deficits of ocular perfusion. Five patients whose recordings were technically suitable for publication are presented to demonstrate the bizarre ocular plethysmographic recordings seen during the dysrhythmic cycle.

  12. Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg

    PubMed Central

    2013-01-01

    Background The function of the peripheral microvascular may be interrogated by measuring perfusion, tissue oxygen concentration, or venous oxygen saturation (SvO2) recovery dynamics following induced ischemia. The purpose of this work is to develop and evaluate a magnetic resonance (MR) technique for simultaneous measurement of perfusion, SvO2, and skeletal muscle T2*. Methods Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT) is comprised of interleaved pulsed arterial spin labeling (PASL) and multi-echo gradient-recalled echo (GRE) sequences. During the PASL post-labeling delay, images are acquired with a multi-echo GRE to quantify SvO2 and T2* at a downstream slice location. Thus time-courses of perfusion, SvO2, and T2* are quantified simultaneously within a single scan. The new sequence was compared to separately measured PASL or multi-echo GRE data during reactive hyperemia in five young healthy subjects. To explore the impairment present in peripheral artery disease patients, five patients were evaluated with PIVOT. Results Comparison of PIVOT-derived data to the standard techniques shows that there was no significant bias in any of the time-course-derived metrics. Preliminary data show that PAD patients exhibited alterations in perfusion, SvO2, and T2* time-courses compared to young healthy subjects. Conclusion Simultaneous quantification of perfusion, SvO2, and T2* is possible with PIVOT. Kinetics of perfusion, SvO2, and T2* during reactive hyperemia may help to provide insight into the function of the peripheral microvasculature in patients with PAD. PMID:23958293

  13. An In Vitro Perfusion System to Enhance Outflow Studies in Mouse Eyes

    PubMed Central

    Kizhatil, Krishnakumar; Chlebowski, Arthur; Tolman, Nicholas G.; Freeburg, Nelson F.; Ryan, Margaret M.; Shaw, Nicholas N.; Kokini, Alexander D. M.; Marchant, Jeffrey K.; John, Simon W. M.

    2016-01-01

    Purpose The molecular mechanisms controlling aqueous humor (AQH) outflow and IOP need much further definition. The mouse is a powerful system for characterizing the mechanistic basis of AQH outflow. To enhance outflow studies in mice, we developed a perfusion system that is based on human anterior chamber perfusion culture systems. Our mouse system permits previously impractical experiments. Methods We engineered a computer-controlled, pump-based perfusion system with a platform for mounting whole dissected mouse eyes (minus lens and iris, ∼45% of drainage tissue is perfused). We tested the system's ability to monitor outflow and tested the effects of the outflow-elevating drug, Y27632, a rho-associated protein kinase (ROCK) inhibitor. Finally, we tested the system's ability to detect genetically determined decreases in outflow by determining if deficiency of the candidate genes Nos3 and Cav1 alter outflow. Results Using our system, the outflow facility (C) of C57BL/6J mouse eyes was found to range between 7.7 and 10.4 nl/minutes/mm Hg (corrected for whole eye). Our system readily detected a 74.4% Y27632-induced increase in C. The NOS3 inhibitor L-NG-nitroarginine methyl ester (L-NAME) and a Nos3 null mutation reduced C by 28.3% and 35.8%, respectively. Similarly, in Cav1 null eyes C was reduced by 47.8%. Conclusions We engineered a unique perfusion system that can accurately measure changes in C. We then used the system to show that NOS3 and CAV1 are key components of mechanism(s) controlling outflow. PMID:27701632

  14. Alkalinization in the Isolated and Perfused Anterior Midgut of the Larval Mosquito, Aedes aegypti

    PubMed Central

    Onken, Horst; Moffett, Stacia B.; Moffett, David F.

    2008-01-01

    In the present study, isolated midguts of larval Aedes aegypti L. (Diptera: Culicidae) were mounted on perfusion pipettes and bathed in high buffer mosquito saline. With low buffer perfusion saline, containing m-cresol purple, transepithelial voltage was monitored and luminal alkalinization became visible through color changes of m-cresol purple after perfusion stop. Lumen negative voltage and alkalinization depended on metabolic energy and were stimulated in the presence of serotonin (0.2 µmol l-1). In some experiments a pH microelectrode in the lumen recorded pH values up to 10 within minutes after perfusion stop. The V-ATPase inhibitor concanamycin (50 µmol l-1) on the hemolymph side almost abolished Vte and inhibited luminal alkalinization. The carbonic anhydrase inhibitor, methazolamide (50 µmol l-1), on either the luminal or hemolymph-side, or the inhibitor of anion transport, DIDS (1 mmol l-1) on the luminal side, had no effect on Vte or alkalinization. Cl- substitution in the lumen or on both sides of the tissue affected Vte, but the color change of m-cresol purple was unchanged from control conditions. Hemolymph-side Na+ substitution or addition of the Na+/H+ exchange inhibitor, amiloride (200 µmol l-1), reduced Vte and luminal alkalinization. Luminal amiloride (200 µmol l-1) was without effects on Vte or alkalinization. High K+ (60 mmol l-1) in the lumen reduced Vte without affecting alkalinization. These results indicate that strong luminal alkalinization in isolated and perfused anterior midgut of larval A. aegypti depends on basolateral V-ATPase, but is apparently independent of carbonic anhydrase, apical Cl-/HCO3- exchange or apical K+/2H+ antiport. PMID:20307229

  15. Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid peroxidation.

    PubMed

    Younes, M; Strubelt, O

    1991-02-11

    The toxic potential of sodium orthovanadate towards isolated perfused rat livers was investigated at a dose of 2 mmol/l. In livers from fasted rats, vanadate led to a release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH] and mitochondrial (glutamate dehydrogenase (GLDH] enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an augmented formation and release of thiobarbituric acid-reactive material by the liver. Furthermore, a marked inhibition of oxygen consumption was observed. Vanadate-induced vasoconstriction resulted in a progressive decrease in perfusate flow rate. Control experiments with similarly reduced flow rates led to a comparable reduction in oxygen consumption. GPT and LDH release and hepatic glutathione depletion were also evident, though to a lesser extent than in the presence of vanadate, but no increase in GLDH release, in tissue calcium content or TBA-reactive material in the liver or the perfusate were observed. Thus, indirect toxic effects due to a reduced flow rate contribute only partly to vanadate hepatotoxicity and do not affect mitochondrial integrity. Omission of calcium from the perfusate did not prevent hepatotoxic responses to vanadate, although less calcium was present in the treated livers than in the control organs, indicating that calcium influx is not involved in vanadate-induced hepatotoxicity in the intact organ, in contrast to isolated hepatocytes. Feeding the animals, resulting in an activation of anaerobic energy conservation reactions, strongly attenuated vanadate hepatotoxicity indicating that the energetic status of the liver is the main target of vanadate. Superoxide dismutase did not affect the hepatotoxic responses of livers from fasted rats towards vanadate, while allopurinol and deferrioxamine inhibited lipid peroxidation and hepatotoxicity due to vanadate. The strong correlation

  16. Inhomogeneity of pulmonary perfusion during sustained microgravity

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; West, John B.

    1994-01-01

    The effects of gravity on the inhomogeneity of pulmonary perfusion in man were studied by performing hyperventilation-breathhold single-breath measurements before, during and after 9 days of continuous exposure to microgravity. In microgravity the indicators of inhomogeneity of perfusion, especially the size of cardiogenic oscillations in expired CO2 and the height of phase 4, were both markedly reduced. Cardiogenic oscillations were reduced to approximately 60 of their preflight standing size, while the height of phase 4 was between 0 and -8% (a terminal fall became a small terminal rise) of preflights standing. The terminal change in CO2 was nearly abolished in microgravity indicating more uniformity of blood flow between lung units that close at the end of expiration and units that remain open. This may result from the disappearance of gravity-dependent topographical inequality of blood flow. The residual cardiographic oscillations in expired CO2 imply a persisting inhomogeneity of perfusion in the absence of gravity at a level larger than acinar.

  17. Vascular perfusion in horses with chronic laminitis.

    PubMed

    Hood, D M; Grosenbaugh, D A; Slater, M R

    1994-05-01

    Vascular perfusion casts were used to define and characterise the macroscopic perfusion defects present in the distal digit of 11 horses affected by chronic laminitis. Five clinically normal horses were used as controls. Based on clinical history and clinical status, horses with chronic laminitis were classified as being potentially treatable or clinically refractory. Eleven macroscopic vascular defects were noted in the casts from horses with laminitis. Four types of lesions were identified in the submural laminar circulation, 3 in the coronary bed and 4 were associated with the solar circulation. Multiple defects were present and a definite trend was noted for the perfusion defects to be worse in the casts of clinically refractory subjects than in those considered treatable. This information suggests that evaluation of circulatory status should add significantly to the ability to separate treatable from clinically refractory patients. Results also indicated that ventral displacement of the third phalanx (sinkers) and compression of the solar vasculature are more prevalent than is presently thought.

  18. Dynamic CT perfusion measurement in a cardiac phantom.

    PubMed

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

    2015-10-01

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

  19. Assessment of free microvascular flap perfusion by intraoperative fluorescence angiography in craniomaxillofacial surgery.

    PubMed

    Preidl, Raimund H M; Schlittenbauer, Tilo; Weber, Manuel; Neukam, Friedrich W; Wehrhan, Falk

    2015-06-01

    Microsurgical tissue transfer represents a standard technique for reconstruction in craniomaxillofacial surgery. The transferred tissue is anastomosed to vessels of varying diameters and different physiological conditions. The aim of this study was to evaluate the blood flow in free flaps at their origin and compare this with the flow after reperfusion. In 24 patients undergoing microsurgical procedures (13 radial forearm free flaps (RFFF) and 11 parascapular/scapular free flaps (PSFF)), blood flow was evaluated by intraoperative fluorescence angiography after flap raising and again after reperfusion in the neck area (Flow800, Carl Zeiss AG, Oberkochen, Germany). Flow is expressed by the blood flow index (BFI), maximum intensity (MaxInt) and half-time to MaxInt (t1/2) and was measured in the flap pedicle itself, as well as in the supplying vessels. Following anastomosis of the free flaps in the head and neck area, both the arterial and the venous BFI and MaxInt significantly increased, whereas t1/2 decreased significantly. There was no significant difference in the perfusion parameters between RFFF and PSFF. Intraoperative fluorescence angiography is a reliable method for assessing the perfusion of free microvascular flaps. In the head and neck area, free flaps undergo a significant increase in perfusion but show no differences between varying flap types.

  20. C-arm cone beam CT perfusion imaging using the SMART-RECON algorithm to improve temporal sampling density and temporal resolution

    NASA Astrophysics Data System (ADS)

    Li, Yinsheng; Niu, Kai; Li, Ke; Schafer, Sebastian; Royalty, Kevin; Strother, Charles; Chen, Guang-Hong

    2016-03-01

    In this work, a newly developed reconstruction algorithm, Synchronized MultiArtifact Reduction with Tomographic RECONstruction (SMART-RECON), was applied to C-arm cone beam CT perfusion (CBCTP) imaging. This algorithm contains a special rank regularizer, designed to reduce limited-view artifacts associated with super- short scan reconstructions. As a result, high temporal sampling and temporal resolution image reconstructions were achieved using an interventional C-arm x-ray system. The algorithm was evaluated in terms of the fidelity of the dynamic contrast update curves and the accuracy of perfusion parameters through numerical simulation studies. Results shows that, not only were the dynamic curves accurately recovered (relative root mean square error ∈ [3%, 5%] compared with [13%, 22%] for FBP), but also the noise in the final perfusion maps was dramatically reduced. Compared with filtered backprojection, SMART-RECON generated CBCTP maps with much improved capability in differentiating lesions with perfusion deficits from the surrounding healthy brain tissues.

  1. Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 mum wavelength.

    PubMed

    Wang, Ruikang K; Hurst, Sawan

    2007-09-03

    Optical micro-angiography (OMAG) was developed to achieve volumetric imaging of the microstructures and dynamic cerebrovascular blood perfusion in mice with capillary level resolution and high signal-to-background ratio. In this paper, we present a high-speed and high-sensitivity OMAG imaging system by using an InGaAs line scan camera and broadband light source at 1.3 mum wavelength for enhanced imaging depth in tissue. We show that high quality imaging of cerebrovascular blood perfusion down to capillary level resolution with the intact skin and cranium are obtained in vivo with OMAG, without the interference from the blood perfusion in the overlaying skin. The results demonstrate the potential of 1.3 mum OMAG for high-speed and high-sensitivity imaging of blood perfusion in human and small animal studies.

  2. Repeatability of Cerebral Perfusion Using Dynamic Susceptibility Contrast MRI in Glioblastoma Patients12

    PubMed Central

    Jafari-Khouzani, Kourosh; Emblem, Kyrre E.; Kalpathy-Cramer, Jayashree; Bjørnerud, Atle; Vangel, Mark G.; Gerstner, Elizabeth R.; Schmainda, Kathleen M.; Paynabar, Kamran; Wu, Ona; Wen, Patrick Y.; Batchelor, Tracy; Rosen, Bruce; Stufflebeam, Steven M.

    2015-01-01

    OBJECTIVES This study evaluates the repeatability of brain perfusion using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a variety of post-processing methods. METHODS Thirty-two patients with newly diagnosed glioblastoma were recruited. On a 3-T MRI using a dual-echo, gradient-echo spin-echo DSC-MRI protocol, the patients were scanned twice 1 to 5 days apart. Perfusion maps including cerebral blood volume (CBV) and cerebral blood flow (CBF) were generated using two contrast agent leakage correction methods, along with testing normalization to reference tissue, and application of arterial input function (AIF). Repeatability of CBV and CBF within tumor regions and healthy tissues, identified by structural images, was assessed with intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs). Coefficients of variation (CVs) were reported for selected methods. RESULTS CBV and CBF were highly repeatable within tumor with ICC values up to 0.97. However, both CBV and CBF showed lower ICCs for healthy cortical tissues (up to 0.83), healthy gray matter (up to 0.95), and healthy white matter (WM; up to 0.93). The values of CV ranged from 6% to 10% in tumor and 3% to 11% in healthy tissues. The values of RC relative to the mean value of measurement within healthy WM ranged from 22% to 42% in tumor and 7% to 43% in healthy tissues. These percentages show how much variation in perfusion parameter, relative to that in healthy WM, we expect to observe to consider it statistically significant. We also found that normalization improved repeatability, but AIF deconvolution did not. CONCLUSIONS DSC-MRI is highly repeatable in high-grade glioma patients. PMID:26055170

  3. Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

    PubMed Central

    2003-01-01

    extent of hyperenhancement was significantly related to the likelihood of improvement in contractility after revascularization. However, the LVEF in the patient population was 43% prior to revascularization. It is important to know whether the technique has the same degree of accuracy in patients who have more severe LV dysfunction and who would most benefit from an assessment of myocardial viability. “Substantial” viability used as a measure of a patient’s ability to recover after revascularization has not been definitively reported (how much viability is enough?). Patients with severe LV dysfunction are more likely to have mixtures of surviving myocardium, including normal, infarcted, stunned and hibernating myocardium (Cowley et al., 1999). This may lead to a lack of homogeneity of response to testing and to revascularization and contribute to inter- and intra-study differences. There is a need for a large prospective study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and an alternate imaging technique. There is some evidence that MRI has comparable sensitivity, specificity and accuracy to PET for determining myocardial viability. However, there is a lack of evidence comparing the accuracy of these two techniques to predict LV function recovery. In addition, some studies refer to PET as the gold standard for the assessment of myocardial viability. Therefore, PET may be an ideal noninvasive imaging comparator to MRI for a prospective study with follow-up. To date, there is a lack of cost-effectiveness analyses (or any economic analyses) of functional cardiac MRI versus an alternate noninvasive imaging method for the assessment of myocardial viability/perfusion. Conclusion There is some evidence that the accuracy of functional cardiac MRI compares favourably with alternate imaging techniques for the assessment of myocardial viability and perfusion. There is insufficient evidence whether functional cardiac MRI can

  4. Development of tissue bank

    PubMed Central

    Narayan, R. P.

    2012-01-01

    The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole. PMID:23162240

  5. Development of tissue bank.

    PubMed

    Narayan, R P

    2012-05-01

    The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

  6. Effect of clinical and RBC hemorheological parameters on myocardial perfusion in patients with type 2 diabetes mellitus.

    PubMed

    Cho, Minhee; Shin, Sehyun; Kwon, Hyuck Moon; Chung, Hyemoon; Lee, Byoung Kwon

    2014-01-01

    Myocardial ischemia may be present even when there is no significant stenosis of the epicardial coronary artery, or after coronary angioplasty for significant coronary artery disease. This phenomenon is related to disturbance of the coronary microcirculation or vasomotor tone. The aim of this study was to determine the influence of clinical and RBC hemorheological factors, such as RBC deformability and aggregation, on myocardial perfusion in patients with type 2 diabetes mellitus (DM) when compared to patients without DM, presenting with stable angina or acute coronary syndrome. Myocardial perfusion was graded using the myocardial blush grade (MBG) which describes the relative "blush" or intensity of the radio-opacity of myocardial tissue observed after an epicardial coronary injection of contrast medium during coronary angiography. MBG was counted before any medical or mechanical intervention, and in the myocardial territory without anatomical flow limitation (<50% of luminal narrowing on coronary angiogram), in order to remove the direct influence of anatomical stenosis. Myocardial perfusion in this region was associated with diabetes, renal function, LV diastolic function, inflammatory biomarkers such as hs-CRP, fibrinogen and ESR, but not with the clinical presentation. Among the hemorheological parameters, reduced myocardial perfusion was linked to increased RBC aggregation, but not to variation in RBC deformability. In conclusion, myocardial perfusion was affected by diabetes, left ventricular diastolic function, and inflammatory activity indicated by clinical parameters, and by the hemorheological factor RBC aggregation.

  7. Implementation and evaluation of a new workflow for registration and segmentation of pulmonary MRI data for regional lung perfusion assessment.

    PubMed

    Böttger, T; Grunewald, K; Schöbinger, M; Fink, C; Risse, F; Kauczor, H U; Meinzer, H P; Wolf, Ivo

    2007-03-07

    Recently it has been shown that regional lung perfusion can be assessed using time-resolved contrast-enhanced magnetic resonance (MR) imaging. Quantification of the perfusion images has been attempted, based on definition of small regions of interest (ROIs). Use of complete lung segmentations instead of ROIs could possibly increase quantification accuracy. Due to the low signal-to-noise ratio, automatic segmentation algorithms cannot be applied. On the other hand, manual segmentation of the lung tissue is very time consuming and can become inaccurate, as the borders of the lung to adjacent tissues are not always clearly visible. We propose a new workflow for semi-automatic segmentation of the lung from additionally acquired morphological HASTE MR images. First the lung is delineated semi-automatically in the HASTE image. Next the HASTE image is automatically registered with the perfusion images. Finally, the transformation resulting from the registration is used to align the lung segmentation from the morphological dataset with the perfusion images. We evaluated rigid, affine and locally elastic transformations, suitable optimizers and different implementations of mutual information (MI) metrics to determine the best possible registration algorithm. We located the shortcomings of the registration procedure and under which conditions automatic registration will succeed or fail. Segmentation results were evaluated using overlap and distance measures. Integration of the new workflow reduces the time needed for post-processing of the data, simplifies the perfusion quantification and reduces interobserver variability in the segmentation process. In addition, the matched morphological data set can be used to identify morphologic changes as the source for the perfusion abnormalities.

  8. Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

    PubMed

    Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

    2016-07-01

    OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

  9. Perfusion phantom: An efficient and reproducible method to simulate myocardial first-pass perfusion measurements with cardiovascular magnetic resonance.

    PubMed

    Chiribiri, Amedeo; Schuster, Andreas; Ishida, Masaki; Hautvast, Gilion; Zarinabad, Niloufar; Morton, Geraint; Otton, James; Plein, Sven; Breeuwer, Marcel; Batchelor, Philip; Schaeffter, Tobias; Nagel, Eike

    2013-03-01

    The aim of this article is to describe a novel hardware perfusion phantom that simulates myocardial first-pass perfusion allowing comparisons between different MR techniques and validation of the results against a true gold standard. MR perfusion images were acquired at different myocardial perfusion rates and variable doses of gadolinium and cardiac output. The system proved to be sensitive to controlled variations of myocardial perfusion rate, contrast agent dose, and cardiac output. It produced distinct signal intensity curves for perfusion rates ranging from 1 to 10 mL/mL/min. Quantification of myocardial blood flow by signal deconvolution techniques provided accurate measurements of perfusion. The phantom also proved to be very reproducible between different sessions and different operators. This novel hardware perfusion phantom system allows reliable, reproducible, and efficient simulation of myocardial first-pass MR perfusion. Direct comparison between the results of image-based quantification and reference values of flow and myocardial perfusion will allow development and validation of accurate quantification methods.

  10. Ultrasound Contrast Materials in Cardiovascular Medicine: from Perfusion Assessment to Molecular Imaging

    PubMed Central

    Klibanov, Alexander L

    2013-01-01

    Ultrasound imaging is widely used in cardiovascular diagnostics. Contrast agents expand the range of tasks that ultrasound can perform. In the clinic in US, endocardial border delineation and left ventricle opacification have been an approved indication for more than a decade. However, myocardial perfusion contrast ultrasound studies are still at the clinical trials stage. Blood pool contrast and perfusion in other tissues might be an easier indication to achieve: general blood pool ultrasound contrast is in wider use in Europe, Canada, Japan, and China. Targeted (molecular) contrast microbubbles will be the next generation of ultrasound imaging probes, capable of specific delineation of the areas of disease by adherence to molecular targets. The shell of targeted microbubbles (currently in the preclinical research and early stage clinical trials) is decorated with the ligands (antibodies, peptides or mimetics, hormones, carbohydrates) that ensure firm binding to the molecular markers of disease. PMID:23913363

  11. Challenges in machine perfusion preservation for liver grafts from donation after circulatory death

    PubMed Central

    2013-01-01

    Donation after circulatory death (DCD) is a promising solution to the critical shortage of donor graft tissue. Maintaining organ viability after donation until transplantation is essential for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in clinical practice. However, ischemic damage present in DCD grafts jeopardizes organ viability during cold storage, and whether static cold storage is the most effective method to prevent deterioration of organ quality in the increasing numbers of organs from DCD is unknown. Here we describe the historical background of DCD liver grafts and a new preservation method for experimental and clinical transplantation. To prevent ischemia-reperfusion injury in DCD liver grafts, a hypothermic machine perfusion (HMP) technique has recently been developed and may be superior to static cold preservation. We present evidence supporting the need for improving liver perfusion performance and discuss how doing so will benefit liver transplantation recipients. PMID:24283383

  12. Comparison of stroke infarction between CT perfusion and diffusion weighted imaging: preliminary results

    NASA Astrophysics Data System (ADS)

    Abd. Rahni, Ashrani Aizzuddin; Arka, Israna Hossain; Chellappan, Kalaivani; Mukari, Shahizon Azura; Law, Zhe Kang; Sahathevan, Ramesh

    2016-03-01

    In this paper we present preliminary results of comparison of automatic segmentations of the infarct core, between that obtained from CT perfusion (based on time to peak parameter) and diffusion weighted imaging (DWI). For each patient, the two imaging volumes were automatically co-registered to a common frame of reference based on an acquired CT angiography image. The accuracy of image registration is measured by the overlap of the segmented brain from both images (CT perfusion and DWI), measured within their common field of view. Due to the limitations of the study, DWI was acquired as a follow up scan up to a week after initial CT based imaging. However, we found significant overlap of the segmented brain (Jaccard indices of approximately 0.8) and the percentage of infarcted brain tissue from the two modalities were still fairly highly correlated (correlation coefficient of approximately 0.9). The results are promising with more data needed in future for clinical inference.

  13. Videofluorometer for imaging tissue metabolism

    NASA Astrophysics Data System (ADS)

    Kelly, Jeffrey J.; Rorvik, Dawn A.; Richmond, Keith N.; Barlow, Clyde H.

    1989-11-01

    A videofluorometer is described that directly acquires digital metabolic images of reduced nicotinamide adenine dinucleotide (NADH) fluorescence in tissue. NADH fluorescence provides an intrinsic indicator of the state of tissue mitochondrial oxidative metabolism. The device combines a computer-controlled fluorescence excitation system with digital image acquisition to quantify tissue bioenergetics in both spatial and time domains. Localized ischemia following coronary artery ligation in a perfused rat heart (model for a coronary artery occlusion heart attack) is used as an example to demonstrate the capabilities of the system. This videofluorometer permits monitoring changes in physiological state of organs and tissue without interfering with tissue metabolism. The digital nature of the acquired image allows detailed analysis of physiological features and their time dependence.

  14. Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues.

    PubMed

    Shimizu, Tatsuya

    2014-01-01

    In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.

  15. 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

  16. 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

  17. Measurement of continuous distributions of ventilation-perfusion ratios - Theory

    NASA Technical Reports Server (NTRS)

    Wagner, P. D.; Saltzman, H. A.; West, J. B.

    1974-01-01

    The resolution of the technique considered is sufficient to describe smooth distributions containing blood flow to unventilated regions (shunt), ventilation to unperfused regions (dead space), and up to three additional modes over the range of finite ventilation-perfusion ratios. In particular, areas whose ventilation-perfusion ratios are low can be separated from unventilated regions and those whose ventilation-perfusion ratios are high can similarly be distinguished from unperfused areas.

  18. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

    Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

  19. C-arm perfusion imaging with a fast penalized maximum-likelihood approach

    NASA Astrophysics Data System (ADS)

    Frysch, Robert; Pfeiffer, Tim; Bannasch, Sebastian; Serowy, Steffen; Gugel, Sebastian; Skalej, Martin; Rose, Georg

    2014-03-01

    Perfusion imaging is an essential method for stroke diagnostics. One of the most important factors for a successful therapy is to get the diagnosis as fast as possible. Therefore our approach aims at perfusion imaging (PI) with a cone beam C-arm system providing perfusion information directly in the interventional suite. For PI the imaging system has to provide excellent soft tissue contrast resolution in order to allow the detection of small attenuation enhancement due to contrast agent in the capillary vessels. The limited dynamic range of flat panel detectors as well as the sparse sampling of the slow rotating C-arm in combination with standard reconstruction methods results in limited soft tissue contrast. We choose a penalized maximum-likelihood reconstruction method to get suitable results. To minimize the computational load, the 4D reconstruction task is reduced to several static 3D reconstructions. We also include an ordered subset technique with transitioning to a small number of subsets, which adds sharpness to the image with less iterations while also suppressing the noise. Instead of the standard multiplicative EM correction, we apply a Newton-based optimization to further accelerate the reconstruction algorithm. The latter optimization reduces the computation time by up to 70%. Further acceleration is provided by a multi-GPU implementation of the forward and backward projection, which fulfills the demands of cone beam geometry. In this preliminary study we evaluate this procedure on clinical data. Perfusion maps are computed and compared with reference images from magnetic resonance scans. We found a high correlation between both images.

  20. Intravenous thrombolysis in acute ischemic stroke patients with negative CT perfusion: a case series

    PubMed Central

    Mehra, Ratnesh; Qahwash, Omar; Richards, Boyd; Fessler, Richard D

    2014-01-01

    Background Computed tomography perfusion (CTP) is a commonly used modality of neurophysiologic imaging to aid the selection of acute ischemic stroke patients for neuroendovascular intervention by identifying the presence of penumbra versus infarcted brain tissue. However many patients present with evidence of cerebral ischemia with normal CTP, and in that case, should intravenous thrombolytics be given? Purpose To demonstrate if tissue-type plasminogen activator (tPA)-eligible stroke patients without perfusion defects demonstrated on CTP would benefit from administration of intravenous thrombolytics. Material and Methods We retrospectively identified patients presenting with acute ischemic symptoms who received intravenous tPA (IV-tPA) from January to June 2012 without a perfusion defect on CTP. Clinical and radiographic findings including the NIHSS at presentation, 24 h, and at discharge, symptomatic and asymptomatic hemorrhagic transformation, and the modified Rankin score at 30 days were collected. A reduction of NIHSS of greater than 4 points or resolution of symptoms was considered significant. Results Seventeen patients were identified with a mean NIHSS of 8.2 prior to administration of intravenous thrombolytics, 3.5 after 24 h, and 2.5 at discharge. Among them, 13 patients had significant improvement of NIHSS with a mean reduction of 6.15 points at 24 h. One patient initially improved but had delayed hemorrhagic transformation and died. Two patients had improvement in NIHSS but were not significant and two patients had increased in NIHSS at 24 h, although one eventually improved at discharge. There was no asymptomatic hemorrhagic transformation. Mean mRS at 3 months is 1.76. Conclusion The failure to identify a perfusion deficit by CTP should not be used as a contraindication for intravenous thrombolytics. Criteria for administration of intravenous thrombolytics should still be based on time from symptom onset as previously published by NINDS. PMID

  1. Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension

    SciTech Connect

    Lisbona, R.; Kreisman, H.; Novales-Diaz, J.; Derbekyan, V.

    1985-01-01

    Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism.

  2. 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.

  3. Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time.

    PubMed

    Taeger, C D; Präbst, K; Beier, J P; Meyer, A; Horch, R E

    2016-04-01

    In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using extracorporeal free flap perfusion in the laboratory have been published in the past, until now this concept has not yet paved its way into clinical routine. This might be due to the complexity of perfusion systems and a lack of standardized tools. Here, we want to present the results of the first extracorporeal free flap perfusion in a clinical setting using a simple approach without the application of a complex perfusion machinery.

  4. Effect of prolonged hypokinesia on tissue blood flow

    NASA Technical Reports Server (NTRS)

    Levites, Z. P.; Fedotova, V. F.

    1979-01-01

    The influence of hypokinesia on the blood flow in the tissues of rabbits was studied. Motor activity of animals was restricted during 90 days and blood flow recorded through resorption rate of NaI-131. Perfusion of tissues under the influence of hypokinesia was found to be reduced.

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

    PubMed

    Malek, Antoine

    2010-01-01

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

  6. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  7. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  8. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  9. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  10. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  11. Real-time ultrasound brain perfusion imaging with analysis of microbubble replenishment in acute MCA stroke.

    PubMed

    Kern, Rolf; Diels, Anna; Pettenpohl, Johanna; Kablau, Micha; Brade, Joachim; Hennerici, Michael G; Meairs, Stephen

    2011-08-01

    Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2 ± 13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau (A) of acoustic intensity, and A × β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β=0.58 ± 0.40 versus 1.25 ± 0.83; P=0.001; A=1.44 ± 1.75 versus 2.63 ± 2.31; P=0.05; A × β=1.14 ± 2.25 versus 2.98 ± 2.70; P=0.01). Real-time time to peak was delayed in ischemic tissue (11.43 ± 2.67 versus 8.88 ± 1.66 seconds; P<0.001). From the analysis of receiver operating characteristic curves, β and A × β had the largest areas under the curve with optimal cutoff values of β<0.76 and A × β<1.91. We conclude that rt-UPI with analysis of microbubble replenishment correctly identifies ischemic brain tissue in acute MCA stroke.

  12. The development of a bioreactor to perfuse radially-confined hydrogel constructs: design and characterization of mass transport properties.

    PubMed

    Eniwumide, Joshua O; Lee, David A; Bader, Dan L

    2009-01-01

    Limitations to nutrient transport provide a challenge to the development of 3D tissue-engineered constructs. A heterogeneous distribution of viable cells and functional matrix within the developing tissue is a common consequence. In the present study, a bioreactor was developed to perfuse fluid through cylindrical agarose constructs. The transport and distribution of dextran molecules (FD-4, FD-500, FD-2000) within the agarose was visualized in order to determine the bioreactors effectiveness for transport enhancement. By 24 h, the perfusion bioreactor achieved 529%, 395% and 294% higher concentrations of FD-4, FD-500 and FD-2000, respectively, than those solely due to diffusion. Of particular interest was the effectiveness of the bioreactor to transport molecules to the central region of the constructs. In this respect, the perfusion bioreactor was found to increase transportation of FD-4, FD-500 and FD-2000 by 30%, 291% and 222% over that of diffusion. Articular chondrocytes were cultured and perfused using the bioreactor. The improved molecular transport achieved led to an average 75% and 1340% increase of DNA and sulphated GAG, respectively at 20 days. More significantly was the 106% and 1603% increase of DNA and GAG, respectively, achieved at the central core of the 3D constructs.

  13. 4D micro-CT for cardiac and perfusion applications with view under sampling.

    PubMed

    Badea, Cristian T; Johnston, Samuel M; Qi, Yi; Johnson, G Allan

    2011-06-07

    Micro-CT is commonly used in preclinical studies to provide anatomical information. There is growing interest in obtaining functional measurements from 4D micro-CT. We report here strategies for 4D micro-CT with a focus on two applications: (i) cardiac imaging based on retrospective gating and (ii) pulmonary perfusion using multiple contrast injections/rotations paradigm. A dual source micro-CT system is used for image acquisition with a sampling rate of 20 projections per second. The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent. Fast scanning of free breathing mice is achieved using retrospective gating. The ECG and respiratory signals are used to sort projections into ten cardiac phases. The pulmonary perfusion protocol uses a conventional contrast agent (Isovue 370) delivered by a micro-injector in four injections separated by 2 min intervals to allow for clearance. Each injection is synchronized with the rotation of the animal, and each of the four rotations is started with an angular offset of 22.5 from the starting angle of the previous rotation. Both cardiac and perfusion protocols result in an irregular angular distribution of projections that causes significant streaking artifacts in reconstructions when using traditional filtered backprojection (FBP) algorithms. The reconstruction involves the use of the point spread function of the micro-CT system for each time point, and the analysis of the distribution of the reconstructed data in the Fourier domain. This enables us to correct for angular inconsistencies via deconvolution and identify regions where data is missing. The missing regions are filled with data from a high quality but temporally averaged prior image reconstructed with all available projections. Simulations indicate that deconvolution successfully removes the streaking artifacts while preserving temporal information. 4D cardiac micro-CT in a mouse was performed with adequate image quality at isotropic

  14. Fluorescence spectroscopy and cryoimaging of rat lung tissue mitochondrial redox state

    NASA Astrophysics Data System (ADS)

    Sepehr, R.; Audi, S.; Staniszewski, K.; Maleki, S.; Ranji, M.

    2011-07-01

    The objective of this study was to demonstrate the utility of optical cryoimaging and fluorometry to evaluate tissue redox state of the mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavin Adenine Dinucleotide) in intact rat lungs. The ratio (NADH/FAD), referred to as mitochondrial redox ratio (RR), is a measure of the lung tissue mitochondrial redox state. Isolated rat lungs were connected to a ventilation-perfused system. Surface NADH and FAD fluorescence signals were acquired before and after lung perfusion in the absence (control perfusate) or presence of potassium cyanide (KCN, complex IV inhibitor) to reduce the mitochondrial respiratory chain (state 5 respiration). Another group of lungs were perfused with control perfusate or KCN-containing perfusate as above, after which the lungs were deflated and frozen rapidly for subsequent 3D cryoimaging. Results demonstrate that lung treatment with KCN increased lung surface NADH signal by 22%, decreased FAD signal by 8%, and as result increased RR by 31% as compared to control perfusate (baseline) values. Cryoimaging results also show that KCN increased mean lung tissue NADH signal by 37%, decreased mean FAD signal by 4%, and increased mean RR by 47%. These results demonstrate the utility of these optical techniques to evaluate the effect of pulmonary oxidative stress on tissue mitochondrial redox state in intact lungs.

  15. The pediatric template of brain perfusion

    PubMed Central

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development. PMID:25977810

  16. The pediatric template of brain perfusion.

    PubMed

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.

  17. A simultaneous multimodal imaging system for tissue functional parameters

    NASA Astrophysics Data System (ADS)

    Ren, Wenqi; Zhang, Zhiwu; Wu, Qiang; Zhang, Shiwu; Xu, Ronald

    2014-02-01

    Simultaneous and quantitative assessment of skin functional characteristics in different modalities will facilitate diagnosis and therapy in many clinical applications such as wound healing. However, many existing clinical practices and multimodal imaging systems are subjective, qualitative, sequential for multimodal data collection, and need co-registration between different modalities. To overcome these limitations, we developed a multimodal imaging system for quantitative, non-invasive, and simultaneous imaging of cutaneous tissue oxygenation and blood perfusion parameters. The imaging system integrated multispectral and laser speckle imaging technologies into one experimental setup. A Labview interface was developed for equipment control, synchronization, and image acquisition. Advanced algorithms based on a wide gap second derivative reflectometry and laser speckle contrast analysis (LASCA) were developed for accurate reconstruction of tissue oxygenation and blood perfusion respectively. Quantitative calibration experiments and a new style of skinsimulating phantom were designed to verify the accuracy and reliability of the imaging system. The experimental results were compared with a Moor tissue oxygenation and perfusion monitor. For In vivo testing, a post-occlusion reactive hyperemia (PORH) procedure in human subject and an ongoing wound healing monitoring experiment using dorsal skinfold chamber models were conducted to validate the usability of our system for dynamic detection of oxygenation and perfusion parameters. In this study, we have not only setup an advanced multimodal imaging system for cutaneous tissue oxygenation and perfusion parameters but also elucidated its potential for wound healing assessment in clinical practice.

  18. Prolonged cerebral "luxury perfusion" after removal of a convexity meningioma.

    PubMed

    Lunsford, L D; Selker, R G

    1979-04-01

    Following total removal of a convexity meningioma, serial computerized tomographic scans disclosed massive hemispheric contrast enhancement compatible with "luxury perfusion". Maximum enhancement occurred one month following the operation and resolved two months postoperatively. Luxury perfusion appeared to be associated with slowly resolving cerebral edema.

  19. Magnetic Resonance Perfusion Imaging in the Study of Language

    ERIC Educational Resources Information Center

    Hillis, Argye E.

    2007-01-01

    This paper provides a brief review of various uses of magnetic resonance perfusion imaging in the investigation of brain/language relationships. The reviewed studies illustrate how perfusion imaging can reveal areas of brain where dysfunction due to low blood flow is associated with specific language deficits, and where restoration of blood flow…

  20. 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.

  1. Prostaglandin E1 Increases Microcirculation in Random Pattern Flaps on Rats Measured with Laser Doppler Perfusion Imaging

    PubMed Central

    Sneistrup, Christian; Berg, Thomas Moe

    2017-01-01

    Background: Reconstructive procedures with pedicled and free flaps are associated with a risk of ischemia. Prostaglandin E1 (PGE1) is a hormone-like substance with known antiischemic and tissue-protective effects. The aim of this study was to evaluate the effect of PGE1 on the microcirculation in random pattern skin flaps on rats. Methods: Twenty-four rats were divided into 2 groups: an intervention group given PGE1 for 6 hours and a control group given saline. The flap (2 × 10 cm) was created on the back of the rats, and the microcirculation was monitored with laser Doppler perfusion imaging in 5 different zones (1, proximal; 5, distal) before surgery and after 60, 180, and 360 minutes postoperatively. Results: Before surgery, there was no difference in the perfusion in any zones between the intervention group and the control group. The mean perfusion values in zone 1 in the intervention group were significantly higher than those in the control group at 60, 180, and 360 minutes postoperatively (P = 0.02, P = 0.05, and P = 0.04, respectively). At 360 minutes, we also found significantly higher levels of perfusion in the intervention group in zones 4 and 5 (P = 0.05 and P = 0.03, respectively) compared with the controls. Comparing the perfusion at 360 to 60 minutes in the intervention group, we found a significant increase in microcirculation in all zones, which were not seen in the control group. Conclusion: PGE1 increased perfusion in the dermal random pattern flaps on rats. PMID:28203503

  2. Determination of the need for selenium by chicks fed practical diets adequate in vitamin E

    SciTech Connect

    Combs, G.F. Jr.; Su, Q.; Liu, C.H.; Sinisalo, M.; Combs, S.B.

    1986-03-01

    Experiments were conducted to compare the dietary needs for selenium (Se) by chicks fed either purified (amino acid-based) or practical (corn- and soy-based) diets that were adequate with respect to vitamin E (i.e., contained 100 IU/kg) and all other known nutrients with the single exception of Se (i.e., contained only 0.10 ppm Se). Studies were conducted in Ithaca using Single Comb White Leghorn chicks fed the purified basal diet and in Beijing using chicks of the same breed fed either the same purified basal diet or the practical diet formulated to be similar to that used in poultry production in some parts of China and the US. Results showed that each basal diet produced severe depletion of Se-dependent glutathione peroxidase (SeGSHpx) in plasma, liver and pancreas according to the same time-course, but that other consequences of severe uncomplicated Se deficiency were much more severe among chicks fed the purified diet (e.g., growth depression, pancreatic dysfunction as indicated by elevated plasma amylase and abnormal pancreatic histology). Chicks fed the practical Se-deficient diet showed reduced pancreas levels of copper, zinc and molybdenum and elevated plasma levels of iron; they required ca. 0.10 ppm dietary Se to sustain normal SeGSHpx in several tissues and to prevent elevated amylase in plasma. The dietary Se requirement of the chick is, therefore, estimated to be 0.10 ppm.

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

    PubMed

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

    2009-07-01

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

  4. In vivo monitoring of external pressure induced hemodynamics in skin tissue using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Hequn; Wang, Ruikang K.

    2015-03-01

    Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT) angiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT angiography to monitor effect of external pressures on blood perfusion in human skin tissue in vivo. Graded external pressure is loaded normal to the surface of the nailfold tissue of a healthy human. The incremental loading is applied step by step and then followed by an immediate release. Concurrent OCT imaging of the nailfold is performed during the pre/post loading. Blood perfusion images including baseline (at pre-loading) and corresponding tissue strain maps are calculated from 3D OCT dataset obtained at the different applied pressures, allowing visualization of capillary perfusion events at stressed nailfold tissue. The results indicate that the perfusion progressively decreases with the constant increase of tissue strain. Reactive hyperemia is occurred right after the removal of the pressure corresponding to quick drop of the increased strain. The perfusion is returned to the baseline level after a few minutes. These findings suggest that OCT microangiography may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

  5. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    SciTech Connect

    Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-09-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.

  6. Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver.

    PubMed

    Shimada, Shingo; Wakayama, Kenji; Fukai, Moto; Shimamura, Tsuyoshi; Ishikawa, Takahisa; Fukumori, Daisuke; Shibata, Maki; Yamashita, Kenichiro; Kimura, Taichi; Todo, Satoru; Ohsawa, Ikuroh; Taketomi, Akinobu

    2016-12-01

    Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2 (+) and H2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2 (-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2 (+) group, these harmful changes were significantly suppressed [vs. H2 (-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter.

  7. Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology.

    PubMed

    Caicedo, Hector H; Hernandez, Maximiliano; Fall, Christopher P; Eddington, David T

    2010-10-01

    Understanding and optimizing fluid flows through in vitro microfluidic perfusion systems is essential in mimicking in vivo conditions for biological research. In a previous study a microfluidic brain slice device (microBSD) was developed for microscale electrophysiology investigations. The device consisted of a standard perfusion chamber bonded to a polydimethylsiloxane (PDMS) microchannel substrate. Our objective in this study is to characterize the flows through the microBSD by using multiphysics simulations of injections into a pourous matrix to identify optimal spacing of ports. Three-dimensional computational fluid dynamic (CFD) simulations are performed with CFD-ACE + software to model, simulate, and assess the transport of soluble factors through the perfusion bath, the microchannels, and a material that mimics the porosity, permeability and tortuosity of brain tissue. Additionally, experimental soluble factor transport through a brain slice is predicted by and compared to simulated fluid flow in a volume that represents a porous matrix material. The computational results are validated with fluorescent dye experiments.

  8. LOW DOSE NITRITE ENHANCES PERFUSION AFTER FLUID RESUSCITATION FROM HEMORRHAGIC SHOCK

    PubMed Central

    Cabrales, Pedro

    2010-01-01

    This study determines the systemic and microvascular hemodynamic consequences of administering a low dose sodium nitrite after fluid resuscitation from hemorrhagic shock. Hemodynamic responses to hemorrhagic shock and resuscitation were studied in the hamster window chamber model. Moderated hemorrhage was induced by arterial controlled bleeding of 50% of the blood volume (BV) and the hypovolemic state was maintained for one hour. Volume restitution was performed by infusion of 25% of BV using Hextend® (6% Hetastarch 670 kDa in lactated electrolyte solution) 10 min after fluid resuscitation 100μl of specific concentrations of sodium nitrite were infused. The experimental groups were named based on the nitrite concentration used, namely: 0 μM, 10 μM and 50 μM. Systemic parameters, microvascular hemodynamics and capillary perfusion (functional capillary density, FCD) were followed during entire protocol. Exogenous 10 μM nitrite maintained systemic and microhemodynamic conditions post fluid resuscitation from hemorrhagic shock, compared to 50 μM or no nitrite. A moderated increase in plasma nitrite during the early phase of resuscitation reversed arteriolar vasoconstriction and increased capillary perfusion and venous return, improving central cardiac function. Nitrite effects on resistance vessels, directly influenced intravascular pressure redistribution, sustained blood flow, and prevented tissue ischemia. In conclusion, increasing nitrite plasma bioavailability after fluid resuscitation from hemorrhagic shock can be a potential therapy to enhance microvascular perfusion and to improve overall outcome. PMID:19804938

  9. A Novel Flow-Perfusion Bioreactor Supports 3D Dynamic Cell Culture

    PubMed Central

    Sailon, Alexander M.; Allori, Alexander C.; Davidson, Edward H.; Reformat, Derek D.; Allen, Robert J.; Warren, Stephen M.

    2009-01-01

    Background. Bone engineering requires thicker three-dimensional constructs than the maximum thickness supported by standard cell-culture techniques (2 mm). A flow-perfusion bioreactor was developed to provide chemotransportation to thick (6 mm) scaffolds. Methods. Polyurethane scaffolds, seeded with murine preosteoblasts, were loaded into a novel bioreactor. Control scaffolds remained in static culture. Samples were harvested at days 2, 4, 6, and 8 and analyzed for cellular distribution, viability, metabolic activity, and density at the periphery and core. Results. By day 8, static scaffolds had a periphery cell density of 67% ± 5.0%, while in the core it was 0.3% ± 0.3%. Flow-perfused scaffolds demonstrated peripheral cell density of 94% ± 8.3% and core density of 76% ± 3.1% at day 8. Conclusions. Flow perfusion provides chemotransportation to thick scaffolds. This system may permit high throughput study of 3D tissues in vitro and enable prefabrication of biological constructs large enough to solve clinical problems. PMID:20037739

  10. Measurement of cerebrospinal fluid formation and absorption by ventriculo-cisternal perfusion: what is really measured?

    PubMed Central

    Orešković, Darko; Klarica, Marijan

    2014-01-01

    The generally accepted hypothesis on cerebrospinal fluid (CSF) hydrodynamics suggests that CSF is actively formed mainly by choroid plexuses, circulates unidirectionally along the brain ventricles and subarachnoid space, and is passively absorbed mainly into the dural venous sinuses. CSF formation rate (Vf) has been extensively studied using the ventriculo-cisternal perfusion technique and the results have been used as the key evidence confirming the mentioned hypothesis. This method and the equation for Vf calculation are based on the assumption that the dilution of the indicator substance is a consequence of the newly formed CSF, ie, that a higher CSF formation rate will result in a higher degree of dilution. However, it has been experimentally shown that the indicator substance dilution inside the CSF system does not occur because of a “newly formed” CSF, but as consequence of a number of other factors (departure of substances into the surrounding tissue, flowing around the collecting cannula into the cortical and spinal subarachnoid space, departure into the contralateral ventricle, etc). This technique allows “calculation” of the CSF formation even in dead animals, in an in vitro model, and in any other part of the CSF system outside the ventricles that is being perfused. Therefore, this method is indirect and any dilution of the indicator substance in the perfusate caused by other reasons would result in questionable and often contradictory conclusions regarding CSF formation rates. PMID:25165046