Sample records for perfused term human

  1. Long-term three-dimensional perfusion culture of human adult bone marrow mononuclear cells in bioreactors.

    PubMed

    Schmelzer, Eva; Finoli, Anthony; Nettleship, Ian; Gerlach, Jörg C

    2015-04-01

    The construction and long-term maintenance of three-dimensional in vitro bone marrow models is of great interest but still quite challenging. Here we describe the use of a multi-compartment hollow-fiber membrane based three-dimensional perfusion bioreactor for long-term culture of whole human bone marrow mononuclear cells. We also investigated bioreactors with incorporated open-porous foamed hydroxyapatite scaffolds, mimicking the in vivo bone matrix. Cells in bioreactors with and without scaffolds were cultured to 6 weeks and compared to Petri dish controls. Cells were analyzed for gene expression, surface markers by flow cytometry, metabolic activity, hematopoietic potential, viability, and attachment by immunocytochemistry. Cells in bioreactors were metabolic active during long-term culture. The percentages of hematopoietic stem cell and mature endothelial cell fractions were maintained in bioreactors. The expression of most of the analyzed genes stabilized and increased after long-term culture of 6 weeks. Compared to Petri dish culture controls, bioreactor perfusion culture improved in both the short and long-term, the colony formation unit capacity of hematopoietic progenitors. Cells attached to the ample surface area provided by hydroxyapatite scaffolds. The implementation of a hydroxyapatite scaffold did not influence colony formation capacity, percentages of cell type specific fractions, gene expression, cell viability or metabolic turnover when compared to control cells cultured in bioreactors without scaffolds. In conclusion, three-dimensional perfusion bioreactor culture enables long-term maintenance of primary human bone marrow cells, with hydroxyapatite scaffolds providing an in vivo-like scaffold for three-dimensional culture. © 2015 Wiley Periodicals, Inc.

  2. The perfused swine uterus model: long-term perfusion

    PubMed Central

    2012-01-01

    Background It has previously been shown that the viability of swine uteri can be maintained within the physiological range in an open perfusion model for up to 8 hours. The aim of this study was to assess medium- to long-term perfusion of swine uteri using a modified Krebs–Ringer bicarbonate buffer solution (KRBB) in the established open perfusion model. Methods In an experimental study at an infertility institute, 30 swine uteri were perfused: group 1: n = 11, KRBB; group 2: n = 8, modified KRBB with drainage of perfusate supernatant; group 3: n = 11, modified KRBB with drainage of perfusate every 2 h and substitution with fresh medium. Modified and conventional KRBB were compared with regard to survival and contraction parameters: intrauterine pressure (IUP), area under the curve (AUC), and frequency of contractions (F). Results Modified KRBB showed significantly higher IUP, AUC, and F values than perfusion with conventional KRBB. In group 3, the organ survival time of up to 17 h, with a 98% rate of effective contraction time, differed significantly from group 1 (P < 0.001). Conclusions Using modified KRBB in combination with perfusate substitution improves the open model for perfusion of swine uteri with regard to survival time and quality of contraction parameters. This model can be used for medium- to long-term perfusion of swine uteri, allowing further metabolic ex vivo studies in a cost-effective way and with little logistic effort. PMID:23241226

  3. 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.

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

    PubMed Central

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

    2014-01-01

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

  5. Energy demand of cardioplegically perfused human hearts.

    PubMed

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

    1985-01-01

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

  6. Normothermic machine perfusion of donor livers without the need for human blood products

    PubMed Central

    Matton, Alix P. M.; Burlage, Laura C.; van Rijn, Rianne; de Vries, Yvonne; Karangwa, Shanice A.; Nijsten, Maarten W.; Gouw, Annette S. H.; Wiersema‐Buist, Janneke; Adelmeijer, Jelle; Westerkamp, Andrie C.; Lisman, Ton

    2018-01-01

    Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin‐based oxygen carrier (HBOC)‐201. Twenty‐four livers declined for transplantation were transported by using static cold storage. Upon arrival, livers underwent NMP for 6 hours using pressure‐controlled portal and arterial perfusion. A total of 12 livers were perfused using a solution based on RBCs and FFPs (historical cohort), 6 livers with HBOC‐201 and FFPs, and another 6 livers with HBOC‐201 and gelofusine, a gelatin‐based colloid solution. Compared with RBC + FFP perfused livers, livers perfused with HBOC‐201 had significantly higher hepatic adenosine triphosphate content, cumulative bile production, and portal and arterial flows. Biliary secretion of bicarbonate, bilirubin, bile salts, and phospholipids was similar in all 3 groups. The alanine aminotransferase concentration in perfusate was lower in the HBOC‐201–perfused groups. In conclusion, NMP of human donor livers can be performed effectively using HBOC‐201 and gelofusine, eliminating the need for human blood products. Perfusing livers with HBOC‐201 is at least similar to perfusion with RBCs and FFP. Some of the biomarkers of liver function and injury even suggest a possible superiority of an HBOC‐201–based perfusion solution and opens a perspective for further optimization of machine perfusion techniques. Liver Transplantation 24 528–538 2018 AASLD. PMID:29281862

  7. A microfluidically perfused three dimensional human liver model.

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2017-01-01

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

  9. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta.

    PubMed

    Myllynen, Päivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysä, Jaana; Pirilä, Rauna; Lastumäki, Anni; Vähäkangas, Kirsi H

    2008-10-15

    We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p<0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75+/-0.10, p=0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of (14)C-PhIP (R=-0.81, p<0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: -0.11, p=0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of (14)C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarcinoma cells.

  10. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta

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

    Myllynen, Paeivi; Kummu, Maria; Kangas, Tiina

    2008-10-15

    We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of {sup 14}C-PhIP (2 {mu}M) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 {+-} 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of {sup 14}C-PhIP from maternal to fetal circulation (FM ratio 0.90 {+-} 0.08 at 6 h, p < 0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75 {+-}more » 0.10, p = 0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of {sup 14}C-PhIP (R = - 0.81, p < 0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: - 0.11, p = 0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of {sup 14}C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells.« less

  11. Ex vivo perfusion of human spleens maintains clearing and processing functions.

    PubMed

    Buffet, Pierre A; Milon, Geneviève; Brousse, Valentine; Correas, Jean-Michel; Dousset, Bertrand; Couvelard, Anne; Kianmanesh, Reza; Farges, Olivier; Sauvanet, Alain; Paye, François; Ungeheuer, Marie-Noëlle; Ottone, Catherine; Khun, Huot; Fiette, Laurence; Guigon, Ghislaine; Huerre, Michel; Mercereau-Puijalon, Odile; David, Peter H

    2006-05-01

    The spleen plays a central role in the pathophysiology of several potentially severe diseases such as inherited red cell membrane disorders, hemolytic anemias, and malaria. Research on these diseases is hampered by ethical constraints that limit human spleen tissue explorations. We identified a surgical situation--left splenopancreatectomy for benign pancreas tumors--allowing spleen retrieval at no risk for patients. Ex vivo perfusion of retrieved intact spleens for 4 to 6 hours maintained a preserved parenchymal structure, vascular flow, and metabolic activity. Function preservation was assessed by testing the ability of isolated-perfused spleens to retain Plasmodium falciparum-infected erythrocytes preexposed to the antimalarial drug artesunate (Art-iRBCs). More than 95% of Art-iRBCs were cleared from the perfusate in 2 hours. At each transit through isolated-perfused spleens, parasite remnants were removed from 0.2% to 0.23% of Art-iRBCs, a proportion consistent with the 0.02% to 1% pitting rate previously established in artesunate-treated patients. Histologic analysis showed that more than 90% of Art-iRBCs were retained and processed in the red pulp, providing the first direct evidence of a zone-dependent parasite clearance by the human spleen. Human-specific physiologic or pathophysiologic mechanisms involving clearing or processing functions of the spleen can now be experimentally explored in a human tissue context.

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

    PubMed

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

    2016-12-01

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

  13. The 24-hour normothermic machine perfusion of discarded human liver grafts.

    PubMed

    Vogel, Thomas; Brockmann, Jens G; Quaglia, Alberto; Morovat, Alireza; Jassem, Wayel; Heaton, Nigel D; Coussios, Constantin C; Friend, Peter J

    2017-02-01

    Donor organ shortage necessitates use of less than optimal donor allografts for transplantation. The current cold storage preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation (NMP) of liver allografts. In this study, we analyze discarded human liver grafts that underwent NMP for the extended period of 24 hours. Thirteen human liver grafts which had been discarded for transplantation were entered into this study. Perfusion was performed with an automated device using an oxygenated, sanguineous perfusion solution at normothermia. Automated control was incorporated for temperature-, flow-, and pressure-regulation as well as oxygenation. All livers were perfused for 24 hours; parameters of biochemical and synthetic liver function as well as histological parameters of liver damage were analyzed. Livers were stratified for expected viability according to the donor's medical history, procurement data, and their macroscopic appearance. Normothermic perfusion preservation of human livers for 24 hours was shown to be technically feasible. Human liver grafts, all of which had been discarded for transplantation, showed levels suggesting organ viability with respect to metabolic and synthetic liver function (to varying degrees). There was positive correlation between instantly available perfusion parameters and generally accepted predictors of posttransplant graft survival. In conclusion, NMP is feasible reliably for periods of at least 24 hours, even in highly suboptimal donor organs. Potential benefits include not only viability testing (as suggested in recent clinical implementations), but also removal of the time constraints associated with the utilization of high-risk livers, and recovery of ischemic and other preretrieval injuries (possibly by enabling therapeutic strategies during NMP). Liver Transplantation 23 207-220 2017 AASLD. © 2016 by the

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

    PubMed

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

    2017-11-01

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

  15. Ex-vivo machine perfusion for kidney preservation.

    PubMed

    Hamar, Matyas; Selzner, Markus

    2018-06-01

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

  16. γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe

    PubMed Central

    Donahue, Manus J; Rane, Swati; Hussey, Erin; Mason, Emily; Pradhan, Subechhya; Waddell, Kevin W; Ally, Brandon A

    2014-01-01

    Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA+]/[NAA–NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA+]/[NAA–NAAG] and perfusion (R=−0.46; P=0.037), yet no relationship between AAT and [GABA+]/[NAA–NAAG] (R=−0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA+]/[NAA–NAAG] and perfusion (R=−0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission. PMID:24398941

  17. Comparing effects of perfusion and hydrostatic pressure on gene profiles of human chondrocyte.

    PubMed

    Zhu, Ge; Mayer-Wagner, Susanne; Schröder, Christian; Woiczinski, Matthias; Blum, Helmut; Lavagi, Ilaria; Krebs, Stefan; Redeker, Julia I; Hölzer, Andreas; Jansson, Volkmar; Betz, Oliver; Müller, Peter E

    2015-09-20

    Hydrostatic pressure and perfusion have been shown to regulate the chondrogenic potential of articular chondrocytes. In order to compare the effects of hydrostatic pressure plus perfusion (HPP) and perfusion (P) we investigated the complete gene expression profiles of human chondrocytes under HPP and P. A simplified bioreactor was constructed to apply loading (0.1 MPa for 2 h) and perfusion (2 ml) through the same piping by pressurizing the medium directly. High-density monolayer cultures of human chondrocytes were exposed to HPP or P for 4 days. Controls (C) were maintained in static cultures. Gene expression was evaluated by sequencing (RNAseq) and quantitative real-time PCR analysis. Both treatments changed gene expression levels of human chondrocytes significantly. Specifically, HPP and P increased COL2A1 expression and decreased COL1A1 and MMP-13 expression. Despite of these similarities, RNAseq revealed a list of cartilage genes including ACAN, ITGA10 and TNC, which were differentially expressed by HPP and P. Of these candidates, adhesion related molecules were found to be upregulated in HPP. Both HPP and P treatment had beneficial effects on chondrocyte differentiation and decreased catabolic enzyme expression. The study provides new insight into how hydrostatic pressure and perfusion enhance cartilage differentiation and inhibit catabolic effects. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

  19. Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

    PubMed

    Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

    2018-02-01

    Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

  20. Organ-specific physiological responses to acute physical exercise and long-term training in humans.

    PubMed

    Heinonen, Ilkka; Kalliokoski, Kari K; Hannukainen, Jarna C; Duncker, Dirk J; Nuutila, Pirjo; Knuuti, Juhani

    2014-11-01

    Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

  1. Blood temperature and perfusion to exercising and non-exercising human limbs.

    PubMed

    González-Alonso, José; Calbet, José A L; Boushel, Robert; Helge, Jørn W; Søndergaard, Hans; Munch-Andersen, Thor; van Hall, Gerrit; Mortensen, Stefan P; Secher, Niels H

    2015-10-01

    What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (TB ), blood flow and oxygen uptake (V̇O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher TB and limb V̇O2. Leg and arm vascular conductance during exercise compared with rest was related closely to TB (r(2) = 0.91; P < 0.05), plasma ATP (r(2) = 0.94; P < 0.05) and limb V̇O2 (r(2) = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in TB and limb V̇O2, whereas ABF, arm TB and V̇O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V̇O2. In 12 trained males, increases in femoral TB and LBF during incremental leg exercise were mirrored by similar pulmonary artery TB and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data

  2. Blood temperature and perfusion to exercising and non‐exercising human limbs

    PubMed Central

    Calbet, José A. L.; Boushel, Robert; Helge, Jørn W.; Søndergaard, Hans; Munch‐Andersen, Thor; van Hall, Gerrit; Mortensen, Stefan P.; Secher, Niels H.

    2015-01-01

    New Findings What is the central question of this study? Temperature‐sensitive mechanisms are thought to contribute to blood‐flow regulation, but the relationship between exercising and non‐exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non‐exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature‐ and metabolism‐sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature‐sensitive mechanisms may contribute to blood‐flow regulation, but the influence of temperature on perfusion to exercising and non‐exercising human limbs is not established. Blood temperature (T B), blood flow and oxygen uptake (V˙O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T B and limb V˙O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T B (r 2 = 0.91; P < 0.05), plasma ATP (r 2 = 0.94; P < 0.05) and limb V˙O2 (r 2 = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T B and limb V˙O2, whereas ABF, arm T B and V˙O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V˙O2. In 12 trained males, increases in femoral T B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T B and cardiac output dynamics, suggesting that processes in active limbs dominate central

  3. Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health

    PubMed Central

    Stephen, Ian D.; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I.

    2009-01-01

    Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice. PMID:19337378

  4. Skin blood perfusion and oxygenation colour affect perceived human health.

    PubMed

    Stephen, Ian D; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I

    2009-01-01

    Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.

  5. Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

    PubMed Central

    Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

    2017-01-01

    Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

  6. Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

    PubMed

    Ward, Andrew; Quinn, Kyle P; Bellas, Evangelia; Georgakoudi, Irene; Kaplan, David L

    2013-01-01

    The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D) vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF). Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

  7. Noninvasive measurements of regional cerebral perfusion in preterm and term neonates by magnetic resonance arterial spin labeling.

    PubMed

    Miranda, Maria J; Olofsson, Kern; Sidaros, Karam

    2006-09-01

    Magnetic resonance arterial spin labeling (ASL) at 3 Tesla has been investigated as a quantitative technique for measuring regional cerebral perfusion (RCP) in newborn infants. RCP values were measured in 49 healthy neonates: 32 preterm infants born before 34 wk of gestation and 17 term-born neonates. Examinations were performed on unsedated infants at postmenstrual age of 39-40 wk in both groups. Due to motion, reliable data were obtained from 23 preterm and 6 term infants. Perfusion in the basal ganglia (39 and 30 mL/100 g/min for preterm and term neonates, respectively) was significantly higher (p < 0.0001) than in cortical gray matter (19 and 16 mL/100 g/min) and white matter (15 and 10 mL/100 g/min), both in preterm neonates at term-equivalent age and in term neonates. Perfusion was significantly higher (p = 0.01) in the preterm group than in the term infants, indicating that RCP may be influenced by developmental and postnatal ages. This study demonstrates, for the first time, that noninvasive ASL at 3T may be used to measure RCP in healthy unsedated preterm and term neonates. ASL is, therefore, a viable tool that will allow serial studies of RCP in high-risk neonates.

  8. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

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

    Myllynen, Paeivi; 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 placentalmore » 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.« less

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

    PubMed

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

    2014-02-01

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

  10. Functional delivery of synthetic naked siRNA to the human trabecular meshwork in perfused organ cultures.

    PubMed

    Comes, Nuria; Borrás, Teresa

    2007-08-01

    To investigate whether naked short-interfering RNA (siRNA) molecules could be directly delivered to perfused intact human trabecular meshwork (TM) tissue, whether this siRNA could silence a trabecular meshwork preferred gene, and whether it could counteract the downstream effect of a deleterious agent (dexamethasone, DEX) by silencing its receptor. Anterior segments from post-mortem normal human donors were perfused at 3.4+/-0.3 microl/min-constant flow or 15 mmHg-constant pressure to stable baseline (outflow facility, C=0.22+/-0.19 microl/min/mmHg; n=14). Commercial siRNAs were diluted in DMEM (Dulbecco's Modified Eagle's Medium) perfusion medium and used without coupling to transfection reagents ("naked"). Perfusion of Cy3-labeled siRNA was performed at 100 nM for 48 h followed by 24 h with DMEM medium (two pairs). Perfusions of Matrix GLA protein (MGP) siRNA (100 nM; right eye [Oculus Dexter]; OD) and scramble-siRNA (control; left eye [Oculus Sinster]; OS) were performed for 48 h (two pairs). Perfusions of glucocorticoid receptor (GR)-siRNA (OD) and scramble-control (OS) were performed for 48 h and continued by adding 100 nM DEX to the perfusion media for an additional 24 h (two pairs). Frozen sections of labeled anterior segments were analyzed by confocal fluorescence microscopy. Differential expression of GR, MGP, myocilin (MYOC), cornea-derived transcript 6 (CDT6), and 18S genes was determined by reverse-transcriptase TaqMan polymerase chain reacion (RT-TaqMan PCR) on RNA extracted from dissected trabecular meshwork. Primary human trabecular meshwork cells were generated from single individuals and transfected using the nucleofector electroporator with program T-23. Levels of secreted MYOC in the effluents were analyzed by western blot. Histological evaluation of anterior segments perfused with Cy3 labeled siRNA followed by unlabeled medium showed intense fluorescence in the trabecular meshwork region. MGP gene expression was silenced in the trabecular

  11. Evaluation of peripheral perfusion in term newborns before and after Yintang (EX-HN 3) massage.

    PubMed

    Tugcu, Ali Ulas; Cabioglu, Tugrul; Abbasoglu, Aslihan; Ecevit, Ayse; Ince, Deniz Anuk; Tarcan, Aylin

    2015-12-01

    To identify how acupressure on the acupoint Yintang (EX-HN 3) impacts oxygen saturation, pulse rate, and peripheral perfusion in term-born infants without underlying disease. Infants born between weeks 37 and 42 of gestation were included in this study. The polyclinic's neonatology room was noise-controlled and made half-dark to prevent the perfusion index from being confounded. A pulse oximeter was linked to the baby's left lower extremity. Acupressure was applied on Yintang (EX-HN 3) for 30 s clockwise, held for 30 s, and then acupressure was applied for another 30 s counterclockwise. The baby's SaO2, pulse rate, and perfusion index were recorded for each minute before and after acupressure. When pre- and post-acupressure pulse rate values were compared, a significant decrease in pulse rate values after acupressure application was observed. When pre- and post-acupressure oxygen saturation values were compared, a significant increase in post-acupressure oxygen saturation was observed. In addition, peripheral perfusion increased significantly after acupressure. Acupressure application has been used in traditional medicine for many years. However, it is not yet widely used in modern medicine. This study shows the impact of acupressure on neonatal skin perfusion, oxygen saturation, and pulse rate.

  12. Examining the transplacental passage of apixaban using the dually perfused human placenta.

    PubMed

    Bapat, P; Pinto, L S R; Lubetsky, A; Aleksa, K; Berger, H; Koren, G; Ito, S

    2016-07-01

    Essentials Apixaban is a novel oral anticoagulant that has not been studied in pregnant patients. Our objective was to determine the rate and extent of the placental transfer of apixaban. Apixaban rapidly crosses the ex vivo term human placenta from maternal to fetal circulation. Fetal apixaban levels in vivo are estimated to be 35-90% of the corresponding maternal levels. Background Apixaban is a novel oral anticoagulant that is increasingly being prescribed to women of reproductive age. However, information regarding its placental transfer is non-existent. Objective To determine the rate and extent of placental transfer of apixaban, using the human placenta ex vivo. Methods Placentae collected after Caesarean or vaginal delivery of healthy term infants were perfused in the respective maternal and fetal circulation. At the start of the experiment, apixaban was added to the maternal circulation at a concentration of 150 ng mL(-1) , and samples from maternal and fetal reservoirs were collected over 3 h. Results There was a rapid decline of apixaban in the maternal compartment, followed by emergence in the fetal compartment with a median fetal-to-maternal drug concentration ratio of 0.77 (interquartile range [IQR], 0.76-0.81) and fetal concentration of 39.0 ng mL(-1) (IQR, 36.8-40.6) after 3 h (n = 5). The perfusion results were subsequently adjusted to account for differences in the concentration of plasma proteins in maternal and fetal blood, as apixaban remains highly bound to albumin and alpha-1 acid glycoprotein. After the adjustment, the predicted fetal-to-maternal ratio of total (bound plus unbound) apixaban concentrations in vivo ranged from 0.35 to 0.90. Conclusions We conclude that unbound apixaban rapidly crosses from the maternal to fetal circulation. We further predict that total apixaban concentrations in cord blood in vivo are 35-90% of the corresponding maternal levels, suggesting that apixaban could have a possible adverse effect on fetal and

  13. Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects

    PubMed Central

    Roberts, Victoria HJ; Lo, Jamie O; Salati, Jennifer A; Lewandowski, Katherine S; Lindner, Jonathan R; Morgan, Terry K; Frias, Antonio E

    2016-01-01

    Background The utero-placental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. Objective Here we demonstrate the feasibility of utilizing contrast-enhanced ultrasound to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. Study design Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n=6/group). Human subjects were recruited immediately prior to scheduled first trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition using a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. Results In macaques, rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and HSP70 as markers of apoptosis, nitrative and oxidative stress respectively were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11wks gestation and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast following first trimester ultrasound studies. Conclusions Use of contrast-enhanced ultrasound did not result in placental structural damage, and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound may offer a safe clinical tool for the identification of

  14. Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

    PubMed

    Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

    2014-09-01

    Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

  15. Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects.

    PubMed

    Shcherbinin, Sergey; Doyle, Orla; Zelaya, Fernando O; de Simoni, Sara; Mehta, Mitul A; Schwarz, Adam J

    2015-11-01

    Resting brain perfusion, measured using the MRI-based arterial spin labelling (ASL) technique, is sensitive to detect central effects of single, clinically effective, doses of pharmacological compounds. However, pharmacological interaction experiments, such as the modulation of one drug response in the presence of another, have not been widely investigated using a task-free ASL approach. We assessed the effects of three psychoactive compounds (ketamine, risperidone and lamotrigine), and their interaction, on resting brain perfusion in healthy human volunteers. A multivariate Gaussian process classification (GPC) and more conventional univariate analyses were applied. The four pre-infusion conditions for each subject comprised risperidone, lamotrigine and two placebo sessions. The two placebo conditions enabled us to evaluate the classification performance in a test-retest setting, in addition to its performance in distinguishing the active oral drugs from placebo (direct effect on brain perfusion). The post ketamine- or saline-infusion scans allowed the effect of ketamine, and its interaction with risperidone and lamotrigine, on brain perfusion to be characterised. The pseudo-continuous ASL measurements of perfusion were sensitive to the effects of ketamine infusion and risperidone. The GPC captured consistent changes in perfusion across the group and contextualised the univariate changes with a larger pattern of regions contributing to accurate discrimination of ketamine from placebo. The findings argue against perfusion changes confounding in the previously described evoked BOLD response to ketamine and emphasise the blockade of the NMDA receptor over neuronal glutamate release in determining the perfusion changes induced by ketamine.

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

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

    2017-07-01

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

  18. Perfusion Stirred-Tank Bioreactors for 3D Differentiation of Human Neural Stem Cells.

    PubMed

    Simão, Daniel; Arez, Francisca; Terasso, Ana P; Pinto, Catarina; Sousa, Marcos F Q; Brito, Catarina; Alves, Paula M

    2016-01-01

    Therapeutic breakthroughs in neurological disorders have been hampered by the lack of accurate central nervous system (CNS) models. The development of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of new therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmental, anatomic, and physiological) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity, etc.). Recapitulation of CNS phenotypic and functional features in vitro requires the implementation of advanced culture strategies, such as 3D culture systems, which enable to mimic the in vivo structural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. The development of robust and scalable processes for the 3D differentiation of hNSC can improve the accuracy of early stage development in preclinical research. In this context, the use of software-controlled stirred-tank bioreactors (STB) provides an efficient technological platform for hNSC aggregation and differentiation. This system enables to monitor and control important physicochemical parameters for hNSC culture, such as dissolved oxygen. Importantly, the adoption of a perfusion operation mode allows a stable flow of nutrients and differentiation/neurotrophic factors, while clearing the toxic by-products. This contributes to a setting closer to the physiological, by mimicking the in vivo microenvironment. In this chapter, we address the technical requirements and procedures for the implementation of 3D differentiation strategies of hNSC, by operating STB under perfusion mode for long-term cultures. This strategy is suitable

  19. Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for auricular vascularized composite tissue engineering.

    PubMed

    Duisit, Jérôme; Amiel, Hadrien; Wüthrich, Tsering; Taddeo, Adriano; Dedriche, Adeline; Destoop, Vincent; Pardoen, Thomas; Bouzin, Caroline; Joris, Virginie; Magee, Derek; Vögelin, Esther; Harriman, David; Dessy, Chantal; Orlando, Giuseppe; Behets, Catherine; Rieben, Robert; Gianello, Pierre; Lengelé, Benoît

    2018-06-01

    Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors

  20. Human dental pulp stem cell adhesion and detachment in polycaprolactone electrospun scaffolds under direct perfusion

    PubMed Central

    Paim, A.; Braghirolli, D.I.; Cardozo, N.S.M.; Pranke, P.; Tessaro, I.C.

    2018-01-01

    Cell adhesion in three-dimensional scaffolds plays a key role in tissue development. However, stem cell behavior in electrospun scaffolds under perfusion is not fully understood. Thus, an investigation was made on the effect of flow rate and shear stress, adhesion time, and seeding density under direct perfusion in polycaprolactone electrospun scaffolds on human dental pulp stem cell detachment. Polycaprolactone scaffolds were electrospun using a solvent mixture of chloroform and methanol. The viable cell number was determined at each tested condition. Cell morphology was analyzed by confocal microscopy after various incubation times for static cell adhesion with a high seeding density. Scanning electron microscopy images were obtained before and after perfusion for the highest flow rate tested. The wall pore shear stress was calculated for all tested flow rates (0.005–3 mL/min). An inversely proportional relationship between adhesion time with cell detachment under perfusion was observed. Lower flow rates and lower seeding densities reduced the drag of cells by shear stress. However, there was an operational limit for the lowest flow rate that can be used without compromising cell viability, indicating that a flow rate of 0.05 mL/min might be more suitable for the tested cell culture in electrospun scaffolds under direct perfusion. PMID:29590258

  1. Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

    PubMed

    Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F

    2015-12-17

    Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Partitioning of glutamine synthesised by the isolated perfused human placenta between the maternal and fetal circulations☆

    PubMed Central

    Day, P.E.L.; Cleal, J.K.; Lofthouse, E.M.; Goss, V.; Koster, G.; Postle, A.; Jackson, J.M.; Hanson, M.A.; Jackson, A.A.; Lewis, R.M.

    2013-01-01

    Introduction Placental glutamine synthesis has been demonstrated in animals and is thought to increase the availability of this metabolically important amino acid to the fetus. Glutamine is of fundamental importance for cellular replication, cellular function and inter-organ nitrogen transfer. The objective of this study was to investigate the role of glutamate/glutamine metabolism by the isolated perfused human placenta in the provision of glutamine to the fetus. Methods Glutamate metabolism was investigated in the isolated dually perfused human placental cotyledon. U–13C-glutamate was used to investigate the movement of carbon and 15N-leucine to study movement of amino-nitrogen. Labelled amino acids were perfused via maternal or fetal arteries at defined flow rates. The enrichment and concentration of amino acids in the maternal and fetal veins were measured following 5 h of perfusion. Results Glutamate taken up from the maternal and fetal circulations was primarily converted into glutamine the majority of which was released into the maternal circulation. The glutamine transporter SNAT5 was localised to the maternal-facing membrane of the syncytiotrophoblast. Enrichment of 13C or 15N glutamine in placental tissue was lower than in either the maternal or fetal circulation, suggesting metabolic compartmentalisation within the syncytiotrophoblast. Discussion Placental glutamine synthesis may help ensure the placenta's ability to supply this amino acid to the fetus does not become limiting to fetal growth. Glutamine synthesis may also influence placental transport of other amino acids, metabolism, nitrogen flux and cellular regulation. Conclusions Placental glutamine synthesis may therefore be a central mechanism in ensuring that the human fetus receives adequate nutrition and is able to maintain growth. PMID:24183194

  3. Meta-Analysis of Stress Myocardial Perfusion Imaging

    ClinicalTrials.gov

    2017-06-06

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

  4. Distribution of perfusion.

    PubMed

    Glenny, Robb; Robertson, H Thomas

    2011-01-01

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

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

    PubMed

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

    2015-08-01

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

  6. Blood Perfusion in Human Eyelid Skin Flaps Examined by Laser Speckle Contrast Imaging-Importance of Flap Length and the Use of Diathermy.

    PubMed

    Nguyen, Cu Dinh; Hult, Jenny; Sheikh, Rafi; Tenland, Kajsa; Dahlstrand, Ulf; Lindstedt, Sandra; Malmsjö, Malin

    2017-10-11

    It is well known that blood perfusion is important for the survival of skin flaps. As no study has been conducted to investigate how the blood perfusion in human eyelid skin flaps is affected by the flap length and diathermy, the present study was carried out to investigate these in patients. Fifteen upper eyelids were dissected as part of a blepharoplastic procedure, releasing a 30-mm long piece of skin, while allowing the 5 mm wide distal part of the skin to remain attached, to mimic a skin flap (hereafter called a "skin flap"). Blood perfusion was measured before and after repeated diathermy, using laser speckle contrast imaging. Blood perfusion decreased from the base to the tip of the flap: 5 mm from the base, the perfusion was 69%, at 10 mm it was 40%, at 15 mm it was 20%, and at 20 mm it was only 13% of baseline values. Diathermy further decreased blood perfusion (measured 15 mm from the base) to 13% after applying diathermy for the first time, to 6% after the second and to 4% after the third applications of diathermy. Blood perfusion falls rapidly with distance from the base of skin flaps on the human eyelid, and diathermy reduces blood perfusion even further. Clinically, it may be advised that flaps with a width of 5 mm be no longer than 15 mm (i.e., a width:length ratio of 1:3), and that the use of diathermy should be carefully considered.

  7. Intravital lectin perfusion analysis of vascular permeability in human micro- and macro- blood vessels.

    PubMed

    Debbage, P L; Sölder, E; Seidl, S; Hutzler, P; Hugl, B; Ofner, D; Kreczy, A

    2001-10-01

    We previously applied intravital lectin perfusion in mouse models to elucidate mechanisms underlying vascular permeability. The present work transfers this technique to human models, analysing vascular permeability in macro- and microvessels. Human vascular endothelial surface carbohydrate biochemistry differs significantly from its murine counterpart, lacking alpha-galactosyl epitopes and expressing the L-fucose moiety in the glycocalyx; the poly-N-lactosamine glycan backbone is common to all mammals. We examined extensively lectin binding specificities in sections and in vivo, and then applied the poly-N-lactosamine-specific lectin LEA and the L-fucose-specific lectin UEA-I in human intravital perfusions. Transendothelial transport differed in macrovessels and microvessels. In microvessels of adult human fat tissue, rectal wall and rectal carcinomas, slow transendothelial transport by vesicles was followed by significant retention at the subendothelial basement membrane; paracellular passage was not observed. Passage time exceeded 1 h. Thus we found barrier mechanisms resembling those we described previously in murine tissues. In both adult and fetal macrovessels, the vena saphena magna and the umbilical vein, respectively, rapid passage across the endothelial lining was observed, the tracer localising completely in the subendothelial tissues within 15 min; vesicular transport was more rapid than in microvessels, and retention at the subendothelial basement membrane briefer.

  8. [ARTCEREB irrigation and perfusion solution for cerebrospinal surgery: pharmacological assessment using human astrocytes exposed to test solutions].

    PubMed

    Nishimura, Masuhiro; Doi, Kazuhisa; Enomoto, Riyo; Lee, Eibai; Naito, Shinsaku; Yamauchi, Aiko

    2009-09-01

    ARTCEREB irrigation and perfusion solution (Artcereb) is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate the effects of Artcereb on brain cells. In vitro assessment of the effects of Artcereb in cell cultures of human fetal astrocytes was conducted in comparison with normal saline and lactated Ringer's solution. The effects of exposure to Artcereb were evaluated based on microscopic images of the mitochondria stained with rhodamine 123. The effects of exposure to Artcereb on cell function were also evaluated by quantitative analysis of mitochondrial activity based on rhodamine 123 and (3)H-thymidine incorporation. Morphological changes in nuclear structure were also evaluated. The results of the present study showed that cell function in cell cultures of human astrocytes was relatively unaffected by exposure to Artcereb as compared with normal saline or lactated Ringer's solution, suggesting that Artcereb has less effect on brain cells than normal saline or lactated Ringer's solution when used for the irrigation or perfusion of the cerebral ventricles.

  9. Perfusion decellularization of a human limb: A novel platform for composite tissue engineering and reconstructive surgery.

    PubMed

    Gerli, Mattia Francesco Maria; Guyette, Jacques Paul; Evangelista-Leite, Daniele; Ghoshhajra, Brian Burns; Ott, Harald Christian

    2018-01-01

    Muscle and fasciocutaneous flaps taken from autologous donor sites are currently the most utilized approach for trauma repair, accounting annually for 4.5 million procedures in the US alone. However, the donor tissue size is limited and the complications related to these surgical techniques lead to morbidities, often involving the donor sites. Alternatively, recent reports indicated that extracellular matrix (ECM) scaffolds boost the regenerative potential of the injured site, as shown in a small cohort of volumetric muscle loss patients. Perfusion decellularization is a bioengineering technology that allows the generation of clinical-scale ECM scaffolds with preserved complex architecture and with an intact vascular template, from a variety of donor organs and tissues. We recently reported that this technology is amenable to generate full composite tissue scaffolds from rat and non-human primate limbs. Translating this platform to human extremities could substantially benefit soft tissue and volumetric muscle loss patients providing tissue- and species-specific grafts. In this proof-of-concept study, we show the successful generation a large-scale, acellular composite tissue scaffold from a full cadaveric human upper extremity. This construct retained its morphological architecture and perfusable vascular conduits. Histological and biochemical validation confirmed the successful removal of nuclear and cellular components, and highlighted the preservation of the native extracellular matrix components. Our results indicate that perfusion decellularization can be applied to produce human composite tissue acellular scaffolds. With its preserved structure and vascular template, these biocompatible constructs, could have significant advantages over the currently implanted matrices by means of nutrient distribution, size-scalability and immunological response.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2012-09-01

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

  12. Oral alprazolam acutely increases nucleus accumbens perfusion

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2017-03-01

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

  14. External-to-Internal Iliac Stent-Graft: Medium-Term Patency Following Exclusion of a Retrogradely Perfused Common Iliac Aneurysm

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

    Nicholls, Marcus John, E-mail: marcusnicholls@hotmail.co; McPherson, Simon

    2010-08-15

    Following complicated aortic aneurysm surgery a complete left iliac occlusion resulted in buttock claudication. A retrogradely perfused right common iliac aneurysm expanded. Exclusion was by external-to-internal iliac stent-graft. No deterioration in claudication occurred with medium-term stent-graft patency.

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

    PubMed

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

    2011-07-01

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

  16. Incubator-independent cell-culture perfusion platform for continuous long-term microelectrode array electrophysiology and time-lapse imaging

    PubMed Central

    Saalfrank, Dirk; Konduri, Anil Krishna; Latifi, Shahrzad; Habibey, Rouhollah; Golabchi, Asiyeh; Martiniuc, Aurel Vasile; Knoll, Alois; Ingebrandt, Sven; Blau, Axel

    2015-01-01

    Most in vitro electrophysiology studies extract information and draw conclusions from representative, temporally limited snapshot experiments. This approach bears the risk of missing decisive moments that may make a difference in our understanding of physiological events. This feasibility study presents a simple benchtop cell-culture perfusion system adapted to commercial microelectrode arrays (MEAs), multichannel electrophysiology equipment and common inverted microscopy stages for simultaneous and uninterrupted extracellular electrophysiology and time-lapse imaging at ambient CO2 levels. The concept relies on a transparent, replica-casted polydimethylsiloxane perfusion cap, gravity- or syringe-pump-driven perfusion and preconditioning of pH-buffered serum-free cell-culture medium to ambient CO2 levels at physiological temperatures. The low-cost microfluidic in vitro enabling platform, which allows us to image cultures immediately after cell plating, is easy to reproduce and is adaptable to the geometries of different cell-culture containers. It permits the continuous and simultaneous multimodal long-term acquisition or manipulation of optical and electrophysiological parameter sets, thereby considerably widening the range of experimental possibilities. Two exemplary proof-of-concept long-term MEA studies on hippocampal networks illustrate system performance. Continuous extracellular recordings over a period of up to 70 days revealed details on both sudden and gradual neural activity changes in maturing cell ensembles with large intra-day fluctuations. Correlated time-lapse imaging unveiled rather static macroscopic network architectures with previously unreported local morphological oscillations on the timescale of minutes. PMID:26543581

  17. Effects of vasopressin on the isolated perfused human collecting tubule.

    PubMed

    Yanagawa, N; Trizna, W; Bar-Khayim, Y; Fine, L G

    1981-05-01

    Cortical collecting tubules (CCT) were dissected from the surviving normal tissue of human kidneys removed at operation for either carcinoma or calculus. These CCT's were perfused in vitro shortly after the nephrectomy was performed. Transtubular potential differences in different tubules varied from +3.2 to -2.0 mV and were reduced towards zero by lowering the temperature or by adding ouabain to the bath. In the absence of vasopressin, tubules were essentially impermeable to water with extremely low net water fluxes even in the presence of a transtubular osmotic gradient. Addition of vasopressin to the bath caused the transtubular osmotic water permeability coefficient to increase to values of 125, 175, and 155 X 10(-4) cm/sec in three tubules thus studied. These results demonstrate close similarities between the human CCT and the more extensively studied rabbit CCT.

  18. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2018-06-15

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

  20. [Contributions of the ex vivo human perfused placenta in the study of placental transfer of drugs].

    PubMed

    Ceccaldi, P-F; Mandelbrot, L; Farinotti, R; Forestier, F; Gil, S

    2010-12-01

    Perfused human placental lobule was developed during the 1970s. Only this model respects the anatomical features of the human placenta. This approach allows different technical conditions (concentrations of drugs…) without ethical problems. Limitations of this ex vivo model are detailed in this review, also its recent contributions in better understanding of placental passage of drugs. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

  3. Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors.

    PubMed

    Stachelscheid, H; Wulf-Goldenberg, A; Eckert, K; Jensen, J; Edsbagge, J; Björquist, P; Rivero, M; Strehl, R; Jozefczuk, J; Prigione, A; Adjaye, J; Urbaniak, T; Bussmann, P; Zeilinger, K; Gerlach, J C

    2013-09-01

    Teratoma formation in mice is today the most stringent test for pluripotency that is available for human pluripotent cells, as chimera formation and tetraploid complementation cannot be performed with human cells. The teratoma assay could also be applied for assessing the safety of human pluripotent cell-derived cell populations intended for therapeutic applications. In our study we examined the spontaneous differentiation behaviour of human embryonic stem cells (hESCs) in a perfused 3D multi-compartment bioreactor system and compared it with differentiation of hESCs and human induced pluripotent cells (hiPSCs) cultured in vitro as embryoid bodies and in vivo in an experimental mouse model of teratoma formation. Results from biochemical, histological/immunohistological and ultrastuctural analyses revealed that hESCs cultured in bioreactors formed tissue-like structures containing derivatives of all three germ layers. Comparison with embryoid bodies and the teratomas revealed a high degree of similarity of the tissues formed in the bioreactor to these in the teratomas at the histological as well as transcriptional level, as detected by comparative whole-genome RNA expression profiling. The 3D culture system represents a novel in vitro model that permits stable long-term cultivation, spontaneous multi-lineage differentiation and tissue formation of pluripotent cells that is comparable to in vivo differentiation. Such a model is of interest, e.g. for the development of novel cell differentiation strategies. In addition, the 3D in vitro model could be used for teratoma studies and pluripotency assays in a fully defined, controlled environment, alternatively to in vivo mouse models. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Myocardial perfusion characteristics during machine perfusion for heart transplantation.

    PubMed

    Peltz, Matthias; Cobert, Michael L; Rosenbaum, David H; West, LaShondra M; Jessen, Michael E

    2008-08-01

    Optimal parameters for machine perfusion preservation of hearts prior to transplantation have not been determined. We sought to define regional myocardial perfusion characteristics of a machine perfusion device over a range of conditions in a large animal model. Dog hearts were connected to a perfusion device (LifeCradle, Organ Transport Systems, Inc, Frisco, TX) and cold perfused at differing flow rates (1) at initial device startup and (2) over the storage interval. Myocardial perfusion was determined by entrapment of colored microspheres. Myocardial oxygen consumption (MVO(2)) was estimated from inflow and outflow oxygen differences. Intra-myocardial lactate was determined by (1)H magnetic resonance spectroscopy. MVO(2) and tissue perfusion increased up to flows of 15 mL/100 g/min, and the ratio of epicardial:endocardial perfusion remained near 1:1. Perfusion at lower flow rates and when low rates were applied during startup resulted in decreased capillary flow and greater non-nutrient flow. Increased tissue perfusion correlated with lower myocardial lactate accumulation but greater edema. Myocardial perfusion is influenced by flow rates during device startup and during the preservation interval. Relative declines in nutrient flow at low flow rates may reflect greater aortic insufficiency. These factors may need to be considered in clinical transplant protocols using machine perfusion.

  5. The transfer of 6-mercaptopurine in the dually perfused human placenta.

    PubMed

    Hutson, J R; Lubetsky, A; Walfisch, A; Ballios, B G; Garcia-Bournissen, F; Koren, G

    2011-11-01

    The immunosuppressant azathioprine is increasingly being used in pregnancy. The human placenta is considered a relative barrier to the major metabolite, 6-mercaptopurine (6-MP), and likely explains the lack of proven teratogenicity in humans. The aim of this study was to determine how the human placenta restricts 6-MP transfer using the human placental perfusion model. After addition of 50 ng/ml (n=4) and 500 ng/ml (n=3) 6-MP into the maternal circulation, there was a biphasic decline in its concentration and a delay in fetal circulation appearance. Under equilibrative conditions, the fetal-to-maternal concentration ratio was >1.0 as a result of ion trapping. Binding to placental tissue and maternal pharmacokinetic parameters are the main factors that restrict placental transfer of 6-MP. Active transport is unlikely to play a significant role and drug interactions involving, or polymorphisms in, placental drug efflux transporters are not likely to put the fetus at risk of higher 6-MP exposure. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. 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

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

    PubMed

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

    2005-01-01

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

  8. Tensile strength decreases and perfusion pressure of 3-holed polyamide epidural catheters increases in long-term epidural infusion.

    PubMed

    Kim, Pascal; Meyer, Urs; Schüpfer, Guido; Rukwied, Roman; Konrad, Christoph; Gerber, Helmut

    2011-01-01

    Epidural analgesia is an established method for pain management. The failure rate is 8% to 12% due to technical difficulties (catheter dislocation and/or disconnection; partial or total catheter occlusion) and management. The mechanical properties of the catheters, like tensile strength and flow rate, may also be affected by the analgesic solution and/or the tissue environment. We investigated the tensile strength and perfusion pressure of new (n=20), perioperatively (n=30), and postoperatively (n=73) used epidural catheters (20-gauge, polyamide, closed tip, 3 side holes; Perifix [B. Braun]). To prevent dislocation, epidural catheters were taped (n=5) or fixed by suture (n=68) to the skin. After removal, mechanical properties were assessed by a tensile-testing machine (INSTRON 4500), and perfusion pressure was measured at flow rates of 10, 20, and 40 mL/h. All catheters demonstrated a 2-step force transmission. Initially, a minimal increase of length could be observed at 15 N followed by an elongation of several cm at additional forces (7 N). Breakage occurred in the control group at 23.5±1.5 N compared with 22.4±1.6 N in perioperative and 22.4±1.7 N in postoperative catheters (P<0.05). Duration of catheter use had no effect on tensile strength, whereas perfusion pressure at clinically used flow rates (10 mL/h) increased significantly from 19±1.3 to 44±72 mm Hg during long-term (≥7 days) epidural analgesia (P<0.05, analysis of variance). Fixation by suture had no influence on tensile strength or perfusion pressure. Epidural catheter use significantly increases the perfusion pressure and decreases the tensile strength. Copyright © 2011 by American Society of Regional Anesthesia and Pain Medicine

  9. Brain Perfusion Is Increased at Term in the White Matter of Very Preterm Newborns and Newborns with Congenital Heart Disease: Does this Reflect Activated Angiogenesis?

    PubMed

    Wintermark, Pia; Lechpammer, Mirna; Kosaras, Bela; Jensen, Frances E; Warfield, Simon K

    2015-10-01

    This study aims to evaluate brain perfusion at term in very preterm newborns and newborns with congenital heart disease before their corrective surgery, and to search for histopathological indicators of whether the brain perfusion abnormalities of these newborns may be related to an activated angiogenesis. Using magnetic resonance imaging and arterial spin labeling, regional cerebral blood flow was measured at a term-equivalent age for three very preterm newborns (born at < 32 weeks), one newborn with congenital heart disease before his corrective surgery and three healthy newborns. In addition, a histopathological analysis was performed on a newborn with congenital heart disease. The very preterm newborns and the newborn with congenital heart disease included in this study all displayed an increased signal in their white matter on T2-weighted imaging. The cerebral blood flow of these newborns was increased in their white matter, compared with the healthy term newborns. The vascular endothelial growth factor was overexpressed in the injured white matter of the newborn with congenital heart disease. Brain perfusion may be increased at term in the white matter, in very preterm newborns, and newborns with congenital heart disease, and it correlates with white matter abnormalities on conventional imaging. Georg Thieme Verlag KG Stuttgart · New York.

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

    PubMed

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

    1998-02-01

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

  11. Optimization of flowrate for expansion of human embryonic stem cells in perfusion microbioreactors.

    PubMed

    Titmarsh, Drew; Hidalgo, Alejandro; Turner, Jennifer; Wolvetang, Ernst; Cooper-White, Justin

    2011-12-01

    Microfluidic systems create significant opportunities to establish highly controlled microenvironmental conditions for screening pluripotent stem cell fate. However, since cell fate is crucially dependent on this microenvironment, it remains unclear as to whether continual perfusion of culture medium supports pluripotent stem cell maintenance in feeder-free, chemically defined conditions, and further, whether optimum perfusion conditions exist for subsequent use of human embryonic stem cell (hESCs) in other microfludic systems. To investigate this, we designed microbioreactors based on resistive flow to screen hESCs under a linear range of flowrates. We report that at low rates (conditions where glucose transport is convection-limited with Péclet number <1), cells are affected by apparent nutrient depletion and waste accumulation, evidenced by reduced cell expansion and altered morphology. At higher rates, cells are spontaneously washed out, and display morphological changes which may be indicative of early-stage differentiation. However, between these thresholds exists a narrow range of flowrates in which hESCs expand comparably to the equivalent static culture system, with regular morphology and maintenance of the pluripotency marker TG30 in >95% of cells over 7 days. For MEL1 hESCs the optimum flowrate also coincided with the time-averaged medium exchange rate in static cultures, which may therefore provide a good first estimate of appropriate perfusion rates. Overall, we demonstrate hESCs can be maintained in microbioreactors under continual flow for up to 7 days, a critical outcome for the future development of microbioreactor-based screening systems and assays for hESC culture. Copyright © 2011 Crown in the right of Canada.

  12. Microfluidic perfusion culture.

    PubMed

    Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

    2014-01-01

    Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion culture system is convenient technique to carry out the perfusion culture of animal cells in a microfluidic device. Here, we describe a general theory on microfluid network design, microfabrication technique, and experimental technique for pressure-driven perfusion culture in an 8 × 8 microchamber array on a glass slide-sized microchip made out of PDMS.

  13. Quantitative Assessment of Foot Blood Flow by Using Dynamic Volume Perfusion CT Technique: A Feasibility Study.

    PubMed

    Hur, Saebeom; Jae, Hwan Jun; Jang, Yeonggul; Min, Seung-Kee; Min, Sang-Il; Lee, Dong Yeon; Seo, Sang Gyo; Kim, Hyo-Cheol; Chung, Jin Wook; Kim, Kwang Gi; Park, Eun-Ah; Lee, Whal

    2016-04-01

    To demonstrate the feasibility of foot blood flow measurement by using dynamic volume perfusion computed tomographic (CT) technique with the upslope method in an animal experiment and a human study. The human study was approved by the institutional review board, and written informed consent was obtained from all patients. The animal study was approved by the research animal care and use committee. A perfusion CT experiment was first performed by using rabbits. A color-coded perfusion map was reconstructed by using in-house perfusion analysis software based on the upslope method, and the measured blood flow on the map was compared with the reference standard microsphere method by using correlation analysis. A total of 17 perfusion CT sessions were then performed (a) once in five human patients and (b) twice (before and after endovascular revascularization) in six human patients. Perfusion maps of blood flow were reconstructed and analyzed. The Wilcoxon signed rank test was used to prove significant differences in blood flow before and after treatment. The animal experiment demonstrated a strong correlation (R(2) = 0.965) in blood flow between perfusion CT and the microsphere method. Perfusion maps were obtained successfully in 16 human clinical sessions (94%) with the use of 32 mL of contrast medium and an effective radiation dose of 0.31 mSv (k factor for the ankle, 0.0002). The plantar dermis showed the highest blood flow among all anatomic structures of the foot, including muscle, subcutaneous tissue, tendon, and bone. After a successful revascularization procedure, the blood flow of the plantar dermis increased by 153% (P = .031). The interpretations of the color-coded perfusion map correlated well with the clinical and angiographic findings. Perfusion CT could be used to measure foot blood flow in both animals and humans. It can be a useful modality for the diagnosis of peripheral arterial disease by providing quantitative information on foot perfusion status.

  14. Localized Spatio-Temporal Constraints for Accelerated CMR Perfusion

    PubMed Central

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

    2013-01-01

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

  15. Long-term stable production of monocyte-colony inhibition factor (M-CIF) from CHO microcarrier perfusion cultures.

    PubMed

    Kong, D; Gentz, R; Zhang, J

    1998-03-01

    Monocyte-colony inhibition factor (M-CIF) was produced in microcarrier perfusion cultures from engineered Chinese hamster ovary (CHO) cells. Three and fifteen liter microcarrier perfusion bioreactors equipped with internal spin filters were operated for over two months. Approximately 60 L and 300 L of culture filtrate were harvested from the 3L and 15L microcarrier perfusion bioreactors respectively. During the perfusion operation, cell density reached 2-6 × 10(6) cells/ml. Importantly, stable expression of M-CIF from the CHO cells under non-selection condition was maintained at a level of 4-10 mg/L. Specific productivity was maintained at 1.8-3.4 mg/billion cells/day. The ability of the recombinant CHO cells to migrate from microcarrier to microcarrier under our proprietary HGS-CHO-3 medium greatly facilitated microcarrier culture scale-up and microcarrier replenishment. Future directions for microcarrier perfusion system scale-up and process development are highlighted.

  16. Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation.

    PubMed

    Davidson, Brian P; Hodovan, James; Belcik, J Todd; Moccetti, Federico; Xie, Aris; Ammi, Azzdine Y; Lindner, Jonathan R

    2017-05-01

    Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging. In normal volunteers, CEU of the calf skeletal muscle was performed on separate days with Sonazoid, Optison, or Definity. Progressive reduction in the ultrasound pulsing interval was used to assess the balance between signal enhancement and agent destruction at escalating mechanical indices (MI, 0.1-0.4). Real-time perfusion imaging at MI 0.1-0.4 using postdestructive replenishment kinetics was performed at rest and during 25 W plantar flexion contractile exercise. For Optison, limb perfusion imaging was unreliable at rest due to very low signal enhancement generated at all MIs and was possible during exercise-induced hyperemia only at MI 0.1 due to agent destruction at higher MIs. For Definity, signal intensity progressively increased with MI but was offset by microbubble destruction, which resulted in modest signal enhancement during CEU perfusion imaging and distortion of replenishment curves at MI ≥ 0.2. For Sonazoid, there strong signal enhancement at MI ≥ 0.2, with little destruction detected only at MI 0.4. Accordingly, high signal intensity and nondistorted perfusion imaging was possible at MI 0.2-0.3 and detected an 8.0- ± 5.7-fold flow reserve. Rest-stress limb perfusion imaging in humans with real-time CEU, which requires only seconds to perform, is possible using microbubbles with viscoelastic properties that produce strong nonlinear signal generation without destruction at intermediate acoustic pressures. Copyright © 2016 American Society of Echocardiography. All rights reserved.

  17. Correlation between cerebral hemodynamic and perfusion pressure changes in non-human primates

    NASA Astrophysics Data System (ADS)

    Ruesch, A.; Smith, M. A.; Wollstein, G.; Sigal, I. A.; Nelson, S.; Kainerstorfer, J. M.

    2017-02-01

    The mechanism that maintains a stable blood flow in the brain despite changes in cerebral perfusion pressure (CPP), and therefore guaranties a constant supply of oxygen and nutrients to the neurons, is known as cerebral auto-regulation (CA). In a certain range of CPP, blood flow is mediated by a vasomotor adjustment in vascular resistance through dilation of blood vessels. CA is known to be impaired in diseases like traumatic brain injury, Parkinson's disease, stroke, hydrocephalus and others. If CA is impaired, blood flow and pressure changes are coupled and thee oxygen supply might be unstable. Lassen's blood flow auto-regulation curve describes this mechanism, where a plateau of stable blood flow in a specific range of CPP corresponds to intact auto-regulation. Knowing the limits of this plateau and maintaining CPP within these limits can improve patient outcome. Since CPP is influenced by both intracranial pressure and arterial blood pressure, long term changes in either can lead to auto-regulation impairment. Non-invasive methods for monitoring blood flow auto-regulation are therefore needed. We propose too use Near infrared spectroscopy (NIRS) too fill this need. NIRS is an optical technique, which measures microvascular changes in cerebral hemoglobin concentration. We performed experiments on non-human primates during exsanguination to demonstrate that thee limits of blood flow auto-regulation can be accessed with NIRS.

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

    PubMed Central

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

    2015-01-01

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

  19. Quantitative lung perfusion evaluation using Fourier decomposition perfusion MRI.

    PubMed

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

    2014-08-01

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

  20. Renal perfusion scintiscan

    MedlinePlus

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

  1. Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion.

    PubMed

    Lakey, J R; Warnock, G L; Shapiro, A M; Korbutt, G S; Ao, Z; Kneteman, N M; Rajotte, R V

    1999-01-01

    Effective intraductal delivery of the enzyme collagenase into the pancreas is crucial to the subsequent ability to isolate viable islets. Most clinical islet transplant centers load the enzyme into the pancreas by retrograde injection using a syringe following cannulation of the pancreatic duct. An alternative approach is to perfuse the pancreas via the pancreatic duct with collagenase solution using a recirculating perfusion device system. This provides control over perfusion pressures and collagenase temperature. This study reports on our evaluation of the delivery of Liberase-HI into the pancreas of 14 consecutive adult multiorgan cadaveric donors. Alternate glands were procured and processed using an identical protocol with the exception of collagenase delivery. The first group of pancreases was loaded using the perfusion technique where cold (4 degrees C) Liberase-HI was perfused at 80 mmHg for 5 min after which the pressure was increased to 180 mmHg. The collagenase solution was then slowly warmed to 35 degrees C, transferred to the dissociation chamber and mechanically dissociated, and then purified using discontinuous gradients of Ficoll. Pancreases in the second group were loaded with collagenase (28-32 degrees C) using the syringe technique before mechanical dissociation and purification. There were no significant differences in pancreas cold ischemia, donor age, body mass index, maximum blood glucose, or serum amylase of the donors between the two groups. Mean collagenase digestion time in the digestion chamber was not different between the two groups; however, the amount of undigested tissue remaining after dissociation was significantly higher in the syringe-loaded group (15.3 +/- 2.6 g vs. 4.6 +/- 2.1 g, mean +/- SEM, p < 0.05). Postdigestion recovery of islets was 471 +/- 83 x 10(3) IE in the perfusion group compared with 391 +/- 57 x 10(3) IE for the syringe-loaded group. Postpurification recovery was higher in the perfused group (379 +/- 45 vs. 251

  2. 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.

  3. Cold-perfusion decellularization of whole-organ porcine pancreas supports human fetal pancreatic cell attachment and expression of endocrine and exocrine markers

    PubMed Central

    Elebring, Erik; Kuna, Vijay K; Kvarnström, Niclas; Sumitran-Holgersson, Suchitra

    2017-01-01

    Despite progress in the field of decellularization and recellularization, the outcome for pancreas has not been adequate. This might be due to the challenging dual nature of pancreas with both endocrine and exocrine tissues. We aimed to develop a novel and efficient cold-perfusion method for decellularization of porcine pancreas and recellularize acellular scaffolds with human fetal pancreatic stem cells. Decellularization of whole porcine pancreas at 4°C with sodium deoxycholate, Triton X-100 and DNase efficiently removed cellular material, while preserving the extracellular matrix structure. Furthermore, recellularization of acellular pieces with human fetal pancreatic stem cells for 14 days showed attached and proliferating cells. Both endocrine (C-peptide and PDX1) and exocrine (glucagon and α-amylase) markers were expressed in recellularized tissues. Thus, cold-perfusion can successfully decellularize porcine pancreas, which when recellularized with human fetal pancreatic stem cells shows relevant endocrine and exocrine phenotypes. Decellularized pancreas is a promising biomaterial and might translate to clinical relevance for treatment of diabetes. PMID:29118967

  4. Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys.

    PubMed

    Petersen, Björn; Ramackers, Wolf; Lucas-Hahn, Andrea; Lemme, Erika; Hassel, Petra; Queisser, Anna-Lisa; Herrmann, Doris; Barg-Kues, Brigitte; Carnwath, Joseph W; Klose, Johannes; Tiede, Andreas; Friedrich, Lars; Baars, Wiebke; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2011-01-01

    The major immunological hurdle to successful porcine-to-human xenotransplantation is the acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and perturbation of coagulation. Heme oxygenase-1 (HO-1) and its derivatives have anti-apoptotic, anti-inflammatory effects and protect against reactive oxygen species, rendering HO-1 a promising molecule to control AVR. Here, we report the production and characterization of pigs transgenic for human heme oxygenase-1 (hHO-1) and demonstrate significant protection in porcine kidneys against xenograft rejection in ex vivo perfusion with human blood and transgenic porcine aortic endothelial cells (PAEC) in a TNF-α-mediated apoptosis assay. Transgenic and non-transgenic PAEC were tested in a TNF-α-mediated apoptosis assay. Expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was measured by real-time PCR. hHO-1 transgenic porcine kidneys were perfused with pooled and diluted human AB blood in an ex vivo perfusion circuit. MHC class-II up-regulation after induction with IFN-γ was compared between wild-type and hHO-1 transgenic PAEC. Cloned hHO-1 transgenic pigs expressed hHO-1 in heart, kidney, liver, and in cultured ECs and fibroblasts. hHO-1 transgenic PAEC were protected against TNF-α-mediated apoptosis. Real-time PCR revealed reduced expression of adhesion molecules like ICAM-1, VCAM-1, and E-selectin. These effects could be abrogated by the incubation of transgenic PAECs with the specific HO-1 inhibitor zinc protoporphorine IX (Zn(II)PPIX, 20 μm). IFN-γ induced up-regulation of MHC class-II molecules was significantly reduced in PAECs from hHO-1 transgenic pigs. hHO-1 transgenic porcine kidneys could successfully be perfused with diluted human AB-pooled blood for a maximum of 240 min (with and without C1 inh), while in wild-type kidneys, blood flow ceased after ∼60 min. Elevated levels of d-Dimer and TAT were detected, but no significant consumption of fibrinogen and

  5. A continuous perfusion microplate for cell culture.

    PubMed

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

    2013-03-21

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

  6. Negative pressure ventilation decreases inflammation and lung edema during normothermic ex-vivo lung perfusion.

    PubMed

    Aboelnazar, Nader S; Himmat, Sayed; Hatami, Sanaz; White, Christopher W; Burhani, Mohamad S; Dromparis, Peter; Matsumura, Nobutoshi; Tian, Ganghong; Dyck, Jason R B; Mengel, Michael; Freed, Darren H; Nagendran, Jayan

    2018-04-01

    Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC). The impact of ventilation strategy on the preservation of 6 unutilized human donor lungs was also evaluated. Physiologic parameters, cytokine profiles, lung injury, bullae and edema formation were compared between treatment groups. Perfused lungs demonstrated acceptable oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen ratio >350 mm Hg) and physiologic parameters. However, there was less generation of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interleukin-8) in human and pig lungs perfused, irrespective of perfusate solution used, when comparing NPV with PPV (p < 0.05), and a reduction in bullae formation with an NPV modality (p = 0.02). Pig lungs developed less edema with NPV (p < 0.01), and EVLP using an acellular perfusate solution had greater edema formation, irrespective of ventilation strategy (p = 0.01). Interestingly, human lungs perfused with NPV developed negative edema, or "drying" (p < 0.01), and lower composite acute lung injury (p < 0.01). Utilization of an NPV strategy during extended EVLP is associated with significantly less inflammation, and lung injury, irrespective of perfusate solution composition. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

    PubMed

    Jain, Arjun; Schneider, Henning; Aliyev, Eldar; Soydemir, Fatimah; Baumann, Marc; Surbek, Daniel; Hediger, Matthias; Brownbill, Paul; Albrecht, Christiane

    2014-08-01

    Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and <3% for hypoxia (as a model for preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (P<0.0001), TNF-α (P=0.032) and IFN-γ (P=0.009) at 360 min in maternal venous samples (n=6). There was also a significant increase in ET-1 levels under hypoxia both on the maternal side at 30 min (P=0.003) and fetal side at 360 min (P=0.036) (n=6). Other markers of oxidative stress, including malondialdehyde and 8-iso-protaglandin F2α (P=0.009) also show increased levels. Overall, these findings indicate that exposure of ex vivo dually perfused placental tissue to hypoxia provides a useful model for mimicking the inflammatory response characteristic of preeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

  8. FABRICA: A Bioreactor Platform for Printing, Perfusing, Observing, & Stimulating 3D Tissues.

    PubMed

    Smith, Lester J; Li, Ping; Holland, Mark R; Ekser, Burcin

    2018-05-15

    We are introducing the FABRICA, a bioprinter-agnostic 3D-printed bioreactor platform designed for 3D-bioprinted tissue construct culture, perfusion, observation, and analysis. The computer-designed FABRICA was 3D-printed with biocompatible material and used for two studies: (1) Flow Profile Study: perfused 5 different media through a synthetic 3D-bioprinted construct and ultrasonically analyzed the flow profile at increasing volumetric flow rates (VFR); (2) Construct Perfusion Study: perfused a 3D-bioprinted tissue construct for a week and compared histologically with a non-perfused control. For the flow profile study, construct VFR increased with increasing pump VFR. Water and other media increased VFR significantly while human and pig blood showed shallow increases. For the construct perfusion study, we confirmed more viable cells in perfused 3D-bioprinted tissue compared to control. The FABRICA can be used to visualize constructs during 3D-bioprinting, incubation, and to control and ultrasonically analyze perfusion, aseptically in real-time, making the FABRICA tunable for different tissues.

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

    PubMed

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

    2017-09-01

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

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

    PubMed

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

    2013-04-21

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

  11. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood.

    PubMed

    Ahrens, Hellen E; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-07-01

    Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a (51)Chromium release assay and by ex vivo kidney perfusions with human blood. Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation.

  12. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood

    PubMed Central

    Ahrens, Hellen E.; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-01-01

    Background Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. Methods The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a 51Chromium release assay and by ex vivo kidney perfusions with human blood. Results Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Conclusions Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation. PMID:27500225

  13. Hyperventilation, cerebral perfusion, and syncope.

    PubMed

    Immink, R V; Pott, F C; Secher, N H; van Lieshout, J J

    2014-04-01

    This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

  14. 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

  15. Human periosteal-derived cell expansion in a perfusion bioreactor system: proliferation, differentiation and extracellular matrix formation.

    PubMed

    Sonnaert, M; Papantoniou, I; Bloemen, V; Kerckhofs, G; Luyten, F P; Schrooten, J

    2017-02-01

    Perfusion bioreactor systems have shown to be a valuable tool for the in vitro development of three-dimensional (3D) cell-carrier constructs. Their use for cell expansion, however, has been much less explored. Since maintenance of the initial cell phenotype is essential in this process, it is imperative to obtain insight into the bioreactor-related variables determining cell fate. Therefore, this study investigated the influence of fluid flow-induced shear stress on the proliferation, differentiation and matrix deposition of human periosteal-derived cells in the absence of additional differentiation-inducing stimuli; 120 000 cells were seeded on additive manufactured 3D Ti6Al4V scaffolds and cultured for up to 28 days at different flow rates in the range 0.04-6 ml/min. DNA measurements showed, on average, a three-fold increase in cell content for all perfused conditions in comparison to static controls, whereas the magnitude of the flow rate did not have an influence. Contrast-enhanced nanofocus X-ray computed tomography showed substantial formation of an engineered neotissue in all perfused conditions, resulting in a filling (up to 70%) of the total internal void volume, and no flow rate-dependent differences were observed. The expression of key osteogenic markers, such as RunX2, OCN, OPN and Col1, did not show any significant changes in comparison to static controls after 28 days of culture, with the exception of OSX at high flow rates. We therefore concluded that, in the absence of additional osteogenic stimuli, the investigated perfusion conditions increased cell proliferation but did not significantly enhance osteogenic differentiation, thus allowing for this process to be used for cell expansion. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Ultrasound evaluation of valsartan therapy for renal cortical perfusion.

    PubMed

    Kishimoto, Noriko; Mori, Yasukiyo; Nishiue, Takashi; Nose, Atsuko; Kijima, Yasuaki; Tokoro, Toshiko; Yamahara, Hideki; Okigaki, Mitsuhiko; Kosaki, Atsushi; Iwasaka, Toshiji

    2004-05-01

    An increase in renal blood flow with a concomitant decrease in filtration fraction at the onset of angiotensin II receptor blocker treatment has been shown to predict a long-term renoprotective effect. However, no studies are available regarding angiotensin receptor blocker-induced changes in renal cortical perfusion observed in the clinical setting. We have recently developed a convenient method of evaluating human renal cortical blood flow with contrast-enhanced harmonic ultrasonography. The goal of this study was to use this method to examine the effect of valsartan, an angiotensin II receptor blocker, on renal cortical perfusion. We performed intermittent second harmonic imaging with venous infusion of a microbubble contrast agent in 7 healthy volunteers. Contrast-enhanced harmonic ultrasonography performed after oral administration of valsartan (80mg) showed a significant increase in microbubble velocity, which correlated well with the increase in total renal blood flow determined by p-aminohippurate clearance (r=0.950, p < 0.001). Although fractional vascular volume was not significantly increased, alterations in renal cortical blood flow calculated by the product of microbubble velocity and fractional volume were also correlated with the change in total renal blood flow (r=0.756, p < 0.05). These results indicate that valsartan increases the renal cortical blood flow in normal kidneys, mainly by increasing blood flow velocity. Contrast-enhanced harmonic ultrasonography is a promising technique for evaluating the precise effect on renal cortical perfusion and optimal dose of valsartan in diseased kidneys.

  17. Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics.

    PubMed

    Sridharan, Gautham Vivek; Bruinsma, Bote Gosse; Bale, Shyam Sundhar; Swaminathan, Anandh; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

    2017-11-13

    Large-scale -omics data are now ubiquitously utilized to capture and interpret global responses to perturbations in biological systems, such as the impact of disease states on cells, tissues, and whole organs. Metabolomics data, in particular, are difficult to interpret for providing physiological insight because predefined biochemical pathways used for analysis are inherently biased and fail to capture more complex network interactions that span multiple canonical pathways. In this study, we introduce a nov-el approach coined Metabolomic Modularity Analysis (MMA) as a graph-based algorithm to systematically identify metabolic modules of reactions enriched with metabolites flagged to be statistically significant. A defining feature of the algorithm is its ability to determine modularity that highlights interactions between reactions mediated by the production and consumption of cofactors and other hub metabolites. As a case study, we evaluated the metabolic dynamics of discarded human livers using time-course metabolomics data and MMA to identify modules that explain the observed physiological changes leading to liver recovery during subnormothermic machine perfusion (SNMP). MMA was performed on a large scale liver-specific human metabolic network that was weighted based on metabolomics data and identified cofactor-mediated modules that would not have been discovered by traditional metabolic pathway analyses.

  18. A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy

    PubMed Central

    Winslow, Timothy B.; Eranki, Annu; Ullas, Soumya; Singh, Anurag K.; Repasky, Elizabeth A.; Sen, Arindam

    2015-01-01

    Purpose The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. Materials and methods SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Results Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Conclusions Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy. PMID:25986432

  19. A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy.

    PubMed

    Winslow, Timothy B; Eranki, Annu; Ullas, Soumya; Singh, Anurag K; Repasky, Elizabeth A; Sen, Arindam

    2015-01-01

    The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy.

  20. CT Perfusion of the Head

    MedlinePlus

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

  1. Development of a microfluidic perfusion 3D cell culture system

    NASA Astrophysics Data System (ADS)

    Park, D. H.; Jeon, H. J.; Kim, M. J.; Nguyen, X. D.; Morten, K.; Go, J. S.

    2018-04-01

    Recently, 3-dimensional in vitro cell cultures have gained much attention in biomedical sciences because of the closer relevance between in vitro cell cultures and in vivo environments. This paper presents a microfluidic perfusion 3D cell culture system with consistent control of long-term culture conditions to mimic an in vivo microenvironment. It consists of two sudden expansion reservoirs to trap incoming air bubbles, gradient generators to provide a linear concentration, and microchannel mixers. Specifically, the air bubbles disturb a flow in the microfluidic channel resulting in the instability of the perfusion cell culture conditions. For long-term stable operation, the sudden expansion reservoir is designed to trap air bubbles by using buoyancy before they enter the culture system. The performance of the developed microfluidic perfusion 3D cell culture system was examined experimentally and compared with analytical results. Finally, it was applied to test the cytotoxicity of cells infected with Ewing’s sarcoma. Cell death was observed for different concentrations of H2O2. For future work, the developed microfluidic perfusion 3D cell culture system can be used to examine the behavior of cells treated with various drugs and concentrations for high-throughput drug screening.

  2. Purification of recombinant human secretory phospholipase A2 (group II) produced in long-term immobilized cell culture.

    PubMed

    Levin, W; Daniel, R F; Stoner, C R; Stoller, T J; Wardwell-Swanson, J A; Angelillo, Y M; Familletti, P C; Crowl, R M

    1992-02-01

    Recombinant human secretory phospholipase A2 (Group II) was expressed in long-term culture of immobilized Chinese hamster ovary cells utilizing a continuous-perfusion airlift bioreactor. The bioreactor was continuously perfused with cell-culture medium supplemented with 5% fetal calf serum at an average flow rate of 5 liters/day for 30 days. Recombinant phospholipase A2, at concentrations ranging from 100 to 500 micrograms/liter, was purified to apparent homogeneity by an efficient two-step procedure involving a silica-based cation-exchange resin and hydrophobic interaction chromatography (greater than 65% recovery of phospholipase A2). The purified recombinant protein has an apparent molecular weight of 16 kDa, identical to that of purified human placental or synovial fluid phospholipase A2, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Application of the purified protein onto several different gel filtration columns resulted in elution of the protein at molecular weights corresponding to 3.1-4.7 kDa, suggesting an interaction of the protein with the column resins. However, analytical ultracentrifugation experiments revealed that the protein behaves as a monomer (13.8-14.2 kDa) over a protein concentration range of approximately 10 micrograms/ml to 5 mg/ml. With autoclaved Escherichia coli membranes as substrate, the recombinant protein has catalytic properties (pH optimum, effects of bovine serum albumin, sodium chloride concentration, and requirement for calcium) similar to those of the protein purified from human placenta.

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

    PubMed

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

    2018-05-01

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

  4. Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused porcine skin.

    PubMed

    Monteiro-Riviere, Nancy A; Baynes, Ronald E; Riviere, Jim E

    2003-02-01

    Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic treatment against organophosphate nerve agent exposure, and were exposed to the insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET). The purpose of this study was to assess the effects of PB to modulate release of inflammatory biomarkers after topical chemical exposure to chemical mixtures containing permethrin and DEET applied in ethanol or water vehicles. Treatments were topically applied to isolated perfused porcine skin flaps (IPPSFs). Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential inflammatory effects after complex mixture application. IPPSFs (n=4/treatment) were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB. Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate low level organophosphate nerve agent exposure. Timed IPPSF venous effluent samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2) release. Effects on TNF-alpha were vehicle dependent. To probe the potential mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these studies suggest that systemic exposure to PB suppressed IL-8 release at multiple time points in two skin model systems. This interaction merits further study.

  5. A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

    PubMed Central

    Heris, Hossein K.; Thomson, Scott L.; Taher, Rani; Kazemirad, Siavash; Sheibani, Sara; Li-Jessen, Nicole Y.K.; Vali, Hojatollah; Mongeau, Luc

    2016-01-01

    The human vocal folds (VFs) undergo complex biomechanical stimulation during phonation. The aim of the present study was to develop and validate a phono-mimetic VF flow perfusion bioreactor, which mimics the mechanical microenvironment of the human VFs in vitro. The bioreactor uses airflow-induced self-oscillations, which have been shown to produce mechanical loading and contact forces that are representative of human phonation. The bioreactor consisted of two synthetic VF replicas within a silicone body. A cell-scaffold mixture (CSM) consisting of human VF fibroblasts, hyaluronic acid, gelatin, and a polyethylene glycol cross-linker was injected into cavities within the replicas. Cell culture medium (CCM) was perfused through the scaffold by using a customized secondary flow loop. After the injection, the bioreactor was operated with no stimulation over a 3-day period to allow for cell adaptation. Phonation was subsequently induced by using a variable speed centrifugal blower for 2 h each day over a period of 4 days. A similar bioreactor without biomechanical stimulation was used as the nonphonatory control. The CSM was harvested from both VF replicas 7 days after the injection. The results confirmed that the phono-mimetic bioreactor supports cell viability and extracellular matrix proteins synthesis, as expected. Many scaffold materials were found to degrade because of challenges from phonation-induced biomechanical stimulation as well as due to biochemical reactions with the CCM. The bioreactor concept enables future investigations of the effects of different phonatory characteristics, that is, voice regimes, on the behavior of the human VF cells. It will also help study the long-term functional outcomes of the VF-specific biomaterials before animal and clinical studies. PMID:27537192

  6. A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications.

    PubMed

    Latifi, Neda; Heris, Hossein K; Thomson, Scott L; Taher, Rani; Kazemirad, Siavash; Sheibani, Sara; Li-Jessen, Nicole Y K; Vali, Hojatollah; Mongeau, Luc

    2016-09-01

    The human vocal folds (VFs) undergo complex biomechanical stimulation during phonation. The aim of the present study was to develop and validate a phono-mimetic VF flow perfusion bioreactor, which mimics the mechanical microenvironment of the human VFs in vitro. The bioreactor uses airflow-induced self-oscillations, which have been shown to produce mechanical loading and contact forces that are representative of human phonation. The bioreactor consisted of two synthetic VF replicas within a silicone body. A cell-scaffold mixture (CSM) consisting of human VF fibroblasts, hyaluronic acid, gelatin, and a polyethylene glycol cross-linker was injected into cavities within the replicas. Cell culture medium (CCM) was perfused through the scaffold by using a customized secondary flow loop. After the injection, the bioreactor was operated with no stimulation over a 3-day period to allow for cell adaptation. Phonation was subsequently induced by using a variable speed centrifugal blower for 2 h each day over a period of 4 days. A similar bioreactor without biomechanical stimulation was used as the nonphonatory control. The CSM was harvested from both VF replicas 7 days after the injection. The results confirmed that the phono-mimetic bioreactor supports cell viability and extracellular matrix proteins synthesis, as expected. Many scaffold materials were found to degrade because of challenges from phonation-induced biomechanical stimulation as well as due to biochemical reactions with the CCM. The bioreactor concept enables future investigations of the effects of different phonatory characteristics, that is, voice regimes, on the behavior of the human VF cells. It will also help study the long-term functional outcomes of the VF-specific biomaterials before animal and clinical studies.

  7. Free-breathing cardiac MR stress perfusion with real-time slice tracking.

    PubMed

    Basha, Tamer A; Roujol, Sébastien; Kissinger, Kraig V; Goddu, Beth; Berg, Sophie; Manning, Warren J; Nezafat, Reza

    2014-09-01

    To develop a free-breathing cardiac MR perfusion sequence with slice tracking for use after physical exercise. We propose to use a leading navigator, placed immediately before each 2D slice acquisition, for tracking the respiratory motion and updating the slice location in real-time. The proposed sequence was used to acquire CMR perfusion datasets in 12 healthy adult subjects and 8 patients. Images were compared with the conventional perfusion (i.e., without slice tracking) results from the same subjects. The location and geometry of the myocardium were quantitatively analyzed, and the perfusion signal curves were calculated from both sequences to show the efficacy of the proposed sequence. The proposed sequence was significantly better compared with the conventional perfusion sequence in terms of qualitative image scores. Changes in the myocardial location and geometry decreased by 50% in the slice tracking sequence. Furthermore, the proposed sequence had signal curves that are smoother and less noisy. The proposed sequence significantly reduces the effect of the respiratory motion on the image acquisition in both rest and stress perfusion scans. Copyright © 2013 Wiley Periodicals, Inc.

  8. 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

  9. 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

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

    PubMed Central

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

    2018-01-01

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

  11. Ventilation-perfusion distribution in normal subjects.

    PubMed

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

    2012-09-01

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

  12. In vivo confocal Raman spectroscopy study of the vitamin A derivative perfusion through human skin

    NASA Astrophysics Data System (ADS)

    dos Santos, Laurita; Téllez Soto, Claudio A.; Favero, Priscila P.; Martin, Airton A.

    2016-03-01

    In vivo confocal Raman spectroscopy is a powerful non-invasive technique able to analyse the skin constituents. This technique was applied to transdermal perfusion studies of the vitamin A derivative in human skin. The composition of the stratum corneum (lipid bilayer) is decisive for the affinity and transport of the vitamin through skin. The vitamin A is significantly absorbed by human skin when applied with water in oil emulsion or hydro-alcoholic gel. The purpose of this study is to elucidate the behaviour of vitamin A derivative into human skin without the presence of enhancers. The results showed that the intensity band of the derivative (around 1600 cm-1), which represents the -C=O vibrational mode, was detected in different stratum corneum depths (up to 20 μm). This Raman peak of vitamin A derivative has non-coincident band with the Raman spectra of the skin epidermis, demonstrating that compound penetrated in forearm skin.

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

    PubMed

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

    2017-12-14

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

  14. 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.

  15. An Optical Oxygen Sensor for Long-Term Continuous Monitoring of Dissolved Oxygen in Perfused Bioreactors

    NASA Technical Reports Server (NTRS)

    Gao, F. G.; Jeevarajan, A. S.; Anderson, M. M.

    2002-01-01

    For long-term growth of man1ITlalian cells in perfused bioreactors, it is essential to monitor the concentration of dissolved oxygen (DO) present in the culture medium to quantitate and control level of DO. Continuous measurement of the amount of DO in the cell culture medium in-line under sterile conditions in NASA's perfused bioreactor requires that the oxygen sensor provide increased sensitivity and be sterilizable and nontoxic. Additionally, long-term cell culture experiments require that the calibration be maintained several weeks or months. Although there are a number of sensors for dissolved oxygen on the market and under development elsewhere, very few meet these stringent conditions. An optical oxygen sensor (BOXY) based on dynamic fluorescent quenching and a pulsed blue LED light source was developed in our laboratory to address these requirements. Tris( 4,7 -diphenyl-l, 1 O-phenanthroline )ruthenium(II) chloride is employed as the fluorescent dye indicator. The sensing element consists of a glass capillary (OD 4.0 mm; ID 2.0 mm) coated internally with a thin layer of the fluorescent dye in silicone matrix and overlayed with a black shielding layer. Irradiation of the sensing element with blue light (blue LED with emission maximum at 475 nm) generates a red fluorescence centered at 626 nm. The fluorescence intensity is correlated to the concentration of DO present in the culture medium, following the modified non-linear Stern-Volmer equation. By using a pulsed irradiating light source, the problem of dye-bleaching, which is often encountered in long-term continuous measurements of tIns type, 'is minimized. To date we achieved sensor resolution of 0.3 mmHg at 50 mmHg p02, and 0.6 mmHg at 100 mmHg p02, with a response time of about one minute. Calibration was accomplished in sterile phosphate-buffered saline with a blood-gas analyzer (BGA) measurement as reference. Stand-alone software was also developed to control the sensor and bioreactor as well as to

  16. In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches.

    PubMed

    Lozoya-Agullo, Isabel; Zur, Moran; Wolk, Omri; Beig, Avital; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival; Dahan, Arik

    2015-03-01

    Intestinal drug permeability has been recognized as a critical determinant of the fraction dose absorbed, with direct influence on bioavailability, bioequivalence and biowaiver. The purpose of this research was to compare intestinal permeability values obtained by two different intestinal rat perfusion methods: the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop) rat perfusion method. A list of 15 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was constructed. We assessed the rat intestinal permeability of these 15 model drugs in both SPIP and the Doluisio methods, and evaluated the correlation between them. We then evaluated the ability of each of these methods to predict the fraction dose absorbed (Fabs) in humans, and to assign the correct BCS permeability class membership. Excellent correlation was obtained between the two experimental methods (r(2)=0.93). An excellent correlation was also shown between literature Fabs values and the predictions made by both rat perfusion techniques. Similar BCS permeability class membership was designated by literature data and by both SPIP and Doluisio methods for all compounds. In conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method are both equally useful for obtaining intestinal permeability values that can be used for Fabs prediction and BCS classification. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Assessment of tissue perfusion changes in port wine stains after vascular targeted photodynamic therapy: a short-term follow-up study.

    PubMed

    Ren, Jie; Li, Pengcheng; Zhao, Hongyou; Chen, Defu; Zhen, Jie; Wang, Ying; Wang, Yucheng; Gu, Ying

    2014-03-01

    The occlusion effect of vascular targeted photodynamic therapy (V-PDT) for malformed vessels in port wine stains (PWS) often last for some time after the treatment. A relatively longer period after V-PDT is needed to accurately assess the final response of PWS microcirculation to the treatment. In this study, we intended to use laser speckle imaging (LSI) to assess the tissue perfusion changes of PWS at follow-up after V-PDT and preliminarily analyze the relationship between perfusion change and color bleaching. Seventeen patients with 40 PWS lesions were scanned by LSI before and 3-6 months after they received V-PDT. The speckle flow indices of PWS lesions and normal skin before and at follow-up after V-PDT were recorded. We also performed analyses on the correlation between perfusion changes and color bleaching. Before V-PDT, the 40 PWS lesions showed higher perfusion than the normal skin (1,421 ± 463 and 1,115 ± 386 perfusion unit (PU), respectively, P < 0.01). The PWS lesions scanned at follow-up showed decreased perfusion level compared to the preoperative values (1,282 ± 460 and 1,421 ± 463 PU, respectively, P < 0.01). After V-PDT, the perfusion change rates coincide well with the color bleaching rates (correlation coefficient, 0.73). In conclusion, the LSI system is capable of imaging PWS perfusion precisely, and it has shown promising results in assessing the changes of tissue perfusion of V-PDT for PWS, with objective and quantitative data, real-time images, and a shorter detection time. It may also provide an effectiveness assessment method for the treatment of PWS.

  18. Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

    PubMed

    Göbel, A; Heldmann, M; Sartorius, A; Göttlich, M; Dirk, A-L; Brabant, G; Münte, T F

    2017-01-01

    Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors. © 2016 British Society for Neuroendocrinology.

  19. Optical mapping of Langendorff-perfused human hearts: establishing a model for the study of ventricular fibrillation in humans.

    PubMed

    Nanthakumar, Kumaraswamy; Jalife, José; Massé, Stéphane; Downar, Eugene; Pop, Mihaela; Asta, John; Ross, Heather; Rao, Vivek; Mironov, Sergey; Sevaptsidis, Elias; Rogers, Jack; Wright, Graham; Dhopeshwarkar, Rajesh

    2007-07-01

    Our objective was to establish a novel model for the study of ventricular fibrillation (VF) in humans. We adopted the established techniques of optical mapping to human ventricles for the first time to determine whether human VF is the result of wave breaks and singularity point formation and is maintained by high-frequency rotors and fibrillatory conduction. We describe the technique of acquiring optical signals in human hearts during VF, their characteristics, and the feasibility of possible analyses that could be performed to elucidate mechanisms of human VF. We used explanted hearts from five cardiomyopathic patients who underwent transplantation. The hearts were Langendorff perfused with Tyrode solution (95% O(2)-5% CO(2)), and the potentiometric dye di-4-ANEPPS was injected as a bolus into the coronary circulation. Fluorescence was excited at 531 +/- 20 nm with a 150-W halogen light source; the emission signal was long-pass filtered at 610 nm and recorded with a mapping camera. Fractional change of fluorescence varied between 2% and 12%. Average signal-to-noise ratio was 40 dB. The mean velocity of VF wave fronts was 0.25 +/- 0.04 m/s. Submillimetric spatial resolution (0.65-0.85 mm), activation mapping, and transformation of the data to phase-based analysis revealed reentrant, colliding, and fractionating wave fronts in human VF. On many occasions the VF wave fronts were as large as the entire vertical length (8 cm) of the mapping field, suggesting that there are a limited number of wave fronts on the human heart during VF. Phase transformation of the optical signals allowed the first demonstration ever of phase singularity point, wave breaks, and rotor formation in human VF. This method provides opportunities for potential analyses toward elucidation of the mechanisms of VF and defibrillation in humans.

  20. Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging.

    PubMed

    Hunt, A P; Frier, M; Johnson, R A; Berezenko, S; Perkins, A C

    2006-01-01

    Human serum albumin (HSA) extracted from pooled blood taken from human donors is used in the production of (99m)Tc-labelled macroaggregated albumin (MAA) for lung perfusion imaging. However, concerns for the safety of blood-derived products due to potential contamination by infective agents (e.g. new variant CJD), make alternative production methods necessary. Recombinant DNA technology is a promising method of albumin production avoiding problems associated with human-derived HSA. This paper presents results comparing MAA prepared from recombinant human albumin (rHA, Recombumin) (rMAA) with in-house produced HSA MAA (hMAA) and commercially available MAA (cMAA). (99m)Tc-MAA was prepared using previously published production methods by heating a mixture of albumin and stannous chloride in acetate buffer (pH 5.4) at 70 degrees C for 20 min. Parameters investigated include aggregate size, radiolabelling efficiency, radiochemical and aggregate stability at 4 degrees C and in vitro (in whole human blood) at 37 degrees C and biodistribution studies. Results showed that rMAA could be produced with similar morphology, labelling efficiency and stability to hMAA and cMAA. Our findings confirm that rHA shows significant potential as a direct replacement for HSA in commercially available MAA.

  1. High cell density suppresses BMP4-induced differentiation of human pluripotent stem cells to produce macroscopic spatial patterning in a unidirectional perfusion culture chamber.

    PubMed

    Tashiro, Shota; Le, Minh Nguyen Tuyet; Kusama, Yuta; Nakatani, Eri; Suga, Mika; Furue, Miho K; Satoh, Taku; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

    2018-04-19

    Spatial pattern formation is a critical step in embryogenesis. Bone morphogenetic protein 4 (BMP4) and its inhibitors are major factors for the formation of spatial patterns during embryogenesis. However, spatial patterning of the human embryo is unclear because of ethical issues and isotropic culture environments resulting from conventional culture dishes. Here, we utilized human pluripotent stem cells (hiPSCs) and a simple anisotropic (unidirectional perfusion) culture chamber, which creates unidirectional conditions, to measure the cell community effect. The influence of cell density on BMP4-induced differentiation was explored during static culture using a conventional culture dish. Immunostaining of the early differentiation marker SSEA-1 and the mesendoderm marker BRACHYURY revealed that high cell density suppressed differentiation, with small clusters of differentiated and undifferentiated cells formed. Addition of five-fold higher concentration of BMP4 showed similar results, suggesting that suppression was not caused by depletion of BMP4 but rather by high cell density. Quantitative RT-PCR array analysis showed that BMP4 induced multi-lineage differentiation, which was also suppressed under high-density conditions. We fabricated an elongated perfusion culture chamber, in which proteins were transported unidirectionally, and hiPSCs were cultured with BMP4. At low density, the expression was the same throughout the chamber. However, at high density, SSEA-1 and BRACHYURY were expressed only in upstream cells, suggesting that some autocrine/paracrine factors inhibited the action of BMP4 in downstream cells to form the spatial pattern. Human iPSCs cultured in a perfusion culture chamber might be useful for studying in vitro macroscopic pattern formation in human embryogenesis. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  2. The impact of age on cerebral perfusion, oxygenation and metabolism during exercise in humans

    PubMed Central

    Braz, Igor D.

    2015-01-01

    Abstract Age is one of the most important risk factors for dementia and stroke. Examination of the cerebral circulatory responses to acute exercise in the elderly may help to pinpoint the mechanisms by which exercise training can reduce the risk of brain diseases, inform the optimization of exercise training programmes and assist with the identification of age‐related alterations in cerebral vascular function. During low‐to‐moderate intensity dynamic exercise, enhanced neuronal activity is accompanied by cerebral perfusion increases of ∼10–30%. Beyond ∼60–70% maximal oxygen uptake, cerebral metabolism remains elevated but perfusion in the anterior portion of the circulation returns towards baseline, substantively because of a hyperventilation‐mediated reduction in the partial pressure of arterial carbon dioxide (P aC O2) and cerebral vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest and during incremental dynamic exercise. Nevertheless, the increase in the estimated cerebral metabolic rate for oxygen and the arterial–internal jugular venous differences for glucose and lactate are similar in young and older individuals exercising at the same relative exercise intensities. Correction for the age‐related reduction in P aC O2 during exercise by the provision of supplementary CO2 is suggested to remove ∼50% of the difference in cerebral perfusion between young and older individuals. A multitude of candidates could account for the remaining difference, including cerebral atrophy, and enhanced vasoconstrictor and blunted vasodilatory pathways. In summary, age‐related reductions in cerebral perfusion during exercise are partly associated with a lower P aC O2 in exercising older individuals; nevertheless the cerebral extraction of glucose, lactate and oxygen appear to be preserved. PMID:26435295

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

    PubMed

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

    2014-04-01

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

  4. Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

    PubMed

    Shaikh, Henna; Lechpammer, Mirna; Jensen, Frances E; Warfield, Simon K; Hansen, Anne H; Kosaras, Bela; Shevell, Michael; Wintermark, Pia

    2015-06-01

    Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.

  5. Brain Perfusion In Asphyxiated Newborns Treated with Therapeutic Hypothermia

    PubMed Central

    Wintermark, Pia; Hansen, Anne; Gregas, Matthew C.; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.

    2012-01-01

    Background and Purpose Induced hypothermia is thought to work partly by mitigating reperfusion injury in asphyxiated term newborns. The purpose of this study is to assess brain perfusion in the first week of life in these newborns. Patients and Methods In this prospective cohort study, magnetic resonance imaging (MRI) and perfusion imaging by arterial spin labeling (ASL-PI) was used to assess brain perfusion in these newborns. We measured regional cerebral blood flow values on 1–2 MRIs obtained during the first week of life and compared them to values obtained in control term newborns. The same or later MRI scans were obtained to define the extent of brain injury. Results Eighteen asphyxiated and four control term newborns were enrolled; eleven asphyxiated newborns were treated with hypothermia. Those developing brain injury despite being treated with induced hypothermia usually displayed hypoperfusion on day of life (DOL) 1, and then hyperperfusion on DOL 2–3 in brain areas subsequently exhibiting injury. Asphyxiated newborns not treated with hypothermia who developed brain injury also displayed hyperperfusion on DOL 1–6 in brain areas displaying injury. Conclusions Our data show that ASL-PI may be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not hypothermia is administered. Since hypothermia for 72 hours may not prevent brain injury when hyperperfusion is found early in the course of neonatal hypoxic-ischemic encephalopathy, such newborns may be candidates for adjustments in their hypothermia therapy or for adjunctive neuroprotective therapies. PMID:21979494

  6. Selective Cerebro-Myocardial Perfusion in Complex Neonatal Aortic Arch Pathology: Midterm Results.

    PubMed

    Hoxha, Stiljan; Abbasciano, Riccardo Giuseppe; Sandrini, Camilla; Rossetti, Lucia; Menon, Tiziano; Barozzi, Luca; Linardi, Daniele; Rungatscher, Alessio; Faggian, Giuseppe; Luciani, Giovanni Battista

    2018-04-01

    Aortic arch repair in newborns and infants has traditionally been accomplished using a period of deep hypothermic circulatory arrest. To reduce neurologic and cardiac dysfunction related to circulatory arrest and myocardial ischemia during complex aortic arch surgery, an alternative and novel strategy for cerebro-myocardial protection was recently developed, where regional low-flow perfusion is combined with controlled and independent coronary perfusion. The aim of the present retrospective study was to assess short-term and mid-term results of selective and independent cerebro-myocardial perfusion in neonatal aortic arch surgery. From April 2008 to August 2015, 28 consecutive neonates underwent aortic arch surgery under cerebro-myocardial perfusion. There were 17 male and 11 female, with median age of 15 days (3-30 days) and median body weight of 3 kg (1.6-4.2 kg), 9 (32%) of whom with low body weight (<2.5 kg). The spectrum of pathologies treated was heterogeneous and included 13 neonates having single-stage biventricular repair (46%), 7 staged biventricular repair (25%), and 8 single-ventricle repair (29%). All operations were performed under moderate hypothermia and with a "beating heart and brain." Average cardiopulmonary bypass time was 131 ± 64 min (42-310 min). A period of cardiac arrest to complete intra-cardiac repair was required in nine patients (32%), and circulatory arrest in 1 to repair total anomalous pulmonary venous connection. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 30 ± 11 min (15-69 min). Renal dysfunction, requiring a period of peritoneal dialysis was observed in 10 (36%) patients, while liver dysfunction was noted only in 3 (11%). There were three (11%) early and two late deaths during a median follow-up of 2.9 years (range 6 months-7.7 years), with an actuarial survival of 82% at 7 years. At latest follow-up, no patient showed signs of cardiac or neurologic dysfunction. The present experience

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

    PubMed

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

    2003-05-01

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

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

    PubMed

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

    2015-06-15

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

  9. Large enhancement of perfusion contribution on fMRI signal

    PubMed Central

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

    2012-01-01

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

  10. Bio-Fluid Dynamics in a Centimeter-Scale Diagnostics Incubator with Integrated Perfusion

    NASA Astrophysics Data System (ADS)

    Vukasinovic, J.; Cullen, D. K.; Glezer, A.; Laplaca, M. C.

    2006-11-01

    Growing demands for long-term incubation of biologically faithful, three-dimensional neuronal and other cultures during extended physiological studies require efficient perfusion platforms with functional vasculatures that mimic the in vivo condition in a thermally regulated environment. While thermostatically controlled incubation baths with capillary action perfusion are available, their use is confined to specific experimental conditions. The interstitial nutrient and gas delivery remains diffusion limited over the long term and cultures decay metabolically. To overcome these problems, we describe simple fabrication and experimental characterization of a compact, diagnostics incubator that allows in situ monitoring of culture activity with a superior control of critical biological functions using convectively enhanced heat and mass transport. To overcome intercellular diffusion barriers culture is exposed to a direct flow of media issuing from an array of micro-nozzles that are directed normal to the substrate upholding the culture, and further improved by 3-D convection induced by jet interactions and biased, peripheral perfusate extraction through an array of microchannels as demonstrated by microPIV measurements.

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

    PubMed

    Fuglevand, A J; Segal, S S

    1997-10-01

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

  12. Simultaneous Myocardial Strain and Dark-Blood Perfusion Imaging Using a Displacement-Encoded MRI Pulse Sequence

    PubMed Central

    Le, Yuan; Stein, Ashley; Berry, Colin; Kellman, Peter; Bennett, Eric E.; Taylor, Joni; Lucas, Katherine; Kopace, Rael; Chefd’Hotel, Christophe; Lorenz, Christine H.; Croisille, Pierre; Wen, Han

    2010-01-01

    The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in 2–3 myocardial slices were repeatedly acquired using a single shot pulse sequence for 3 to 4 minutes, which covers a bolus infusion of Gd. The magnitudes of the images were T1 weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n=9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R2 = 0.765, Bland-Altman standard deviation = 0.15 ml/min/g). In a group of ST-elevation myocardial infarction(STEMI) patients (n=11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R2=0.72), and the pixel-wise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images. PMID:20544714

  13. Myocardial perfusion imaging with PET

    PubMed Central

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

    2013-01-01

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

  14. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    PubMed

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

    2016-01-01

    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

  15. Temporal similarity perfusion mapping: A standardized and model-free method for detecting perfusion deficits in stroke

    PubMed Central

    Song, Sunbin; Luby, Marie; Edwardson, Matthew A.; Brown, Tyler; Shah, Shreyansh; Cox, Robert W.; Saad, Ziad S.; Reynolds, Richard C.; Glen, Daniel R.; Cohen, Leonardo G.; Latour, Lawrence L.

    2017-01-01

    Introduction Interpretation of the extent of perfusion deficits in stroke MRI is highly dependent on the method used for analyzing the perfusion-weighted signal intensity time-series after gadolinium injection. In this study, we introduce a new model-free standardized method of temporal similarity perfusion (TSP) mapping for perfusion deficit detection and test its ability and reliability in acute ischemia. Materials and methods Forty patients with an ischemic stroke or transient ischemic attack were included. Two blinded readers compared real-time generated interactive maps and automatically generated TSP maps to traditional TTP/MTT maps for presence of perfusion deficits. Lesion volumes were compared for volumetric inter-rater reliability, spatial concordance between perfusion deficits and healthy tissue and contrast-to-noise ratio (CNR). Results Perfusion deficits were correctly detected in all patients with acute ischemia. Inter-rater reliability was higher for TSP when compared to TTP/MTT maps and there was a high similarity between the lesion volumes depicted on TSP and TTP/MTT (r(18) = 0.73). The Pearson's correlation between lesions calculated on TSP and traditional maps was high (r(18) = 0.73, p<0.0003), however the effective CNR was greater for TSP compared to TTP (352.3 vs 283.5, t(19) = 2.6, p<0.03.) and MTT (228.3, t(19) = 2.8, p<0.03). Discussion TSP maps provide a reliable and robust model-free method for accurate perfusion deficit detection and improve lesion delineation compared to traditional methods. This simple method is also computationally faster and more easily automated than model-based methods. This method can potentially improve the speed and accuracy in perfusion deficit detection for acute stroke treatment and clinical trial inclusion decision-making. PMID:28973000

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

    PubMed

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

    2014-12-07

    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.

  17. Monitoring peripheral perfusion and microcirculation.

    PubMed

    Dubin, Arnaldo; Henriquez, Elizabeth; Hernández, Glenn

    2018-06-01

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

  18. Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y.

    PubMed

    Constantinescu, R; Constantinescu, A T; Reichmann, H; Janetzky, B

    2007-01-01

    Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in industrialized countries. Present cell culture models for PD rely on either primary cells or immortal cell lines, neither of which allow for long-term experiments on a constant population, a crucial requisite for a realistic model of slowly progressing neurodegenerative diseases. We differentiated SH-SY5Y human dopaminergic neuroblastoma cells to a neuronal-like state in a perfusion culture system using a combination of retinoic acid and mitotic inhibitors. The cells could be cultivated for two months without the need for passage. We show, by various means, that the differentiated cells exhibit, at the molecular level, many neuronal properties not characteristic to the starting line. This approach opens the possibility to develop chronic models, in which the effect of perturbations and putative counteracting strategies can be monitored over long periods of time in a quasi-stable cell population.

  19. Dynamic Seeding of Perfusing Human Umbilical Vein Endothelial Cells (HUVECs) onto Dual-Function Cell Adhesion Ligands: Arg-Gly-Asp (RGD)-Streptavidin and Biotinylated Fibronectin

    PubMed Central

    Anamelechi, Charles C.; Clermont, Edward C.; Novak, Matthew T.; Reichert, William M.

    2014-01-01

    Surfaces decorated with high affinity ligands can be used to facilitate rapid attachment of endothelial cells; however, standard equilibrium cell detachment studies are poorly suited for assessing these initial adhesion events. Here, a dynamic seeding and cell retention method was used to examine the initial attachment of perfusing human umbilical vein endothelial cells (HUVECs) to bare Teflon-AF substrates, substrates pre-adsorbed with fibronectin alone, or substrates co-pre-adsorbed with two dual-function cell-adhesion ligands: biotinylated fibronectin (bFN) and RGD-streptavidin mutant (RGD-SA). Cell attachment was evaluated as a function of cell trypsinization (integrin digestion), surface protein formulation, and cell perfusion rate. Surfaces co-pre-adsorbed with bFN and RGD-SA showed the highest density of attached cells after 8 min of perfusion and the highest percent retention when subjected to shear flow at 60 dynes/cm2 for 2 min. Surfaces with no ligand treatment showed the lowest cell attachment and retention under flow in all cases. HUVECs trypsinized with mild 0.025% trypsin/ethylenediaminetetraacetic acid (EDTA) showed greater cell adhesion after perfusion and higher percent retention after shear flow than those trypsinized using harsher 0.05% trypsin/EDTA. The preferential affinities of the two dual-function ligands for α5β1 and αvβ3 integrins were also examined by surface plasmon resonance (SPR) spectroscopy. The dynamic cell seeding studies confirmed that the dual-function ligand system promotes HUVEC adhesion and retention at short time points when tested using a perfusion assay. SPR studies showed that the two ligands exhibited equal affinity for both α5β1 and αvβ3 integrins but that the combined ligands bound more total integrins than the two ligands tested separately. PMID:19348476

  20. 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

  1. Cochlear perfusion with a viscous fluid

    PubMed Central

    Wang, Yi; Olson, Elizabeth S.

    2016-01-01

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

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

    PubMed

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

    2009-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Does machine perfusion decrease ischemia reperfusion injury?

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-12-01

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

  7. A miniaturized bioreactor system for the evaluation of cell interaction with designed substrates in perfusion culture.

    PubMed

    Sun, T; Donoghue, P S; Higginson, J R; Gadegaard, N; Barnett, S C; Riehle, M O

    2012-12-01

    In tissue engineering, chemical and topographical cues are normally developed using static cell cultures but then applied directly to tissue cultures in three dimensions (3D) and under perfusion. As human cells are very sensitive to changes in the culture environment, it is essential to evaluate the performance of any such cues in a perfused environment before they are applied to tissue engineering. Thus, the aim of this research was to bridge the gap between static and perfusion cultures by addressing the effect of perfusion on cell cultures within 3D scaffolds. For this we developed a scaled-down bioreactor system, which allows evaluation of the effectiveness of various chemical and topographical cues incorporated into our previously developed tubular ε-polycaprolactone scaffold under perfused conditions. Investigation of two exemplary cell types (fibroblasts and cortical astrocytes) using the miniaturized bioreactor indicated that: (a) quick and firm cell adhesion in the 3D scaffold was critical for cell survival in perfusion culture compared with static culture; thus, cell-seeding procedures for static cultures might not be applicable, therefore it was necessary to re-evaluate cell attachment on different surfaces under perfused conditions before a 3D scaffold was applied for tissue cultures; (b) continuous medium perfusion adversely influenced cell spread and survival, which could be balanced by intermittent perfusion; (c) micro-grooves still maintained their influences on cell alignment under perfused conditions, while medium perfusion demonstrated additional influence on fibroblast alignment but not on astrocyte alignment on grooved substrates. This research demonstrated that the mini-bioreactor system is crucial for the development of functional scaffolds with suitable chemical and topographical cues by bridging the gap between static culture and perfusion culture. Copyright © 2011 John Wiley & Sons, Ltd.

  8. 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

  9. Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell-Derived Endothelial Cells Encapsulated in a Nanomatrix Gel.

    PubMed

    Lee, Shin-Jeong; Sohn, Young-Doug; Andukuri, Adinarayana; Kim, Sangsung; Byun, Jaemin; Han, Ji Woong; Park, In-Hyun; Jun, Ho-Wook; Yoon, Young-Sup

    2017-11-14

    Human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) have limited clinical utility because of undefined components in the differentiation system and poor cell survival in vivo. Here, we aimed to develop a fully defined and clinically compatible system to differentiate hPSCs into ECs. Furthermore, we aimed to enhance cell survival, vessel formation, and therapeutic potential by encapsulating hPSC-ECs with a peptide amphiphile (PA) nanomatrix gel. We induced differentiation of hPSCs into the mesodermal lineage by culturing on collagen-coated plates with a glycogen synthase kinase 3β inhibitor. Next, vascular endothelial growth factor, endothelial growth factor, and basic fibroblast growth factor were added for endothelial lineage differentiation, followed by sorting for CDH5 (VE-cadherin). We constructed an extracellular matrix-mimicking PA nanomatrix gel (PA-RGDS) by incorporating the cell adhesive ligand Arg-Gly-Asp-Ser (RGDS) and a matrix metalloproteinase-2-degradable sequence. We then evaluated whether the encapsulation of hPSC-CDH5 + cells in PA-RGDS could enhance long-term cell survival and vascular regenerative effects in a hind-limb ischemia model with laser Doppler perfusion imaging, bioluminescence imaging, real-time reverse transcription-polymerase chain reaction, and histological analysis. The resultant hPSC-derived CDH5 + cells (hPSC-ECs) showed highly enriched and genuine EC characteristics and proangiogenic activities. When injected into ischemic hind limbs, hPSC-ECs showed better perfusion recovery and higher vessel-forming capacity compared with media-, PA-RGDS-, or human umbilical vein EC-injected groups. However, the group receiving the PA-RGDS-encapsulated hPSC-ECs showed better perfusion recovery, more robust and longer cell survival (> 10 months), and higher and prolonged angiogenic and vascular incorporation capabilities than the bare hPSC-EC-injected group. Surprisingly, the engrafted hPSC-ECs demonstrated previously unknown

  10. Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

    PubMed

    Sakai, Yusuke; Hattori, Koji; Yanagawa, Fumiki; Sugiura, Shinji; Kanamori, Toshiyuki; Nakazawa, Kohji

    2014-07-01

    Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

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

    2017-04-01

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

  12. Acute effects of ethanol on the transfer of nicotine and two dietary carcinogens in human placental perfusion.

    PubMed

    Veid, Jenni; Karttunen, Vesa; Myöhänen, Kirsi; Myllynen, Päivi; Auriola, Seppo; Halonen, Toivo; Vähäkangas, Kirsi

    2011-09-10

    Many mothers use, against instructions, alcohol during pregnancy. Simultaneously mothers are exposed to a wide range of other environmental chemicals. These chemicals may also harm the developing fetus, because almost all toxic compounds can go through human placenta. Toxicokinetic effects of ethanol on the transfer of other environmental compounds through human placenta have not been studied before. It is known that ethanol has lytic properties and increases the permeability and fluidity of cell membranes. We studied the effects of ethanol on the transfer of three different environmental toxins: nicotine, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and NDMA (N-nitrosodimethylamine) in placental perfusion. We tested in human breast cancer adenocarcinoma cell line MCF-7 whether ethanol affects ABCG2/BCRP, which is also the major transporter in human placenta. We found that the transfer of ethanol is comparable to that of antipyrine, which points to passive diffusion as the transfer mechanism. Unexpectedly, ethanol had no statistically significant effect on the transfer of the other studied compounds. Neither did ethanol inhibit the function of ABCG2/BCRP. These experiments represent only the effects of acute exposure to ethanol and chronic exposure remains to be studied. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2018-04-24

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

  14. Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

    PubMed

    D'Andrea, Antonello; De Rimini, Maria Luisa; America, Raffaella; Cirillo, Chiara; Riegler, Lucia; Limongelli, Giuseppe; D'Alto, Michele; Salerno, Gemma; Maiello, Ciro; Muto, Pietro; Russo, Maria Giovanna; Calabrò, Raffaele; Bossone, Eduardo; Pacileo, Giuseppe

    2017-10-01

    The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up. © 2017, Wiley Periodicals, Inc.

  15. Assessment of right liver graft perfusion effectiveness between one and two-catheter infusion methods.

    PubMed

    Jung, Bo-Hyun; Hwang, Shin; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Kim, Ki-Hun; Ahn, Chul-Soo; Moon, Deok-Bog; Park, Gil-Chun; Kang, Sung-Hwa; Yoon, Young-In; Lee, Sung-Gyu

    2014-05-01

    Conventional graft perfusion method using one small-caliber catheter takes a relatively long time for right liver graft perfusion, thus some modification is needed. In this study, we intended to assess the effectiveness of right liver graft perfusion methods through comparison of different infusion catheters. The study consisted of two parts including one bench experiment to obtain data of hydraulic infusion and one clinical trial of 40 cases on graft perfusion with one- versus two-catheter infusion methods. These two graft infusion methods were compared in terms of the perfusion time and washing-out efficiency. At bench experiment, the infusion flow rate and infusion pressure were 3.3 ml/sec and 1.9 cmH20 in one blood transfusion catheter group, and 11.7 ml/sec and 3.1 cmH20 in single transurethral resection of prostate irrigation catheter group, and 6.6 ml/sec and 2.0 cmH20 in two blood transfusion catheters group, respectively. In clinical trial with 40 right liver grafts, two-catheter group had a shorter graft portal perfusion time for the first 2 L of histidine-tryptophan-ketoglutarate (HTK) solution than the conventional one-catheter group (375±25 seconds vs. 662±34 seconds; p=0.001) and a lower rate of incomplete blood washing-out after the initial 2 L portal perfusion (40% vs. 85%; p=0.03). The two-catheter infusion method appears to be more effective than the conventional one-catheter infusion method for right liver graft perfusion at the back table. Large size of right liver grafts seems to be its good indication.

  16. Applicability of quantitative optical imaging techniques for intraoperative perfusion diagnostics: a comparison of laser speckle contrast imaging, sidestream dark-field microscopy, and optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Jansen, Sanne M.; de Bruin, Daniel M.; Faber, Dirk J.; Dobbe, Iwan J. G. G.; Heeg, Erik; Milstein, Dan M. J.; Strackee, Simon D.; van Leeuwen, Ton G.

    2017-08-01

    Patient morbidity and mortality due to hemodynamic complications are a major problem in surgery. Optical techniques can image blood flow in real-time and high-resolution, thereby enabling perfusion monitoring intraoperatively. We tested the feasibility and validity of laser speckle contrast imaging (LSCI), optical coherence tomography (OCT), and sidestream dark-field microscopy (SDF) for perfusion diagnostics in a phantom model using whole blood. Microvessels with diameters of 50, 100, and 400 μm were constructed in a scattering phantom. Perfusion was simulated by pumping heparinized human whole blood at five velocities (0 to 20 mm/s). Vessel diameter and blood flow velocity were assessed with LSCI, OCT, and SDF. Quantification of vessel diameter was feasible with OCT and SDF. LSCI could only visualize the 400-μm vessel, perfusion units scaled nonlinearly with blood velocity. OCT could assess blood flow velocity in terms of inverse OCT speckle decorrelation time. SDF was not feasible to measure blood flow; however, for diluted blood the measurements were linear with the input velocity up to 1 mm/s. LSCI, OCT, and SDF were feasible to visualize blood flow. Validated blood flow velocity measurements intraoperatively in the desired parameter (mL·g-1) remain challenging.

  17. INTRAVENOUS REGIONAL ANTIBIOTIC PERFUSION THERAPY AS AN ADJUNCTIVE TREATMENT FOR DIGITAL LESIONS IN SEABIRDS.

    PubMed

    Fiorello, Christine V

    2017-03-01

    Foot infections are a common problem among seabirds in wildlife rehabilitation. Pododermatitis and digital infections are often challenging to treat because of the presence of suboptimal substrates, abnormal weight-bearing due to injuries, and suboptimal nutritional or health status. Seabirds represent the majority of animals requiring rehabilitation after oil spills, and foot problems are a common reason for euthanasia among these birds. Antibiotic intravenous regional perfusion therapy is frequently used in humans and other species to treat infections of the distal extremities, but it has not been evaluated in seabirds. During the 2015 Refugio oil spill response, four birds with foot lesions (pododermatitis, osteomyelitis, or both) were treated with ampicillin/sulbactam administered intravenously to the affected limb(s) in addition to systemic antibiotics and anti-inflammatories. Three of the birds, all brown pelicans ( Pelecanus occidentalis ) recovered rapidly and were released. Two of these birds had acute pododermatitis and were treated once with intravenous regional perfusion. They were released approximately 3 wk after the perfusion therapy. The third pelican had osteomyelitis of a digit. It was treated twice with intravenous regional perfusion and was released about 1 mo after the initial perfusion therapy. The fourth bird, a Pacific loon ( Gavia pacifica ), was treated once with perfusion therapy but did not respond to treatment and was euthanatized. No serious adverse effects were observed. This technique should be explored further in avian species.

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

    PubMed

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

    2014-11-01

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

  19. Pancreas transplants: Evaluation using perfusion scintigraphy

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

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

    1989-07-01

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

  20. Vicarious audiovisual learning in perfusion education.

    PubMed

    Rath, Thomas E; Holt, David W

    2010-12-01

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

  1. Regional glucose utilization in infarcted and remote myocardium: its relation to coronary anatomy and perfusion.

    PubMed

    Fragasso, G; Chierchia, S L; Landoni, C; Lucignani, G; Rossetti, E; Sciammarella, M; Vanoli, G E; Fazio, F

    1998-07-01

    We studied the relationship between coronary anatomy, perfusion and metabolism in myocardial segments exhibiting transient and persistent perfusion defects on stress/rest 99Tcm-MIBI single photon emission tomography in 35 patients (31 males, 4 females, mean age 56 +/- 7 years) with a previous myocardial infarction. Quantitative coronary angiography and assessment of myocardial perfusion reserve and glucose metabolism were performed within 1 week of one another. Perfusion was assessed by SPET after the intravenous injection of 740 MBq of 99Tcm-MIBI at rest and after exercise. Regional myocardial glucose metabolism was assessed by position emission tomography at rest (200 MBq of 18F-2-deoxyglucose, FDG) after an overnight fast with no glucose loading. All 35 patients exhibited persistent perfusion defects consistent with the clinically identified infarct site, and 27 (77%) also showed various degrees of within-infarct FDG uptake; 11 patients developed exercise-induced transient perfusion defects within, or in the vicinity of, 15 infarct segments and resting FDG uptake was present in 10 of these segments (67%). Five patients also showed exercise-induced transient perfusion defects in nine segments remote from the site of infarct: resting FDG uptake was present in six of these regions (67%). Finally, nine patients had increased glucose uptake in non-infarcted regions not showing transient perfusion defects upon exercise testing and perfused by coronary arteries with only minor irregularities. Our results confirm the presence of viable tissue in a large proportion of infarct sites. Moreover, FDG uptake can be seen in regions perfused by coronary arteries showing minor irregularities, not necessarily resulting in detectable transient perfusion defects on a MIBI stress scan. Since the clinical significance of such findings is not clear, further studies should be conducted to assess the long-term evolution of perfusion, function and metabolism in non

  2. Hypothermic machine perfusion in kidney transplantation.

    PubMed

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

    2016-06-01

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

  3. Cerebral perfusion computed tomography deconvolution via structure tensor total variation regularization

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

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

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

  4. The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

    PubMed

    Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

    2016-10-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-12-01

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

  7. Differential nephrotoxicity of low molecular weight proteins including Bence Jones proteins in the perfused rat nephron in vivo.

    PubMed Central

    Sanders, P W; Herrera, G A; Chen, A; Booker, B B; Galla, J H

    1988-01-01

    To investigate the pathogenetic mechanisms of tubule nephrotoxicity of low molecular weight proteins (LMWP), proximal tubules (PT) of rats were perfused in vivo with artificial tubule fluid (ATF) containing one of five LMWPs: three human Bence Jones proteins (BJP), beta-lactoglobulin (BLG), and rabbit myoglobin (MYG). Volume (JV), chloride (JCl) and glucose (JG) fluxes in these perfused PTs were compared with those determined using ATF alone. In separate experiments, perfused nephrons were examined with electron and immunoelectron microscopy. After exposure to BJP1 or BLG, JV, JCl, and JG were less (P less than 0.05) than corresponding control fluxes. Cell damage of these perfused PTs, along with cellular debris in the distal tubules, was prominent. The PT lysosomes often appeared atypical and contained crystals. In contrast, perfusion with BJP2, BJP3, or MYG did not alter JV, JCl, or JG. These findings were corroborated by the normal ultrastructure of these PTs despite immunohistochemical evidence of endocytosis of the BJPs. Isoelectric point, molecular form, and isotype were not factors associated with PT damage. In addition, proteins with pI less than 7.4 precipitated in the distal nephron, forming acellular casts. Thus, certain nephrotoxic LMWPs damaged the PT, while others precipitated in the distal tubule, obstructing the nephron. These two pathogenetic mechanisms may independently be responsible for tubulointerstitial nephropathy of LMWPs in humans. Images PMID:3198767

  8. Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Chen, Chieh-Li; Bojikian, Karine D.; Xin, Chen; Wen, Joanne C.; Gupta, Divakar; Zhang, Qinqin; Mudumbai, Raghu C.; Johnstone, Murray A.; Chen, Philip P.; Wang, Ruikang K.

    2016-06-01

    Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000-based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV≤3.7% (intravisit) and ≤5.2% (intervisit)] and interobserver reproducibility (ICC≤0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice.

  9. GPU-Accelerated Voxelwise Hepatic Perfusion Quantification

    PubMed Central

    Wang, H; Cao, Y

    2012-01-01

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

  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. Perfusion lung imaging in the adult respiratory distress syndrome

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

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

    1986-07-01

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

  12. Inhomogeneity of pulmonary perfusion during sustained microgravity on SLS-1

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; West, John B.

    1994-01-01

    We studied the effects of gravity on the inhomogeneity of pulmonary perfusion in humans by performing hyperventilation-breath-hold single-breath measurements before, during, and after 9 days of continuous exposure to microgravity during the Spacelab Life Sciences-1 (SLS-1) mission. In microgravity the indicators of inhomogeneity of perfusion, especially the size of cardiogenic oscillations in expired CO2 and the height of phase IV, were markedly reduced. Cardiogenic oscillations were reduced to approximately 60% of their preflight standing size, and the height of phase IV was between 0 and -8% (a terminal fall became a small terminal rise) of the preflight standing value. The terminal change in expired CO2 was nearly abolished in microgravity, indicating more uniformity of blood flow between lung units that close and those that remain open at the end of expiration. A possible explanation of this observation is the disappearance of gravity-dependent topographic inequality of blood flow. The residual cardiogenic oscillations in expired CO2 imply a persisting inhomogeneity of perfusion in the absence of gravity, probably in lung regions that are not within the same acinus.

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

    PubMed Central

    2013-01-01

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

  14. High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline.

    PubMed

    Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F; Chopra, Manisha; Chen, Yasheng; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

    2015-09-01

    We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

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

    PubMed

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

    2017-07-05

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

  16. Arterial Perfusion Imaging–Defined Subvolume of Intrahepatic Cancer

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

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

    2014-05-01

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

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

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

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

    2012-02-01

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

  18. Scaling of cerebral blood perfusion in primates and marsupials.

    PubMed

    Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

    2015-08-01

    The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates. © 2015. Published by The Company of Biologists Ltd.

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

    PubMed

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

    2013-02-28

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

  20. 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

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

    PubMed

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

    2016-04-25

    National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety

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

    PubMed

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

    2001-08-01

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

  3. Optimized retrograde cerebral perfusion reduces ischemic energy depletion.

    PubMed

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

    2004-01-01

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

  4. Creation of an ensemble of simulated cardiac cases and a human observer study: tools for the development of numerical observers for SPECT myocardial perfusion imaging

    NASA Astrophysics Data System (ADS)

    O'Connor, J. Michael; Pretorius, P. Hendrik; Gifford, Howard C.; Licho, Robert; Joffe, Samuel; McGuiness, Matthew; Mehurg, Shannon; Zacharias, Michael; Brankov, Jovan G.

    2012-02-01

    Our previous Single Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (MPI) research explored the utility of numerical observers. We recently created two hundred and eighty simulated SPECT cardiac cases using Dynamic MCAT (DMCAT) and SIMIND Monte Carlo tools. All simulated cases were then processed with two reconstruction methods: iterative ordered subset expectation maximization (OSEM) and filtered back-projection (FBP). Observer study sets were assembled for both OSEM and FBP methods. Five physicians performed an observer study on one hundred and seventy-nine images from the simulated cases. The observer task was to indicate detection of any myocardial perfusion defect using the American Society of Nuclear Cardiology (ASNC) 17-segment cardiac model and the ASNC five-scale rating guidelines. Human observer Receiver Operating Characteristic (ROC) studies established the guidelines for the subsequent evaluation of numerical model observer (NO) performance. Several NOs were formulated and their performance was compared with the human observer performance. One type of NO was based on evaluation of a cardiac polar map that had been pre-processed using a gradient-magnitude watershed segmentation algorithm. The second type of NO was also based on analysis of a cardiac polar map but with use of a priori calculated average image derived from an ensemble of normal cases.

  5. Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

    PubMed Central

    Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

    2012-01-01

    Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

  6. A reappraisal of retrograde cerebral perfusion.

    PubMed

    Ueda, Yuichi

    2013-05-01

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

  7. An alternative method for neonatal cerebro-myocardial perfusion.

    PubMed

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

    2012-05-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2018-04-01

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

  10. An alternative method for neonatal cerebro-myocardial perfusion

    PubMed Central

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

    2012-01-01

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

  11. Beam hardening correction in CT myocardial perfusion measurement

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

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

  12. Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

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

    Burgmans, Mark C., E-mail: m.c.burgmans@lumc.nl; Leede, Eleonora M. de, E-mail: e.m.de-leede@lumc.nl; Martini, Christian H., E-mail: c.h.martini@lumc.nl

    2016-06-15

    Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest andmore » the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.« less

  13. The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion.

    PubMed

    Andreasson, Anders S I; Borthwick, Lee A; Gillespie, Colin; Jiwa, Kasim; Scott, Jonathan; Henderson, Paul; Mayes, Jonny; Romano, Rosalba; Roman, Marius; Ali, Simi; Fildes, James E; Marczin, Nandor; Dark, John H; Fisher, Andrew J

    2017-09-01

    Extended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study. Longitudinal samples of perfusate, bronchoalveolar lavage, and tissue from 42 human donor lungs undergoing clinical EVLP assessments were analyzed for markers of inflammation and tissue injury. Levels were compared according to EVLP success and post-transplant outcomes. Neutrophil adhesion to human pulmonary microvascular endothelial cells (HPMECs) conditioned with perfusates from EVLP assessments was investigated on a microfluidic platform. The most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (area under the curve = 1.00, p = 0.002) and tumor necrosis factor-α (area under the curve = 0.95, p = 0.006) after 30 minutes of EVLP. IL-1β levels in perfusate correlated with upregulation of intracellular adhesion molecule-1 in donor lung vasculature (R 2 = 0.68, p < 0.001) and to a lesser degree upregulation of intracellular adhesion molecule-1 (R 2 = 0.30, p = 0.001) and E-selectin (R 2 = 0.29, p = 0.001) in conditioned HPMECs and neutrophil adhesion to conditioned HPMECs (R 2 = 0.33, p < 0.001). Neutralization of IL-1β in perfusate effectively inhibited neutrophil adhesion to conditioned HPMECs (91% reduction, p = 0.002). Donor lungs develop a detectable and discriminatory pro-inflammatory signature in perfusate during EVLP. Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion; this requires further investigation in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This

  16. Application of a cell-once-through perfusion strategy for production of recombinant antibody from rCHO cells in a Centritech Lab II centrifuge system.

    PubMed

    Kim, Byoung Jin; Chang, Ho Nam; Oh, Duk Jae

    2007-01-01

    Based upon the results of scale-down intermittent perfusion processes, a cell-once-through (COT) perfusion concept was applied to a dual bioreactor system coupled to a Centritech Lab II centrifuge for culture of recombinant Chinese hamster ovary (rCHO) cells for monoclonal antibody production. In this new culture mode, i.e., the COT perfusion process, total spent medium was transferred to the centrifuge and a fixed percentage was removed. Approximately 99% of the viable cells are transferred to another bioreactor filled with fresh medium by single operation of the Centritech Lab II centrifuge system for about 30 min. Accordingly, a significant reduction of the cell-passage frequency to the centrifuge led to minimization of cell damage caused by mechanical shear stress, oxygen limitation, nutrient limitation, and low temperature outside the bioreactor. The effects of culture temperature shift and fortified medium on cell growth and recombinant antibody production in the COT perfusion process were investigated. Although the suppressive effects of low culture temperature on cell growth led to a loss of stability in a long-term COT perfusion culture system, the average antibody concentration at 33 degrees C was 157.8 mg/L, approximately 2.4-fold higher than that at 37 degrees C. By the use of a fortified medium at 37 degrees C, rCHO cells were maintained at high density above 1.2 x 10(7) cells/mL, and antibody was produced continuously in a range of 260-280 mg/L in a stable long-term COT perfusion culture. The proposed new culture mode, the COT perfusion approach, guarantees the recovery of rCHO cells damaged by lowered temperature or high lactate and ammonium concentration. It will be an attractive choice for minimization of cell damage and stable long-term antibody production with high cell density.

  17. 3D ECG- and respiratory-gated non-contrast-enhanced (CE) perfusion MRI for postoperative lung function prediction in non-small-cell lung cancer patients: A comparison with thin-section quantitative computed tomography, dynamic CE-perfusion MRI, and perfusion scan.

    PubMed

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

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  19. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

    PubMed Central

    Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

    2016-01-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

  20. Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue.

    PubMed

    Keeler, Geoffrey D; Durdik, Jeannine M; Stenken, Julie A

    2014-06-16

    Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer's solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy.

    PubMed

    Menjoge, Anupa R; Rinderknecht, Amber L; Navath, Raghavendra S; Faridnia, Masoud; Kim, Chong J; Romero, Roberto; Miller, Richard K; Kannan, Rangaramanujam M

    2011-03-30

    Dendrimers offer significant potential as nanocarriers for targeted delivery of drugs and imaging agents. The objectives of this study were to evaluate the transplacental transport, kinetics and biodistribution of PAMAM dendrimers ex-vivo across the human placenta in comparison with antipyrine, a freely diffusible molecule, using dually perfused re-circulating term human placental lobules. The purpose of this study is to determine if dendrimers as drug carriers can be used to design drug delivery systems directed at selectively treating either the mother or the fetus. The transplacental transfers of fluorescently (Alexa 488) tagged PAMAM dendrimer (16 kDa) and antipyrine (188 Da) from maternal to fetal circulation were measured using HPLC/dual UV and fluorescent detector (sensitivity of 10 ng/mL for dendrimer and 100 ng/mL for antipyrine respectively). C(max) for the dendrimer-Alexa (DA) in maternal perfusate (T(max)=15 min) was 18 times higher than in the fetal perfusate and never equilibrated with the maternal perfusate during 5.5 h of perfusion (n=4). DA exhibited a measurable but low transplacental transport of 2.26±0.12 μg/mL during 5.5h, where the mean transplacental transfer was 0.84±0.11% of the total maternal concentration and the feto-maternal ratio as percent was 0.073%±0.02. The biochemical and physiological analysis of the placentae perfused with DA demonstrated normal function throughout the perfusion. The immunofluorescence histochemistry confirmed that the biodistribution of DA in perfused placenta was sparsely dispersed, and when noted was principally seen in the inter-villous spaces and outer rim of the villous branches. In a few cases, DA was found internalized and localized in nuclei and cytoplasm of syncytiotrophoblast and inside the villous core; however, DA was mostly absent from the villous capillaries. In conclusion, the PAMAM dendrimers exhibited a low rate of transfer from maternal to the fetal side across the perfused human placenta

  2. Australian and New Zealand Perfusion Survey: Management and Procedure

    PubMed Central

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

    2009-01-01

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

  3. 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

  4. Perfusion scintigraphy and patient selection for lung volume reduction surgery.

    PubMed

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

    2010-10-01

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

  5. Synergistic effect between bioactive glass foam and a perfusion bioreactor on osteogenic differentiation of human adipose stem cells.

    PubMed

    Silva, A R P; Paula, A C C; Martins, T M M; Goes, A M; Pereria, M M

    2014-03-01

    Tissue engineering is a multidisciplinary science that combines a structural scaffold and cells to form a construct able to promote regeneration of injured tissue. Bioactive glass foam produced by sol-gel is an osteoinductive material with a network of interconnected macropores necessary for cell colonization. The use of human adipose-derived stem cell (hASC) presents advantages as the potential for a large number of cells, rapid expansion in vitro and the capability of differentiating into osteoblasts. The use of a bioreactor in three-dimensional cell culture enables greater efficiency for cell nutrition and application of mechanical forces, important modulators of bone physiology. The hASC seeded in a bioactive glass scaffold and cultured in osteogenic Leibovitz L-15 medium in a bioreactor with a flow rate of 0.1 mL min(-1) demonstrated a significant increase in cell proliferation and viability and alkaline phosphatase (ALP) activity peak after 14 days. The immunofluorescence assay revealed an expression of osteopontin, osteocalcin and type I collagen from 7 to 21 days after culture. The cells changed from a spindle shape to a cuboidal morphology characteristic of osteoblasts. The polymerase chain reaction assay confirmed that osteopontin, osteocalcin, and ALP genes were expressed. These results indicate that hASCs differentiated into an osteogenic phenotype when cultured in bioactive glass scaffold, osteogenic Leibovitz L-15 medium and a perfusion bioreactor. Therefore, these results highlight the synergism between a bioactive glass scaffold and the effect of perfusion on cells and indicate the differentiation into an osteogenic phenotype. Copyright © 2013 Wiley Periodicals, Inc.

  6. Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network.

    PubMed

    Piety, Nathaniel Z; Reinhart, Walter H; Pourreau, Patrick H; Abidi, Rajaa; Shevkoplyas, Sergey S

    2016-04-01

    The shape of human red blood cells (RBCs) deteriorates progressively throughout hypothermic storage, with echinocytosis being the most prevalent pathway of this morphologic lesion. As a result, each unit of stored blood contains a heterogeneous mixture of cells in various stages of echinocytosis and normal discocytes. Here we studied how the change in shape of RBCs following along the path of the echinocytic transformation affects perfusion of an artificial microvascular network (AMVN). Blood samples were obtained from healthy consenting volunteers. RBCs were leukoreduced, resuspended in saline, and treated with various concentrations of sodium salicylate to induce shape changes approximating the stages of echinocytosis experienced by RBCs during hypothermic storage (e.g., discocyte, echinocyte I, echinocyte II, echinocyte III, spheroechinocyte, and spherocyte). The AMVN perfusion rate was measured for 40% hematocrit suspensions of RBCs with different shapes. The AMVN perfusion rates for RBCs with discocyte and echinocyte I shapes were similar, but there was a significant decline in the AMVN perfusion rate between RBCs with shapes approximating each subsequent stage of echinocytosis. The difference in AMVN perfusion between discocytes and spherocytes (the last stage of the echinocytic transformation) was 34%. The change in shape of RBCs from normal discocytes progressively through various stages of echinocytosis to spherocytes produced a substantial decline in the ability of these cells to perfuse an AMVN. Echinocytosis induced by hypothermic storage could therefore be responsible for a similarly substantial impairment of deformability previously observed for stored RBCs. © 2015 AABB.

  7. Perfusion-related stimuli for compensatory lung growth following pneumonectomy

    PubMed Central

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

    2016-01-01

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

  8. [Influence of valproic acid (depakine I.V.) on human placenta metabolism--experimental model].

    PubMed

    Semczuk-Sikora, Anna; Rogowska, Wanda; Semczuk, Marian

    2003-08-01

    The pregnancy in women with epilepsy is associated with an increased incidence of congenital malformations in offspring. Currently, anti-epileptic drugs (AEDs) are concerned to be a major etiologic factor of abnormal fetal development but the pathomechanism of teratogenicity of AEDs is complex and not well understood. The purpose of this study was to evaluate an influence of one of the AED-valproic acid (VPA) on placental metabolism (glucose consumption and lactate production). Term human placental cotyledons were perfused in vitro using a recycling perfusion of maternal and fetal circulations. A total 18 placentas were perfused either with 75 micrograms/ml of VPA (therapeutic dose) or with 225 micrograms/ml of VPA (toxic dose). Eight placentas were perfused with a medium without VPA and served as controls. During 2.5 h of experiment, both maternal and fetal glucose consumption and lactate production were measured every 30 minutes. The introduction of different concentrations of VPA into the perfusion system did not effect placental glucose consumption and lactate production rates in both maternal and fetal compartments. The teratogenic effect of valproic acid is not associated with metabolic disturbances of glucose or lactate in the placental tissue.

  9. The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network

    PubMed Central

    Sosa, Jose M.; Nielsen, Nathan D.; Vignes, Seth M.; Chen, Tanya G.; Shevkoplyas, Sergey S.

    2013-01-01

    The ability of red blood cells (RBC) to undergo a wide range of deformations while traversing the microvasculature is crucial for adequate perfusion. Interpretation of RBC deformability measurements performed in vitro in the context of microvascular perfusion has been notoriously difficult. This study compares the measurements of RBC deformability performed using micropore filtration and ektacytometry with the RBC ability to perfuse an artificial microvascular network (AMVN). Human RBCs were collected from healthy consenting volunteers, leukoreduced, washed and exposed to graded concentrations (0% – 0.08%) of glutaraldehyde (a non-specific protein cross-linker) and diamide (a spectrin-specific protein cross-linker) to impair the deformability of RBCs. Samples comprising cells with two different levels of deformability were created by adding non-deformable RBCs (hardened by exposure to 0.08% glutaraldehyde) to the sample of normal healthy RBCs. Ektacytometry indicated a nearly linear decline in RBC deformability with increasing glutaraldehyde concentration. Micropore filtration showed a significant reduction only for concentrations of glutaraldehyde higher than 0.04%. Neither micropore filtration nor ektacytometry measurements could accurately predict the AMVN perfusion. Treatment with diamide reduced RBC deformability as indicated by ektacytometry, but had no significant effect on either micropore filtration or the AMVN perfusion. Both micropore filtration and ektacytometry showed a linear decline in effective RBC deformability with increasing fraction of non-deformable RBCs in the sample. The corresponding decline in the AMVN perfusion plateaued above 50%, reflecting the innate ability of blood flow in the microvasculature to bypass occluded capillaries. Our results suggest that in vitro measurements of RBC deformability performed using either micropore filtration or ektacytometry may not represent the ability of same RBCs to perfuse microvascular networks

  10. The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network.

    PubMed

    Sosa, Jose M; Nielsen, Nathan D; Vignes, Seth M; Chen, Tanya G; Shevkoplyas, Sergey S

    2014-01-01

    The ability of red blood cells (RBC) to undergo a wide range of deformations while traversing the microvasculature is crucial for adequate perfusion. Interpretation of RBC deformability measurements performed in vitro in the context of microvascular perfusion has been notoriously difficult. This study compares the measurements of RBC deformability performed using micropore filtration and ektacytometry with the RBC ability to perfuse an artificial microvascular network (AMVN). Human RBCs were collected from healthy consenting volunteers, leukoreduced, washed and exposed to graded concentrations (0-0.08%) of glutaraldehyde (a non-specific protein cross-linker) and diamide (a spectrin-specific protein cross-linker) to impair the deformability of RBCs. Samples comprising cells with two different levels of deformability were created by adding non-deformable RBCs (hardened by exposure to 0.08% glutaraldehyde) to the sample of normal healthy RBCs. Ektacytometry indicated a nearly linear decline in RBC deformability with increasing glutaraldehyde concentration. Micropore filtration showed a significant reduction only for concentrations of glutaraldehyde higher than 0.04%. Neither micropore filtration nor ektacytometry measurements could accurately predict the AMVN perfusion. Treatment with diamide reduced RBC deformability as indicated by ektacytometry, but had no significant effect on either micropore filtration or the AMVN perfusion. Both micropore filtration and ektacytometry showed a linear decline in effective RBC deformability with increasing fraction of non-deformable RBCs in the sample. The corresponding decline in the AMVN perfusion plateaued above 50%, reflecting the innate ability of blood flow in the microvasculature to bypass occluded capillaries. Our results suggest that in vitro measurements of RBC deformability performed using either micropore filtration or ektacytometry may not represent the ability of same RBCs to perfuse microvascular networks. Further

  11. 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.

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

    PubMed

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

    2016-09-01

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

  13. Nuclear cardiology: Myocardial perfusion and function

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

    Seldin, D.W.

    1991-08-01

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

  14. 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

  15. Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor.

    PubMed

    Burdorf, L; Riner, A; Rybak, E; Salles, I I; De Meyer, S F; Shah, A; Quinn, K J; Harris, D; Zhang, T; Parsell, D; Ali, F; Schwartz, E; Kang, E; Cheng, X; Sievert, E; Zhao, Y; Braileanu, G; Phelps, C J; Ayares, D L; Deckmyn, H; Pierson, R N; Azimzadeh, A M; Dandro, Amy; Karavi, Kasinath

    2016-05-01

    Here, we ask whether platelet GPIb and GPIIb/IIIa receptors modulate platelet sequestration and activation during GalTKO.hCD46 pig lung xenograft perfusion. GalTKO.hCD46 transgenic pig lungs were perfused with heparinized fresh human blood. Results from perfusions in which αGPIb Fab (6B4, 10 mg/l blood, n = 6), αGPIIb/IIIa Fab (ReoPro, 3.5 mg/l blood, n = 6), or both drugs (n = 4) were administered to the perfusate were compared to two additional groups in which the donor pig received 1-desamino-8-d-arginine vasopressin (DDAVP), 3 μg/kg (to pre-deplete von Willebrand Factor (pVWF), the main GPIb ligand), with or without αGPIb (n = 6 each). Platelet sequestration was significantly delayed in αGPIb, αGPIb+DDAVP, and αGPIb+αGPIIb/IIIa groups. Median lung "survival" was significantly longer (>240 vs. 162 min reference, p = 0.016), and platelet activation (as CD62P and βTG) were significantly inhibited, when pigs were pre-treated with DDAVP, with or without αGPIb Fab treatment. Pulmonary vascular resistance rise was not significantly attenuated in any group, and was associated with residual thromboxane and histamine elaboration. The GPIb-VWF and GPIIb/IIIa axes play important roles in platelet sequestration and coagulation cascade activation during GalTKO.hCD46 lung xenograft injury. GPIb blockade significantly reduces platelet activation and delays platelet sequestration in this xenolung rejection model, an effect amplified by adding αGPIIb/IIIa blockade or depletion of VWF from pig lung. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2005-09-01

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

  17. Computed Tomography Perfusion Imaging for the Diagnosis of Hepatic Alveolar Echinococcosis

    PubMed Central

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

    2018-01-01

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

  18. Characterization of breast lesion using T1-perfusion magnetic resonance imaging: Qualitative vs. quantitative analysis.

    PubMed

    Thakran, S; Gupta, P K; Kabra, V; Saha, I; Jain, P; Gupta, R K; Singh, A

    2018-06-14

    The objective of this study was to quantify the hemodynamic parameters using first pass analysis of T 1 -perfusion magnetic resonance imaging (MRI) data of human breast and to compare these parameters with the existing tracer kinetic parameters, semi-quantitative and qualitative T 1 -perfusion analysis in terms of lesion characterization. MRI of the breast was performed in 50 women (mean age, 44±11 [SD] years; range: 26-75) years with a total of 15 benign and 35 malignant breast lesions. After pre-processing, T 1 -perfusion MRI data was analyzed using qualitative approach by two radiologists (visual inspection of the kinetic curve into types I, II or III), semi-quantitative (characterization of kinetic curve types using empirical parameters), generalized-tracer-kinetic-model (tracer kinetic parameters) and first pass analysis (hemodynamic-parameters). Chi-squared test, t-test, one-way analysis-of-variance (ANOVA) using Bonferroni post-hoc test and receiver-operating-characteristic (ROC) curve were used for statistical analysis. All quantitative parameters except leakage volume (Ve), qualitative (type-I and III) and semi-quantitative curves (type-I and III) provided significant differences (P<0.05) between benign and malignant lesions. Kinetic parameters, particularly volume transfer coefficient (K trans ) provided a significant difference (P<0.05) between all grades except grade-II vs III. The hemodynamic parameter (relative-leakage-corrected-breast-blood-volume [rBBVcorr) provided a statistically significant difference (P<0.05) between all grades. It also provided highest sensitivity and specificity among all parameters in differentiation between different grades of malignant breast lesions. Quantitative parameters, particularly rBBVcorr and K trans provided similar sensitivity and specificity in differentiating benign from malignant breast lesions for this cohort. Moreover, rBBVcorr provided better differentiation between different grades of malignant breast

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

    PubMed

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

    2018-03-01

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

  20. Spatio-temporal analysis of blood perfusion by imaging photoplethysmography

    NASA Astrophysics Data System (ADS)

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

    2018-02-01

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

  1. 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.

  2. 3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

    PubMed Central

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

    2016-01-01

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

  3. Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

    PubMed

    Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

    2014-01-15

    The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Near-Infrared Spectroscopy versus Magnetic Resonance Imaging To Study Brain Perfusion in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

    PubMed Central

    Wintermark, P.; Hansen, A.; Warfield, SK.; Dukhovny, D.; Soul, JS.

    2014-01-01

    Background The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. Objective The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. Design/Methods In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow values (CBF), measured from 1–2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Results Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r = 0.88; p value = 0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. Conclusions NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. PMID:23631990

  5. The use of hemoglobin solutions in kidney perfusions.

    PubMed

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

    1984-01-01

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

  6. Automated multi-slice extracellular and patch-clamp experiments using the WinLTP data acquisition system with automated perfusion control

    PubMed Central

    Anderson, William W.; Fitzjohn, Stephen M.; Collingridge, Graham L.

    2012-01-01

    WinLTP is a data acquisition program for studying long-term potentiation (LTP) and other aspects of synaptic function. Earlier versions of WinLTP (J. Neurosci. Methods, 162:346–356, 2007) provided automated electrical stimulation and data acquisition capable of running nearly an entire synaptic plasticity experiment, with the primary exception that perfusion solutions had to be changed manually. This automated stimulation and acquisition was done by using ‘Sweep’, ‘Loop’ and ‘Delay’ events to build scripts using the ‘Protocol Builder’. However, this did not allow automatic changing of many solutions while running multiple slice experiments, or solution changing when this had to be performed rapidly and with accurate timing during patch-clamp experiments. We report here the addition of automated perfusion control to WinLTP. First, perfusion change between sweeps is enabled by adding the ‘Perfuse’ event to Protocol Builder scripting and is used in slice experiments. Second, fast perfusion changes during as well as between sweeps is enabled by using the Perfuse event in the protocol scripts to control changes between sweeps, and also by changing digital or analog output during a sweep and is used for single cell single-line perfusion patch-clamp experiments. The addition of stepper control of tube placement allows dual- or triple-line perfusion patch-clamp experiments for up to 48 solutions. The ability to automate perfusion changes and fully integrate them with the already automated stimulation and data acquisition goes a long way toward complete automation of multi-slice extracellularly recorded and single cell patch-clamp experiments. PMID:22524994

  7. Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired-tracer dilution: studies with calcium and choline.

    PubMed

    Sweiry, J H; Page, K R; Dacke, C G; Abramovich, D R; Yudilevich, D L

    1986-12-01

    Rapid uptake and efflux of 45Ca2+ and [3H]choline at the maternal and fetal interfaces of the syncytiotrophoblast in the dually-perfused human placenta was investigated by application of the single circulation paired-tracer dilution method (Yudilevich, Eaton, Short & Leichtweiss 1979). Cotyledons were perfused with Krebs-bicarbonate containing dextran (30 g/l; MW = 60-70,000) at 20 and 6 ml/min on maternal and fetal sides, respectively. The paired-tracer (test substrate and extracellular marker) technique consisted of an intra-arterial injection of a tracer bolus, followed by venous sampling over 5-6 min. There was a rapid (sec) uptake of 45Ca2+, followed by backflux (efflux into the ipsilateral circulation) which, over 5-6 min, was 59-100% on the fetal side. It was more variable but generally lower on the maternal interface. At 0.1 mM calcium, 45Ca2+ maximal uptake (Umax) was about 53% on the fetal side but on the maternal side it was variable and averaged 17%. At 2.4 mM calcium fetal side Umax was reduced to 40%. However, on the maternal side the effect was not consistent. Unidirectional influx (nmol/min per g) appeared to be not different on the two sides of the placenta. For [3H]choline (in choline-free perfusates) Umax was about 50% and 30% on fetal and maternal sides, respectively; tracer backflux was variable on the maternal side and averaged 50% on the fetal side. [3H]Choline uptake was highly inhibited by either 1.0 mM choline or the specific competitive inhibitor, hemicholinium-3 (0.1 mM). Specific transplacental transfer of 45Ca2+ (i.e. in excess of the extracellular marker) was not significant in either direction. For [3H]choline there was an apparent small excess (about 4%) preferential towards the fetal circulation. These findings in the human placenta are similar to those demonstrated previously in the guinea-pig placenta which suggested the existence of specific transport systems for choline and calcium on both sides of the syncytiotrophoblast.

  8. Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells*

    PubMed Central

    Shestov, Alexander A.; Mancuso, Anthony; Lee, Seung-Cheol; Guo, Lili; Nelson, David S.; Roman, Jeffrey C.; Henry, Pierre-Gilles; Leeper, Dennis B.; Blair, Ian A.; Glickson, Jerry D.

    2016-01-01

    A network model for the determination of tumor metabolic fluxes from 13C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-13C2]glucose under normoxic conditions at 37 °C and monitored by 13C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ∼50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ∼6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism. PMID:26703469

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

    PubMed Central

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

    2016-01-01

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

  10. Patient-specific coronary blood supply territories for quantitative perfusion analysis

    PubMed Central

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

    2018-01-01

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

  11. Magnetic Resonance Imaging of Ventilation and Perfusion in the Lung

    NASA Technical Reports Server (NTRS)

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

    2017-01-01

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

  12. Developments in laser Doppler blood perfusion monitoring

    NASA Astrophysics Data System (ADS)

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

    2003-03-01

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

  13. MDMA ‘ecstasy’ increases cerebral cortical perfusion determined by bolus-tracking arterial spin labelling (btASL) MRI

    PubMed Central

    Rouine, J; Gobbo, O L; Campbell, M; Gigliucci, V; Ogden, I; McHugh Smith, K; Duffy, P; Behan, B; Byrne, D; Kelly, M E; Blau, C W; Kerskens, C M; Harkin, A

    2013-01-01

    Background and Purpose The purpose of this study was to assess cerebral perfusion changes following systemic administration of the recreational drug 3,4-methylendioxymethamphetamine (MDMA ‘ecstasy’) to rats. Experimental Approach Cerebral perfusion was quantified using bolus-tracking arterial spin labelling (btASL) MRI. Rats received MDMA (20 mg·kg−1; i.p.) and were assessed 1, 3 or 24 h later. Rats received MDMA (5 or 20 mg·kg−1; i.p.) and were assessed 3 h later. In addition, rats received MDMA (5 or 10 mg·kg−1; i.p.) or saline four times daily over 2 consecutive days and were assessed 8 weeks later. Perfusion-weighted images were generated in a 7 tesla (7T) MRI scanner and experimental data was fitted to a quantitative model of cerebral perfusion to generate mean transit time (MTT), capillary transit time (CTT) and signal amplitude. Key Results MDMA reduces MTT and CTT and increases amplitude in somatosensory and motor cortex 1 and 3 h following administration, indicative of an increase in perfusion. Prior exposure to MDMA provoked a long-term reduction in cortical 5-HT concentration, but did not produce a sustained effect on cerebral cortical perfusion. The response to acute MDMA challenge (20 mg·kg−1; i.p.) was attenuated in these animals indicating adaptation in response to prior MDMA exposure. Conclusions and Implications MDMA provokes changes in cortical perfusion, which are quantifiable by btASL MRI, a neuroimaging tool with translational potential. Future studies are directed towards elucidation of the mechanisms involved and correlating changes in cerebrovascular function with potential behavioural deficits associated with drug use. PMID:23517012

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

    PubMed

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

    2013-05-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2014-01-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  16. Vasoactive mediators and splanchnic perfusion.

    PubMed

    Reilly, P M; Bulkley, G B

    1993-02-01

    To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

  17. Limited use of Centritech Lab II Centrifuge in perfusion culture of rCHO cells for the production of recombinant antibody.

    PubMed

    Kim, Byoung Jin; Oh, Duk Jae; Chang, Ho Nam

    2008-01-01

    Perfusion cultures of recombinant Chinese hamster ovary cells, producing recombinant antibody against the S surface antigen of Hepatitis B virus, were carried out in continuous and intermittent mode using a Centritech Lab II Centrifuge. In the continuous perfusion process, despite the absence of shear stress from the pump head, long-term operation was not possible because of continuously repeated exposure to oxygen limitation and low temperature, as well as shear stress from centrifugal force. In the intermittent perfusion processes, the frequency of cell-passage through the centrifuge was substantially reduced, compared with the continuous perfusion mode; however, the degree of reduction could not guarantee stable long-term operation. Although various operating parameters were applied in the intermittent perfusion cultures, high cell densities could not be maintained stably. In a single bioreactor culture system, a specific cell that is returned from the centrifuge to the bioreactor could be transferred from the bioreactor to the centrifuge again in the next cycle. These repetitive damages, caused by shear stress from the pump head and centrifugal force, as well as exposure to suboptimal conditions such as oxygen limitation and low temperature below 37 degrees C, were more serious at higher perfusion rates. Subsequently, damaged cells and dead cells were continuously accumulated in the bioreactor. Culture temperature shift from 37 to 33 degrees C increased antibody concentrations but showed inhibitory effects on cell growth. The negative effects of lowering culture temperature on cell growth overwhelmed the positive effects on antibody production. To protect cells from shear stress, Pluronic F-68 was 2-fold concentrated in the culture medium; nevertheless, a significantly higher concentration of Pluronic F-68 (2 g/L) may have inhibitory effects on cell growth.

  18. Impact of basal inferolateral scar burden determined by automatic analysis of 99mTc-MIBI myocardial perfusion SPECT on the long-term prognosis of cardiac resynchronization therapy.

    PubMed

    Morishima, Itsuro; Okumura, Kenji; Tsuboi, Hideyuki; Morita, Yasuhiro; Takagi, Kensuke; Yoshida, Ruka; Nagai, Hiroaki; Tomomatsu, Toshiro; Ikai, Yoshihiro; Terada, Kazushi; Sone, Takahito; Murohara, Toyoaki

    2017-04-01

    Left-ventricular (LV) scarring may be associated with a poor response to cardiac resynchronization therapy (CRT). The automatic analysis of myocardial perfusion single-photon emission computed tomography (MP-SPECT) may provide objective quantification of LV scarring. We investigated the impact of LV scarring determined by an automatic analysis of MP-SPECT on short-term LV volume response as well as long-term outcome. We studied consecutive 51 patients who were eligible to undergo 99mTc-MIBI MP-SPECT both at baseline and 6 months after CRT (ischaemic cardiomyopathies 31%). Quantitative perfusion SPECT was used to evaluate the defect extent (an index of global scarring) and the LV 17-segment regional uptake ratio (an inverse index of regional scar burden). The primary outcome was the composite of overall mortality or first hospitalization for worsening heart failure. A high global scar burden and a low mid/basal inferolateral regional uptake ratio were associated with volume non-responders to CRT at 6 months. The basal inferolateral regional uptake ratio remained as a predictor of volume non-response after adjusting for the type of cardiomyopathy. During a median follow-up of 36.1 months, the outcome occurred in 28 patients. The patients with a low basal inferolateral regional uptake ratio with a cutoff value of 57% showed poor prognosis (log-rank P= 0.006). The scarring determined by automatic analysis of MP-SPECT images may predict a poor response to CRT regardless of the pathogenesis of cardiomyopathy. The basal inferolateral scar burden in particular may have an adverse impact on long-term prognosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  19. 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

  20. Correlation of human papilloma virus status with quantitative perfusion/diffusion/metabolic imaging parameters in the oral cavity and oropharyngeal squamous cell carcinoma: comparison of primary tumour sites and metastatic lymph nodes.

    PubMed

    Han, M; Lee, S J; Lee, D; Kim, S Y; Choi, J W

    2018-05-17

    To investigate the differences in perfusion/diffusion/metabolic imaging parameters according to human papilloma virus (HPV) status in the oral cavity and oropharyngeal squamous cell carcinoma (OC-OPSCC), separately in primary tumour sites and metastatic lymph nodes. This retrospective study comprised 41 patients with primary OC-OPSCCs and 29 patients with metastatic lymph nodes. The perfusion/diffusion/metabolic imaging parameters were measured at the primary tumour and the largest ipsilateral metastatic lymph node. The quantitative parameters were compared between the HPV-positive and -negative groups. The HPV-positivity was 39% (16 patients) for the primary tumours and 51.7% (15 patients) for the metastatic lymph nodes. Patients with HPV-positive tumours had a lower T stage (p=0.034). The metastatic lymph nodes for the HPV-positive patients were bulkier (p=0.016) and more frequently had cystic morphology (p=0.005). The perfusion parameters were not different, regardless of HPV status. The diffusion parameter (ADC min , p=0.011) of the metastatic lymph nodes in the HPV-positive groups was lower and metabolic parameter (metabolic tumour volume p=0.035 and total lesion glycolysis p=0.037) were higher than those in HPV-negative groups. The diffusion and metabolic parameters of metastatic lymph nodes from OC-OPSCC were different according to HPV status. The perfusion parameters did not clearly represent HPV status. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-08-14

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

  2. CT Perfusion of the Liver: Principles and Applications in Oncology

    PubMed Central

    Kim, Se Hyung; Kamaya, Aya

    2014-01-01

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

  3. Can we predict necrosis intra-operatively? Real-time optical quantitative perfusion imaging in surgery: study protocol for a prospective, observational, in vivo pilot study.

    PubMed

    Jansen, Sanne M; de Bruin, Daniel M; van Berge Henegouwen, Mark I; Strackee, Simon D; Veelo, Denise P; van Leeuwen, Ton G; Gisbertz, Suzanne S

    2017-01-01

    Compromised perfusion as a result of surgical intervention causes a reduction of oxygen and nutrients in tissue and therefore decreased tissue vitality. Quantitative imaging of tissue perfusion during reconstructive surgery, therefore, may reduce the incidence of complications. Non-invasive optical techniques allow real-time tissue imaging, with high resolution and high contrast. The objectives of this study are, first, to assess the feasibility and accuracy of optical coherence tomography (OCT), sidestream darkfield microscopy (SDF), laser speckle contrast imaging (LSCI), and fluorescence imaging (FI) for quantitative perfusion imaging and, second, to identify/search for criteria that enable risk prediction of necrosis during gastric tube and free flap reconstruction. This prospective, multicenter, observational in vivo pilot study will assess tissue perfusion using four optical technologies: OCT, SDF, LSCI, and FI in 40 patients: 20 patients who will undergo gastric tube reconstruction after esophagectomy and 20 patients who will undergo free flap surgery. Intra-operative images of gastric perfusion will be obtained directly after reconstruction at four perfusion areas. Feasibility of perfusion imaging will be analyzed per technique. Quantitative parameters directly related to perfusion will be scored per perfusion area, and differences between biologically good versus reduced perfusion will be tested statistically. Patient outcome will be correlated to images and perfusion parameters. Differences in perfusion parameters before and after a bolus of ephedrine will be tested for significance. This study will identify quantitative perfusion-related parameters for an objective assessment of tissue perfusion during surgery. This will likely allow early risk stratification of necrosis development, which will aid in achieving a reduction of complications in gastric tube reconstruction and free flap transplantation. Clinicaltrials.gov registration number NCT02902549

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

    PubMed

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

    2018-02-01

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

  5. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung

    PubMed Central

    Sá, Rui Carlos; Theilmann, Rebecca J.; Buxton, Richard B.; Prisk, G. Kim; Hopkins, Susan R.

    2013-01-01

    The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V̇a/Q̇) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V̇a/Q̇ ratio, the gravitational gradients in proton density, ventilation, perfusion, and V̇a/Q̇ ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min−1·ml−1) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min−1·ml−1) images to obtain regional V̇a/Q̇ ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (−0.17 ± 0.10 ml·min−1·ml−1·cm−1 supine, −0.040 ± 0.03 prone ml·min−1·ml−1·cm−1, P = 0.02) as was the slope of the perfusion-height relationship (−0.14 ± 0.05 ml·min−1·ml−1·cm−1 supine, −0.08 ± 0.09 prone ml·min−1·ml−1·cm−1, P = 0.02). There was a significant gravitational gradient in V̇a/Q̇ ratio in both postures (P < 0.05) that was less in prone (0.09 ± 0.08 cm−1 supine, 0.04 ± 0.03 cm−1 prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional V̇a/Q̇ ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of

  6. Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.

    PubMed

    Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

    2018-03-15

    The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP ( p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.

  7. Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions

    PubMed Central

    Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

    2018-01-01

    The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP (p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP (p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP (p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions. PMID:29543727

  8. Ethical aspects in placental perfusion studies: views of the researchers.

    PubMed

    Halkoaho, A; Pietilä, A-M; Vähäkangas, K

    2011-07-01

    Within the EU-project NewGeneris human placental perfusion has been used for predicting fetal exposure to food carcinogens. Within the work package of ethical aspects of the research, we studied opinions of the researchers (n = 23) who carried out perfusions of human placenta. Data were collected by focus group interviews (n = 12) and an open-ended questionnaire (n =19 of which 8 were also attending the group session) from scientists representing 9 different nationalities. Both types of data were analysed together thematically and with data triangulation. Studied researchers considered communication between all stakeholders extremely important. Good communication was considered a prerequisite for the recruitment of mothers to donate the placenta, as well as for the process of getting the informed consent. Voluntariness, confidentiality and societal meaning were mentioned as important by all studied researchers. Educating the hospital personnel was regarded as essential in order to provide the best possible information to the mothers. The researchers also pointed out that cultural aspects should be respected, and that in Western thinking placenta is mostly considered as waste. Some researchers suggested that current guidelines and processes for obtaining informed consent should be reviewed also from a cultural perspective. With the development of biobanks, the use of human tissues, including placenta will most probably increase in the future, and the awareness of ethical considerations both in legislation and in practice need support. Thus, continuous effort for better research ethics is essential and requires research on research ethics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

    PubMed

    Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

    2015-06-27

    The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Alteration of cerebral perfusion in patients with idiopathic normal pressure hydrocephalus measured by 3D perfusion weighted magnetic resonance imaging.

    PubMed

    Walter, Christof; Hertel, F; Naumann, E; Mörsdorf, M

    2005-12-01

    It is controversial whether alteration of cerebral perfusion plays an important role in the pathophysiology of patients with idiopathic normal pressure hydrocephalus (NPH) and can help to predict the outcome after shunt surgery. 28 patients with suspected NPH were examined clinically (Homburg Hydrocephalus Scale, walking test, incontinence protocol) and by 3D dynamic susceptibility based perfusion weighted magnetic resonance imaging (PWI-MRI) before and after cerebrospinal fluid release (spinal tap test, STT). The perfusion parameters (negative integral (NI), time of arrival (T0), time to peak (TTP), mean transit time, and the difference TTP-T0 were analysed. Three different groups of patients were identified preoperatively: In group 1 seven patients showed an increase in the cerebral perfusion and a clinical improvement after STT. The second group (9 patients) also revealed an increase of the cerebral perfusion, but no significant alteration of the clinical assessment could be found. In the third group neither the cerebral perfusion nor the clinical assessment changed. 14 of the 16 patients (group 1 and 2) were examined three months after shunt placement. 11 patients showed a good or excellent result, 2 patients revealed a fair assessment, and only 1 patient had transiently improved. No patient was downgraded after shunting. In the patient group 1 and 2 the NI increased significantly (effect size: 34%), whereas in group 3 no significant alteration of NI was observed. PWI-MRI improves the prediction of outcome after shunt placement in patients with NPH and can offer new insights into the pathophysiology.

  11. In Search of the Optimal Heart Perfusion Ultrasound Imaging Platform.

    PubMed

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

    2015-09-01

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

  12. Evaluation of Microvascular Perfusion and Resuscitation after Severe Injury.

    PubMed

    Lee, Yann-Leei L; Simmons, Jon D; Gillespie, Mark N; Alvarez, Diego F; Gonzalez, Richard P; Brevard, Sidney B; Frotan, Mohammad A; Schneider, Andrew M; Richards, William O

    2015-12-01

    Achieving adequate perfusion is a key goal of treatment in severe trauma; however, tissue perfusion has classically been measured by indirect means. Direct visualization of capillary flow has been applied in sepsis, but application of this technology to the trauma population has been limited. The purpose of this investigation was to compare the efficacy of standard indirect measures of perfusion to direct imaging of the sublingual microcirculatory flow during trauma resuscitation. Patients with injury severity scores >15 were serially examined using a handheld sidestream dark-field video microscope. In addition, measurements were also made from healthy volunteers. The De Backer score, a morphometric capillary density score, and total vessel density (TVD) as cumulative vessel area within the image, were calculated using Automated Vascular Analysis (AVA3.0) software. These indices were compared against clinical and laboratory parameters of organ function and systemic metabolic status as well as mortality. Twenty severely injured patients had lower TVD (X = 14.6 ± 0.22 vs 17.66 ± 0.51) and De Backer scores (X = 9.62 ± 0.16 vs 11.55 ± 0.37) compared with healthy controls. These scores best correlated with serum lactate (TVD R(2) = 0.525, De Backer R(2) = 0.576, P < 0.05). Mean arterial pressure, heart rate, oxygen saturation, pH, bicarbonate, base deficit, hematocrit, and coagulation parameters correlated poorly with both TVD and De Backer score. Direct measurement of sublingual microvascular perfusion is technically feasible in trauma patients, and seems to provide real-time assessment of microcirculatory perfusion. This study suggests that in severe trauma, many indirect measurements of perfusion do not correlate with microvascular perfusion. However, visualized perfusion deficiencies do reflect a shift toward anaerobic metabolism.

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

    PubMed

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

    2018-06-08

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

  14. 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.

  15. A microfluidic perfusion platform for cultivation and screening study of motile microalgal cells

    PubMed Central

    Eu, Young-Jae; Park, Hye-Sun; Kim, Dong-Pyo; Wook Hong, Jong

    2014-01-01

    Systematic screening of algal cells is getting huge interest due to their capability of producing lipid-based biodiesel. Here, we introduce a new microfluidic platform composed of an array of perfusion chambers designed for long-term cultivation and preliminary screening of motile microalgal cells through loading and releasing of cells to and from the chambers. The chemical environment in each perfusion chamber was independently controlled for 5 days. The effect of nitrogen-depletion on the lipid production, phototaxis behavior in the absence of Ca2+, and cytotoxic effect of herbicide on microalgal cells was successfully monitored and compared with simultaneous control experiments on the platform. The present methodology could be extended to effective screening of algal cells and various cell lines for the production of biodiesel and other useful chemicals. PMID:24803962

  16. Evaluating blood perfusion of the corpus luteum in beef cows during fescue toxicosis.

    PubMed

    Cline, G F; Muth-Spurlock, A M; Voelz, B E; Lemley, C O; Larson, J E

    2016-01-01

    altered at the onset of fescue toxicosis in this short-term study, indicating that a decrease in blood perfusion of the CL may not be a primary mechanism involved in decreased reproductive efficiency of cattle during fescue toxicosis.

  17. Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion.

    PubMed

    Sierra-Parraga, Jesus Maria; Eijken, Marco; Hunter, James; Moers, Cyril; Leuvenink, Henri; Møller, Bjarne; Ploeg, Rutger J; Baan, Carla C; Jespersen, Bente; Hoogduijn, Martin J

    2017-08-15

    There is great demand for transplant kidneys for the treatment of end-stage kidney disease patients. To expand the donor pool, organs from older and comorbid brain death donors, so-called expanded criteria donors (ECD), as well as donation after circulatory death donors, are considered for transplantation. However, the quality of these organs may be inferior to standard donor organs. A major issue affecting graft function and survival is ischemia/reperfusion injury, which particularly affects kidneys from deceased donors. The development of hypothermic machine perfusion has been introduced in kidney transplantation as a preservation technique and has improved outcomes in ECD and marginal organs compared to static cold storage. Normothermic machine perfusion (NMP) is the most recent evolution of perfusion technology and allows assessment of the donor organ before transplantation. The possibility to control the content of the perfusion fluid offers opportunities for damage control and reparative therapies during machine perfusion. Mesenchymal stromal cells (MSC) have been demonstrated to possess potent regenerative properties via the release of paracrine effectors. The combination of NMP and MSC administration at the same time is a promising procedure in the field of transplantation. Therefore, the MePEP consortium has been created to study this novel modality of treatment in preparation for human trials. MePEP aims to assess the therapeutic effects of MSC administered ex vivo by NMP in the mechanisms of injury and repair in a porcine kidney autotransplantation model.

  18. 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.

  19. Liver perfusion imaging in patients with primary and metastatic liver malignancy: prospective comparison between 99mTc-MAA spect and dynamic CT perfusion.

    PubMed

    Reiner, Caecilia S; Goetti, Robert; Burger, Irene A; Fischer, Michael A; Frauenfelder, Thomas; Knuth, Alexander; Pfammatter, Thomas; Schaefer, Niklaus; Alkadhi, Hatem

    2012-05-01

    To prospectively analyze the correlation between parameters of liver perfusion from technetium99m-macroaggregates of albumin (99mTc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy. Twenty-five consecutive patients (11 women, 14 men; mean age 60.9 ± 10.8; range: 32-78 years) with primary (n = 5) or metastatic (n = 20) liver malignancy planned to undergo selective internal radiotherapy underwent dynamic contrast-enhanced CT liver perfusion imaging (four-dimensional spiral mode, scan range 14.8 cm, 15 scans, cycle time 3 seconds) and 99m)Tc-MAA SPECT after intraarterial injection of 180 MBq 99mTc-MAA on the same day. Data were evaluated by two blinded and independent readers for the parameters arterial liver perfusion (ALP), portal venous perfusion (PVP), and total liver perfusion (TLP) from CT, and the 99mTc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT. Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90-0.98, each P < .01) and 99mTc -MAA SPECT (r = 0.91, P < .01). Significant correlation was found between 99mTc-MAA uptake ratio and ALP (r = 0.7, P < .01) in liver tumors. No significant correlation was found between 99mTc-MAA uptake ratio, PVP (r = -0.381, P = .081), and TLP (r = 0.039, P = .862). This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the 99mTc-MAA uptake ratio obtained by SPECT. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

  20. Variability and Reproducibility of 3rd-generation dual-source dynamic volume perfusion CT Parameters in Comparison to MR-perfusion Parameters in Rectal Cancer.

    PubMed

    Sudarski, Sonja; Henzler, Thomas; Floss, Teresa; Gaa, Tanja; Meyer, Mathias; Haubenreisser, Holger; Schoenberg, Stefan O; Attenberger, Ulrike I

    2018-05-02

    To compare in patients with untreated rectal cancer quantitative perfusion parameters calculated from 3 rd -generation dual-source dynamic volume perfusion CT (dVPCT) with 3-Tesla-MR-perfusion with regard to data variability and tumour differentiation. In MR-perfusion, plasma flow (PF), plasma volume (PV) and mean transit time (MTT) were assessed in two measurements (M1 and M2) by the same reader. In dVPCT, blood flow (BF), blood volume (BV), MTT and permeability (PERM) were assessed respectively. CT dose values were calculated. 20 patients (60 ± 13 years) were analysed. Intra-individual and intra-reader variability of duplicate MR-perfusion measurements was higher compared to duplicate dVPCT measurements. dVPCT-derived BF, BV and PERM could differentiate between tumour and normal rectal wall (significance level for M1 and M2, respectively, regarding BF: p < 0.0001*/0.0001*; BV: p < 0.0001*/0.0001*; MTT: p = 0.93/0.39; PERM: p < 0.0001*/0.0001*), with MR-perfusion this was true for PF and PV (p-values M1/M2 for PF: p = 0.04*/0.01*; PV: p = 0.002*/0.003*; MTT: p = 0.70/0.27*). Mean effective dose of CT-staging incl. dVPCT was 29 ± 6 mSv (20 ± 5 mSv for dVPCT alone). In conclusion, dVPCT has a lower data variability than MR-perfusion while both dVPCT and MR-perfusion could differentiate tumour tissue from normal rectal wall. With 3 rd -generation dual-source CT dVPCT could be included in a standard CT-staging without exceeding national dose reference values.

  1. Arterial Spin Labeling: a one-stop-shop for measurement of brain perfusion in the clinical settings.

    PubMed

    Golay, Xavier; Petersen, Esben T; Zimine, Ivan; Lim, Tchoyoson C C

    2007-01-01

    Arterial Spin Labeling (ASL) has opened a unique window into the human brain function and perfusion physiology. Altogether fast and of intrinsic high spatial resolution, ASL is a technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience for the follow-up of small perfusion changes occurring during brain activation. However, due to limited signal-to-noise ratio and complex flow kinetics, ASL is one of the more challenging disciplines within magnetic resonance imaging. In this paper, the theoretical background and main implementations of ASL are revisited. In particular, the different uses of ASL, the pitfalls and possibilities are described and illustrated using clinical cases.

  2. Myocardial perfusion imaging: Lessons learned and work to be done-update.

    PubMed

    Iskandrian, Ami E; Dilsizian, Vasken; Garcia, Ernest V; Beanlands, Rob S; Cerqueira, Manuel; Soman, Prem; Berman, Daniel S; Cuocolo, Alberto; Einstein, Andrew J; Morgan, Charity J; Hage, Fadi G; Schelbert, Heinrich R; Bax, Jeroen J; Wu, Joseph C; Shaw, Leslee J; Sadeghi, Mehran M; Tamaki, Nagara; Kaufmann, Philipp A; Gropler, Robert; Dorbala, Sharmila; Van Decker, William

    2018-02-01

    As the second term of our commitment to Journal begins, we, the editors, would like to reflect on a few topics that have relevance today. These include prognostication and paradigm shifts; Serial testing: How to handle data? Is the change in perfusion predictive of outcome and which one? Ischemia-guided therapy: fractional flow reserve vs perfusion vs myocardial blood flow; positron emission tomography (PET) imaging using Rubidium-82 vs N-13 ammonia vs F-18 Flurpiridaz; How to differentiate microvascular disease from 3-vessel disease by PET? The imaging scene outside the United States, what are the differences and similarities? Radiation exposure; Special issues with the new cameras? Is attenuation correction needed? Are there normal databases and are these specific to each camera system? And finally, hybrid imaging with single-photon emission tomography or PET combined with computed tomography angiography or coronary calcium score. We hope these topics are of interest to our readers.

  3. Silk screen based dual spin-filter module for perfusion culture of adherent and non-adherent mammalian cells.

    PubMed

    Kamthan, Shweta; Gomes, James; Roychoudhury, Pradip K

    2014-08-01

    Spin-filters have been primarily used for producing therapeutic proteins from mammalian cells. However, disposability and/or high filter clogging of the existing spin-filter systems affect the process economy and productivity. Hence, to address these drawbacks a reusable dual spin-filter module for perfusion culture of adherent and non-adherent mammalian cells was designed. Two non-woven Bombyx mori silk layers were used as filter screen; the outer layer was conducive to cell attachment whilst the inner was non-conducive. Adherent cells can be cultured either in suspended mode using its inner single module or as monolayer of cells using its dual concentric module. We achieved 30 % higher urokinase productivity as compared to the stainless-steel spin-filter during perfusion experiments of adherent human kidney cells in suspended mode. This was due to the hydrophobic and negatively-charged silk screen that allows clog-free perfusion culture for prolonged periods.

  4. 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

  5. Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.

    PubMed

    Koike, Terumoto; Yeung, Jonathan C; Cypel, Marcelo; Rubacha, Matthew; Matsuda, Yasushi; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Keshavjee, Shaf

    2011-12-01

    Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Positron emission tomography to assess hypoxia and perfusion in lung cancer

    PubMed Central

    Verwer, Eline E; Boellaard, Ronald; van der Veldt, Astrid AM

    2014-01-01

    In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed. PMID:25493221

  7. A non-linear regression method for CT brain perfusion analysis

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  8. Feasibility of high-resolution quantitative perfusion analysis in patients with heart failure.

    PubMed

    Sammut, Eva; Zarinabad, Niloufar; Wesolowski, Roman; Morton, Geraint; Chen, Zhong; Sohal, Manav; Carr-White, Gerry; Razavi, Reza; Chiribiri, Amedeo

    2015-02-12

    Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF. A group of 58 patients with heart failure (HF; left ventricular ejection fraction, LVEF ≤ 50%) and 33 patients with normal LVEF (LVEF >50%), referred for suspected coronary artery disease, were studied. All subjects underwent quantitative first-pass stress perfusion imaging using adenosine according to standard acquisition protocols. The feasibility of quantitative perfusion analysis was then assessed using high-resolution, 3 T kt perfusion and voxel-wise Fermi deconvolution. 30/58 (52%) subjects in the HF group had underlying ischaemic aetiology. Perfusion abnormalities were seen amongst patients with ischaemic HF and patients with normal LV function. No regional perfusion defect was observed in the non-ischaemic HF group. Good agreement was found between visual and quantitative analysis across all groups. Absolute stress perfusion rate, myocardial perfusion reserve (MPR) and endocardial-epicardial MPR ratio identified areas with abnormal perfusion in the ischaemic HF group (p = 0.02; p = 0.04; p = 0.02, respectively). In the Normal LV group, MPR and endocardial-epicardial MPR ratio were able to distinguish between normal and abnormal segments (p = 0.04; p = 0.02 respectively). No significant differences of absolute stress perfusion rate or MPR were observed comparing visually normal segments amongst groups. Our results demonstrate the feasibility of high-resolution voxel-wise perfusion assessment in patients with HF.

  9. Ex vivo lung perfusion: a comprehensive review of the development and exploration of future trends.

    PubMed

    Roman, Marius A; Nair, Sukumaran; Tsui, Steven; Dunning, John; Parmar, Jasvir S

    2013-09-01

    There is a critical mismatch between the number of donor lungs available and the demand for lungs for transplantation. This has created unacceptably high waiting-list mortality for lung transplant recipients. Currently (2012) in the United Kingdom, there are 216 patients on the lung transplant waiting list and 17 on heart and lung transplant list. The waiting times for suitable lungs average 412 days, with an increasing mortality and morbidity among the patients on the lung transplant list. Ex vivo lung perfusion (EVLP) has emerged as a technique for the assessment, resuscitation, and potential repair of suboptimal donor lungs. This is a rapidly developing field with significant clinical implications. In this review article, we critically appraise the background developments that have led to our current clinical practice. In particular, we focus on the human and animal experience, the different perfusion-ventilation strategies, and the impact of different perfusates and leukocyte filters. Finally, we examine EVLP as a potential research tool. This will provide insight into EVLP and its future development in the field of clinical lung transplantation.

  10. Correlation between acoustic radiation force impulse (ARFI)-based tissue elasticity measurements and perfusion parameters acquired by perfusion CT in cirrhotic livers: a proof of principle.

    PubMed

    Esser, Michael; Bitzer, Michael; Kolb, Manuel; Fritz, Jan; Kurucay, Mustafa; Ruff, Christer; Horger, Marius

    2018-06-13

    To investigate whether liver stiffness measured by acoustic radiation force impulse (ARFI) sonoelastography always correlates with the liver perfusion parameters quantified by perfusion CT in patients with known liver cirrhosis. Sonoelastography and perfusion CT were performed in 50 patients (mean age 65.5; range 45-87 years) with liver cirrhosis, who were classified according to Child-Pugh into class A (30/50, 60%), B (17/50, 34%), and C (3/50, 6%). For standardized ARFI measurements in the left liver lobe at a depth of 4 cm, a convex 6-MHz probe was used. CT examinations were performed using 80 kV, 100 mAs, and 50 ml of iodinated contrast agent injected at 5 ml/s. Using standardized region-of-interest measurements, we quantified arterial, portal venous, and total liver perfusion. There was a significant linear correlation between tissue stiffness and arterial liver perfusion (p = 0.015), and also when limiting the analysis to patients with histology (p = 0.019). In addition, there was a positive correlation between the total blood supply (arterial + portal-venous liver perfusion) to the liver and tissue stiffness (p = 0.001; with histology, p = 0.027). Shear wave velocity increased with higher Child-Pugh stages (p = 0.013). The degree of tissue stiffness in cirrhotic livers correlates expectedly-even if only moderately-with the magnitude of arterial liver perfusion and total liver perfusion. As such, liver elastography remains the leading imaging tool in assessing liver fibrosis.

  11. Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI.

    PubMed

    Bauman, Grzegorz; Puderbach, Michael; Deimling, Michael; Jellus, Vladimir; Chefd'hotel, Christophe; Dinkel, Julien; Hintze, Christian; Kauczor, Hans-Ulrich; Schad, Lothar R

    2009-09-01

    Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow-up of pulmonary diseases. In this work a new method of non-contrast-enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion- and ventilation-weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non-contrast-enhanced perfusion and ventilation data.

  12. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... take a ventilation and perfusion scan and then evaluate it with a chest x-ray. All parts ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  13. Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance.

    PubMed

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

    2018-05-01

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

  14. Estimation of the minimum permeability coefficient in rats for perfusion-limited tissue distribution in whole-body physiologically-based pharmacokinetics.

    PubMed

    Jeong, Yoo-Seong; Yim, Chang-Soon; Ryu, Heon-Min; Noh, Chi-Kyoung; Song, Yoo-Kyung; Chung, Suk-Jae

    2017-06-01

    The objective of the current study was to determine the minimum permeability coefficient, P, needed for perfusion-limited distribution in PBPK. Two expanded kinetic models, containing both permeability and perfusion terms for the rate of tissue distribution, were considered: The resulting equations could be simplified to perfusion-limited distribution depending on tissue permeability. Integration plot analyses were carried out with theophylline in 11 typical tissues to determine their apparent distributional clearances and the model-dependent permeabilities of the tissues. Effective surface areas were calculated for 11 tissues from the tissue permeabilities of theophylline and its PAMPA P. Tissue permeabilities of other drugs were then estimated from their PAMPA P and the effective surface area of the tissues. The differences between the observed and predicted concentrations, as expressed by the sum of squared log differences with the present models were at least comparable to or less than the values obtained using the traditional perfusion-limited distribution model for 24 compounds with diverse PAMPA P values. These observations suggest that the use of a combination of the proposed models, PAMPA P and the effective surface area can be used to reasonably predict the pharmacokinetics of 22 out of 24 model compounds, and is potentially applicable to calculating the kinetics for other drugs. Assuming that the fractional distribution parameter of 80% of the perfusion rate is a reasonable threshold for perfusion-limited distribution in PBPK, our theoretical prediction indicates that the pharmacokinetics of drugs having an apparent PAMPA P of 1×10 -6 cm/s or more will follow the traditional perfusion-limited distribution in PBPK for major tissues in the body. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

    PubMed

    Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

    2016-02-01

    The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

  16. Simultaneous acquisition of perfusion image and dynamic MR angiography using time‐encoded pseudo‐continuous ASL

    PubMed Central

    Helle, Michael; Koken, Peter; Van Cauteren, Marc; van Osch, Matthias J. P.

    2017-01-01

    Purpose Both dynamic magnetic resonance angiography (4D‐MRA) and perfusion imaging can be acquired by using arterial spin labeling (ASL). While 4D‐MRA highlights large vessel pathology, such as stenosis or collateral blood flow patterns, perfusion imaging provides information on the microvascular status. Therefore, a complete picture of the cerebral hemodynamic condition could be obtained by combining the two techniques. Here, we propose a novel technique for simultaneous acquisition of 4D‐MRA and perfusion imaging using time‐encoded pseudo‐continuous arterial spin labeling. Methods The time‐encoded pseudo‐continuous arterial spin labeling module consisted of a first subbolus that was optimized for perfusion imaging by using a labeling duration of 1800 ms, whereas the other six subboli of 130 ms were used for encoding the passage of the labeled spins through the arterial system for 4D‐MRA acquisition. After the entire labeling module, a multishot 3D turbo‐field echo‐planar‐imaging readout was executed for the 4D‐MRA acquisition, immediately followed by a single‐shot, multislice echo‐planar‐imaging readout for perfusion imaging. The optimal excitation flip angle for the 3D turbo‐field echo‐planar‐imaging readout was investigated by evaluating the image quality of the 4D‐MRA and perfusion images as well as the accuracy of the estimated cerebral blood flow values. Results When using 36 excitation radiofrequency pulses with flip angles of 5 or 7.5°, the saturation effects of the 3D turbo‐field echo‐planar‐imaging readout on the perfusion images were relatively moderate and after correction, there were no statistically significant differences between the obtained cerebral blood flow values and those from traditional time‐encoded pseudo‐continuous arterial spin labeling. Conclusions This study demonstrated that simultaneous acquisition of 4D‐MRA and perfusion images can be achieved by using time‐encoded pseudo

  17. Right Ventricular Perfusion: Physiology and Clinical Implications.

    PubMed

    Crystal, George J; Pagel, Paul S

    2018-01-01

    Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular

  18. Blood perfusion construction for infrared face recognition based on bio-heat transfer.

    PubMed

    Xie, Zhihua; Liu, Guodong

    2014-01-01

    To improve the performance of infrared face recognition for time-lapse data, a new construction of blood perfusion is proposed based on bio-heat transfer. Firstly, by quantifying the blood perfusion based on Pennes equation, the thermal information is converted into blood perfusion rate, which is stable facial biological feature of face image. Then, the separability discriminant criterion in Discrete Cosine Transform (DCT) domain is applied to extract the discriminative features of blood perfusion information. Experimental results demonstrate that the features of blood perfusion are more concentrative and discriminative for recognition than those of thermal information. The infrared face recognition based on the proposed blood perfusion is robust and can achieve better recognition performance compared with other state-of-the-art approaches.

  19. Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement.

    PubMed

    Tanaka, Akiko; Estrera, Anthony L

    2018-01-01

    Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field-and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution.

  20. Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement

    PubMed Central

    Tanaka, Akiko

    2018-01-01

    Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field—and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution. PMID:29682460

  1. CT perfusion imaging of the liver and the spleen in patients with cirrhosis: Is there a correlation between perfusion and portal venous hypertension?

    PubMed

    Talakić, Emina; Schaffellner, Silvia; Kniepeiss, Daniela; Mueller, Helmut; Stauber, Rudolf; Quehenberger, Franz; Schoellnast, Helmut

    2017-10-01

    To correlate hepatic and splenic CT perfusion parameters with hepatic venous pressure gradient (HVPG) measurements in patients with cirrhosis. Twenty-one patients with cirrhosis (males, 17; females, 4; mean ± SD age, 57 ± 7 years) underwent hepatic and splenic perfusion CT on a 320-detector row volume scanner as well as invasive measurement of HVPG. Different CT perfusion algorithms (maximum slope analysis and Patlak plot) were used to measure hepatic arterial flow (HAF), portal venous flow (PVF), hepatic perfusion index (HPI), splenic arterial flow (SAF), splenic blood volume (SBV) and splenic clearance (SCL). Hepatic and splenic perfusion parameters were correlated with HVPG, and sensitivity and specificity for detection of severe portal hypertension (≥12 mmHg) were calculated. The Spearman correlation coefficient was -0.53 (p < 0.05) between SAF and HVPG, and -0.68 (p < 0.01) between HVPG and SCL. Using a cut-off value of 125 ml/min/100 ml for SCL, sensitivity for detection of a HVPG of ≥12 mmHg was 94%, and specificity 100%. There was no significant correlation between hepatic perfusion parameters and HVPG. CT perfusion in patients with cirrhosis showed a strong correlation between SCL and HVPG and may be used for detection of severe portal hypertension. • SAF and SCL are statistically significantly correlated with HVPG • SCL showed stronger correlation with HVPG than SAF • 125 ml/min/100 ml SCL-cut-off yielded 94 % sensitivity, 100 % specificity for severe PH • HAF, PVF and HPI showed no statistically significant correlation with HVPG.

  2. High-frequency Electrocardiogram Analysis in the Ability to Predict Reversible Perfusion Defects during Adenosine Myocardial Perfusion Imaging

    NASA Technical Reports Server (NTRS)

    Tragardh, Elin; Schlegel, Todd T.; Carlsson, Marcus; Pettersson, Jonas; Nilsson, Klas; Pahlm, Olle

    2007-01-01

    Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

  3. Split Bregman multicoil accelerated reconstruction technique: A new framework for rapid reconstruction of cardiac perfusion MRI

    PubMed Central

    Kamesh Iyer, Srikant; Tasdizen, Tolga; Likhite, Devavrat; DiBella, Edward

    2016-01-01

    Purpose: Rapid reconstruction of undersampled multicoil MRI data with iterative constrained reconstruction method is a challenge. The authors sought to develop a new substitution based variable splitting algorithm for faster reconstruction of multicoil cardiac perfusion MRI data. Methods: The new method, split Bregman multicoil accelerated reconstruction technique (SMART), uses a combination of split Bregman based variable splitting and iterative reweighting techniques to achieve fast convergence. Total variation constraints are used along the spatial and temporal dimensions. The method is tested on nine ECG-gated dog perfusion datasets, acquired with a 30-ray golden ratio radial sampling pattern and ten ungated human perfusion datasets, acquired with a 24-ray golden ratio radial sampling pattern. Image quality and reconstruction speed are evaluated and compared to a gradient descent (GD) implementation and to multicoil k-t SLR, a reconstruction technique that uses a combination of sparsity and low rank constraints. Results: Comparisons based on blur metric and visual inspection showed that SMART images had lower blur and better texture as compared to the GD implementation. On average, the GD based images had an ∼18% higher blur metric as compared to SMART images. Reconstruction of dynamic contrast enhanced (DCE) cardiac perfusion images using the SMART method was ∼6 times faster than standard gradient descent methods. k-t SLR and SMART produced images with comparable image quality, though SMART was ∼6.8 times faster than k-t SLR. Conclusions: The SMART method is a promising approach to reconstruct good quality multicoil images from undersampled DCE cardiac perfusion data rapidly. PMID:27036592

  4. 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.

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

    PubMed Central

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

    2015-01-01

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

  6. Tumoricidal responses in spontaneous canine neoplasms after extracorporeal perfusion over immobilized protein A.

    PubMed

    Terman, D S

    1981-01-01

    I describe morphologic, histologic, immunohistochemical, and serologic changes in dogs with spontaneous breast adenocarcinoma, squamous cell carcinoma, hemangiopericytoma, and fibrosarcoma after extracorporeal perfusion of plasma over heat-killed and formalin-stabilized Staphylococcus aureus Cowans I (SAC), which was embedded in a membrane filtration system. In 12 dogs with breast adenocarcinoma, tumor necrosis was observed within 12 hours after perfusion; 24 hours after perfusion, multiple visible lesions in 6 of 6 dogs exhibited necrosis, but there was no reaction in uninvolved normal mammary tissue. In 8 dogs, healing of large ulcerated areas of cutaneous tumor was observed within 8 to 18 days after perfusion. Similar tumoricidal responses were observed in dogs with other neoplasms after SAC perfusion. Tumor cell necrosis oserved within 4 hours after extracorporeal perfusion was associated with immunohistochemical deposits of IgG and C'3 and ultrastructural evidence of lytic lesions on tumor cell membranes. No tumoricidal effects were observed after perfusion over Staphylococcus aureus Woods (SAW) (non-protein A bearing) in 3 dogs that previously or subsequently responded to SAC perfusion. No tumoricidal reactions were noted after phlebotomy of up to 50% of plasma volume in 6 tumor-bearing dogs that subsequently responded to SAC perfusion. SAC but not SAW perfusion was followed by increases in circulating tumor associated antibodies (TAA) for up to 48 hours after perfusion. Immune complexes increased after perfusion and remained elevated fo 72 hours. Findings suggest that the acute tumoricial responses are not due to mere removal of circulating immune reactants and may be initiated by TAA that are rendered operational after extracorporeal perfusion over SAC. The rapidity, specificity, and magnitude of the observed tumoricidal effects in various canine neoplastic diseases suggests that this may have potentially broad-based therapeutic and biologic implications

  7. Measurement of Choroidal Perfusion and Thickness Following Systemic Sildenafil (Viagra®)

    PubMed Central

    Kim, David Y.; Silverman, Ronald H.; Chan, R.V. Paul; Khanifar, Aziz A.; Rondeau, Mark; Lloyd, Harriet; Schlegel, Peter; Coleman, D. Jackson

    2011-01-01

    Objective To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (ViagraR) using enhanced depth imaging spectral domain-optical coherence tomography (EDI-OCT) and swept-scan high frequency digital ultrasound. Methods Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and two hours after ingesting 50 mg of sildenafil. Swept-scan high frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyze differences in choroidal flow and thickness at baseline and two hours after ingestion of sildenafil. Results Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47 to 7.80 times baseline (p=0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea, and 10.7% underneath the fovea (p<0.001 for all values). Conclusions Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms, and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow. PMID:22974308

  8. 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. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Neonatal repair of right interrupted aortic arch with cerebro-myocardial perfusion technique.

    PubMed

    Takeuchi, Koh; Masuzawa, Akihiro; Kobayashi, Jotaro; Tsuchiya, Keiji

    2011-10-01

    Right interrupted aortic arch and descending aorta is exceedingly rare and most likely cause respiratory presentation, since patent ductus arteriosus (PDA) courses over the right mainstem bronchus. We report a case of successful neonatal biventricular repair of a right interrupted aortic arch (type B), with an aberrant right subclavian artery ventricular septal defect (VSD) in a 2.7 kg term neonate with DiGeorge syndrome. Patient presented in severe respiratory distress and acidosis at one day old. Two-dimensional (2D) echocardiography revealed aortic arch interruption beyond the common carotid arteries with large perimembranous outlet VSD. Aortic annulus diameter was 4.8 mm and there was no left ventricle (LV) outflow tract obstruction. Three-dimensional (3D) CT-scan confirmed these findings and identified a right-sided ductal arch that continued over the right mainstem bronchus into a right-sided descending aorta and aberrant right subclavian artery. Brachiocephalic perfusion and ductal perfusion was employed for cooling during cardiopulmonary bypass. Under deep hypothermia (27 °C rectal temperature), selective cerebro-myocardial perfusion was used for successful aortic arch repair without sacrificing the aberrant right subclavian artery. A direct tension-free anastomosis was attained. Her postoperative course was uneventful and her respiratory symptoms disappeared postoperatively. Early surgical correction is mandatory for these patients with unique anatomy and presentation.

  10. [Intratympanic corticosteroid perfusion in the therapy of Meniere's disease].

    PubMed

    Sanković-Babić, Snezana; Kosanović, Rade; Ivanković, Zoran; Babac, Snezana; Tatović, Milica

    2014-01-01

    Over the last two decades the intratympanic perfusion of corticosteroids has been used as a minimally invasive surgical therapy of Meniere's disease. According to experimental studies the antiinflammatory, immunoprotective, antioxidant and neuroprotective role of the locally perfused corticosteroids was noticed in the inner ear structures. The recovery of action potentials in the cells of the Corti organ was confirmed as well as a decreased expression of aquaporine-1, a glycoprotein responsible for labyrinth hydrops and N and K ions derangement. The study showed results of intratympanic perfusion therapy with dexamethasone in patients with retractable Meniere's disease who are resistant to conservative treatment. Single doses of 4 mg/ml dexamethasone were given intratympanically in 19 patients with retractable Meniere's disease. Six single successive doses of dexamethasone were administered in the posteroinferior quadrant of the tympanic membrane. Follow-up of the patients was conducted by using a clinical questionnaire a month after completed perfusion series as well as on every third month up to one year. One month after completed first course of perfusions, in 78% of patients, vertigo problems completely ceased or were markedly reduced. The recovery of hearing function was recorded in 68% and marked tinnitus reduction in 84% of patients. After a year of follow-up, in 63% of patients the reduction of vertigo persisted, while hearing function was satisfactory in 52%. Tinitus reduction was present in 73% of patients. Intratympanic perfusion of dexamethasone in patients with Meniere's disease is a minimally invasive therapeutic method that contributes to the reduction of the intensity of vertigo recurrent attacks, decrease of the intensity of tinnitus and improvement of the average hearing threshold. Patients with chronic diseases and Meniere's disease who are contraindicted for systemic administration of cortocosteroids (hypertension, diabetes, glaucoma, peptic

  11. Three-dimensional co-culture of human hepatocytes and mesenchymal stem cells: improved functionality in long-term bioreactor cultures.

    PubMed

    Rebelo, Sofia P; Costa, Rita; Silva, Marta M; Marcelino, Paulo; Brito, Catarina; Alves, Paula M

    2017-07-01

    The development of human cell models that can efficiently restore hepatic functionality and cope with the reproducibility and scalability required for preclinical development poses a significant effort in tissue engineering and biotechnology. Primary cultures of human hepatocytes (HHs), the preferred model for in vitro toxicity testing, dedifferentiate and have short-term viability in two-dimensional (2D) cultures. In this study, hepatocytes isolated from human liver tissue were co-cultured with human bone marrow mesenchymal stem cells (BM-MSCs) as spheroids in automated, computer-controlled, stirred-tank bioreactors with perfusion operation mode. A dual-step inoculation strategy was used, resulting in an inner core of parenchymal liver tissue with an outer layer of stromal cells. Hepatocyte polarization and morphology as well as the mesenchymal phenotype of BM-MSCs were maintained throughout the culture period and the crosstalk between the two cell types was depicted. The viability, compact morphology and phenotypic stability of hepatocytes were enhanced in co-cultures in comparison to monocultures. Gene expression of phase I and II enzymes was higher and CYP3A4 and CYP1A2 activity was inducible until week 2 of culture, being applicable for repeated-dose toxicity testing. Moreover, the excretory activity was maintained in co-cultures and the biosynthetic hepatocellular functions (albumin and urea secretion) were not affected by the presence of BM-MSCs. This strategy might be extended to other hepatic cell sources and the characterization performed brings knowledge on the interplay between the two cell types, which may be relevant for therapeutic applications. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. 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

  13. Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

    PubMed Central

    Qi, Qi; Yeung, Timothy Pok Chi; Lee, Ting-Yim; Bauman, Glenn; Crukley, Cathie; Morrison, Laura; Hoffman, Lisa; Yartsev, Slav

    2016-01-01

    Background Tumor hypoxia is associated with treatment resistance to cancer therapies. Hypoxia can be investigated by immunohistopathologic methods but such procedure is invasive. A non-invasive method to interrogate tumor hypoxia is an attractive option as such method can provide information before, during, and after treatment for personalized therapies. Our study evaluated the correlations between computed tomography (CT) perfusion parameters and immunohistopathologic measurement of tumor hypoxia. Methods Wistar rats, 18 controls and 19 treated with stereotactic radiosurgery (SRS), implanted with the C6 glioma tumor were imaged using CT perfusion on average every five days to monitor tumor growth. A final CT perfusion scan and the brain were obtained on average 14 days (8–22 days) after tumor implantation. Tumor hypoxia was detected immunohistopathologically with pimonidazole. The tumor, necrotic, and pimonidazole-positive areas on histology samples were measured. Percent necrotic area and percent hypoxic areas were calculated. Tumor volume (TV), blood flow (BF), blood volume (BV), and permeability-surface area product (PS) were obtained from the CT perfusion studies. Correlations between CT perfusion parameters and histological parameters were assessed by Spearman’s ρ correlation. A Bonferroni-corrected P value < 0.05 was considered significant. Results BF and BV showed significant correlations with percent hypoxic area ρ = -0.88, P < 0.001 and ρ = -0.81, P < 0.001, respectively, for control animals and ρ = -0.7, P < 0.001 and ρ = -0.6, P = 0.003, respectively, for all animals, while TV and BV were correlated (ρ = -0.64, P = 0.01 and ρ = -0.43, P = 0.043, respectively) with percent necrotic area. PS was not correlated with either percent necrotic or percent hypoxic areas. Conclusions Percent hypoxic area provided significant correlations with BF and BV, suggesting that CT perfusion parameters are potential non-invasive imaging biomarkers of tumor

  14. Going skin deep: A direct comparison of penetration potential of lipid-based nanovesicles on the isolated perfused human skin flap model.

    PubMed

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

    2017-12-01

    Phospholipid-based nanocarriers are attractive drug carriers for improved local skin therapy. In the present study, the recently developed isolated perfused human skin flap (IPHSF) model was used to directly compare the skin penetration enhancing potential of the three commonly used nanocarriers, namely conventional liposomes (CLs), deformable liposomes (DLs) and solid lipid nanoparticles (SLNs). Two fluorescent markers, calcein (hydrophilic) or rhodamine (lipophilic), were incorporated individually in the three nanosystems. The nanocarrier size ranged between 200 and 300nm; the surface charge and entrapment efficiency for both markers were dependent on the lipid composition and the employed surfactant. Both carrier-associated markers could not penetrate the full thickness human skin, confirming their suitability for dermal drug delivery. CLs exhibited higher retention of both markers on the skin surface compared to DLs and SLNs, indicating a depo formation. DLs and SLNs enabled the deeper penetration of the two markers into the skin layers. In vitro and ex vivo skin penetration studies performed on the cellophane membrane and full thickness pig/human skin, respectively, confirmed the findings. In conclusion, efficient dermal drug delivery can be achieved by optimization of a lipid nanocarrier on the suitable skin-mimicking model to assure system's accumulation in the targeted skin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Tissue-Negative Transient Ischemic Attack: Is There a Role for Perfusion MRI?

    PubMed

    Grams, Raymond W; Kidwell, Chelsea S; Doshi, Amish H; Drake, Kendra; Becker, Jennifer; Coull, Bruce M; Nael, Kambiz

    2016-07-01

    Approximately 60% of patients with a clinical transient ischemic attack (TIA) do not have DWI evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of perfusion MRI in the evaluation of patients with TIA who have normal DWI findings. The inclusion criteria for this retrospective study were clinical presentation of TIA at admission with a discharge diagnosis of TIA confirmed by a stroke neurologist, MRI including both DWI and perfusion-weighted imaging within 48 hours of symptom onset, and no DWI lesion. Cerebral blood flow (CBF) and time to maximum of the residue function (Tmax) maps were evaluated independently by two observers. Multivariate analysis was used to assess perfusion findings; clinical variables; age, blood pressure, clinical symptoms, diabetes (ABCD2) score; duration of TIA; and time between MRI and onset and resolution of symptoms. Fifty-two patients (33 women, 19 men; age range, 20-95 years) met the inclusion criteria. A regional perfusion abnormality was identified on either Tmax or CBF maps of 12 of 52 (23%) patients. Seven (58%) of the patients with perfusion abnormalities had hypoperfused lesions best detected on Tmax maps; the other five had hyperperfusion best detected on CBF maps. In 11 of 12 (92%) patients with abnormal perfusion MRI findings, the regional perfusion deficit correlated with the initial neurologic deficits. Multivariable analysis revealed no significant difference in demographics, ABCD2 scores, or presentation characteristics between patients with and those without perfusion abnormalities. Perfusion MRI that includes Tmax and CBF parametric maps adds diagnostic value by depicting regions with delayed perfusion or postischemic hyperperfusion in approximately one-fourth of TIA patients who have normal DWI findings.

  16. Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

    PubMed

    Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

    2011-03-01

    There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

  17. Intrauterine insemination versus fallopian tube sperm perfusion in non-tubal infertility

    PubMed Central

    Shekhawat, G.S.

    2012-01-01

    Background Controlled ovarian hyperstimulation (COH) combined with intrauterine insemination (IUI), using a volume of 0.5 ml of inseminate is commonly offered to couples with non-tubal sub fertility. Another method is Fallopian tube sperm perfusion (FSP) which is based on a pressure injection of 4 ml of sperm suspension while attempting to seal the cervix to prevent semen reflux. This technique ensures the presence of higher sperm density in the fallopian tubes at the time of ovulation than standard IUI. The aim of this study was to compare the efficiency of standard intrauterine insemination (IUI) and Fallopian tube sperm perfusion (FSP) in the treatment of non-tubal infertility. Methods 200 consecutive patients with infertility in 404 stimulated cycles were included in the study. Those randomized to standard IUI included 100 patients in 184 cycles [158 clomiphene citrate/human menopausal gonadotrophin cycles and 26 Letrozole/FSH cycles exclusively for polycystic ovarian disease patients] (group A). Patients subjected to FSP included 100 patients in 220 cycles (193 clomiphene citrate/human menopausal gonadotrophin cycles and 27 Letrozole/FSH cycles exclusively for polycystic ovarian disease patients] (group B). Swim up semen preparation technique was used in all cases. Insemination was performed in both groups 34–37 h after hCG administration. Standard IUI was performed using 0.5 ml of inseminate. In FSP 4 ml inseminate was used. Results In group A (184 IUI cycles in 100 patients), 22 clinical pregnancies (presence of gestational sac with fetal cardiac activity) occurred (11.95% per cycle over four cycles). In group B, (220 cycles of FSP in 100 patients), 48 clinical pregnancies occurred (21.81% per cycle over four cycles) and this difference was statistically significant (p < 0.05). Conclusions For non-tubal sub fertility, the results indicate clear benefit for FSP (Fallopian tube sperm perfusion) over IUI (Intrauterine insemination). PMID:24532873

  18. A semi-automated volumetric software for segmentation and perfusion parameter quantification of brain tumors using 320-row multidetector computed tomography: a validation study.

    PubMed

    Chae, Soo Young; Suh, Sangil; Ryoo, Inseon; Park, Arim; Noh, Kyoung Jin; Shim, Hackjoon; Seol, Hae Young

    2017-05-01

    We developed a semi-automated volumetric software, NPerfusion, to segment brain tumors and quantify perfusion parameters on whole-brain CT perfusion (WBCTP) images. The purpose of this study was to assess the feasibility of the software and to validate its performance compared with manual segmentation. Twenty-nine patients with pathologically proven brain tumors who underwent preoperative WBCTP between August 2012 and February 2015 were included. Three perfusion parameters, arterial flow (AF), equivalent blood volume (EBV), and Patlak flow (PF, which is a measure of permeability of capillaries), of brain tumors were generated by a commercial software and then quantified volumetrically by NPerfusion, which also semi-automatically segmented tumor boundaries. The quantification was validated by comparison with that of manual segmentation in terms of the concordance correlation coefficient and Bland-Altman analysis. With NPerfusion, we successfully performed segmentation and quantified whole volumetric perfusion parameters of all 29 brain tumors that showed consistent perfusion trends with previous studies. The validation of the perfusion parameter quantification exhibited almost perfect agreement with manual segmentation, with Lin concordance correlation coefficients (ρ c ) for AF, EBV, and PF of 0.9988, 0.9994, and 0.9976, respectively. On Bland-Altman analysis, most differences between this software and manual segmentation on the commercial software were within the limit of agreement. NPerfusion successfully performs segmentation of brain tumors and calculates perfusion parameters of brain tumors. We validated this semi-automated segmentation software by comparing it with manual segmentation. NPerfusion can be used to calculate volumetric perfusion parameters of brain tumors from WBCTP.

  19. Fully quantitative pixel-wise analysis of cardiovascular magnetic resonance perfusion improves discrimination of dark rim artifact from perfusion defects associated with epicardial coronary stenosis.

    PubMed

    Ta, Allison D; Hsu, Li-Yueh; Conn, Hannah M; Winkler, Susanne; Greve, Anders M; Shanbhag, Sujata M; Chen, Marcus Y; Patricia Bandettini, W; Arai, Andrew E

    2018-03-08

    Dark rim artifacts in first-pass cardiovascular magnetic resonance (CMR) perfusion images can mimic perfusion defects and affect diagnostic accuracy for coronary artery disease (CAD). We evaluated whether quantitative myocardial blood flow (MBF) can differentiate dark rim artifacts from true perfusion defects in CMR perfusion. Regadenoson perfusion CMR was performed at 1.5 T in 76 patients. Significant CAD was defined by quantitative invasive coronary angiography (QCA) ≥ 50% diameter stenosis. Non-significant CAD (NonCAD) was defined as stenosis by QCA < 50% diameter stenosis or computed tomographic coronary angiography (CTA) < 30% in all major epicardial arteries. Dark rim artifacts had study specific and guideline-based definitions for comparison purposes. MBF was quantified at the pixel-level and sector-level. In a NonCAD subgroup with dark rim artifacts, stress MBF was lower in the subendocardial than midmyocardial and epicardial layers (2.17 ± 0.61 vs. 3.06 ± 0.75 vs. 3.24 ± 0.80 mL/min/g, both p < 0.001) and was also 30% lower than in remote regions (2.17 ± 0.61 vs. 2.83 ± 0.67 mL/min/g, p < 0.001). However, subendocardial stress MBF in dark rim artifacts was 37-56% higher than in true perfusion defects (2.17 ± 0.61 vs. 0.95 ± 0.43 mL/min/g, p < 0.001). Absolute stress MBF differentiated CAD from NonCAD with an accuracy ranging from 86 to 89% (all p < 0.001) using pixel-level analyses. Similar results were seen at a sector level. Quantitative stress MBF is lower in dark rim artifacts than remote myocardium but significantly higher than in true perfusion defects. If confirmed in larger series, this approach may aid the interpretation of clinical stress perfusion exams. ClinicalTrials.gov Identifier: NCT00027170 ; first posted 11/28/2001; updated 11/27/2017.

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

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

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

    2013-01-01

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

  1. Optimization of flow-sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain.

    PubMed

    Nasrallah, Fatima A; Lee, Eugene L Q; Chuang, Kai-Hsiang

    2012-11-01

    Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow-sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Experience with the first 50 ex vivo lung perfusions in clinical transplantation.

    PubMed

    Cypel, Marcelo; Yeung, Jonathan C; Machuca, Tiago; Chen, Manyin; Singer, Lianne G; Yasufuku, Kazuhiro; de Perrot, Marc; Pierre, Andrew; Waddell, Thomas K; Keshavjee, Shaf

    2012-11-01

    Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo lung perfusion. A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pao(2)/Fio(2) <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pao(2)/Fio(2) greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls). A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pao(2)/Fio(2) was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group (P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group (P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction (P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group (P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control

  3. Machine vs. human translation of SNOMED CT terms.

    PubMed

    Schulz, Stefan; Bernhardt-Melischnig, Johannes; Kreuzthaler, Markus; Daumke, Philipp; Boeker, Martin

    2013-01-01

    In the context of past and current SNOMED CT translation projects we compare three kinds of SNOMED CT translations from English to German by: (t1) professional medical translators; (t2) a free Web-based machine translation service; (t3) medical students. 500 SNOMED CT fully specified names from the (English) International release were randomly selected. Based on this, German translations t1, t2, and t3 were generated. A German and an Austrian physician rated the translations for linguistic correctness and content fidelity. Kappa for inter-rater reliability was 0.4 for linguistic correctness and 0.23 for content fidelity. Average ratings of linguistic correctness did not differ significantly between human translation scenarios. Content fidelity was rated slightly better for student translators compared to professional translators. Comparing machine to human translation, the linguistic correctness differed about 0.5 scale units in favour of the human translation and about 0.25 regarding content fidelity, equally in favour of the human translation. The results demonstrate that low-cost translation solutions of medical terms may produce surprisingly good results. Although we would not recommend low-cost translation for producing standardized preferred terms, this approach can be useful for creating additional language-specific entry terms. This may serve several important use cases. We also recommend testing this method to bootstrap a crowdsourcing process, by which term translations are gathered, improved, maintained, and rated by the user community.

  4. Influence of perfusate temperature on nasal potential difference.

    PubMed

    Bronsveld, Inez; Vermeulen, François; Sands, Dorotha; Leal, Teresinha; Leonard, Anissa; Melotti, Paola; Yaakov, Yasmin; de Nooijer, Roel; De Boeck, Kris; Sermet, Isabelle; Wilschanski, Michael; Middleton, Peter G

    2013-08-01

    Nasal potential difference (NPD) quantifies abnormal ion transport in cystic fibrosis. It has gained acceptance as an outcome measure for the investigation of new therapies. To quantify the effect of solution temperature on NPD, we first examined the effect of switching from room temperature (20-25°C) to warmed (32-37°C) solutions and vice versa during each perfusion step. Secondly, standard protocols were repeated at both temperatures in the same subjects. Changing solution temperature did not alter NPD during perfusion with Ringer's solution (<1 mV) (p>0.1). During perfusion with zero chloride solution, changing from room temperature to warmed solutions tended to decrease absolute NPD (i.e. it became less negative) by 0.9 mV (p>0.1); changing from warmed to room temperature increased NPD by 2.1 mV (p<0.05). During isoprenaline perfusion, changing from room temperature to warmed solutions increased NPD by 1.5 mV (p<0.01) and from warmed to room temperature decreased NPD by 1.4 mV (p<0.05). For full protocols at room temperature or warmed in the same subjects, mean values were similar (n = 24). During warmed perfusion, group results for total chloride response had a larger standard deviation. As this increased variability will probably decrease the power of trials, this study suggests that solutions at room temperature should be recommended for the measurement of NPD.

  5. Cell-controlled hybrid perfusion fed-batch CHO cell process provides significant productivity improvement over conventional fed-batch cultures.

    PubMed

    Hiller, Gregory W; Ovalle, Ana Maria; Gagnon, Matthew P; Curran, Meredith L; Wang, Wenge

    2017-07-01

    A simple method originally designed to control lactate accumulation in fed-batch cultures of Chinese Hamster Ovary (CHO) cells has been modified and extended to allow cells in culture to control their own rate of perfusion to precisely deliver nutritional requirements. The method allows for very fast expansion of cells to high density while using a minimal volume of concentrated perfusion medium. When the short-duration cell-controlled perfusion is performed in the production bioreactor and is immediately followed by a conventional fed-batch culture using highly concentrated feeds, the overall productivity of the culture is approximately doubled when compared with a highly optimized state-of-the-art fed-batch process. The technology was applied with near uniform success to five CHO cell processes producing five different humanized monoclonal antibodies. The increases in productivity were due to the increases in sustained viable cell densities. Biotechnol. Bioeng. 2017;114: 1438-1447. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

    PubMed

    Forman, Mervyn B; Jackson, Edwin K

    2007-11-01

    High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

  7. Low-Dose Dynamic Cerebral Perfusion Computed Tomography Reconstruction via Kronecker-Basis Representation Tensor Sparsity Regularization

    PubMed Central

    Zeng, Dong; Xie, Qi; Cao, Wenfei; Lin, Jiahui; Zhang, Hao; Zhang, Shanli; Huang, Jing; Bian, Zhaoying; Meng, Deyu; Xu, Zongben; Liang, Zhengrong; Chen, Wufan

    2017-01-01

    Dynamic cerebral perfusion computed tomography (DCPCT) has the ability to evaluate the hemodynamic information throughout the brain. However, due to multiple 3-D image volume acquisitions protocol, DCPCT scanning imposes high radiation dose on the patients with growing concerns. To address this issue, in this paper, based on the robust principal component analysis (RPCA, or equivalently the low-rank and sparsity decomposition) model and the DCPCT imaging procedure, we propose a new DCPCT image reconstruction algorithm to improve low dose DCPCT and perfusion maps quality via using a powerful measure, called Kronecker-basis-representation tensor sparsity regularization, for measuring low-rankness extent of a tensor. For simplicity, the first proposed model is termed tensor-based RPCA (T-RPCA). Specifically, the T-RPCA model views the DCPCT sequential images as a mixture of low-rank, sparse, and noise components to describe the maximum temporal coherence of spatial structure among phases in a tensor framework intrinsically. Moreover, the low-rank component corresponds to the “background” part with spatial–temporal correlations, e.g., static anatomical contribution, which is stationary over time about structure, and the sparse component represents the time-varying component with spatial–temporal continuity, e.g., dynamic perfusion enhanced information, which is approximately sparse over time. Furthermore, an improved nonlocal patch-based T-RPCA (NL-T-RPCA) model which describes the 3-D block groups of the “background” in a tensor is also proposed. The NL-T-RPCA model utilizes the intrinsic characteristics underlying the DCPCT images, i.e., nonlocal self-similarity and global correlation. Two efficient algorithms using alternating direction method of multipliers are developed to solve the proposed T-RPCA and NL-T-RPCA models, respectively. Extensive experiments with a digital brain perfusion phantom, preclinical monkey data, and clinical patient data clearly

  8. Diagnostic performance of dual-energy CT stress myocardial perfusion imaging: direct comparison with cardiovascular MRI.

    PubMed

    Ko, Sung Min; Song, Meong Gun; Chee, Hyun Kun; Hwang, Hweung Kon; Feuchtner, Gudrun Maria; Min, James K

    2014-12-01

    The purpose of this study was to assess the diagnostic performance of stress perfusion dual-energy CT (DECT) and its incremental value when used with coronary CT angiography (CTA) for identifying hemodynamically significant coronary artery disease. One hundred patients with suspected or known coronary artery disease without chronic myocardial infarction detected with coronary CTA underwent stress perfusion DECT, stress cardiovascular perfusion MRI, and invasive coronary angiography (ICA). Stress perfusion DECT and cardiovascular stress perfusion MR images were used for detecting perfusion defects. Coronary CTA and ICA were evaluated in the detection of ≥50% coronary stenosis. The diagnostic performance of coronary CTA for detecting hemo-dynamically significant stenosis was assessed before and after stress perfusion DECT on a per-vessel basis with ICA and cardiovascular stress perfusion MRI as the reference standard. The performance of stress perfusion DECT compared with cardiovascular stress perfusion MRI on a per-vessel basis in the detection of perfusion defects was sensitivity, 89%; specificity, 74%; positive predictive value, 73%; negative predictive value, 90%. Per segment, these values were sensitivity, 76%; specificity, 80%; positive predictive value, 63%; and negative predictive value, 88%. Compared with ICA and cardiovascular stress perfusion MRI per vessel territory the sensitivity, specificity, positive predictive value, and negative predictive value of coronary CTA were 95%, 61%, 61%, and 95%. The values for stress perfusion DECT were 92%, 72%, 68%, and 94%. The values for coronary CTA and stress perfusion DECT were 88%, 79%, 73%, and 91%. The ROC AUC increased from 0.78 to 0.84 (p=0.02) with the use of coronary CTA and stress perfusion DECT compared with coronary CTA alone. Stress perfusion DECT plays a complementary role in enhancing the accuracy of coronary CTA for identifying hemodynamically significant coronary stenosis.

  9. Lateral parapatellar and subvastus approaches are superior to the medial parapatellar approach in terms of soft tissue perfusion.

    PubMed

    Koçak, Aykut; Özmeriç, Ahmet; Koca, Gökhan; Senes, Mehmet; Yumuşak, Nihat; Iltar, Serkan; Korkmaz, Meliha; Alemdaroğlu, Kadir Bahadır

    2017-08-23

    The arthrotomy techniques of knee surgery may cause varying degrees of disruption to the tissue blood supply. The aim of this study was to investigate the effects of the medial parapatellar (MPPa), midvastus (MVa), subvastus (SVa) and lateral parapatellar (LPPa) approaches on regional tissue perfusion of the knee. In this experimental study, a total of 28 female rabbits were applied with four different arthrotomy techniques as Group MPPa, Group MVa, Group SVa and Group LPPa. The blood supply of the tissue around the knee was examined by scintigraphic imaging including the perfusion reserve and T max , and biochemical alteration of the oxidative stress parameters including malondialdehyde (MDA), fluorescent oxidation products (FlOPs), and histopathological findings were evaluated on tissue samples after 3 weeks. The perfusion reserve was increased in all four groups compared to the healthy, contralateral knees. In the Group LPPa, the vascularity was significantly increased compared to the Group MPPa (p = 0.006). In the examination of biochemical parameters, the increase in MDA levels was statistically significant in the Group MPPa compared with the Group LPPa (p = 0.004), and in the Group MVa compared with the Group LPPa (p = 0.006). The increase in the value of MDA levels was striking in the Group MPPa and Group MVa compared with the control group (p = 0.004, p = 0.004, respectively). The increase in another oxidative stress parameter, the tissue FlOPs levels, was statistically significant in the Group MPPa compared with the control group (p = 0.035). The LPPa and SVa caused less oxidative stress and less disruption of the muscle blood supply, in biochemical and scintigraphic parameters, compared to the MPPa and MVa. Therefore, in clinical practice, the SVa is preferable to the MPPa and MVa in total knee arthroplasty and the LPPa should be preferred more frequently in selected cases with critical soft tissue viability.

  10. Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

    PubMed Central

    Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

    2014-01-01

    Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

  11. Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

    PubMed Central

    de Moura, R; Lopes, M A

    1995-01-01

    1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669485

  12. Changes in canine cerebral perfusion after accelerated high frequency repetitive transcranial magnetic stimulation (HF-rTMS): A proof of concept study.

    PubMed

    Dockx, R; Baeken, C; Duprat, R; De Vos, F; Saunders, J H; Polis, I; Audenaert, K; Peremans, K

    2018-04-01

    Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for several neuropsychiatric disorders in human beings, but the neurobiological effects of rTMS in dogs have not been investigated to date. A proof of concept study was designed to evaluate the effect of rTMS on cerebral perfusion, measured with single photon emission computed tomography (SPECT), in dogs. An accelerated high frequency (aHF)-rTMS (20Hz) protocol was applied to the canine left frontal cortex. To accurately target this area, eight dogs underwent a 3 Tesla magnetic resonance imaging (MRI) scan before stimulation. The left frontal cortex was subjected to five consecutive aHF-rTMS sessions with a figure-of-eight coil designed for human beings at an intensity of 110% of the motor threshold. The dogs underwent 99m Tc-d,1 hexamethylpropylene amine oxime (HMPAO) SPECT scans 1 week prior to and 1day after the stimulations. Perfusion indices (PIs) were determined semi-quantitatively; aHF-rTMS resulted in significantly increased PIs in the left frontal cortex and the subcortical region, whereas no significant differences were noted for the other regions. Behaviour was not influenced by the stimulation sessions. As has been observed in human beings, aHF-rTMS applied to the left frontal cortex alters regional cerebral perfusion in dogs. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-06-16

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

  14. Does water-perfused catheter overdiagnose anismus compared to balloon probe?

    PubMed

    Savoye, G; Leroi, A M; Bertot-Sassigneux, P; Touchais, J Y; Devroede, G; Denis, P

    2002-12-01

    The purpose of this study was to compare the manometric assessment of straining effort as if to defecate and rectoanal inhibitory reflex obtained with a rectosphincteric balloon probe and with a water-perfused catheter in the same subject. Twelve healthy volunteers underwent two manometric assessments of anal sphincter function and electromyographic (EMG) surface recordings. one with a rectosphincteric balloon and one with a water-perfused catheter, 7 days apart in random order. Increased EMG activity in the external anal sphincter in the midst of the rectoanal inhibitory reflex (P < 0.001) and during straining for defecation (P < 0.001) was more frequently observed with the perfused system than with the balloon probe. There was a discrepancy between the EMG activity of the external anal sphincter and the anal pressures during straining recorded with the perfused system. Duration of the reflex elicited by rectal distension with 10 and 20 ml of air was significantly greater with the rectosphincteric balloon than with the perfused catheter (P = 0.02 and P = 0.05, respectively). Water instilled in the anal canal by the perfused system induces artifacts in EMG recording and active anal contractions. These artifacts and induced contractions could lead to an erroneous diagnosis of anismus, particularly if pelvic floor EMG is only taken into account for the diagnosis of anismus.

  15. Improvement of myocardial perfusion in coronary patients after intermittent hypobaric hypoxia.

    PubMed

    del Pilar Valle, Maria; García-Godos, Félix; Woolcott, Orison O; Marticorena, José M; Rodríguez, Víctor; Gutiérrez, Isabel; Fernández-Dávila, Luis; Contreras, Abel; Valdivia, Luis; Robles, Juan; Marticorena, Emilio A

    2006-01-01

    Persons living at high altitude (exposed to hypoxia) have a greater number of coronary and peripheral branches in the heart than persons living at sea level. In this study we investigated the effect of intermittent hypobaric hypoxia on myocardial perfusion in patients with coronary heart disease. We studied 6 male patients (aged>or=53 years) with severe stable coronary heart disease. All patients were born at sea level and lived in that environment. They underwent 14 sessions of exposure to intermittent hypobaric hypoxia (equivalent to a simulated altitude of 4200 m). Myocardial perfusion was assessed at baseline and after treatment with hypoxia by use of exercise perfusion imaging with technetium 99m sestamibi. After the sessions of hypoxia, myocardial perfusion was significantly improved. The summed stress score for hypoperfusion, in arbitrary units, decreased from 9.5+ to 4.5+ after treatment (P=.036). There was no evidence of impairment of myocardial perfusion in any patient after treatment. Intermittent hypobaric hypoxia improved myocardial perfusion in patients with severe coronary heart disease. Though preliminary, our results suggest that exposure to intermittent hypobaric hypoxia could be an alternative for the management of patients with chronic coronary heart disease.

  16. Organic anion transporter 4 (OAT 4) modifies placental transfer of perfluorinated alkyl acids PFOS and PFOA in human placental ex vivo perfusion system.

    PubMed

    Kummu, M; Sieppi, E; Koponen, J; Laatio, L; Vähäkangas, K; Kiviranta, H; Rautio, A; Myllynen, P

    2015-10-01

    Perfluorinated alkyl acids (PFAAs) are widely used in industry and consumer products. Pregnant women are exposed to PFAAs and their presence in umbilical cord blood represents fetal exposure. Interestingly, PFAAs are substrates for organic anion transporters (OAT) of which OAT4 is expressed in human placenta. To evaluate the contribution of OAT4 and ATP-binding cassette transporter G2 (ABCG2) proteins in the transplacental transfer of perfluoro octane sulfonate (PFOS) and perfluoro octanoate (PFOA) an ex vivo dual recirculating human placental perfusion was used. Altogether 8 placentas from healthy mothers with uncomplicated pregnancies were successfully perfused. Both PFOS and PFOA crossed the placenta as suggested by in vivo data in the literature. The expression of OAT4 and ABCG2 proteins were studied by immunoblotting and correlation with the transfer index %(TI %) of PFOS and PFOA at 120 and 240 min (n = 4) was studied. The expression of OAT4 was in negative correlation with TI % of PFOA (R(2) = 0.92, p = 0.043) and PFOS (R(2) = 0.99, p = 0.007) at 120 min while at 240 min the correlation was statistically significant only with PFOA. The expression of ABCG2 did not correlate with TI% of PFOS or PFOA. Data obtained in this study suggest the involvement of OAT4 in placental passage of PFAAs. Placental passage of PFOS and PFOA is modified by the transporter protein OAT4 but not by ABCG2. This is the first study indicating that OAT4 may decrease the fetal exposure to PFAAs and protect the fetus after maternal exposure to PFAAs but further studies are needed to confirm our findings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Vascularized osseous flaps and assessing their bipartate perfusion pattern via intraoperative fluorescence angiography.

    PubMed

    Valerio, Ian; Green, J Marshall; Sacks, Justin M; Thomas, Shane; Sabino, Jennifer; Acarturk, T Oguz

    2015-01-01

    Large segmental bone and composite tissue defects often require vascularized osseous flaps for definitive reconstruction. However, failed osseous flaps due to inadequate perfusion can lead to significant morbidity. Utilization of indocyanine green (ICG) fluorescence angiography has been previously shown to reliably assess soft tissue perfusion. Our group will outline the application of this useful intraoperative tool in evaluating the perfusion of vascularized osseous flaps. A retrospective review was performed to identify those osseous and/or osteocutaneous bone flaps, where ICG angiography was employed. Data analyzed included flap types, success and failure rates, and perfusion-related complications. All osseous flaps were evaluated by ICG angiography to confirm periosteal and endosteal perfusion. Overall 16 osseous free flaps utilizing intraoperative ICG angiography to assess vascularized osseous constructs were performed over a 3-year period. The flaps consisted of the following: nine osteocutaneous fibulas, two osseous-only fibulas, two scapular/parascapular with scapula bone, two quadricep-based muscle flaps, containing a vascularized femoral bone component, and one osteocutaneous fibula revision. All flap reconstructions were successful with the only perfusion-related complication being a case of delayed partial skin flap loss. Intraoperative fluorescence angiography is a useful adjunctive tool that can aid in flap design through angiosome mapping and can also assess flap perfusion, vascular pedicle flow, tissue perfusion before flap harvest, and flap perfusion after flap inset. Our group has successfully extended the application of this intraoperative tool to assess vascularized osseous flaps in an effort to reduce adverse outcomes related to preventable perfusion-related complications. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Foetal exposure to food and environmental carcinogens in human beings.

    PubMed

    Myöhänen, Kirsi; Vähäkangas, Kirsi

    2012-02-01

    Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  19. Progressive Cortical Neuronal Damage and Extracranial-Intracranial Bypass Surgery in Patients with Misery Perfusion.

    PubMed

    Yamauchi, H; Kagawa, S; Kishibe, Y; Takahashi, M; Higashi, T

    2017-05-01

    Misery perfusion may cause selective neuronal damage in atherosclerotic ICA or MCA disease. Bypass surgery can improve misery perfusion and may prevent neuronal damage. On the other hand, surgery conveys a risk for neuronal damage. The purpose of this retrospective study was to determine whether progression of cortical neuronal damage in surgically treated patients with misery perfusion is larger than that in surgically treated patients without misery perfusion or medically treated patients with misery perfusion. We evaluated the distribution of benzodiazepine receptors twice by using PET and 11 C-labeled flumazenil in 18 surgically treated patients with atherosclerotic ICA or MCA disease (9 with misery perfusion and 9 without) and no perioperative stroke before and after bypass surgery; in 8 medically treated patients with misery perfusion and no intervening ischemic event; and in 7 healthy controls. We quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the MCA distribution and compared changes in the benzodiazepine receptor index among the 3 groups. The change in the benzodiazepine receptor index in surgically treated patients with misery perfusion (27.5 ± 15.6) during 7 ± 5 months was significantly larger than that in surgically treated patients without misery perfusion (-5.2 ± 9.4) during 6 ± 4 months ( P < .001) and in medically treated patients with misery perfusion (3.2 ± 15.4) during 16 ± 6 months ( P < .01). Progression of cortical neuronal damage in surgically treated patients with misery perfusion and no perioperative stroke may occur and may be larger than that in medically treated patients with misery perfusion and no intervening ischemic event. © 2017 by American Journal of Neuroradiology.

  20. Cerebral misery perfusion due to carotid occlusive disease

    PubMed Central

    Maddula, Mohana; Sprigg, Nikola; Bath, Philip M; Munshi, Sunil

    2017-01-01

    Purpose Cerebral misery perfusion (CMP) is a condition where cerebral autoregulatory capacity is exhausted, and cerebral blood supply in insufficient to meet metabolic demand. We present an educational review of this important condition, which has a range of clinical manifestations. Method A non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease, using Pubmed and Sciencedirect. Findings Patients with CMP may present with strokes in watershed territories, collapses and transient ischaemic attacks or episodic movements associated with an orthostatic component. While positron emission tomography is the gold standard investigation for misery perfusion, advanced MRI is being increasingly used as an alternative investigation modality. The presence of CMP increases the risk of strokes. In addition to the devastating effect of stroke, there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease (COD) and misery perfusion. The evidence for revascularisation in the setting of complete carotid occlusion is weak. Medical management constitutes careful blood pressure management while addressing other vascular risk factors. Discussion The evidence for the management of patients with COD and CMP is discussed, together with recommendations based on our local experience. In this review, we focus on misery perfusion due to COD. Conclusion Patients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many specialties. Early identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow, while avoiding potentially harmful treatment. PMID:28959496

  1. The effects of whole ovarian perfusion and cryopreservation on endothelial cell-related gene expression in the ovarian medulla and pedicle.

    PubMed

    Onions, V J; Webb, R; Pincott-Allen, C; Picton, H M; Campbell, B K

    2013-04-01

    Fertility preservation by whole ovarian cryopreservation requires successful cryopreservation of both the ovary and its vascular supply. Previous work has indicated detrimental effects of both perfusion and cryopreservation on the ovarian vasculature. This study assessed the effects of blood perfusion, alone or in combination with cryopreservation, on functional effects in the follicle population and ovarian function in vivo following short-term autotransplantation of the tissue after vascular reanastomosis and measured acute changes in endothelial cell-related gene expression within the ovarian medulla and pedicle. Following autotransplantation for 7 days, primordial, transitional and primary follicle densities were significantly reduced (P < 0.05) and stromal Ki67 and caspase-3 expression significantly increased (P < 0.05) in cryopreserved but not fresh or perfused whole ovaries. There was evidence of clot formation and fluorescent microsphere (FMS) extravasation in the medulla of all cryopreserved ovaries, indicating vascular damage. Utilizing a customized RT-PCR array or conventional RT-PCR, we found that perfusion alone resulted in down-regulation in the expression of caspase 6 and thrombospondin 1 (THBS1) genes in the medulla. Following additional cryopreservation, endothelial nitric oxide synthase (eNOS), endothelin 1, endothelin receptor A and Bcl-2 expression were significantly (P < 0.05) down-regulated. In the pedicle, both perfusion and cryopreservation caused a (P < 0.05) down-regulation of eNOS and THBS1, and an up-regulation in Bax expression. Perfusion also caused a down-regulation of TNF and up-regulation of endothelin-2 expression (P < 0.05). In conclusion, this study has identified a number of endothelial cell-related genes expressed in the medulla which are acutely affected by both cryopreservation and perfusion, supporting the hypothesis that both interventions have deleterious effects on endothelial cell function.

  2. Imaging lung perfusion

    PubMed Central

    Wielpütz, Mark O.; Kauczor, Hans-Ulrich

    2012-01-01

    From the first measurements of the distribution of pulmonary blood flow using radioactive tracers by West and colleagues (J Clin Invest 40: 1–12, 1961) allowing gravitational differences in pulmonary blood flow to be described, the imaging of pulmonary blood flow has made considerable progress. The researcher employing modern imaging techniques now has the choice of several techniques, including magnetic resonance imaging (MRI), computerized tomography (CT), positron emission tomography (PET), and single photon emission computed tomography (SPECT). These techniques differ in several important ways: the resolution of the measurement, the type of contrast or tag used to image flow, and the amount of ionizing radiation associated with each measurement. In addition, the techniques vary in what is actually measured, whether it is capillary perfusion such as with PET and SPECT, or larger vessel information in addition to capillary perfusion such as with MRI and CT. Combined, these issues affect quantification and interpretation of data as well as the type of experiments possible using different techniques. The goal of this review is to give an overview of the techniques most commonly in use for physiological experiments along with the issues unique to each technique. PMID:22604884

  3. Patterns of postictal cerebral perfusion in idiopathic generalized epilepsy: a multi-delay multi-parametric arterial spin labelling perfusion MRI study.

    PubMed

    Chen, Guangxiang; Lei, Du; Ren, Jiechuan; Zuo, Panli; Suo, Xueling; Wang, Danny J J; Wang, Meiyun; Zhou, Dong; Gong, Qiyong

    2016-07-04

    The cerebral haemodynamic status of idiopathic generalized epilepsy (IGE) is a very complicated process. Little attention has been paid to cerebral blood flow (CBF) alterations in IGE detected by arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI). However, the selection of an optimal delay time is difficult for single-delay ASL. Multi-delay multi-parametric ASL perfusion MRI overcomes the limitations of single-delay ASL. We applied multi-delay multi-parametric ASL perfusion MRI to investigate the patterns of postictal cerebral perfusion in IGE patients with absence seizures. A total of 21 IGE patients with absence seizures and 24 healthy control subjects were enrolled. IGE patients exhibited prolonged arterial transit time (ATT) in the left superior temporal gyrus. The mean CBF of IGE patients was significantly increased in the left middle temporal gyrus, left parahippocampal gyrus and left fusiform gyrus. Prolonged ATT in the left superior temporal gyrus was negatively correlated with the age at onset in IGE patients. This study demonstrated that cortical dysfunction in the temporal lobe and fusiform gyrus may be related to epileptic activity in IGE patients with absence seizures. This information can play an important role in elucidating the pathophysiological mechanism of IGE from a cerebral haemodynamic perspective.

  4. 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.

  5. 21 CFR 876.5880 - Isolated kidney perfusion and transport system and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Isolated kidney perfusion and transport system and....5880 Isolated kidney perfusion and transport system and accessories. (a) Identification. An isolated kidney perfusion and transport system and accesssories is a device that is used to support a donated or a...

  6. 21 CFR 876.5880 - Isolated kidney perfusion and transport system and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Isolated kidney perfusion and transport system and....5880 Isolated kidney perfusion and transport system and accessories. (a) Identification. An isolated kidney perfusion and transport system and accesssories is a device that is used to support a donated or a...

  7. MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

    PubMed

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

    2012-01-01

    Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all

  8. Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion during deep hypothermic circulatory arrest in aortic surgery: a meta-analysis of 7023 patients.

    PubMed

    Guo, Shasha; Sun, Yanhua; Ji, Bingyang; Liu, Jinping; Wang, Guyan; Zheng, Zhe

    2015-04-01

    In aortic arch surgery, deep hypothermic circulatory arrest (DHCA) combined with cerebral perfusion is employed worldwide as a routine practice. Even though antegrade cerebral perfusion (ACP) is more widely used than retrograde cerebral perfusion (RCP), the difference in benefit and risk between ACP and RCP during DHCA is uncertain. The purpose of this meta-analysis is to compare neurologic outcomes and early mortality between ACP and RCP in patients who underwent aortic surgery during DHCA. PubMed, EMBASE, and the Cochrane Library were searched using the key words "antegrade," "retrograde," "cerebral perfusion," "cardiopulmonary bypass," "extracorporeal circulation," and "cardiac surgery" for studies reporting on clinical endpoints including early mortality, stroke, temporary neurologic dysfunction (TND), and permanent neurologic dysfunction (PND) in aortic surgery requiring DHCA with ACP or RCP. Heterogeneity was analyzed with the Cochrane Q statistic and I(2) statistic. Publication bias was tested with Begg's funnel plot and Egger's test. Thirty-four studies were included in this meta-analysis, with 4262 patients undergoing DHCA + ACP and 2761 undergoing DHCA + RCP. The overall pooled relative risk for TND was 0.722 (95% CI = [0.579, 0.900]), and the z-score for overall effect was 2.9 (P = 0.004). There was low heterogeneity (I(2) = 18.7%). The analysis showed that patients undergoing DHCA + ACP had better outcomes than those undergoing DHCA + RCP in terms of TND, while there were no significant differences between groups in terms of PND, stroke, and early mortality. This meta-analysis indicates that DHCA + ACP has an advantage over DHCA + RCP in terms of TND, while the two methods show similar results in terms of PND, early mortality, and stroke. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  9. 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. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. A study on cerebral hemodynamic analysis of moyamoya disease by using perfusion MRI

    NASA Astrophysics Data System (ADS)

    Dong, Kyung-Rae; Goo, Eun-Hoe; Lee, Jae-Seung; Chung, Woon-Kwan

    2013-10-01

    This study examined the clinical applications of perfusion magnetic resonance imaging (MRI) in patients with moyamoya disease (MMD). Twenty-two patients with moyamoya disease (9 men and 13 women) with a mean age of 9.3 years (range: 4-22 years) were enrolled in this study. Perfusion MRI was performed by scanning the patients7.5 cm upward from the base of the cerebellum before their being process for post-treatment. The scan led to the acquisition of the following four map images: the cerebral blood volume (CBV), the cerebral blood flow (CBF), the mean transit time (MTT) for the contrast medium, and the time to peak (TTP) for the contrast medium. The lesions were assessed using the CBV, the CBF, the MTT and the TTP maps of perfusion MRI; the MTT and the TTP were measured in the lesion areas, as well as in the normal and the symmetric areas. Perfusion defects were recognizable in all four perfusion MRI maps, and the MTT and the TTP showed a conspicuous delay in the parts where perfusion defects were recognized. The MTT and the TTP images of perfusion MRI reflected a significant correlation between the degrees of stenosis and occlusion in the posterior cerebral artery (PCA), as well as the development of collateral vessels. The four perfusion MRI maps could be used to predict the degrees of stenosis and occlusion in the posterior circulation, as well as the development of the collateral vessels, which enabled a hemodynamic evaluation of the parts with perfusion defects. Overall, perfusion MRI is useful for the diagnosis and the treatment of moyamoya disease and can be applied to clinical practice.

  11. Job Analysis and Student Assessment Tool: Perfusion Education Clinical Preceptor

    PubMed Central

    Riley, Jeffrey B.

    2007-01-01

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

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

    PubMed

    Riley, Jeffrey B

    2007-09-01

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

  13. Multiwell cell culture plate format with integrated microfluidic perfusion system

    NASA Astrophysics Data System (ADS)

    Domansky, Karel; Inman, Walker; Serdy, Jim; Griffith, Linda G.

    2006-01-01

    A new cell culture analog has been developed. It is based on the standard multiwell cell culture plate format but it provides perfused three-dimensional cell culture capability. The new capability is achieved by integrating microfluidic valves and pumps into the plate. The system provides a means to conduct high throughput assays for target validation and predictive toxicology in the drug discovery and development process. It can be also used for evaluation of long-term exposure to drugs or environmental agents or as a model to study viral hepatitis, cancer metastasis, and other diseases and pathological conditions.

  14. 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

  15. Feasibility of ASL spinal bone marrow perfusion imaging with optimized inversion time.

    PubMed

    Xing, Dong; Zha, Yunfei; Yan, Liyong; Wang, Kejun; Gong, Wei; Lin, Hui

    2015-11-01

    To assess the correlation between flow-sensitive alternating inversion recovery (FAIR) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the measurement of spinal bone marrow (SBM) perfusion; in addition, to assess for an optimized inversion time (TI) as well as the reproducibility of SBM FAIR perfusion. The optimized TI of a FAIR SBM perfusion experiment was carried out on 14 volunteers; two adjacent vertebral bodies were selected from each volunteer to measure the change of signal intensity (ΔM) and the signal-to-noise ratio (SNR) of FAIR perfusion MRI with five different TIs. Then, reproducibility of FAIR data from 10 volunteers was assessed by the reposition SBM FAIR experiments. Finally, FAIR and DCE-MRI were performed on 27 subjects. The correlation between the blood flow on FAIR (BFASL ) and perfusion-related parameters on DCE-MRI was evaluated. The maximum value of ΔM and SNR were 36.39 ± 12.53 and 2.38 ± 0.97, respectively; both were obtained when TI was near 1200 msec. There were no significant difference between the two successive measurements of SBM BFASL perfusion (P = 0.879), and the within-subject coefficients of variation (wCV) of the measurements was 3.28%. The BFASL showed a close correlation with K(trans) (P < 0.001) and Kep (P = 0.004), and no correlation with Ve (P = 0.082) was found. 1200 msec was the optimal TI for the SBM ASL perfusion image, which led to the maximum ΔM and a good quality perfusion image. The SBM FAIR perfusion scan protocol has good reproducibility, and as blood flow measurement on FAIR is reliable and closely related with the parameters on DCE-MRI, FAIR is feasible for measuring SBM blood flow. © 2015 Wiley Periodicals, Inc.

  16. Suppression of pulmonary vasculature in lung perfusion MRI using correlation analysis.

    PubMed

    Risse, Frank; Kuder, Tristan A; Kauczor, Hans-Ulrich; Semmler, Wolfhard; Fink, Christian

    2009-11-01

    The purpose of the study was to evaluate the feasibility of suppressing the pulmonary vasculature in lung perfusion MRI using cross-correlation analysis (CCA). Perfusion magnetic resonance imaging (MRI) (3D FLASH, TR/TE/flip angle: 0.8 ms/2.1 ms/40 degrees ) of the lungs was performed in seven healthy volunteers at 1.5 Tesla after injection of Gd-DTPA. CCA was performed pixel-wise in lung segmentations using the signal time-course of the main pulmonary artery and left atrium as references. Pixels with high correlation coefficients were considered as arterial or venous and excluded from further analysis. Quantitative perfusion parameters [pulmonary blood flow (PBF) and volume (PBV)] were calculated for manual lung segmentations separately, with the entire left and right lung with all intrapulmonary vessels (IPV) included, excluded manually or excluded using CCA. The application of CCA allowed reliable suppression of hilar and large IPVs. Using vascular suppression by CCA, perfusion parameters were significantly reduced (p perfusion in MRI. Overestimation of perfusion parameters caused by pulmonary vessels is significantly reduced.

  17. Cerebral perfusion imaging with bolus harmonic imaging (Honorable Mention Poster Award)

    NASA Astrophysics Data System (ADS)

    Kier, Christian; Toth, Daniel; Meyer-Wiethe, Karsten; Schindler, Angela; Cangur, Hakan; Seidel, Gunter; Aach, Til

    2005-04-01

    Fast visualisation of cerebral microcirculation supports diagnosis of acute stroke. However, the commonly used CT/MRI-based methods are time consuming, costly and not applicable to every patient. The bolus perfusion harmonic imaging (BHI) method is an ultrasound imaging technique which makes use of the fact, that ultrasound contrast agents unlike biological tissues resonate at harmonic frequencies. Exploiting this effect, the contrast between perfused and non-perfused areas can be improved. Thus, BHI overcomes the low signal-to-noise ratio of transcranial ultrasound and the high impedance of the skull. By analysing image sequences, visualising the qualitative characteristics of an US contrast agent bolus injection becomes possible. The analysis consists of calculating four perfusion-related parameters, Local Peak Intensity, Time To Peak, Area Under Curve, and Average Rising, from the time/intensity curve and providing them as colour-coded images. For calculating these parameters the fundamental assumption is that image intensity corresponds to contrast agent concentration which in turn shows the perfusion of the corresponding brain region. In a clinical study on patients suffering from acute ischemic stroke it is shown that some of the parameters correlate significantly to the infarction area. Thus, BHI becomes a less time-consuming and inexpensive bedside method for diagnosis of cerebral perfusion deficits.

  18. Pulsatile perfusion bioreactor for cardiac tissue engineering.

    PubMed

    Brown, Melissa A; Iyer, Rohin K; Radisic, Milica

    2008-01-01

    Cardiovascular disease is the number one cause of mortality in North America. Cardiac tissue engineering aims to engineer a contractile patch of physiological thickness to use in surgical repair of diseased heart tissue. We previously reported that perfusion of engineered cardiac constructs resulted in improved tissue assembly. Because heart tissues respond to mechanical stimuli in vitro and experience rhythmic mechanical forces during contraction in vivo, we hypothesized that provision of pulsatile interstitial medium flow to an engineered cardiac patch would result in enhanced tissue assembly by way of mechanical conditioning and improved mass transport. Thus, we constructed a novel perfusion bioreactor capable of providing pulsatile fluid flow at physiologically relevant shear stresses and flow rates. Pulsatile perfusion (PP) was achieved by incorporation of a normally closed solenoid pinch valve into the perfusion loop and was carried out at a frequency of 1 Hz and a flow rate of 1.50 mL/min (PP) or 0.32 mL/min (PP-LF). Nonpulsatile flow at 1.50 mL/min (NP) or 0.32 mL/min (NP-LF) served as controls. Static controls were cultivated in well plates. The main experimental groups were seeded with cells enriched for cardiomyocytes by one preplating step (64% cardiac Troponin I+, 34% prolyl-4-hydroxylase+), whereas pure cardiac fibroblasts and cells enriched for cardiomyocytes by two preplating steps (81% cardiac Troponin I+, 16% prolyl-4-hydroxylase+) served as controls. Cultivation under pulsatile flow had beneficial effects on contractile properties. Specifically, the excitation threshold was significantly lower in the PP condition (pulsatile perfusion at 1.50 mL/min) than in the Static control, and the contraction amplitude was the highest; whereas high maximum capture rate was observed for the PP-LF conditions (pulsatile perfusion at 0.32 mL/min). The enhanced hypertrophy index observed for the PP-LF group was consistent with the highest cellular length and

  19. Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

    PubMed

    Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

    2017-02-01

    Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

  20. Microfluidic perfusion culture system for multilayer artery tissue models.

    PubMed

    Yamagishi, Yuka; Masuda, Taisuke; Matsusaki, Michiya; Akashi, Mitsuru; Yokoyama, Utako; Arai, Fumihito

    2014-11-01

    We described an assembly technique and perfusion culture system for constructing artery tissue models. This technique differed from previous studies in that it does not require a solid biodegradable scaffold; therefore, using sheet-like tissues, this technique allowed the facile fabrication of tubular tissues can be used as model. The fabricated artery tissue models had a multilayer structure. The assembly technique and perfusion culture system were applicable to many different sizes of fabricated arteries. The shape of the fabricated artery tissue models was maintained by the perfusion culture system; furthermore, the system reproduced the in vivo environment and allowed mechanical stimulation of the arteries. The multilayer structure of the artery tissue model was observed using fluorescent dyes. The equivalent Young's modulus was measured by applying internal pressure to the multilayer tubular tissues. The aim of this study was to determine whether fabricated artery tissue models maintained their mechanical properties with developing. We demonstrated both the rapid fabrication of multilayer tubular tissues that can be used as model arteries and the measurement of their equivalent Young's modulus in a suitable perfusion culture environment.

  1. A highly printable and biocompatible hydrogel composite for direct printing of soft and perfusable vasculature-like structures.

    PubMed

    Suntornnond, Ratima; Tan, Edgar Yong Sheng; An, Jia; Chua, Chee Kai

    2017-12-04

    Vascularization is one major obstacle in bioprinting and tissue engineering. In order to create thick tissues or organs that can function like original body parts, the presence of a perfusable vascular system is essential. However, it is challenging to bioprint a hydrogel-based three-dimensional vasculature-like structure in a single step. In this paper, we report a new hydrogel-based composite that offers impressive printability, shape integrity, and biocompatibility for 3D bioprinting of a perfusable complex vasculature-like structure. The hydrogel composite can be used on a non-liquid platform and is printable at human body temperature. Moreover, the hydrogel composite supports both cell proliferation and cell differentiation. Our results represent a potentially new vascularization strategy for 3D bioprinting and tissue engineering.

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

    PubMed

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

    2013-11-01

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

  3. Modeling of nanotherapeutics delivery based on tumor perfusion

    PubMed Central

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

    2013-01-01

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

  4. 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.

  5. First-pass myocardial perfusion imaging with whole-heart coverage using L1-SPIRiT accelerated variable density spiral trajectories

    PubMed Central

    Yang, Yang; Kramer, Christopher M.; Shaw, Peter W.; Meyer, Craig H.; Salerno, Michael

    2015-01-01

    Purpose To design and evaluate 2D L1-SPIRiT accelerated spiral pulse sequences for first-pass myocardial perfusion imaging with whole heart coverage capable of measuring 8 slices at 2 mm in-plane resolution at heart rates up to 125 beats per minute (BPM). Methods Combinations of 5 different spiral trajectories and 4 k-t sampling patterns were retrospectively simulated in 25 fully sampled datasets and reconstructed with L1-SPIRiT to determine the best combination of parameters. Two candidate sequences were prospectively evaluated in 34 human subjects to assess in-vivo performance. Results A dual density broad transition spiral trajectory with either angularly uniform or golden angle in time k-t sampling pattern had the largest structural similarity (SSIM) and smallest root mean square error (RMSE) from the retrospective simulation, and the L1-SPIRiT reconstruction had well-preserved temporal dynamics. In vivo data demonstrated that both of the sampling patterns could produce high quality perfusion images with whole-heart coverage. Conclusion First-pass myocardial perfusion imaging using accelerated spirals with optimized trajectory and k-t sampling pattern can produce high quality 2D-perfusion images with wholeheart coverage at the heart rates up to 125 BPM. PMID:26538511

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-02-01

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

  8. Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

    PubMed

    Reitmeir, Raluca; Eyding, Jens; Oertel, Markus F; Wiest, Roland; Gralla, Jan; Fischer, Urs; Giquel, Pierre-Yves; Weber, Stefan; Raabe, Andreas; Mattle, Heinrich P; Z'Graggen, Werner J; Beck, Jürgen

    2017-04-01

    In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson's chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

  9. Repeatability of Bolus Kinetics Ultrasound Perfusion Imaging for the Quantification of Cerebral Blood Flow.

    PubMed

    Vinke, Elisabeth J; Eyding, Jens; de Korte, Chris L; Slump, Cornelis H; van der Hoeven, Johannes G; Hoedemaekers, Cornelia W E

    2017-12-01

    Ultrasound perfusion imaging (UPI) can be used for the quantification of cerebral perfusion. In a neuro-intensive care setting, repeated measurements are required to evaluate changes in cerebral perfusion and monitor therapy. The aim of this study was to determine the repeatability of UPI in quantification of cerebral perfusion. UPI measurement of cerebral perfusion was performed three times in healthy patients. The coefficients of variation of the three bolus injections were calculated for both time- and volume-derived perfusion parameters in the macro- and microcirculation. The UPI time-dependent parameters had overall the lowest CVs in both the macro- and microcirculation. The volume-related parameters had poorer repeatability, especially in the microcirculation. Both intra-observer variability and inter-observer variability were low. Although UPI is a promising tool for the bedside measurement of cerebral perfusion, improvement of the technique is required before implementation in routine clinical practice. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  10. 99mTc-ECD brain perfusion SPECT imaging for the assessment of brain perfusion in cerebral palsy (CP) patients with evaluation of the effect of hyperbaric oxygen therapy.

    PubMed

    Asl, Mina Taghizadeh; Yousefi, Farzaneh; Nemati, Reza; Assadi, Majid

    2015-01-01

    The present study was carried out to evaluate cerebral perfusion in different types of cerebral palsy (CP) patients. For those patients who underwent hyperbaric oxygen therapy, brain perfusion before and after the therapy was compared. A total of 11 CP patients were enrolled in this study, of which 4 patients underwent oxygen therapy. Before oxygen therapy and at the end of 40 sessions of oxygen treatment, 99mTc-ECD brain perfusion single photon emission computed tomography (SPECT) was performed , and the results were compared. A total of 11 CP patients, 7 females and 4 males with an age range of 5-27 years participated in the study. In brain SPECT studies, all the patients showed perfusion impairments. The region most significantly involved was the frontal lobe (54.54%), followed by the temporal lobe (27.27%), the occipital lobe (18.18%), the visual cortex (18.18%), the basal ganglia (9.09%), the parietal lobe (9.09%), and the cerebellum (9.09%). Frontal-lobe hypoperfusion was seen in all types of cerebral palsy. Two out of 4 patients (2 males and 2 females) who underwent oxygen therapy revealed certain degree of brain perfusion improvement. This study demonstrated decreased cerebral perfusion in different types of CP patients. The study also showed that hyperbaric oxygen therapy improved cerebral perfusion in a few CP patients. However, it could keep the physiological discussion open and strenghten a link with other areas of neurology in which this approach may have some value.

  11. ANTONIA perfusion and stroke. A software tool for the multi-purpose analysis of MR perfusion-weighted datasets and quantitative ischemic stroke assessment.

    PubMed

    Forkert, N D; Cheng, B; Kemmling, A; Thomalla, G; Fiehler, J

    2014-01-01

    The objective of this work is to present the software tool ANTONIA, which has been developed to facilitate a quantitative analysis of perfusion-weighted MRI (PWI) datasets in general as well as the subsequent multi-parametric analysis of additional datasets for the specific purpose of acute ischemic stroke patient dataset evaluation. Three different methods for the analysis of DSC or DCE PWI datasets are currently implemented in ANTONIA, which can be case-specifically selected based on the study protocol. These methods comprise a curve fitting method as well as a deconvolution-based and deconvolution-free method integrating a previously defined arterial input function. The perfusion analysis is extended for the purpose of acute ischemic stroke analysis by additional methods that enable an automatic atlas-based selection of the arterial input function, an analysis of the perfusion-diffusion and DWI-FLAIR mismatch as well as segmentation-based volumetric analyses. For reliability evaluation, the described software tool was used by two observers for quantitative analysis of 15 datasets from acute ischemic stroke patients to extract the acute lesion core volume, FLAIR ratio, perfusion-diffusion mismatch volume with manually as well as automatically selected arterial input functions, and follow-up lesion volume. The results of this evaluation revealed that the described software tool leads to highly reproducible results for all parameters if the automatic arterial input function selection method is used. Due to the broad selection of processing methods that are available in the software tool, ANTONIA is especially helpful to support image-based perfusion and acute ischemic stroke research projects.

  12. 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.

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

    PubMed

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

    2013-12-18

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

  14. Measuring Tissue Perfusion During Pressure Relief Maneuvers: Insights Into Preventing Pressure Ulcers

    PubMed Central

    Makhsous, Mohsen; Priebe, Michael; Bankard, James; Rowles, Diana; Zeigler, Mary; Chen, David; Lin, Fang

    2007-01-01

    Background/Objective: To study the effect on tissue perfusion of relieving interface pressure using standard wheelchair pushups compared with a mechanical automated dynamic pressure relief system. Design: Repeated measures in 2 protocols on 3 groups of subjects. Participants: Twenty individuals with motor-complete paraplegia below T4, 20 with motor-complete tetraplegia, and 20 able-bodied subjects. Methods: Two 1-hour sitting protocols: dynamic protocol, sitting configuration alternated every 10 minutes between a normal sitting configuration and an off-loading configuration; wheelchair pushup protocol, normal sitting configuration with standard wheelchair pushup once every 20 minutes. Main Outcome Measures: Transcutaneous partial pressures of oxygen and carbon dioxide measured from buttock overlying the ischial tuberosity and interface pressure measured at the seat back and buttocks. Perfusion deterioration and recovery times were calculated during changes in interface pressures. Results: In the off-loading configuration, concentrated interface pressure during the normal sitting configuration was significantly diminished, and tissue perfusion was significantly improved. Wheelchair pushups showed complete relief of interface pressure but incomplete recovery of tissue perfusion. Conclusions: Interface pressure analysis does not provide complete information about the effectiveness of pressure relief maneuvers. Measures of tissue perfusion may help establish more effective strategies. Relief achieved by standard wheelchair pushups may not be sufficient to recover tissue perfusion compromised during sitting; alternate maneuvers may be necessary. The dynamic seating system provided effective pressure relief with sustained reduction in interface pressure adequate for complete recovery of tissue perfusion. Differences in perfusion recovery times between subjects with spinal cord injury (SCI) and controls raise questions about the importance of changes in vascular responses

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

    PubMed Central

    Cano, I; Roca, J; Wagner, P D

    2015-01-01

    Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation–perfusion and skeletal muscle metabolism–perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake ( and on mitochondrial (). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial () at sea level by 32 mmHg, but muscle by only 122 ml min−1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced by less than 1 mmHg and by 32 ml min−1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential among muscle regions, a range that becomes narrower as increases, and in regions with a low ratio of metabolic capacity to blood flow, can exceed that of mixed muscle venous blood. For patients with severe COPD, peak was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known. PMID:25640017

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

    PubMed Central

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

    2016-01-01

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

  17. Differential physiologic effects of perfusion of scala tympani versus scala vestibuli in the ischemic cochlea.

    PubMed

    Kobayashi, T; Rokugo, M; Takasaka, T; Thalmann, R

    1993-07-01

    The effectiveness of perilymphatic perfusion with oxygenated artificial media upon the endocochlear potential (EP) was measured during systemic ischemia in the guinea pig. Differences in the effects of perfusion of the two perilymphatic scalae were determined. Perfusion of scala vestibuli with oxygenated artificial perilymph at a high flow rate resulted in complete recovery of the EP to the pre-ischemic level, whereas perfusion of scala tympani with the same medium was unable to effect complete recovery. The recovery obtained by perfusion of scala tympani was about half that obtained of scala vestibuli. The pO2 in scala media was measured during perfusion by means of oxygen-sensitive microelectrodes. perfusion of scala vestibuli led to an approximately two-fold higher pO2 in scala media than perfusion of scala tympani. During perfusion, the pO2 in scala media varied dependent upon depth of electrode insertion, with a gradient decreasing toward the stria vascularis, a direction opposite to that seen under normal metabolic conditions. These findings suggest that, in the ischemic cochlea, oxygen enters scala media more easily from scala vestibuli across Reissner's membrane than from scala tympani via the basilar membrane/organ of Corti complex.

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

    PubMed

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

    2012-08-01

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

  19. Towards Whole-Body Fluorescence Imaging in Humans

    PubMed Central

    Piper, Sophie K.; Habermehl, Christina; Schmitz, Christoph H.; Kuebler, Wolfgang M.; Obrig, Hellmuth; Steinbrink, Jens; Mehnert, Jan

    2013-01-01

    Dynamic near-infrared fluorescence (DNIF) whole-body imaging of small animals has become a popular tool in experimental biomedical research. In humans, however, the field of view has been limited to body parts, such as rheumatoid hands, diabetic feet or sentinel lymph nodes. Here we present a new whole-body DNIF-system suitable for adult subjects. We explored whether this system (i) allows dynamic whole-body fluorescence imaging and (ii) can detect modulations in skin perfusion. The non-specific fluorescent probe indocyanine green (ICG) was injected intravenously into two subjects, and fluorescence images were obtained at 5 Hz. The in- and out-flow kinetics of ICG have been shown to correlate with tissue perfusion. To validate the system, skin perfusion was modulated by warming and cooling distinct areas on the chest and the abdomen. Movies of fluorescence images show a bolus passage first in the face, then in the chest, abdomen and finally in the periphery (∼10, 15, 20 and 30 seconds, respectively). When skin perfusion is augmented by warming, bolus arrives about 5 seconds earlier than when the skin is cooled and perfusion decreased. Calculating bolus arrival times and spatial fitting of basis time courses extracted from different regions of interest allowed a mapping of local differences in subcutaneous skin perfusion. This experiment is the first to demonstrate the feasibility of whole-body dynamic fluorescence imaging in humans. Since the whole-body approach demonstrates sensitivity to circumscribed alterations in skinperfusion, it may be used to target autonomous changes in polyneuropathy and to screen for peripheral vascular diseases. PMID:24391820

  20. Acute baclofen diminishes resting baseline blood flow to limbic structures: A perfusion fMRI study

    PubMed Central

    Franklin, Teresa R.; Shin, Joshua; Jagannathan, Kanchana; Suh, Jesse J.; Detre, John A.; O’Brien, Charles P.; Childress, Anna Rose

    2012-01-01

    Background Preclinical and clinical evidence show that the GABA B agonist, baclofen is a promising treatment for addictive disorders; however, until recently its mechanism of action in the human brain was unknown. In previous work we utilized a laboratory model that included a medication versus placebo regimen to examine baclofen’s actions on brain circuitry. Perfusion fMRI [measure of cerebral blood flow (CBF)] data acquired ‘at rest’ before and on the last day of the 21-day medication regimen showed that baclofen diminished CBF bilaterally in the VS, insula and medial orbitofrontal cortex (mOFC). In the present study, we hypothesized that a single dose of baclofen would have effects similar to repeated dosing. Methods To test our hypothesis, in a crossover design, CBF data were acquired using pseudo continuous arterial spin labeled (pCASL) perfusion fMRI. Subjects were either un-medicated or were administered a 20 mg dose of baclofen approximately 110 min prior to scanning. Results Acute baclofen diminished mOFC, amygdala, and ventral anterior insula CBF without causing sedation (family-wise error corrected at p = 0.001). Conclusions Results demonstrate that similar to repeated dosing, an acute dose of baclofen blunts the ‘limbic’ substrate that is hyper-responsive to drugs and drug cues. Smokers often manage their craving and can remain abstinent for extended periods after quitting, however the risk of eventual relapse approaches 90%. Given that chronic medication may not be a practical solution to the long-term risk of relapse, acute baclofen may be useful on an ‘as-needed’ basis to block craving during ‘at risk’ situations. PMID:22513380

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

    PubMed

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

    2014-03-01

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

  2. Design and validation of a clinical-scale bioreactor for long-term isolated lung culture.

    PubMed

    Charest, Jonathan M; Okamoto, Tatsuya; Kitano, Kentaro; Yasuda, Atsushi; Gilpin, Sarah E; Mathisen, Douglas J; Ott, Harald C

    2015-06-01

    The primary treatment for end-stage lung disease is lung transplantation. However, donor organ shortage remains a major barrier for many patients. In recent years, techniques for maintaining lungs ex vivo for evaluation and short-term (<12 h) resuscitation have come into more widespread use in an attempt to expand the donor pool. In parallel, progress in whole organ engineering has provided the potential perspective of patient derived grafts grown on demand. As both of these strategies advance to more complex interventions for lung repair and regeneration, the need for a long-term organ culture system becomes apparent. Herein we describe a novel clinical scale bioreactor capable of maintaining functional porcine and human lungs for at least 72 h in isolated lung culture (ILC). The fully automated, computer controlled, sterile, closed circuit system enables physiologic pulsatile perfusion and negative pressure ventilation, while gas exchange function, and metabolism can be evaluated. Creation of this stable, biomimetic long-term culture environment will enable advanced interventions in both donor lungs and engineered grafts of human scale. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

    PubMed

    Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar

    2014-07-01

    We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Application of a Parallelizable Perfusion Bioreactor for Physiologic 3D Cell Culture.

    PubMed

    Egger, Dominik; Spitz, Sarah; Fischer, Monica; Handschuh, Stephan; Glösmann, Martin; Friemert, Benedikt; Egerbacher, Monika; Kasper, Cornelia

    2017-01-01

    It is crucial but challenging to keep physiologic conditions during the cultivation of 3D cell scaffold constructs for the optimization of 3D cell culture processes. Therefore, we demonstrate the benefits of a recently developed miniaturized perfusion bioreactor together with a specialized incubator system that allows for the cultivation of multiple samples while screening different conditions. Hence, a decellularized bone matrix was tested towards its suitability for 3D osteogenic differentiation under flow perfusion conditions. Subsequently, physiologic shear stress and hydrostatic pressure (HP) conditions were optimized for osteogenic differentiation of human mesenchymal stem cells (MSCs). X-ray computed microtomography and scanning electron microscopy (SEM) revealed a closed cell layer covering the entire matrix. Osteogenic differentiation assessed by alkaline phosphatase activity and SEM was found to be increased in all dynamic conditions. Furthermore, screening of different fluid shear stress (FSS) conditions revealed 1.5 mL/min (equivalent to ∼10 mPa shear stress) to be optimal. However, no distinct effect of HP compared to flow perfusion without HP on osteogenic differentiation was observed. Notably, throughout all experiments, cells cultivated under FSS or HP conditions displayed increased osteogenic differentiation, which underlines the importance of physiologic conditions. In conclusion, the bioreactor system was used for biomaterial testing and to develop and optimize a 3D cell culture process for the osteogenic differentiation of MSCs. Due to its versatility and higher throughput efficiency, we hypothesize that this bioreactor/incubator system will advance the development and optimization of a variety of 3D cell culture processes. © 2017 S. Karger AG, Basel.

  5. Flow cytometric cell cycle analysis of muscle precursor cells cultured within 3D scaffolds in a perfusion bioreactor.

    PubMed

    Flaibani, Marina; Luni, Camilla; Sbalchiero, Elisa; Elvassore, Nicola

    2009-01-01

    It has been widely demonstrated that perfusion bioreactors improve in vitro three-dimensional (3D) cultures in terms of high cell density and uniformity of cell distribution; however, the studies reported in literature were primarily based on qualitative analysis (histology, immunofluorescent staining) or on quantitative data averaged on the whole population (DNA assay, PCR). Studies on the behavior, in terms of cell cycle, of a cell population growing in 3D scaffolds in static or dynamic conditions are still absent. In this work, a perfusion bioreactor suitable to culture C(2)C(12) muscle precursor cells within 3D porous collagen scaffolds was designed and developed and a method based on flowcytometric analyses for analyzing the cell cycle in the cell population was established. Cells were extracted by enzymatic digestion of the collagen scaffolds after 4, 7, and 10 days of culture, and flow cytometric live/dead and cell cycle analyses were performed with Propidium Iodide. A live/dead assay was used for validating the method for cell extraction and staining. Moreover, to investigate spatial heterogeneity of the cell population under perfusion conditions, two stacked scaffolds in the 3D domain, of which only the upstream layer was seeded, were analyzed separately. All results were compared with those obtained from static 3D cultures. The live/dead assay revealed the presence of less than 20% of dead cells, which did not affect the cell cycle analysis. Cell cycle analyses highlighted the increment of cell fractions in proliferating phases (S/G(2)/M) owing to medium perfusion in long-term cultures. After 7-10 days, the percentage of proliferating cells was 8-12% for dynamic cultures and 3-5% for the static controls. A higher fraction of proliferating cells was detected in the downstream scaffold. From a general perspective, this method provided data with a small standard deviation and detected the differences between static and dynamic cultures and between upper and

  6. Contrast-enhanced CT- and MRI-based perfusion assessment for pulmonary diseases: basics and clinical applications

    PubMed Central

    Ohno, Yoshiharu; Koyama, Hisanobu; Lee, Ho Yun; Miura, Sachiko; Yoshikawa, Takeshi; Sugimura, Kazuro

    2016-01-01

    Assessment of regional pulmonary perfusion as well as nodule and tumor perfusions in various pulmonary diseases are currently performed by means of nuclear medicine studies requiring radioactive macroaggregates, dual-energy computed tomography (CT), and dynamic first-pass contrast-enhanced perfusion CT techniques and unenhanced and dynamic first-pass contrast enhanced perfusion magnetic resonance imaging (MRI), as well as time-resolved three-dimensional or four-dimensional contrast-enhanced magnetic resonance angiography (MRA). Perfusion scintigraphy, single-photon emission tomography (SPECT) and SPECT fused with CT have been established as clinically available scintigraphic methods; however, they are limited by perfusion information with poor spatial resolution and other shortcomings. Although positron emission tomography with 15O water can measure absolute pulmonary perfusion, it requires a cyclotron for generation of a tracer with an extremely short half-life (2 min), and can only be performed for academic purposes. Therefore, clinicians are concentrating their efforts on the application of CT-based and MRI-based quantitative and qualitative perfusion assessment to various pulmonary diseases. This review article covers 1) the basics of dual-energy CT and dynamic first-pass contrast-enhanced perfusion CT techniques, 2) the basics of time-resolved contrast-enhanced MRA and dynamic first-pass contrast-enhanced perfusion MRI, and 3) clinical applications of contrast-enhanced CT- and MRI-based perfusion assessment for patients with pulmonary nodule, lung cancer, and pulmonary vascular diseases. We believe that these new techniques can be useful in routine clinical practice for not only thoracic oncology patients, but also patients with different pulmonary vascular diseases. PMID:27523813

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

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

    Hoffman, J; Martin, T; Young, S

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

  8. Antibody and complement reduce renal hemodynamic function in isolated perfused rat kidney.

    PubMed

    Jocks, T; Zahner, G; Helmchen, U; Kneissler, U; Stahl, R A

    1996-01-01

    To evaluate the effect of antibody and complement on renal hemodynamic changes, glomerular injury was induced in isolated perfused kidneys by an anti-thymocyte antibody (ATS) and rat serum (RS). Glomerular filtration rate (GFR), renal vascular resistance (RVR), and renal perfusate flow (RPF) were assessed over an 80-min period. The possible role of thromboxane (Tx) was tested by the application of the Tx synthesis inhibitor UK-38485 and the Tx receptor blocker daltroban. Perfusion of kidneys with ATS and RS significantly reduced GFR at 10 min (control, 501 +/- 111; ATS + RS, 138 +/- 86 ml.g kidney-1.min-1, significance of F = 0.000) after RS. Similarly, RPF (ml.g kidney-1.min-1) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0 (significance of F = 0.000), whereas RVR (mmHg.ml-1.g.min) increased threefold from 5.2 +/- 0.4 to 17.9 +/- 5.0 at 10 min. These changes were ameliorated by the pretreatment of the rats with daltroban and UK-38485. Addition of erythrocytes to the perfusate increased RVR and GFR, whereas RPF decreased compared with cell-free perfused kidneys. ATS and RS in this preparation also decrease GFR and RPF. The hemodynamic alterations appeared without changes in filtration fraction. Compared with untreated, perfused control kidneys, glomerular Tx formation was significantly increased in ATS and RS perfused kidneys. These data demonstrate that antibody and RS induce impairment of renal hemodynamics, which are mediated by increased Tx formation.

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

    PubMed

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

    2014-08-01

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

  10. Metabolism of valine and 3-methyl-2-oxobutanoate by the isolated perfused rat kidney.

    PubMed Central

    Miller, R H; Harper, A E

    1984-01-01

    Metabolism of branched-chain amino and 2-oxo acids was studied in the isolated perfused kidney. Significant amounts of 2-oxo acids were released by perfused kidney with all concentrations of amino acids tested (0.1-1.0 mM each), despite the high activity of branched-chain 2-oxo acid dehydrogenase in kidney. As perfusate valine concentration was increased from 0.2 to 1.0 mM, [1-14C]valine transamination (2-oxo acid oxidized + released) increased roughly linearly; [1-14C]valine oxidation, however, increased exponentially. Increasing perfusate concentration of 3-methyl-2-oxo[1-14C]butanoate from 0 to 1.0 mM resulted in a linear increase in the rate of its oxidation and a rise in perfusate valine concentration; at the same time significant decreases occurred in perfusate isoleucine and leucine concentrations, with corresponding increases in rates of release of their respective 2-oxo acids. Comparison of rates of oxidation of [1-14C]valine and 3-methyl-2-oxo[1-14C]butanoate suggests that 2-oxo acid arising from [1-14C]valine transamination has freer access to the 2-oxo acid dehydrogenase than has the 2-oxo acid from the perfusate. The observations indicate that, when branched-chain amino and 2-oxo acids are present in perfusate at near-physiological concentrations, rates of transamination of the amino and 2-oxo acids by isolated perfused kidney are greater than rates of oxidation. PMID:6508752

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

    PubMed

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

    2009-12-01

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

  12. Ultrasonic contrast agents in transcranial perfusion sonography (TPS) for follow-up of patients with high grade gliomas.

    PubMed

    Ickenstein, G W; Valaikiene, J; Koch, H; Hau, P; Erban, P; Schlachetzki, F

    2008-04-01

    The aim of this study was to evaluate brain perfusion differences in patients with high grade gliomas after partial tumor resection and irradiation/chemotherapy between tumor and non-tumor hemisphere by transcranial perfusion sonography (TPS) employing a contrast burst imaging (CBI) technique. Six patients with glioblastoma (WHO Grade IV) in the temporoparietal region within the defined axial diencephalic scanning plane were examined by TPS during follow-up. All subjects had an adequate acoustic temporal bone window. Transtemporal insonation on brain tumor and non-tumor hemisphere was performed with a bolus-injection of sulphur hexafluoride-based contrast agent (10 mg i.v., 5mg/ml--SonoVue, Bracco, Altana, Switzerland). Recorded images were analysed off-line by Quanticon Software (3D-Echotech, Munich, Germany) and time intensity curve parameters [area under the curve (AUC, dB s), peak intensity (PI, dB), time to peak (TTP, s)] in five regions of interest (ROI) [thalamus anterior, thalamus posterior, nucleus lentiformis, white matter, whole hemisphere] were evaluated. Statistical analyses were performed. Perfusion differences between brain tumor and non-tumor hemispheres were detected with contrast burst imaging (CBI) technique with a significantly greater mean AUC (5343.69 dB s vs. 4625.04 dB s, p<0.028) and a significantly prolonged TTP (32.72 s vs. 28.91 s, p<0.046) in the tumor hemisphere. Within our study population, TTP and AUC seem to be the most robust parameters for the evaluation of cerebral perfusion differences assessed by transcranial perfusion sonography with CBI technique. We hypothesize that these results correlate with microvascular changes due to treatment regimens, such as microvessel necrosis after irradiation and chemotherapy. Above that, TPS may be of value for the long-term follow-up of brain tumor therapy concept.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    1998-11-01

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

  15. Indocyanine Green Fluorescence for Free-Flap Perfusion Imaging Revisited: Advanced Decision Making by Virtual Perfusion Reality in Visionsense Fusion Imaging Angiography.

    PubMed

    Bigdeli, Amir Khosrow; Gazyakan, Emre; Schmidt, Volker Juergen; Hernekamp, Frederick Jochen; Harhaus, Leila; Henzler, Thomas; Kremer, Thomas; Kneser, Ulrich; Hirche, Christoph

    2016-06-01

    Near-infrared indocyanine green video angiography (ICG-NIR-VA) has been introduced for free-flap surgery and may provide intraoperative flap designing as well as postoperative monitoring. Nevertheless, the technique has not been established in clinical routine because of controversy over benefits. Improved technical features of the novel Visionsense ICG-NIR-VA surgery system are promising to revisit the field of application. It features a unique real-time fusion image of simultaneous NIR and white light visualization, with highlighted perfusion, including a color-coded perfusion flow scale for optimized anatomical understanding. In a feasibility study, the Visionsense ICG-NIR-VA system was applied during 10 free-flap surgeries in 8 patients at our center. Indications included anterior lateral thigh (ALT) flap (n = 4), latissimus dorsi muscle flap (n = 1), tensor fascia latae flap (n = 1), and two bilateral deep inferior epigastric artery perforator flaps (n = 4). The system was used intraoperatively and postoperatively to investigate its impact on surgical decision making and to observe perfusion patterns correlated to clinical monitoring. Visionsense ICG-NIR-VA aided assessing free-flap design and perfusion patterns in all cases and correlated with clinical observations. Additional interventions were performed in 2 cases (22%). One venous anastomosis was revised, and 1 flap was redesigned. Indicated by ICG-NIR-VA, 1 ALT flap developed partial flap necrosis (11%). The Visionsense ICG-NIR-VA system allowed a virtual view of flap perfusion anatomy by fusion imaging in real-time. The system improved decision making for flap design and surgical decisions. Clinical and ICG-NIR-VA parameters correlated. Its future implementation may aid in improving outcomes for free-flap surgery, but additional experience is needed to define its final role. © The Author(s) 2015.

  16. The Future of the Perfusion Record: Automated Data Collection vs. Manual Recording

    PubMed Central

    Ottens, Jane; Baker, Robert A.; Newland, Richard F.; Mazzone, Annette

    2005-01-01

    Abstract: The perfusion record, whether manually recorded or computer generated, is a legal representation of the procedure. The handwritten perfusion record has been the most common method of recording events that occur during cardiopulmonary bypass. This record is of significant contrast to the integrated data management systems available that provide continuous collection of data automatically or by means of a few keystrokes. Additionally, an increasing number of monitoring devices are available to assist in the management of patients on bypass. These devices are becoming more complex and provide more data for the perfusionist to monitor and record. Most of the data from these can be downloaded automatically into online data management systems, allowing more time for the perfusionist to concentrate on the patient while simultaneously producing a more accurate record. In this prospective report, we compared 17 cases that were recorded using both manual and electronic data collection techniques. The perfusionist in charge of the case recorded the perfusion using the manual technique while a second perfusionist entered relevant events on the electronic record generated by the Stockert S3 Data Management System/Data Bahn (Munich, Germany). Analysis of the two types of perfusion records showed significant variations in the recorded information. Areas that showed the most inconsistency included measurement of the perfusion pressures, flow, blood temperatures, cardioplegia delivery details, and the recording of events, with the electronic record superior in the integrity of the data. In addition, the limitations of the electronic system were also shown by the lack of electronic gas flow data in our hardware. Our results confirm the importance of accurate methods of recording of perfusion events. The use of an automated system provides the opportunity to minimize transcription error and bias. This study highlights the limitation of spot recording of perfusion events in

  17. Fast analytical spectral filtering methods for magnetic resonance perfusion quantification.

    PubMed

    Reddy, Kasireddy V; Mitra, Abhishek; Yalavarthy, Phaneendra K

    2016-08-01

    The deconvolution in the perfusion weighted imaging (PWI) plays an important role in quantifying the MR perfusion parameters. The PWI application to stroke and brain tumor studies has become a standard clinical practice. The standard approach for this deconvolution is oscillatory-limited singular value decomposition (oSVD) and frequency domain deconvolution (FDD). The FDD is widely recognized as the fastest approach currently available for deconvolution of MR perfusion data. In this work, two fast deconvolution methods (namely analytical fourier filtering and analytical showalter spectral filtering) are proposed. Through systematic evaluation, the proposed methods are shown to be computationally efficient and quantitatively accurate compared to FDD and oSVD.

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

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

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

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

  19. Dynamic CT myocardial perfusion imaging: performance of 3D semi-automated evaluation software.

    PubMed

    Ebersberger, Ullrich; Marcus, Roy P; Schoepf, U Joseph; Lo, Gladys G; Wang, Yining; Blanke, Philipp; Geyer, Lucas L; Gray, J Cranston; McQuiston, Andrew D; Cho, Young Jun; Scheuering, Michael; Canstein, Christian; Nikolaou, Konstantin; Hoffmann, Ellen; Bamberg, Fabian

    2014-01-01

    To evaluate the performance of three-dimensional semi-automated evaluation software for the assessment of myocardial blood flow (MBF) and blood volume (MBV) at dynamic myocardial perfusion computed tomography (CT). Volume-based software relying on marginal space learning and probabilistic boosting tree-based contour fitting was applied to CT myocardial perfusion imaging data of 37 subjects. In addition, all image data were analysed manually and both approaches were compared with SPECT findings. Study endpoints included time of analysis and conventional measures of diagnostic accuracy. Of 592 analysable segments, 42 showed perfusion defects on SPECT. Average analysis times for the manual and software-based approaches were 49.1 ± 11.2 and 16.5 ± 3.7 min respectively (P < 0.01). There was strong agreement between the two measures of interest (MBF, ICC = 0.91, and MBV, ICC = 0.88, both P < 0.01) and no significant difference in MBF/MBV with respect to diagnostic accuracy between the two approaches for both MBF and MBV for manual versus software-based approach; respectively; all comparisons P > 0.05. Three-dimensional semi-automated evaluation of dynamic myocardial perfusion CT data provides similar measures and diagnostic accuracy to manual evaluation, albeit with substantially reduced analysis times. This capability may aid the integration of this test into clinical workflows. • Myocardial perfusion CT is attractive for comprehensive coronary heart disease assessment. • Traditional image analysis methods are cumbersome and time-consuming. • Automated 3D perfusion software shortens analysis times. • Automated 3D perfusion software increases standardisation of myocardial perfusion CT. • Automated, standardised analysis fosters myocardial perfusion CT integration into clinical practice.

  20. Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method

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

    Tao, Yinghua; Chen, Guang-Hong; Hacker, Timothy A.

    Purpose: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. Methods: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan wasmore » performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. Results: Forin vivo studies, the 500 mA FBP maps gave −88.4%, −96.0%, −76.7%, and −65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring −94.7%, −81.6%, −84.0%, and −72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, −11.8%, and −3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was −9.7%, 8.8%, −3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and

  1. Exercise thallium-201 perfusion scintigraphy in the assessment of coronary artery disease

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

    Mahmarian, J.J.; Verani, M.S.

    1991-05-21

    Exercise thallium-201 perfusion scintigraphy has been used extensively over the last decade for the detection and localization of coronary artery disease. Single-photon emission computed tomography (SPECT) is a refinement of presently available techniques, offering improved identification over planar imaging of individual vessel stenosis and quantification of the extent of abnormally perfused myocardium. In this review, the planar and SPECT techniques are discussed in light of the most recently published large patient series, and with regard to the many factors that affect the sensitivity and specificity of perfusion imaging in identifying coronary artery disease. The clinical implications of exercise perfusion scintigraphymore » and its future applications in cardiology practice are discussed.67 references.« less

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  3. Perfluorocarbon perfused vitrectomy: animal studies.

    PubMed

    Quiroz-Mercado, Hugo; Suarez-Tatá, Luis; Magdalenic, Rudi; Murillo-López, Sergio; García-Aguirre, Gerardo; Guerrero-Naranjo, Jose; Rodríguez-Reyes, Abelardo A

    2004-02-01

    To investigate the feasibility and advantages of using perfluorocarbon liquid (PCL) perfusion to remove vitreous during suction-cutting vitrectomy in rabbit and pig eyes. Experimental study. Balanced salt solution (BSS) was replaced by PCL perfusion during experimental vitrectomy. Oxygenated or nonoxygenated PCL was used in a recycling or a nonrecycling system. Recycling was achieved by two systems: a manual recycling system or a closed-loop system. The experiments in this study consisted of: an in vitro solubility observation, safety and feasibility of vitrectomy in rabbit eyes, effectiveness of vitrectomy with equal vitrectomy time in rabbit eyes, and retinal stability and pigment and blood dispersion in porcine eyes. Toxicity was assessed by a complete ophthalmic examination, endothelial cell count, electroretinography, and histopathology. Vitreous, blood, and pigments were immiscible in PCL. Manual recycling required less amounts of PCL than nonrecycling (15 vs 25 cc). Oxygenated and nonoxygenated PCL were not toxic. Perfluorocarbon liquid infusion removed more vitreous than balanced salt solution in a 3-minute vitrectomy time using the same settings on the vitrectomy machine. The PCL infusion in porcine eyes stabilized the retina and isolated vitreous cavity from pigment and blood and maintained a clear vitreous cavity. These data indicate that perfusion of PCL can be used to remove vitreous with a suction-cutting probe in rabbit and pig eyes. Retinal stability and isolation of the vitreous cavity at the time of vitreous removal along with PCL immiscibility and its specific gravity suggest that PCL has a potential clinical use as an irrigating solution to remove vitreous.

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

    PubMed

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

    2007-05-01

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

  5. A novel perfused rotary bioreactor for cardiomyogenesis of embryonic stem cells.

    PubMed

    Teo, Ailing; Mantalaris, Athanasios; Song, Kedong; Lim, Mayasari

    2014-05-01

    Developments in bioprocessing technology play an important role for overcoming challenges in cardiac tissue engineering. To this end, our laboratory has developed a novel rotary perfused bioreactor for supporting three-dimensional cardiac tissue engineering. The dynamic culture environments provided by our novel perfused rotary bioreactor and/or the high-aspect rotating vessel produced constructs with higher viability and significantly higher cell numbers (up to 4 × 10(5) cells/bead) than static tissue culture flasks. Furthermore, cells in the perfused rotary bioreactor showed earlier gene expressions of cardiac troponin-T, α- and β-myosin heavy chains with higher percentages of cardiac troponin-I-positive cells and better uniformity of sacromeric α-actinin expression. A dynamic and perfused environment, as provided by this bioreactor, provides a superior culture performance in cardiac differentiation for embryonic stem cells particularly for larger 3D constructs.

  6. Dynamic perfusion assessment during perforator flap surgery: an up-to-date

    PubMed Central

    MUNTEAN, MAXIMILIAN VLAD; MUNTEAN, VALENTIN; ARDELEAN, FILIP; GEORGESCU, ALEXANDRU

    2015-01-01

    Flap monitoring technology has progressed alongside flap design. The highly variable vascular anatomy and the complexity associated with modern perforator flaps demands dynamic, real-time, intraoperative information about the vessel location, perfusion patterns and flap physiology. Although most surgeons still assess flap perfusion and viability based solely on clinical experience, studies have shown that results may be highly variable and often misleading. Poor judgment of intraoperative perfusion leads to major complications. Employing dynamic perfusion imaging during flap reconstruction has led to a reduced complication rate, lower morbidity, shorter hospital stay, and an overall better result. With the emergence of multiple systems capable of intraoperative flap evaluation, the purpose of this article is to review the two systems that have been widely accepted and are currently used by plastic surgeons: Indocyanine green angiography (ICGA) and dynamic infrared thermography (DIRT). PMID:26609259

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

    PubMed

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

    2018-06-18

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

  8. Renal blood flow measurement with contrast-enhanced harmonic ultrasonography: evaluation of dopamine-induced changes in renal cortical perfusion in humans.

    PubMed

    Kishimoto, N; Mori, Y; Nishiue, T; Shibasaki, Y; Iba, O; Nose, A; Uchiyama-Tanaka, Y; Masaki, H; Matsubara, H; Iwasaka, T

    2003-06-01

    An accessible non-invasive method for evaluating renal regional blood flow in real time is highly desirable in the clinical setting. Recent progress in ultrasonography with microbubble contrast has allowed quantification of regional blood flow in animal models. Goal ofthis study was to establish a convenient contrast--enhanced harmonic ultrasonography (CEHU) method for evaluating renal cortical blood flow in humans. We carried out intermittent second harmonic imaging in 9 healthy volunteers. Pulse interval was progressively decreased from 4 s - 0.2 s during continuous venous infusion of the microbubble contrast agent. Pulse interval versus CEHU-derived acoustic intensity plots provided microbubble velocity (MV) and fractional vascular volume (FVV) during renal cortical perfusion in humans. Low-dose dopamine infusion (2 microg/min/kg) resulted in a significant increase in MV which correlated well with the increase in total renal blood flow (RBF) determined by a conventional study of p-aminohippurate clearance (C(PAH)) (r = 0.956, p < 0.0001). Although FVV was not significantly increased, alterations in CEHU-derived renal cortical blood flow calculated by the products of MV and FVV were also correlated with alterations in total RBF (r = 0.969, p < 0.0001). Thus, low-dose dopamine infusion increases renal cortical blood flow observed in CEHU, mainly by increasing MV. The present study shows that renal cortical blood flow in humans can be measured non-invasively by CEHU and that CEHU can be used for quantitatively evaluating changes induced by a therapeutic agent such as dopamine in flow velocity and in FVV.

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

    PubMed

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

    2013-07-21

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

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

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

    Han, H; Xing, L; Liang, Z

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-11-01

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

  12. Atlas-derived perfusion correlates of white matter hyperintensities in patients with reduced cardiac output.

    PubMed

    Jefferson, Angela L; Holland, Christopher M; Tate, David F; Csapo, Istvan; Poppas, Athena; Cohen, Ronald A; Guttmann, Charles R G

    2011-01-01

    Reduced cardiac output is associated with increased white matter hyperintensities (WMH) and executive dysfunction in older adults, which may be secondary to relations between systemic and cerebral perfusion. This study preliminarily describes the regional distribution of cerebral WMH in the context of a normal cerebral perfusion atlas and aims to determine if these variables are associated with reduced cardiac output. Thirty-two participants (72 ± 8 years old, 38% female) with cardiovascular risk factors or disease underwent structural MRI acquisition at 1.5T using a standard imaging protocol that included FLAIR sequences. WMH distribution was examined in common anatomical space using voxel-based morphometry and as a function of normal cerebral perfusion patterns by overlaying a single photon emission computed tomography (SPECT) atlas. Doppler echocardiogram data was used to dichotomize the participants on the basis of low (n=9) and normal (n=23) cardiac output. Global WMH count and volume did not differ between the low and normal cardiac output groups; however, atlas-derived SPECT perfusion values in regions of hyperintensities were reduced in the low versus normal cardiac output group (p<0.001). Our preliminary data suggest that participants with low cardiac output have WMH in regions of relatively reduced perfusion, while normal cardiac output participants have WMH in regions with relatively higher regional perfusion. This spatial perfusion distribution difference for areas of WMH may occur in the context of reduced systemic perfusion, which subsequently impacts cerebral perfusion and contributes to subclinical or clinical microvascular damage. Copyright © 2009 Elsevier Inc. All rights reserved.

  13. Decreased Regional Cerebral Perfusion in Moderate-Severe Obstructive Sleep Apnoea during Wakefulness.

    PubMed

    Innes, Carrie R H; Kelly, Paul T; Hlavac, Michael; Melzer, Tracy R; Jones, Richard D

    2015-05-01

    To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). N/A. There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes. © 2015 Associated Professional Sleep Societies, LLC.

  14. First-pass myocardial perfusion imaging with whole-heart coverage using L1-SPIRiT accelerated variable density spiral trajectories.

    PubMed

    Yang, Yang; Kramer, Christopher M; Shaw, Peter W; Meyer, Craig H; Salerno, Michael

    2016-11-01

    To design and evaluate two-dimensional (2D) L1-SPIRiT accelerated spiral pulse sequences for first-pass myocardial perfusion imaging with whole heart coverage capable of measuring eight slices at 2 mm in-plane resolution at heart rates up to 125 beats per minute (BPM). Combinations of five different spiral trajectories and four k-t sampling patterns were retrospectively simulated in 25 fully sampled datasets and reconstructed with L1-SPIRiT to determine the best combination of parameters. Two candidate sequences were prospectively evaluated in 34 human subjects to assess in vivo performance. A dual density broad transition spiral trajectory with either angularly uniform or golden angle in time k-t sampling pattern had the largest structural similarity and smallest root mean square error from the retrospective simulation, and the L1-SPIRiT reconstruction had well-preserved temporal dynamics. In vivo data demonstrated that both of the sampling patterns could produce high quality perfusion images with whole-heart coverage. First-pass myocardial perfusion imaging using accelerated spirals with optimized trajectory and k-t sampling pattern can produce high quality 2D perfusion images with whole-heart coverage at the heart rates up to 125 BPM. Magn Reson Med 76:1375-1387, 2016. © 2015 International Society for Magnetic Resonance in Medicine. © 2015 International Society for Magnetic Resonance in Medicine.

  15. Sensitivity of mechanical and metabolic functions to changes in coronary perfusion: A metabolic basis of perfusion-contraction coupling.

    PubMed

    Askenasy, N

    2000-05-01

    Experimental evidence indicates a metabolic basis of contraction-perfusion coupling during an increase in cardiac work load. This study aims to characterize adjustment of myocardial energy metabolism in response to acute low flow ischemia (LFI), and to determine its involvement in perfusion-contraction coupling. Intracellular parameters were measured in isolated rat hearts by NMR spectroscopy and biochemical methods during 30 min of graded LFI and reperfusion as compared to continuous perfusion (control). Oxygen pressure was set to reach maximal oxygen extraction at 70% coronary flow rate (CFR), therefore oxygen limitation was proportional to coronary underperfusion. At 69, 38 and 10% CFR left ventricular pressures decreased to 71, 43 and 25% of pre-ischemic values respectively (P<0.005 v 97% in control) without an increase in diastolic tone, and recovered to 92+/-3% after 30 min of reperfusion. Despite hydrolysis of high energy phosphates and cellular acidification, ADP concentrations were stable in underperfused hearts. At 69, 38 and 10% CFR, cytosolic phosphorylation potentials (PP) decreased from 74+/-10 m M(-1)during pre-ischemia to 40+/-6, 25+/-4 and 14+/-4 m M(-1)respectively (P<0.05 v 63+/-9 m M(-1)in control), and lactate efflux increased to 256+/-18, 386+/-22 and 490+/-43 micromol /gdw respectively (P<0.005 v 186+/-22 micromol/gdw in control). Glycogen contents decreased (P<0.005 v control) and accounted for 27-30% of lactate efflux. These results indicate: (a) proportionate depression of contraction force and glycogen contents, and increased glucose uptake and anaerobic energy production in the underperfused myocardium. Coordinated modulation of these parameters attributes cytosolic PP a regulatory function; (b) resetting of cytosolic PP to lower levels mediates perfusion-contraction coupling during graded LFI. The data are consistent with the concept that glycolytic energy production improves myocardial tolerance to ischemia. Copyright 2000 Academic

  16. Perfusion CT in acute stroke: effectiveness of automatically-generated colour maps.

    PubMed

    Ukmar, Maja; Degrassi, Ferruccio; Pozzi Mucelli, Roberta Antea; Neri, Francesca; Mucelli, Fabio Pozzi; Cova, Maria Assunta

    2017-04-01

    To evaluate the accuracy of perfusion CT (pCT) in the definition of the infarcted core and the penumbra, comparing the data obtained from the evaluation of parametric maps [cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT)] with software-generated colour maps. A retrospective analysis was performed to identify patients with suspected acute ischaemic strokes and who had undergone unenhanced CT and pCT carried out within 4.5 h from the onset of the symptoms. A qualitative evaluation of the CBV, CBF and MTT maps was performed, followed by an analysis of the colour maps automatically generated by the software. 26 patients were identified, but a direct CT follow-up was performed only on 19 patients after 24-48 h. In the qualitative analysis, 14 patients showed perfusion abnormalities. Specifically, 29 perfusion deficit areas were detected, of which 15 areas suggested the penumbra and the remaining 14 areas suggested the infarct. As for automatically software-generated maps, 12 patients showed perfusion abnormalities. 25 perfusion deficit areas were identified, 15 areas of which suggested the penumbra and the other 10 areas the infarct. The McNemar's test showed no statistically significant difference between the two methods of evaluation in highlighting infarcted areas proved later at CT follow-up. We demonstrated how pCT provides good diagnostic accuracy in the identification of acute ischaemic lesions. The limits of identification of the lesions mainly lie at the pons level and in the basal ganglia area. Qualitative analysis has proven to be more efficient in identification of perfusion lesions in comparison with software-generated maps. However, software-generated maps have proven to be very useful in the emergency setting. Advances in knowledge: The use of CT perfusion is requested in increasingly more patients in order to optimize the treatment, thanks also to the technological evolution of CT, which now allows a whole

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

    PubMed

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

    2011-02-01

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

  18. Design and validation of a pulsatile perfusion bioreactor for 3D high cell density cultures.

    PubMed

    Chouinard, Julie A; Gagnon, Serge; Couture, Marc G; Lévesque, Alain; Vermette, Patrick

    2009-12-15

    This study presents the design and validation of a pulsatile flow perfusion bioreactor able to provide a suitable environment for 3D high cell density cultures for tissue engineering applications. Our bioreactor system is mobile, does not require the use of traditional cell culture incubators and is easy to sterilize. It provides real-time monitoring and stable control of pH, dissolved oxygen concentration, temperature, pressure, pulsation frequency, and flow rate. In this bioreactor system, cells are cultured in a gel within a chamber perfused by a culture medium fed by hollow fibers. Human umbilical vein endothelial cells (HUVEC) suspended in fibrin were found to be living, making connections and proliferating up to five to six times their initial seeding number after a 48-h culture period. Cells were uniformly dispersed within the 14.40 mm x 17.46 mm x 6.35 mm chamber. A larger fraction of the cells suspended in 6.35-mm thick gels and cultured in a traditional CO(2) incubator were found to be round and dead [corrected]. In control experiments carried out in a traditional cell culture incubator, the scarcely found living cells were mostly on top of the gels, while cells cultured under perfusion bioreactor conditions were found to be alive and uniformly distributed across the gel. 2009 Wiley Periodicals, Inc.

  19. Calculation of the Respiratory Modulation of the Photoplethysmogram (DPOP) Incorporating a Correction for Low Perfusion

    PubMed Central

    Addison, Paul S.; Wang, Rui; McGonigle, Scott J.; Bergese, Sergio D.

    2014-01-01

    DPOP quantifies respiratory modulations in the photoplethysmogram. It has been proposed as a noninvasive surrogate for pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. The correlation between DPOP and PPV may degrade due to low perfusion effects. We implemented an automated DPOP algorithm with an optional correction for low perfusion. These two algorithm variants (DPOPa and DPOPb) were tested on data from 20 mechanically ventilated OR patients split into a benign “stable region” subset and a whole record “global set.” Strong correlation was found between DPOP and PPV for both algorithms when applied to the stable data set: R = 0.83/0.85 for DPOPa/DPOPb. However, a marked improvement was found when applying the low perfusion correction to the global data set: R = 0.47/0.73 for DPOPa/DPOPb. Sensitivities, Specificities, and AUCs were 0.86, 0.70, and 0.88 for DPOPa/stable region; 0.89, 0.82, and 0.92 for DPOPb/stable region; 0.81, 0.61, and 0.73 for DPOPa/global region; 0.83, 0.76, and 0.86 for DPOPb/global region. An improvement was found in all results across both data sets when using the DPOPb algorithm. Further, DPOPb showed marked improvements, both in terms of its values, and correlation with PPV, for signals exhibiting low percent modulations. PMID:25177348

  20. Reduced Cerebrovascular Reactivity and Increased Resting Cerebral Perfusion in Rats Exposed to a Cafeteria Diet.

    PubMed

    Gomez-Smith, Mariana; Janik, Rafal; Adams, Conner; Lake, Evelyn M; Thomason, Lynsie A M; Jeffers, Matthew S; Stefanovic, Bojana; Corbett, Dale

    2018-02-10

    To better understand the effects of a diet high in fat, sugar, and sodium on cerebrovascular function, Sprague Dawley rats were chronically exposed to a Cafeteria diet. Resting cerebral perfusion and cerebrovascular reactivity was quantified using continuous arterial spin labeling (CASL) magnetic resonance imaging (MRI). In addition, structural changes to the cerebrovasculature and susceptibility to ischemic lesion were examined. Compared to control animals fed standard chow (SD), Cafeteria diet (CAF) rats exhibited increased resting brain perfusion in the hippocampus and reduced cerebrovascular reactivity in response to 10% inspired CO 2 challenges in both the hippocampus and the neocortex. CAF rats switched to chow for one month (SWT) exhibited improved resting perfusion in the hippocampus as well as improved cerebrovascular reactivity in the neocortex. However, the diet switch did not correct cerebrovascular reactivity in the hippocampus. These changes were not accompanied by alterations in the structural integrity of the cerebral microvasculature, examined using rat endothelial cell antigen-1 (RECA-1) and immunoglobulin G (IgG) immunostaining. Also, the extent of tissue damage induced by endothelin-1 injection into sensorimotor cortex was not affected by the Cafeteria diet. These results demonstrate that short-term consumption of an ultra-processed diet reduces cerebrovascular reactivity. This effect persists after dietary normalization despite recovery of peripheral symptomatology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    1994-08-01

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

  2. Differences in cerebral perfusion deficits in mild traumatic brain injury and depression using single-photon emission computed tomography.

    PubMed

    Romero, Kristoffer; Black, Sandra E; Feinstein, Anthony

    2014-01-01

    Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI. Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major depressive disorder (MDD), but no TBI were given 99m T-ECD single-photon emission computed tomography (SPECT) scans within 2 weeks of injury. All subjects completed tests of information processing speed, complex attention, and executive functioning, and a self-report questionnaire measuring symptoms of psychological distress. Between-group comparisons of quantified SPECT perfusion were undertaken using univariate and multivariate (partial least squares) analyses. mTBI-D and mTBI-noD groups did not differ in terms of cerebral perfusion. However, patients with MDD showed hypoperfusion compared to both TBI groups in several frontal (orbitofrontal, middle frontal, and superior frontal cortex), superior temporal, and posterior cingulate regions. The mTBI-D group showed poorer performance on a measure of complex attention and working memory compared to both the mTBI-noD and MDD groups. These results suggest that depressive symptoms do not affect SPECT perfusion in the sub-acute phase following a mild TBI. Conversely, MDD is associated with hypoperfusion primarily in frontal regions.

  3. Normal Databases for the Relative Quantification of Myocardial Perfusion

    PubMed Central

    Rubeaux, Mathieu; Xu, Yuan; Germano, Guido; Berman, Daniel S.; Slomka, Piotr J.

    2016-01-01

    Purpose of review Myocardial perfusion imaging (MPI) with SPECT is performed clinically worldwide to detect and monitor coronary artery disease (CAD). MPI allows an objective quantification of myocardial perfusion at stress and rest. This established technique relies on normal databases to compare patient scans against reference normal limits. In this review, we aim to introduce the process of MPI quantification with normal databases and describe the associated perfusion quantitative measures that are used. Recent findings New equipment and new software reconstruction algorithms have been introduced which require the development of new normal limits. The appearance and regional count variations of normal MPI scan may differ between these new scanners and standard Anger cameras. Therefore, these new systems may require the determination of new normal limits to achieve optimal accuracy in relative myocardial perfusion quantification. Accurate diagnostic and prognostic results rivaling those obtained by expert readers can be obtained by this widely used technique. Summary Throughout this review, we emphasize the importance of the different normal databases and the need for specific databases relative to distinct imaging procedures. use of appropriate normal limits allows optimal quantification of MPI by taking into account subtle image differences due to the hardware and software used, and the population studied. PMID:28138354

  4. Women in perfusion: a survey of North American female perfusionists.

    PubMed

    Brewer, Stacey L; Mongero, Linda B

    2013-09-01

    Perfusion as a career has long been dominated by men (American Board of Cardiovascular Perfusion, Booklet of information since 1975). Women represent 33.3% of the present workforce in North America (1187 certified women). In the 1900s, fewer than 20% of women participated in the labor force compared with 75% today and growing (1). In addition women make only 77 cents for every dollar that men earn and the more education a woman has, the greater the disparity in her wages (2). Only 53% of employers provide at least some replacement pay during periods of maternity leave (2). The purpose of this survey was to poll women in perfusion to evaluate concerns and opinions in their careers and to compare this with the female labor force. In October 2011, a 40-question survey (surveymonkey.com) was made available to all female perfusionists in North American by postcard mailing through the American Board of Cardiovascular Perfusion. There were 538 responses to the survey, which is 45% of all female certified perfusionists in North America. A total of 32.6% of the survey participants have been in perfusion for more than 20 years and 75% are staff perfusionists, working for a hospital (59.5%) rather than a contract group (36.7%). A total of 44.7% of women who had children during their employment were out on leave 10 weeks or less. A total of 95.9% feel they miss important family functions as a result of their work schedules and 63% consider themselves under moderate stress. Direct supervision of the participants by men occurred in 76.5% of cases, and 68.2% felt that they were treated with the same respect as male coworkers. Nonetheless, 50.9% felt discriminated against because of gender. This survey suggests that the female perfusionists in North America share the same difficulties as women in the labor force. The role of women in society in general is clearly changing. Female perfusionists will be part of that change. Seventy percent of those surveyed would recommend perfusion

  5. Computation of ventilation-perfusion ratio with Kr-81m in pulmonary embolism

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

    Meignan, M.; Simonneau, G.; Oliveira, L.

    1984-02-01

    Diagnostic difficulties occur in pulmonary embolism (PE) during visual analysis of ventilation-perfusion images in matched defects or in chronic obstructive lung disease (COPD). In 44 patients with angiographically confirmed PE and in 40 patients with COPD, the regional ventilation-perfusion ratios (V/Q) were therefore computed using krypton-81m for each perfusion defect, and were displayed in a functional image. In patients with PE and mismatched defects, a high V/Q (1.96) was observed. A V/Q > 1.25 was also found in nine of 11 patients having PE and indeterminate studies (studies with perfusion abnormalities matched by radiographic abnormalities). COPD was characterized by matchedmore » defects and low V/Q. The percentage of patients correctly classified as having PE or COPD increased from 56% when considering the match or mismatched character to 88% when based on a V/Q of 1.25 in the region of the perfusion defect. This quantitative analysis, therefore, seems useful in classifying patients with scintigraphic suspicion of PE.« less

  6. [Significance and mechanism of MSCT perfusion scan on differentiation of NSCLC].

    PubMed

    Liu, Jin-Kang; Hu, Cheng-Ping; Zhou, Mo-Ling; Zhou, Hui; Xiong, Zeng; Xia, Yu; Chen, Wei

    2009-06-01

    To determine the significance of MSCT perfusion scan on differentiation of NSCLC and to investigate its possible mechanisms. Forty four NSCLC patients underwent CT perfusion scan by MSCT. Among them, 22 cases were selected to detected the two-dimensional tumor microvascular architecture phenotype (2D-TMAP), the relationships between CT perfusion parameters (BF, BV, PEI, TIP), and the differentiation of NSCLC were analysed by using the correlation analysis and trend test. Spearman correlation analysis was used to study the relationships between CT perfusion parameters, differentiation, and 2D-TMAP. The total BF, BV and PEI decreased with decreasing differentiation of NSCLC (P<0.05). The total PEI showed a positive correlation with the total MVD (P<0.05). There were negative correlations between the surrounding area BF, the total BF, BV, and PEI, the uncomplete lumen of the surrounding area MVD, and expression of PCNA, respectively (P<0.05). There were positive correlations between degree of differentiation and the uncomplete lumen of the surrounding area MVD (P<0.05). It was the same as degree of differentiation and expression of PCNA, VEGF, respectively. There were positive correlations between the uncomplete lumen of the surrounding area MVD and expression of VEGF, ephrinB2, EphB4, and PCNA, respectively (P<0.05). Perfusion parameters reflect the difference of density of vassels with mature functional lumen. Careful evaluation of the differences of blood flow pattern in pulmonary space-occupying lesions by MSCT perfusion scan can be used to identify the degree of NSCLC differentiation.

  7. Scanning Electron Microscopy Findings of Machine Perfused Liver Graft After Warm Ischemia Between Hypothermic and Rewarming Machine Perfusion in Pigs.

    PubMed

    Meng, L; Matsuno, N; Watanabe, K; Furukori, M; Obara, H; Bochimoto, H; Watanabe, T; Fukukawa, H

    2016-09-01

    The shortage of organ donors is a universal problem. Use of grafts from donors after cardiac death would greatly contribute to the expansion of the donor organ pool. The two major methods of preservation are cold storage and machine perfusion (MP) preservation, and each has its own advantages. Several studies have reported the relative merits of MP for the preservation for grafts from donors after cardiac death. In this study, we used scanning electron microscopy (SEM) to assess the damage to the liver between hypothermic and rewarming preservation conditions. Porcine livers were perfused with a newly developed MP system. The livers were perfused for 4 hours with a modified University of Wisconsin solution-gluconate solution. In group 1, grafts were preserved with warm ischemic time for 60 minutes and hypothermic machine perfusion (HMP) for 4 hours. In group 2, grafts were preserved with warn ischemic time for 60 minutes and had rewarming up to 22°C by MP (RMP) for 4 hours. A significant enlargement of the mitochondria were observed in both the HMP and RMP groups under higher magnification, Additionally, vacuoles appeared occasionally in hepatocytes in the RMP for 4 hours group, but not in the HMP for 4 hours group. An analysis by scanning electron microscope appears to be useful to evaluate the levels of damage of hepatocytes compared with transmission electron microscopy, and further study is needed to analyze the significance of the appearance of swelling of mitochondria and vacuolization during preservation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Myocardial perfusion imaging with thallium-201: correlation with coronary arteriography and electrocardiography

    PubMed Central

    Sternberg, Leonard; Wald, Robert W.; Feiglin, David H.I.; Morch, John E.

    1978-01-01

    Myocardial perfusion imaging with thallium-201 and electrocardiography with the subject at rest and undergoing submaximal treadmill exercise were performed in 19 men and 3 women. Selective coronary arteriography and left ventriculography showed that 7 had normal coronary arteries and 15 had coronary artery disease. The 11 persons with electrocardiographic evidence of an old myocardial infarct (q waves) had a perfusion defect at rest in the area of the infarct and a segmental abnormality of wall motion apparent on the left ventriculogram corresponding to the perfusion defect. Myocardial perfusion imaging and electrocardiography were equally sensitive in detecting coronary artery disease in exercising individuals: perfusion defects were noted in 7 of the 15 persons with coronary artery disease, and diagnostic ST-segment depression was present in 8 of the 15. Combination of the results of the two tests with exercise permitted the identification of 11 of the 15 persons and improved the sensitivity. Combination of the results of rest and exercise imaging and electrocardiography permitted the identification of 94% of the patients with coronary artery disease. Myocardial perfusion imaging with 201TI in the subject at rest is a sensitive indicator of previous myocardial infarction. Imaging after the subject has exercised is a useful adjunct to conventional exercise electrocardiography, especially in those whose exercise electrocardiogram is non-interpretable. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:630487

  9. Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety

    PubMed Central

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

    2016-01-01

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

  10. Dependence of quantitative accuracy of CT perfusion imaging on system parameters

    NASA Astrophysics Data System (ADS)

    Li, Ke; Chen, Guang-Hong

    2017-03-01

    Deconvolution is a popular method to calculate parametric perfusion parameters from four dimensional CT perfusion (CTP) source images. During the deconvolution process, the four dimensional space is squeezed into three-dimensional space by removing the temporal dimension, and a prior knowledge is often used to suppress noise associated with the process. These additional complexities confound the understanding about deconvolution-based CTP imaging system and how its quantitative accuracy depends on parameters and sub-operations involved in the image formation process. Meanwhile, there has been a strong clinical need in answering this question, as physicians often rely heavily on the quantitative values of perfusion parameters to make diagnostic decisions, particularly during an emergent clinical situation (e.g. diagnosis of acute ischemic stroke). The purpose of this work was to develop a theoretical framework that quantitatively relates the quantification accuracy of parametric perfusion parameters with CTP acquisition and post-processing parameters. This goal was achieved with the help of a cascaded systems analysis for deconvolution-based CTP imaging systems. Based on the cascaded systems analysis, the quantitative relationship between regularization strength, source image noise, arterial input function, and the quantification accuracy of perfusion parameters was established. The theory could potentially be used to guide developments of CTP imaging technology for better quantification accuracy and lower radiation dose.

  11. A practical guide to microfluidic perfusion culture of adherent mammalian cells.

    PubMed

    Kim, Lily; Toh, Yi-Chin; Voldman, Joel; Yu, Hanry

    2007-06-01

    Culturing cells at microscales allows control over microenvironmental cues, such as cell-cell and cell-matrix interactions; the potential to scale experiments; the use of small culture volumes; and the ability to integrate with microsystem technologies for on-chip experimentation. Microfluidic perfusion culture in particular allows controlled delivery and removal of soluble biochemical molecules in the extracellular microenvironment, and controlled application of mechanical forces exerted via fluid flow. There are many challenges to designing and operating a robust microfluidic perfusion culture system for routine culture of adherent mammalian cells. The current literature on microfluidic perfusion culture treats microfluidic design, device fabrication, cell culture, and micro-assays independently. Here we systematically present and discuss important design considerations in the context of the entire microfluidic perfusion culture system. These design considerations include the choice of materials, culture configurations, microfluidic network fabrication and micro-assays. We also present technical issues such as sterilization; seeding cells in both 2D and 3D configurations; and operating the system under optimized mass transport and shear stress conditions, free of air-bubbles. The integrative and systematic treatment of the microfluidic system design and fabrication, cell culture, and micro-assays provides novices with an effective starting point to build and operate a robust microfludic perfusion culture system for various applications.

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

    PubMed

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

    2017-09-01

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

  13. Improved rat liver decellularization by arterial perfusion under oscillating pressure conditions.

    PubMed

    Struecker, Benjamin; Butter, Antje; Hillebrandt, Karl; Polenz, Dietrich; Reutzel-Selke, Anja; Tang, Peter; Lippert, Steffen; Leder, Anne; Rohn, Susanne; Geisel, Dominik; Denecke, Timm; Aliyev, Khalid; Jöhrens, Korinna; Raschzok, Nathanael; Neuhaus, Peter; Pratschke, Johann; Sauer, Igor M

    2017-02-01

    One approach of regenerative medicine to generate functional hepatic tissue in vitro is decellularization and recellularization, and several protocols for the decellularization of livers of different species have been published. This appears to be the first report on rat liver decellularization by perfusion under oscillating pressure conditions, intending to optimize microperfusion and minimize damage to the ECM. Four decellularization protocols were compared: perfusion via the portal vein (PV) or the hepatic artery (HA), with (+P) or without (-P) oscillating pressure conditions. All rat livers (n = 24) were perfused with 1% Triton X-100 and 1% sodium dodecyl sulphate, each for 90 min with a perfusion rate of 5 ml/min. Perfusion decellularization was observed macroscopically and the decellularized liver matrices were analysed by histology and biochemical analyses (e.g. levels of DNA, glycosaminoglycans and hepatocyte growth factor). Livers decellularized via the hepatic artery and under oscillating pressure showed a more homogeneous decellularization and less remaining DNA, compared with the livers of the other experimental groups. The novel decellularization method described is effective, quick (3 h) and gentle to the extracellular matrix and thus represents an improvement of existing methodology. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Is rate-pressure product of any use in the isolated rat heart? Assessing cardiac 'effort' and oxygen consumption in the Langendorff-perfused heart.

    PubMed

    Aksentijević, Dunja; Lewis, Hannah R; Shattock, Michael J

    2016-02-01

    What is the central question of this study? Rate-pressure product (RPP) is commonly used as an index of cardiac 'effort'. In canine and human hearts (which have a positive force-frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species-independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force-frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac 'effort') in the Langendorff-perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β-adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate-pressure product (RPP); a rather ill-defined index of 'work' or, more correctly, 'effort'. Rate-pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV̇O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force-frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV̇O2 in Langendorff-perfused rat hearts. Paced hearts (300-750 beats min(-1)) were perfused either with Krebs-Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV̇O2) was recorded. Metabolic status was assessed using (31) P magnetic resonance spectroscopy and lactate efflux. Experiments were repeated in the presence of

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

    PubMed

    Rohan, Eduard; Lukeš, Vladimír; Jonášová, Alena

    2018-01-24

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

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

    PubMed

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

    2015-02-01

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

  17. Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

    PubMed

    Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

    2017-09-01

    Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

  18. Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition.

    PubMed

    Wolf, Moritz K F; Closet, Aurélie; Bzowska, Monika; Bielser, Jean-Marc; Souquet, Jonathan; Broly, Hervé; Morbidelli, Massimo

    2018-05-21

    Mammalian cell perfusion cultures represent a promising alternative to the current fed-batch technology for the production of various biopharmaceuticals. Long-term operation at a fixed viable cell density (VCD) requires a viable culture and a constant removal of excessive cells. Product loss in the cell removing bleed stream deteriorates the process yield. In this study, the authors investigate the use of chemical and environmental growth inhibition on culture performance by either adding valeric acid (VA) to the production media or by reducing the culture temperature (33.0 °C) with respect to control conditions (36.5 °C, no VA). Low temperature significantly reduces cellular growth, thus, resulting in lower bleed rates accompanied by a reduced product loss of 11% compared to 26% under control conditions. Additionally, the cell specific productivity of the target protein improves and maintained stable leading to media savings per mass of product. VA shows initially an inhibitory effect on cellular growth. However, cells seemed to adapt to the presence of the inhibitor resulting in a recovery of the cellular growth. Cell cycle and Western blot analyses support the observed results. This work underlines the role of temperature as a key operating variable for the optimization of perfusion cultures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Do perfume additives termed human pheromones warrant being termed pheromones?

    PubMed

    Winman, Anders

    2004-09-30

    Two studies of the effects of perfume additives, termed human pheromones by the authors, have conveyed the message that these substances can promote an increase in human sociosexual behaviour [Physiol. Behav. 75 (2003) R1; Arch. Sex. Behav. 27 (1998) R2]. The present paper presents an extended analysis of this data. It is shown that in neither study is there a statistically significant increase in any of the sociosexual behaviours for the experimental groups. In the control groups of both studies, there are, however, moderate but statistically significant decreases in the corresponding behaviour. Most notably, there is no support in data for the claim that the substances increase the attractiveness of the wearers of the substances to the other sex. It is concluded that more research using matched homogenous groups of participants is needed. Copyright 2004 Elsevier Inc.

  20. Hypothermic machine perfusion permits extended cold ischemia times with improved early graft function.

    PubMed

    Guy, Alison; McGrogan, Damian; Inston, Nicholas; Ready, Andrew

    2015-04-01

    The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time. Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list. There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications. This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

  1. Non-invasive monitoring of muscle blood perfusion by photoplethysmography: evaluation of a new application.

    PubMed

    Sandberg, M; Zhang, Q; Styf, J; Gerdle, B; Lindberg, L-G

    2005-04-01

    To evaluate a specially developed photoplethysmographic (PPG) technique, using green and near-infrared light sources, for simultaneous non-invasive monitoring of skin and muscle perfusion. Evaluation was based on assessments of changes in blood perfusion to various provocations, such as post-exercise hyperaemia and hyperaemia following the application of liniment. The deep penetrating feature of PPG was investigated by measurement of optical radiation inside the muscle. Simultaneous measurements using ultrasound Doppler and the new PPG application were performed to elucidate differences between the two methods. Specific problems related to the influence of skin temperature on blood flow were highlightened, as well. Following static and dynamic contractions an immediate increase in muscle perfusion was shown, without increase in skin perfusion. Liniment application to the skin induced a rapid increase in skin perfusion, but not in muscle. Both similarities and differences in blood flow measured by Ultrasound Doppler and PPG were demonstrated. The radiant power measured inside the muscle, by use of an optical fibre, showed that the near-infrared light penetrates down to the vascular depth inside the muscle. The results of this study indicate the potentiality of the method for non-invasive measurement of local muscle perfusion, although some considerations still have to be accounted for, such as influence of temperature on blood perfusion.

  2. The influence of the position of the oxygen dissociation curve on oxygen-dependent functions of the isolated perfused rat liver. III. Studies at different levels of anaemic hypoxia.

    PubMed

    Bakker, J C; Gortmaker, G C; de Vries-van Rossen, A; Offerijns, F G

    1977-03-11

    The influence of a 2,3-diphosphoglycerate (2,3-DPG)-induced displacement of the oxygen dissociation curve (O.D.C.) on the isolated perfused rat liver was studied at different levels of anaemic hypoxia. Rat livers were perfused either with fresh or with 2,3-DPG-depleted human erythrocytes at different haematocrit values (from 30% to 2.5%) at constant Po2 of the inflowing perfusate and at constant blood flow rate. The 2,3-DPG-induced difference in oxygen affinity of the red cells did not cause a significant difference in perfusion pressure during the perfusion experiments. Therefore, there is no evidence that 2,3-DPG did alter the vascular resistance of the liver, since blood flow rate could be adusted at equal values. The decrease in oxygen supply brought about by decrease of haematocrit caused a decrease of O2 consumption, of bile flow rate and of venous Po2 and an increase of lactate/pyruvate (L/P) ratio and of beta-hydroxybutyrate/acetoacetate (betaOH/Acac) ratio. There was no influence of a difference in 2,3-DPG content of the erythrocytes on the above-metioned parameters during severe anaemic hypoxia. At moderate anaemic hypoxia the venous Po2 was higher during perfusion with fresh erythrocytes than during perfusion with 2,3-DPG-depleted erythrocytes. Thus, although 2,3-DPG may play a compensatory role during conditions of mild anaemia, no such effects can be observed during conditions of severe hypoxia.

  3. Tissue oxygen saturation and finger perfusion index in central hypovolemia: influence of pain.

    PubMed

    Høiseth, Lars Ø; Hisdal, Jonny; Hoff, Ingrid E; Hagen, Ove A; Landsverk, Svein A; Kirkebøen, Knut A

    2015-04-01

    Tissue oxygen saturation and peripheral perfusion index are proposed as early indirect markers of hypovolemia in trauma patients. Hypovolemia is associated with increased sympathetic nervous activity. However, many other stimuli, such as pain, also increase sympathetic activity. Since pain is often present in trauma patients, its effect on the indirect measures of hypovolemia needs to be clarified. The aim of this study was, therefore, to explore the effects of hypovolemia and pain on tissue oxygen saturation (measurement sites: cerebral, deltoid, forearm, and thenar) and finger photoplethysmographic perfusion index. Experimental study. University hospital clinical circulation and research laboratory. Twenty healthy volunteers. Central hypovolemia was induced with lower body negative pressure (-60 mm Hg) and pain by the cold pressor test (ice water exposure). Interventions were performed in a 2×2 fashion with the combination of lower body negative pressure or not (normovolemia), and ice water or not (sham). Each subject was thus exposed to four experimental sequences, each lasting for 8 minutes. Measurements were averaged over 30 seconds. For each person and sequence, the minimal value was analyzed. Tissue oxygenation in all measurement sites and finger perfusion index were reduced during hypovolemia/sham compared with normovolemia/sham. Tissue oxygen saturation (except cerebral) and perfusion index were reduced by pain during normovolemia. There was a larger reduction in tissue oxygenation (all measurement sites) and perfusion index during hypovolemia and pain than during normovolemia and pain. Pain (cold pressor test) reduces tissue oxygen saturation in all measurement sites (except cerebral) and perfusion index. In the presence of pain, tissue oxygen saturation and perfusion index are further reduced by hypovolemia (lower body negative pressure, -60 mm Hg). Thus, pain must be considered when evaluating tissue oxygen saturation and perfusion index as markers of

  4. Myocardial Perfusion Pattern for Stratification of Ischemic Mitral Regurgitation Response to Percutaneous Coronary Intervention

    PubMed Central

    Goyal, Parag; Kim, Jiwon; Feher, Attila; Ma, Claudia L.; Gurevich, Sergey; Veal, David R.; Szulc, Massimiliano; Wong, Franklin J.; Ratcliffe, Mark B.; Levine, Robert A.; Devereux, Richard B.; Weinsaft, Jonathan W.

    2015-01-01

    Objective Ischemic mitral regurgitation (MR) is common, but its response to percutaneous coronary intervention (PCI) is poorly understood. This study tested utility of myocardial perfusion imaging (MPI) for stratification of MR response to PCI. Methods MPI and echo were performed among patients undergoing PCI. MPI was used to assess stress/rest myocardial perfusion. MR was assessed via echo (performed pre- and post-PCI). Results 317 patients with abnormal myocardial perfusion on MPI underwent echo 25±39 days prior to PCI. MR was present in 52%, among whom 24% had advanced (≥moderate) MR. MR was associated with LV chamber dilation on MPI and echo (both p<0.001). Magnitude of global LV perfusion deficits increased in relation to MR severity (p<0.01). Perfusion differences were greatest for global summed rest scores, which were 1.6-fold higher among patients with advanced MR vs. those with mild MR (p=0.004), and 2.4-fold higher vs. those without MR (p<0.001). In multivariate analysis, advanced MR was associated with fixed perfusion defect size on MPI (OR 1.16 per segment [CI 1.002–1.34], p=0.046) independent of LV volume (OR 1.10 per 10ml [CI 1.04–1.17], p=0.002). Follow-up via echo (1.0±0.6 years) demonstrated MR to decrease (≥1 grade) in 31% of patients, and increase in 12%. Patients with increased MR after PCI had more severe inferior perfusion defects on baseline MPI (p=0.028), whereas defects in other distributions and LV volumes were similar (p=NS). Conclusions Extent and distribution of SPECT-evidenced myocardial perfusion defects impacts MR response to revascularization. Increased magnitude of inferior fixed perfusion defects predicts post-PCI progression of MR. PMID:26049923

  5. Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

    PubMed

    Milks, Michael Wesley; Upadhya, Bharathi; Hall, Michael E; Vasu, Sujethra; Hundley, William Gregory; Stacey, Richard Brandon

    2015-01-01

    The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

  6. Compact Cell Settlers for Perfusion Cultures of Microbial (and Mammalian) Cells.

    PubMed

    Freeman, Cassandra A; Samuel, Premsingh S D; Kompala, Dhinakar S

    2017-07-01

    As microbial secretory expression systems have become well developed for microbial yeast cells, such as Saccharomyces cerevisiae and Pichia pastoris, it is advantageous to develop high cell density continuous perfusion cultures of microbial yeast cells to retain the live and productive yeast cells inside the perfusion bioreactor while removing the dead cells and cell debris along with the secreted product protein in the harvest stream. While the previously demonstrated inclined or lamellar settlers can be used for such perfusion bioreactors for microbial cells, the size and footprint requirements of such inefficiently scaled up devices can be quite large in comparison to the bioreactor size. Faced with this constraint, we have now developed novel, patent-pending compact cell settlers that can be used more efficiently with microbial perfusion bioreactors to achieve high cell densities and bioreactor productivities. Reproducible results from numerous month-long perfusion culture experiments using these devices attached to the 5 L perfusion bioreactor demonstrate very high cell densities due to substantial sedimentation of the larger live yeast cells which are returned to the bioreactor, while the harvest stream from the top of these cell settlers is a significantly clarified liquid, containing less than 30% and more typically less than 10% of the bioreactor cell concentration. Size of cells in the harvest is smaller than that of the cells in the bioreactor. Accumulated protein collected from the harvest and rate of protein accumulation is significantly (> 6x) higher than the protein produced in repeated fed-batch cultures over the same culture duration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:913-922, 2017. © 2017 American Institute of Chemical Engineers.

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

    PubMed

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

    2001-05-01

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

  8. How to Perfuse: Concepts of Cerebral Protection during Arch Replacement

    PubMed Central

    Habertheuer, Andreas; Wiedemann, Dominik; Kocher, Alfred; Laufer, Guenther; Vallabhajosyula, Prashanth

    2015-01-01

    Arch surgery remains undoubtedly among the most technically and strategically challenging endeavors in cardiovascular surgery. Surgical interventions of thoracic aneurysms involving the aortic arch require complete circulatory arrest in deep hypothermia (DHCA) or elaborate cerebral perfusion strategies with varying degrees of hypothermia to achieve satisfactory protection of the brain from ischemic insults, that is, unilateral/bilateral antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). Despite sophisticated and increasingly individualized surgical approaches for complex aortic pathologies, there remains a lack of consensus regarding the optimal method of cerebral protection and circulatory management during the time of arch exclusion. Many recent studies argue in favor of ACP with various degrees of hypothermic arrest during arch reconstruction and its advantages have been widely demonstrated. In fact ACP with more moderate degrees of hypothermia represents a paradigm shift in the cardiac surgery community and is widely adopted as an emergent strategy; however, many centers continue to report good results using other perfusion strategies. Amidst this important discussion we review currently available surgical strategies of cerebral protection management and compare the results of recent European multicenter and single-center data. PMID:26713319

  9. Perfusion seed cultures improve biopharmaceutical fed-batch production capacity and product quality.

    PubMed

    Yang, William C; Lu, Jiuyi; Kwiatkowski, Chris; Yuan, Hang; Kshirsagar, Rashmi; Ryll, Thomas; Huang, Yao-Ming

    2014-01-01

    Volumetric productivity and product quality are two key performance indicators for any biopharmaceutical cell culture process. In this work, we showed proof-of-concept for improving both through the use of alternating tangential flow perfusion seed cultures coupled with high-seed fed-batch production cultures. First, we optimized the perfusion N-1 stage, the seed train bioreactor stage immediately prior to the production bioreactor stage, to minimize the consumption of perfusion media for one CHO cell line and then successfully applied the optimized perfusion process to a different CHO cell line. Exponential growth was observed throughout the N-1 duration, reaching >40 × 10(6) vc/mL at the end of the perfusion N-1 stage. The cultures were subsequently split into high-seed (10 × 10(6) vc/mL) fed-batch production cultures. This strategy significantly shortened the culture duration. The high-seed fed-batch production processes for cell lines A and B reached 5 g/L titer in 12 days, while their respective low-seed processes reached the same titer in 17 days. The shortened production culture duration potentially generates a 30% increase in manufacturing capacity while yielding comparable product quality. When perfusion N-1 and high-seed fed-batch production were applied to cell line C, higher levels of the active protein were obtained, compared to the low-seed process. This, combined with correspondingly lower levels of the inactive species, can enhance the overall process yield for the active species. Using three different CHO cell lines, we showed that perfusion seed cultures can optimize capacity utilization and improve process efficiency by increasing volumetric productivity while maintaining or improving product quality. © 2014 American Institute of Chemical Engineers.

  10. 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.

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

    PubMed

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

    2015-04-17

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

  12. Skin perfusion evaluation between laser speckle contrast imaging and laser Doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Humeau-Heurtier, Anne; Mahe, Guillaume; Durand, Sylvain; Abraham, Pierre

    2013-03-01

    In the biomedical field, laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) are two optical techniques aiming at monitoring - non-invasively - the microvascular blood perfusion. LDF has been used for nearly 40 years whereas LSCI is a recent technique that overcomes some drawbacks of LDF. Both LDF and LSCI give perfusion assessments in arbitrary units. However, the possible relationship existing between perfusions given by LDF and by LSCI over large blood flow values has not been completely studied yet. We therefore herein evaluate the relationship between the LDF and LSCI perfusion values across a broad range of skin blood flows. For this purpose, LDF and LSCI data were acquired simultaneously on the forearm of 12 healthy subjects, at rest, during different durations of vascular occlusion and during reactive hyperemia. For the range of skin blood flows studied, the power function fits the data better than the linear function: powers for individual subjects go from 1.2 to 1.7 and the power is close to 1.3 when all the subjects are studied together. We thus suggest distinguishing perfusion values given by the two optical systems.

  13. First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

    PubMed

    Dutkowski, Philipp; Polak, Wojciech G; Muiesan, Paolo; Schlegel, Andrea; Verhoeven, Cornelia J; Scalera, Irene; DeOliveira, Michelle L; Kron, Philipp; Clavien, Pierre-Alain

    2015-11-01

    Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation. HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.

  14. Validation of polyethylene glycol 3350 as a poorly absorbable marker for intestinal perfusion studies.

    PubMed

    Schiller, L R; Santa Ana, C A; Porter, J; Fordtran, J S

    1997-01-01

    Polyethylene glycol (PEG) has been used as a poorly absorbable marker in intestinal perfusion studies, but there is controversy about the absorbability of PEG, particularly when glucose-sodium cotransport is occurring. Total intestinal perfusion studies were done in five normal humans using three solutions containing 1 g/liter PEG 3350 and designed to produce low rates of water absorption, high rates of water absorption, or high rates of glucose-sodium cotransport. Water absorption rates were calculated by traditional nonabsorbable marker equations and by a novel balance technique in which absorption was taken as the difference between the volumes of solution infused and recovered during steady-state conditions. Effluent PEG recovery was 99 +/- 4%, 109 +/- 2%, and 104 +/- 6% of the amount infused with each solution. Water absorption rates measured by use of PEG concentrations were similar to those calculated by the balance technique (r = 0.99). The complete recovery of PEG confirms the poor absorbability of PEG 3350, and the excellent agreement between techniques validates PEG as a poorly absorbed marker, even when glucose-sodium cotransport is occurring.

  15. Myocardial perfusion MRI with sliding-window conjugate-gradient HYPR.

    PubMed

    Ge, Lan; Kino, Aya; Griswold, Mark; Mistretta, Charles; Carr, James C; Li, Debiao

    2009-10-01

    First-pass perfusion MRI is a promising technique for detecting ischemic heart disease. However, the diagnostic value of the method is limited by the low spatial coverage, resolution, signal-to-noise ratio (SNR), and cardiac motion-related image artifacts. In this study we investigated the feasibility of using a method that combines sliding window and CG-HYPR methods (SW-CG-HYPR) to reduce the acquisition window for each slice while maintaining the temporal resolution of one frame per heartbeat in myocardial perfusion MRI. This method allows an increased number of slices, reduced motion artifacts, and preserves the relatively high SNR and spatial resolution of the "composite images." Results from eight volunteers demonstrate the feasibility of SW-CG-HYPR for accelerated myocardial perfusion imaging with accurate signal intensity changes of left ventricle blood pool and myocardium. Using this method the acquisition time per cardiac cycle was reduced by a factor of 4 and the number of slices was increased from 3 to 8 as compared to the conventional technique. The SNR of the myocardium at peak enhancement with SW-CG-HYPR (13.83 +/- 2.60) was significantly higher (P < 0.05) than the conventional turbo-FLASH protocol (8.40 +/- 1.62). Also, the spatial resolution of the myocardial perfection images was significantly improved. SW-CG-HYPR is a promising technique for myocardial perfusion MRI. (c) 2009 Wiley-Liss, Inc.

  16. Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety.

    PubMed

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

    2016-11-15

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

  17. Oxygen saturation and perfusion changes during dermatological methylaminolaevulinate photodynamic therapy.

    PubMed

    Tyrrell, J; Thorn, C; Shore, A; Campbell, S; Curnow, A

    2011-12-01

    Methylaminolaevulinate (MAL)-photodynamic therapy (PDT) is a successful topical treatment for a number of (pre)cancerous dermatological conditions. In combination, light of the appropriate wavelength, the photosensitizer protoporphyrin IX (PpIX) and tissue oxygen result in the production of singlet oxygen and reactive oxygen species inducing cell death. This study investigates real-time changes in localized tissue blood oxygen saturation and perfusion in conjunction with PpIX fluorescence monitoring for the first time during dermatological MAL-PDT. Oxygen saturation, perfusion and PpIX fluorescence were monitored noninvasively utilizing optical reflectance spectroscopy, laser Doppler perfusion imaging and a fluorescence imaging system, respectively. Patients attending for standard dermatological MAL-PDT were recruited to this ethically approved study and monitored prior to, during and after light irradiation. Significant reductions in mean blood oxygen saturation (P < 0·005) and PpIX fluorescence (P < 0·001) were observed within the first minute of irradiation (4·75 J cm(-2) ) while, in contrast, perfusion was observed to increase significantly (P < 0·01) during treatment. The changes in oxygen saturation and PpIX fluorescence were positively correlated during the initial phase of treatment (r(2) = 0·766). Rapid reductions in the localized blood oxygen saturation have been observed for the first time to occur clinically within the initial minutes of light irradiation and positively correlate with the concurrent PpIX photobleaching. Furthermore, perfusion increases, suggesting that the microvasculature compensates for the PDT-induced oxygen depletion. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  18. The influence of the position of the oxygen dissociation curve on oxygen-dependent functions of the isolated perfused rat liver. I. Studies at different levels of hypoxic hypoxia.

    PubMed

    Bakker, J C; Gortmaker, G C; Vrolijk, A C; Offerijns, F G

    1976-03-11

    Isolated rat livers were perfused with fresh and 2,3-DPG (2,3-diphosphoglycerate)-depleted human erythrocytes at different levels of hypoxia. The mean P50 values of the measured actual oxygen dissociation curves (O.D.C.) were 24.5 and 18 mm Hg. No changes in flow rate and perfusion pressure occurred under the different experimental conditons. It was shown that an advantage or disadvantage of a shift of the O.D.C. depends on the degree of hypoxia, as reflected in the venous PO2. Perfusions with fresh erythrocytes showed higher venous PO2 values during normoxia or moderate hypoxia and lower venous PO2 values at severe hypoxia. A cross-over point was found at a PO2 in the portal vein of 36 mm Hg. The disadvantage of perfusions with fresh erythrocytes at severre hypoxia was also reflected in higher cytoplasmatic and mitochondrial redox levels. Using bile flow rate as an indirect measure for the rate of hydroxylation-dependent O2 consumption a favourable effect of perfusion with fresh erythrocytes was found at a PO2 in the portal vein of 100 and 40 mm Hg.

  19. Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

    PubMed

    Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

    2000-08-01

    Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

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

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  1. Short fasting does not protect perfused ex vivo rat liver against ischemia-reperfusion. On the importance of a minimal cell energy charge.

    PubMed

    Papegay, Bérengère; Stadler, Michaela; Nuyens, Vincent; Kruys, Véronique; Boogaerts, Jean G; Vamecq, Joseph

    2017-03-01

    Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores are differently available in time and cell energetic charges (ratio of adenosine triphosphate plus half of the adenosine diphosphate concentrations to the sum of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate concentrations), adenosine phosphates, and glycogen, which were further measured at different time points in livers. Short fasting versus feeding failed to protect perfused ex vivo rat livers against ischemia/reperfusion, increasing the release of cytolysis markers (potassium, cytochrome c, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) in the perfusate during reoxygenation phase. Toxicity of short fasting versus feeding was associated with lower glycogen and energetic charges in livers and lower lactate levels in the perfusate. High energetic charge, intracellular content in glycogen, and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question how much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it suggests that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Is rate–pressure product of any use in the isolated rat heart? Assessing cardiac ‘effort’ and oxygen consumption in the Langendorff‐perfused heart

    PubMed Central

    Aksentijević, Dunja; Lewis, Hannah R.

    2016-01-01

    New Findings What is the central question of this study? Rate–pressure product (RPP) is commonly used as an index of cardiac ‘effort’. In canine and human hearts (which have a positive force–frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species‐independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force–frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac ‘effort’) in the Langendorff‐perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β‐adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate–pressure product (RPP); a rather ill‐defined index of ‘work’ or, more correctly, ‘effort’. Rate–pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV˙O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force–frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV˙O2 in Langendorff‐perfused rat hearts. Paced hearts (300–750 beats min−1) were perfused either with Krebs–Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV˙O2) was recorded. Metabolic status was assessed using 31P magnetic resonance spectroscopy and lactate efflux

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

    PubMed

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

    2017-07-01

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

  4. Biodistribution and Stability Studies of [18F]Fluoroethylrhodamine B, a Potential PET Myocardial Perfusion Agent

    PubMed Central

    Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederick H; Treves, S. Ted; Packard, Alan B.

    2010-01-01

    Introduction Fluorine-18-labeled rhodamine B was developed as a potential PET tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was, therefore, undertaken to further evaluate this hypothesis. Methods [18F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 °C in human, rat and mouse serum and in PBS. Samples were removed periodically and assayed by HPLC. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results In vitro stability studies demonstrated that [18F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but <30% intact in mouse serum. The microPET imaging and biodistribution studies in rats confirmed this result showing high and persistent tracer accumulation in the myocardium compared with the absence of uptake by the myocardium in mice thereby validating our original hypothesis that 18F-labeled rhodamines should accumulate in the heart. Conclusions [18F]Fluoroethyl rhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion. PMID:20346876

  5. Hemodynamic directed cardiopulmonary resuscitation improves short-term survival from ventricular fibrillation cardiac arrest.

    PubMed

    Friess, Stuart H; Sutton, Robert M; Bhalala, Utpal; Maltese, Matthew R; Naim, Maryam Y; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A

    2013-12-01

    During cardiopulmonary resuscitation, adequate coronary perfusion pressure is essential for establishing return of spontaneous circulation. Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Randomized interventional study. Preclinical animal laboratory. Twenty-four 3-month-old female swine. After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Forty-five-minute survival was higher in the coronary perfusion pressure-20 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p < 0.01). Total epinephrine dosing and defibrillation attempts were not different. Hemodynamic directed resuscitation targeting coronary perfusion pressures greater than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival

  6. The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation.

    PubMed

    Bochimoto, Hiroki; Matsuno, Naoto; Ishihara, Yo; Shonaka, Tatsuya; Koga, Daisuke; Hira, Yoshiki; Nishikawa, Yuji; Furukawa, Hiroyuki; Watanabe, Tsuyoshi

    2017-01-01

    The effects of warm machine perfusion preservation of liver grafts donated after cardiac death on the intracellular three-dimensional ultrastructure of the organelles in hepatocytes remain unclear. Here we analyzed comparatively the ultrastructure of the endomembrane systems in porcine hepatocytes under warm ischemia and successive hypothermic and midthermic machine perfusion preservation, a type of the warm machine perfusion. Porcine liver grafts which had a warm ischemia time of 60 minutes were perfused for 4 hours with modified University of Wisconsin gluconate solution. Group A grafts were preserved with hypothermic machine perfusion preservation at 8°C constantly for 4 hours. Group B grafts were preserved with rewarming up to 22°C by warm machine perfusion preservation for 4 hours. An analysis of hepatocytes after 60 minutes of warm ischemia by scanning electron microscope revealed the appearance of abnormal vacuoles and invagination of mitochondria. In the hepatocytes preserved by subsequent hypothermic machine perfusion preservation, strongly swollen mitochondria were observed. In contrast, the warm machine perfusion preservation could preserve the functional appearance of mitochondria in hepatocytes. Furthermore, abundant vacuoles and membranous structures sequestrating cellular organelles like autophagic vacuoles were frequently observed in hepatocytes after warm machine perfusion preservation. In conclusion, the ultrastructure of the endomembrane systems in the hepatocytes of liver grafts changed in accordance with the temperature conditions of machine perfusion preservation. In addition, temperature condition of the machine perfusion preservation may also affect the condition of the hepatic graft attributed to autophagy systems, and consequently alleviate the damage of the hepatocytes.

  7. Differences in Cerebral Perfusion Deficits in Mild Traumatic Brain Injury and Depression Using Single-Photon Emission Computed Tomography

    PubMed Central

    Romero, Kristoffer; Black, Sandra E.; Feinstein, Anthony

    2014-01-01

    Background: Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI. Methods: Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major depressive disorder (MDD), but no TBI were given 99m T-ECD single-photon emission computed tomography (SPECT) scans within 2 weeks of injury. All subjects completed tests of information processing speed, complex attention, and executive functioning, and a self-report questionnaire measuring symptoms of psychological distress. Between-group comparisons of quantified SPECT perfusion were undertaken using univariate and multivariate (partial least squares) analyses. Results: mTBI-D and mTBI-noD groups did not differ in terms of cerebral perfusion. However, patients with MDD showed hypoperfusion compared to both TBI groups in several frontal (orbitofrontal, middle frontal, and superior frontal cortex), superior temporal, and posterior cingulate regions. The mTBI-D group showed poorer performance on a measure of complex attention and working memory compared to both the mTBI-noD and MDD groups. Conclusion: These results suggest that depressive symptoms do not affect SPECT perfusion in the sub-acute phase following a mild TBI. Conversely, MDD is associated with hypoperfusion primarily in frontal regions. PMID:25191305

  8. Tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders.

    PubMed

    López Cadenas, Cristina; Fernández Martínez, Nélida; Sierra Vega, Matilde; Diez Liébana, Maria J; Gonzalo Orden, Jose M; Sahagún Prieto, Ana M; García Vieitez, Juan J

    2012-11-01

    To determine the tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders by measuring its concentration at various sample collection sites. 26 udders (obtained following euthanasia) from 26 healthy lactating sheep. For each isolated udder, 1 mammary gland was perfused with warmed, gassed Tyrode solution. Enrofloxacin (1 g of enrofloxacin/5 g of ointment) was administered into the perfused gland via the intramammary route or systemically via the perfusion fluid (equivalent to a dose of 5 mg/kg). Samples of the perfusate were obtained every 30 minutes for 180 minutes; glandular tissue samples were obtained at 2, 4, 6, and 8 cm from the teat base after 180 minutes. The enrofloxacin content of the perfusate and tissue samples was analyzed via high-performance liquid chromatography with UV detection. After intramammary administration, maximun perfusate enrofloxacin concentration was detected at 180 minutes and, at this time, mean tissue enrofloxacin concentration was detected and mean tissue enrofloxacin concentration was 123.80, 54.48, 36.72, and 26.42 μg/g of tissue at 2, 4, 6, and 8 cm from the teat base, respectively. Following systemic administration, perfusate enrofloxacin concentration decreased with time and, at 180 minutes, tissue enrofloxacin concentrations ranged from 40.38 to 35.58 μg/g of tissue. By 180 minutes after administration via the intramammary or systemic route in isolated perfused sheep mammary glands, mean tissue concentration of enrofloxacin was greater than the minimum inhibitory concentration required to inhibit growth of 90% of many common mastitis pathogens in sheep. Use of either route of administration (or in combination) appears suitable for the treatment of acute mastitis in sheep.

  9. Short-term and long-term plasticity interaction in human primary motor cortex.

    PubMed

    Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

    2011-05-01

    Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. Reliable harvest of a dorsal scapular artery perforator flap by augmenting its perfusion.

    PubMed

    Kim, So-Young; Lee, Kyeong-Tae; Mun, Goo-Hyun

    2016-02-01

    Despite confirmation of a reliable perforasome in the dorsal scapular artery in an anatomic study, a true perforator flap has not been recommended in previous clinical studies because of concerns regarding insufficient perfusion in the distal region. In this report, we present two cases of reconstruction for occipital defects caused by tumor extirpation using pedicled dorsal scapular artery perforator flaps without a muscle component. To secure the perfusion of the dorsal scapular artery perforator flap, inclusion of an additional perforator was attempted for perfusion augmentation. The second dorsal scapular artery perforator was harvested in one case. In an additional case, the sixth dorsal intercostal artery perforator with a branch that directly connected with the dorsal scapular artery within the trapezius muscle was additionally harvested. The flaps survived without any perfusion-related complications, including tip necrosis, and no donor site morbidities were observed. We suggest that a perfusion augmented dorsal scapular artery perforator flap by harvesting multiple perforators could be a safe and useful alternative for reconstructive surgery of head and neck defects. © 2014 Wiley Periodicals, Inc.

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

    DTIC Science & Technology

    1998-12-01

    is similar to those of the study by Ivey et al. [9] in which high intensity fields were used to produce cavitation bubbles for ultrasound contrast...ft * * AD AWARD NUMBER DAMD17-94-J-4144 TITLE: ^ Examination of Ultrasound Measured Tissue Perfusion on Breast Cancer...Examination of Ultrasound Measured Tissue Perfusion on Breast Cancer 3. REPORT TYPE AND DATES COVERED Final (1 Jun 94 - 30 Nov 98) 5. FUNDING

  12. Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

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

    Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.

    1990-05-01

    A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is oftenmore » needed for accurate differential diagnosis.« less

  13. Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

    PubMed

    Bowtell, Joanna L; Aboo-Bakkar, Zainie; Conway, Myra E; Adlam, Anna-Lynne R; Fulford, Jonathan

    2017-07-01

    Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m -2 ) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m -2 ). Pre- and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p < 0.001) as well as significant improvements in grey matter perfusion in the parietal (5.0 ± 1.8 vs -2.9 ± 2.4%, p = 0.013) and occipital (8.0 ± 2.6 vs -0.7 ± 3.2%, p = 0.031) lobes. There was also evidence suggesting improvement in working memory (2-back test) after blueberry versus placebo supplementation (p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

  14. Androgen dynamics in vitro in the human prostate gland. Effect of oestradiol-17β

    PubMed Central

    Giorgi, Eleonora P.; Stewart, Joan C.; Grant, J. K.; Shirley, I. M.

    1972-01-01

    Normal, hyperplastic and adenocarcinomatous human prostatic tissue was perfused in vitro with radioactively labelled androstenedione, testosterone and 5α-dihydrotestosterone with and without added oestradiol-17β. Various parameters of tissue–steroid relationship were measured at the steady state. When oestradiol (0.11 or 0.22μmol/l) was added to the perfusing medium, the entry of the steroids into the tissue and their metabolism was increased in the majority of the glands studied. The `uptake' of all the steroids varied, in response to the addition of oestradiol, in both normal and adenocarcinomatous glands in a way differing from the response of hyperplastic glands. As a consequence, the tissue clearance of the steroids, particularly of androstenedione and testosterone, increased in normal and adenocarcinomatous glands in the presence of oestradiol, and decreased in the hyperplastic tissues. At a concentration 0.33μmol/l, oestradiol decreased the entry of the steroids in all the tissues studied, while the clearance of steroids tended to decrease. The significance of these findings in terms of the regulation of androgen dynamics in vivo in the normal and diseased human prostate, with particular regard to the response to oestrogen treatment, is discussed. PMID:5075225

  15. Effects of insulin under normal and low glucose on retinal electrophysiology in the perfused cat eye.

    PubMed

    Lansel, N; Niemeyer, G

    1997-04-01

    To investigate the short-term effects of fast-acting insulin on the electroretinogram-b-wave, optic nerve response, standing potential, and flow rate in the arterially perfused cat eye under normal conditions and during low glucose levels. Enucleated cat eyes were perfused with a glucose- and insulin-free tissue culture medium, to which glucose was applied at normal (5.5 mM) and reduced (2 and 1 mM) concentrations. Photic stimulation was performed in the rod-matched intensity range before, during, and after insulin application at postprandial (5 ng/ml) and at 10 and 20 x higher concentrations. Insulin failed to affect retinal signals at normal glucose levels. However, insulin enhanced the low glucose-induced decrease in rod-driven b-wave amplitude (P < 0.05 at 2 mM; P < 0.01 at 1 mM) without affecting the corresponding changes in the optic nerve response. The standing potential increased by as much as 0.75 mV in response to insulin. The perfusate flow rate was not altered by insulin. Insulin was not required for normal retinal function as observed during 10 hours of perfusion. The differential responsiveness to insulin under low glucose of the b-wave versus the optic nerve response is thought to reflect suppression of glucose use by Müller (glial) cells rather than neuromodulation, as the neuronal optic nerve response is unaffected. The postulated insulin sensitivity of Müller cells (changes in b-wave amplitude) indicates a possible difference in the mechanism of glucose metabolism of glia versus neurons. The electrophysiological effect of insulin under low glucose suggests its passage across the blood-retina barrier. The increase in the standing potential is likely to be a receptor-mediated retinal pigment epithelium effect. These results provide evidence in the retina for the reported multifunctional nature of the insulin receptor.

  16. Blood perfusion and pH monitoring in organs by laser-induced fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Vari, Sandor G.; Papazoglou, Theodore G.; Pergadia, Vani R.; Stavridi, Marigo; Snyder, Wendy J.; Papaioannou, Thanassis; Duffy, J. T.; Weiss, Andrew B.; Thomas, Reem; Grundfest, Warren S.

    1994-01-01

    Sensitivity of laser-induced fluorescence spectroscopy (LIFS) in detecting a change in tissue pH, and blood perfusion was determined. Rabbits were anesthetized, paralyzed, and mechanically ventilated. The arterial and venous blood supplies of the kidney were isolated and ligated to alter the perfusion. The femoral artery was cannulated to extract samples for blood gas analysis. A 308-nm XeCl was used as an excitation source. A 600 micrometers core diameter fiber was used for fluorescence acquisition, and the spectra analyzed by an optical multichannel analyzer (EG & G, OMA III). the corresponding intensity ratio R equals INADH / ICOLL was used as an index for respiratory acidosis. Blood perfusion was assessed using the following algorithm: (IELAS minus ICOLL) divided by (INADH minus ICOLL). The intensity ratio linearly decreased with the reduction of blood perfusion. When we totally occluded the artery the ratio decreased tenfold when compared to the ratio of a fully perfused kidney. Results of monitoring blood acidosis by laser-induced fluorescence spectroscopy shows a significant trend between pH and intensity ratio. Since all the slopes were negative, there is an obvious significant correlation between the pH and NADH.COLLAGEN RATIO. Blue-light-induced fluorescence measurements and ratio fluorometry is a sensitive method for monitoring blood perfusion and acidity or alkalinity of an organ.

  17. Tumors exposed to acute cyclic hypoxic stress show enhanced angiogenesis, perfusion and metastatic dissemination.

    PubMed

    Rofstad, Einar K; Gaustad, Jon-Vidar; Egeland, Tormod A M; Mathiesen, Berit; Galappathi, Kanthi

    2010-10-01

    Clinical studies have shown that patients with highly hypoxic primary tumors may have poor disease-free and overall survival rates. Studies of experimental tumors have revealed that acutely hypoxic cells may be more metastatic than normoxic or chronically hypoxic cells. In the present work, causal relations between acute cyclic hypoxia and metastasis were studied by periodically exposing BALB/c nu/nu mice bearing A-07 human melanoma xenografts to a low oxygen atmosphere. The hypoxia treatment consisted of 12 cycles of 10 min of 8% O(2) in N(2) followed by 10 min of air for a total of 4 hr, began on the first day after tumor cell inoculation and was given daily until the tumors reached a volume of 100 mm(3). Twenty-four hours after the last hypoxia exposure, the primary tumors were subjected to dynamic contrast-enhanced magnetic resonance imaging for assessment of blood perfusion before being resected and processed for immunohistochemical examinations of microvascular density and expression of proangiogenic factors. Mice exposed to acute cyclic hypoxia showed increased incidence of pulmonary metastases, and the primary tumors of these mice showed increased blood perfusion, microvascular density and vascular endothelial growth factor-A (VEGF-A) expression; whereas, the expression of interleukin-8, platelet-derived endothelial cell growth factor and basic fibroblast growth factor was unchanged. The increased pulmonary metastasis was most likely a consequence of hypoxia-induced VEGF-A upregulation, which resulted in increased angiogenic activity and blood perfusion in the primary tumor and thus facilitated tumor cell intravasation and hematogenous transport into the general circulation.

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

    PubMed

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

    2010-11-01

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

  19. Brain perfusion correlates of cognitive and nigrostriatal functions in de novo Parkinson's disease.

    PubMed

    Nobili, Flavio; Arnaldi, Dario; Campus, Claudio; Ferrara, Michela; De Carli, Fabrizio; Brugnolo, Andrea; Dessi, Barbara; Girtler, Nicola; Morbelli, Silvia; Abruzzese, Giovanni; Sambuceti, Gianmario; Rodriguez, Guido

    2011-12-01

    Subtle cognitive impairment is recognized in the first stages of Parkinson's disease (PD), including executive, memory and visuospatial dysfunction, but its pathophysiological basis is still debated. Twenty-six consecutive, drug-naïve, de novo PD patients underwent an extended neuropsychological battery, dopamine transporter (DAT) and brain perfusion single photon emission computed tomography (SPECT). We previously reported that nigrocaudate impairment correlates with executive functions, and nigroputaminal impairment with visuospatial abilities. Here perfusion SPECT was first compared between the PD group and age-matched controls (CTR). Then, perfusion SPECT was correlated with both DAT SPECT and four neuropsychological factors by means of voxel-based analysis (SPM8) with a height threshold of p < 0.005 at peak level and p < 0.05 false discovery rate-corrected at cluster level. Both perfusion and DAT SPECT images were flipped in order to have the more affected hemisphere (MAH), defined clinically, on the same side. Significant hypoperfusion was found in an occipital area of the MAH in PD patients as compared to CTR. Executive functions directly correlated with brain perfusion in bilateral posterior cingulate cortex and precuneus in the less affected hemisphere (LAH), while verbal memory directly correlated with perfusion in the precuneus, inferior parietal lobule and superior temporal gyrus in the LAH. Furthermore, positive correlation was highlighted between nigrocaudate and nigroputaminal impairment and brain perfusion in the precuneus, posterior cingulate and parahippocampal gyri of the LAH. These data support the evidence showing an early involvement of the cholinergic system in the early cognitive dysfunction and point to a more relevant role of parietal lobes and posterior cingulate in executive functions in PD.

  20. Review: comparison of PET rubidium-82 with conventional SPECT myocardial perfusion imaging

    PubMed Central

    Ghotbi, Adam A; Kjær, Andreas; Hasbak, Philip

    2014-01-01

    Nuclear cardiology has for many years been focused on gamma camera technology. With ever improving cameras and software applications, this modality has developed into an important assessment tool for ischaemic heart disease. However, the development of new perfusion tracers has been scarce. While cardiac positron emission tomography (PET) so far largely has been limited to centres with on-site cyclotron, recent developments with generator produced perfusion tracers such as rubidium-82, as well as an increasing number of PET scanners installed, may enable a larger patient flow that may supersede that of gamma camera myocardial perfusion imaging. PMID:24028171

  1. Design of a flow perfusion bioreactor system for bone tissue-engineering applications.

    PubMed

    Bancroft, Gregory N; Sikavitsas, Vassilios I; Mikos, Antonios G

    2003-06-01

    Several different bioreactors have been investigated for tissue-engineering applications. Among these bioreactors are the spinner flask and the rotating wall vessel reactor. In addition, a new type of culture system has been developed and investigated, the flow perfusion culture bioreactor. Flow perfusion culture offers several advantages, notably the ability to mitigate both external and internal diffusional limitations as well as to apply mechanical stress to the cultured cells. For such investigation, a flow perfusion culture system was designed and built. This design is the outgrowth of important design requirements and incorporates features crucial to successful experimentation with such a system.

  2. Intestinal permeability of forskolin by in situ single pass perfusion in rats.

    PubMed

    Liu, Zhen-Jun; Jiang, Dong-bo; Tian, Lu-Lu; Yin, Jia-Jun; Huang, Jian-Ming; Weng, Wei-Yu

    2012-05-01

    The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney

    PubMed Central

    Engbersen, Richard; Moons, Miek M; Wouterse, Alfons C; Dijkman, Henry B; Kramers, Cees; Smits, Paul; Russel, Frans G M

    2000-01-01

    Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 μM) and glibenclamide (10 μM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3±1.5 for hypoxic perfusions vs 4.9±1.6 for normoxic perfusions, mean±s.e.mean, P<0.05), which could be completely restored by 200 μM tolbutamide (5.7±0.4 for tolbutamide vs 14.3±1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220±100 mU for tolbutamide vs 1220±160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 μM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations. PMID:10928974

  4. Complete inhibition of creatine kinase in isolated perfused rat hearts

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

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts aremore » able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.« less

  5. Optical bedside monitoring of cerebral perfusion: technological and methodological advances applied in a study on acute ischemic stroke

    NASA Astrophysics Data System (ADS)

    Steinkellner, Oliver; Gruber, Clemens; Wabnitz, Heidrun; Jelzow, Alexander; Steinbrink, Jens; Fiebach, Jochen B.; MacDonald, Rainer; Obrig, Hellmuth

    2010-11-01

    We present results of a clinical study on bedside perfusion monitoring of the human brain by optical bolus tracking. We measure the kinetics of the contrast agent indocyanine green using time-domain near-IR spectroscopy (tdNIRS) in 10 patients suffering from acute unilateral ischemic stroke. In all patients, a delay of the bolus over the affected when compared to the unaffected hemisphere is found (mean: 1.5 s, range: 0.2 s to 5.2 s). A portable time-domain near-IR reflectometer is optimized and approved for clinical studies. Data analysis based on statistical moments of time-of-flight distributions of diffusely reflected photons enables high sensitivity to intracerebral changes in bolus kinetics. Since the second centralized moment, variance, is preferentially sensitive to deep absorption changes, it provides a suitable representation of the cerebral signals relevant for perfusion monitoring in stroke. We show that variance-based bolus tracking is also less susceptible to motion artifacts, which often occur in severely affected patients. We present data that clearly manifest the applicability of the tdNIRS approach to assess cerebral perfusion in acute stroke patients at the bedside. This may be of high relevance to its introduction as a monitoring tool on stroke units.

  6. Phosphorus NMR of isolated perfused morris hepatomas

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

    Graham, R.A.; Meyer, R.A.; Brown, T.R.

    1986-03-05

    The authors are developing techniques for the study of perfused solid tumors by NMR. Tissue-isolated solid hepatomas were grown to 1-2 cm diameter as described previously. The arterial supply was isolated and the tumors perfused (0.5 - 1.0 ml/min) in vitro at 25 C with a 15% suspension of red blood cells in Krebs-Henseliet solution. /sup 31/P-NMR spectra were acquired at 162 MHz in a specially-designed NMR probe using a solenoidal coil. Intracellular pH (monitored from the chemical shift of inorganic phosphate) and ATP levels were stable for up to 6 hrs during perfusion. During 30 min of global ischemia,more » ATP decreased by 75% and pH fell from 7.0 to 6.7. These changes were reversed by 1 hr reperfusion. In addition to ATP and phosphate, the spectra included a large resonance due to phosphomonoesters, as well as peaks consistent with glycerylphosphocholine, glyceryl-phosphoethanolamine, phosphocreatine, NAD, and UDPG. However, the most novel feature of the spectra was the presence of an unidentified peak in the phosphonate region (+ 16.9 ppm). The peak was not present in spectra of muscle, liver, brain, kidney, or fat tissues excised from the same animals. They are presently attempting to identify the compound that gives rise to this peak and to establish its metabolic origin.« less

  7. Critical cerebral perfusion pressure at high intracranial pressure measured by induced cerebrovascular and intracranial pressure reactivity.

    PubMed

    Bragin, Denis E; Statom, Gloria L; Yonas, Howard; Dai, Xingping; Nemoto, Edwin M

    2014-12-01

    The lower limit of cerebral blood flow autoregulation is the critical cerebral perfusion pressure at which cerebral blood flow begins to fall. It is important that cerebral perfusion pressure be maintained above this level to ensure adequate cerebral blood flow, especially in patients with high intracranial pressure. However, the critical cerebral perfusion pressure of 50 mm Hg, obtained by decreasing mean arterial pressure, differs from the value of 30 mm Hg, obtained by increasing intracranial pressure, which we previously showed was due to microvascular shunt flow maintenance of a falsely high cerebral blood flow. The present study shows that the critical cerebral perfusion pressure, measured by increasing intracranial pressure to decrease cerebral perfusion pressure, is inaccurate but accurately determined by dopamine-induced dynamic intracranial pressure reactivity and cerebrovascular reactivity. Cerebral perfusion pressure was decreased either by increasing intracranial pressure or decreasing mean arterial pressure and the critical cerebral perfusion pressure by both methods compared. Cortical Doppler flux, intracranial pressure, and mean arterial pressure were monitored throughout the study. At each cerebral perfusion pressure, we measured microvascular RBC flow velocity, blood-brain barrier integrity (transcapillary dye extravasation), and tissue oxygenation (reduced nicotinamide adenine dinucleotide) in the cerebral cortex of rats using in vivo two-photon laser scanning microscopy. University laboratory. Male Sprague-Dawley rats. At each cerebral perfusion pressure, dopamine-induced arterial pressure transients (~10 mm Hg, ~45 s duration) were used to measure induced intracranial pressure reactivity (Δ intracranial pressure/Δ mean arterial pressure) and induced cerebrovascular reactivity (Δ cerebral blood flow/Δ mean arterial pressure). At a normal cerebral perfusion pressure of 70 mm Hg, 10 mm Hg mean arterial pressure pulses had no effect on

  8. Long-term Culture of Human iPS Cell-derived Telencephalic Neuron Aggregates on Collagen Gel.

    PubMed

    Oyama, Hiroshi; Takahashi, Koji; Tanaka, Yoshikazu; Takemoto, Hiroshi; Haga, Hisashi

    2018-01-01

    It takes several months to form the 3-dimensional morphology of the human embryonic brain. Therefore, establishing a long-term culture method for neuronal tissues derived from human induced pluripotent stem (iPS) cells is very important for studying human brain development. However, it is difficult to keep primary neurons alive for more than 3 weeks in culture. Moreover, long-term adherent culture to maintain the morphology of telencephalic neuron aggregates induced from human iPS cells is also difficult. Although collagen gel has been widely used to support long-term culture of cells, it is not clear whether human iPS cell-derived neuron aggregates can be cultured for long periods on this substrate. In the present study, we differentiated human iPS cells to telencephalic neuron aggregates and examined long-term culture of these aggregates on collagen gel. The results indicated that these aggregates could be cultured for over 3 months by adhering tightly onto collagen gel. Furthermore, telencephalic neuronal precursors within these aggregates matured over time and formed layered structures. Thus, long-term culture of telencephalic neuron aggregates derived from human iPS cells on collagen gel would be useful for studying human cerebral cortex development.Key words: Induced pluripotent stem cell, forebrain neuron, collagen gel, long-term culture.

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

    PubMed

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

    2002-06-01

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

  10. Design modification and optimisation of the perfusion system of a tri-axial bioreactor for tissue engineering.

    PubMed

    Hussein, Husnah; Williams, David J; Liu, Yang

    2015-07-01

    A systematic design of experiments (DOE) approach was used to optimize the perfusion process of a tri-axial bioreactor designed for translational tissue engineering exploiting mechanical stimuli and mechanotransduction. Four controllable design parameters affecting the perfusion process were identified in a cause-effect diagram as potential improvement opportunities. A screening process was used to separate out the factors that have the largest impact from the insignificant ones. DOE was employed to find the settings of the platen design, return tubing configuration and the elevation difference that minimise the load on the pump and variation in the perfusion process and improve the controllability of the perfusion pressures within the prescribed limits. DOE was very effective for gaining increased knowledge of the perfusion process and optimizing the process for improved functionality. It is hypothesized that the optimized perfusion system will result in improved biological performance and consistency.

  11. Diffusion, Perfusion, and Histopathologic Characteristics of Desmoplastic Infantile Ganglioglioma.

    PubMed

    Ho, Chang Y; Gener, Melissa; Bonnin, Jose; Kralik, Stephen F

    2016-07-01

    We present a case series of a rare tumor, the desmoplastic infantile ganglioglioma (DIG) with MRI diffusion and perfusion imaging quantification as well as histopathologic characterization. Four cases with pathologically-proven DIG had diffusion weighted imaging (DWI) and two of the four had dynamic susceptibility contrast imaging. All four tumors demonstrate DWI findings compatible with low-grade pediatric tumors. For the two cases with perfusion imaging, a higher relative cerebral blood volume was associated with higher proliferation index on histopathology for one of the cases. Our results are discussed in conjunction with a literature review.

  12. Uptake of Free Choline by Isolated Perfused Rat Liver

    NASA Astrophysics Data System (ADS)

    Zeisel, Steven H.; Story, David L.; Wurtman, Richard J.; Brunengraber, Henri

    1980-08-01

    The uptake of free choline by isolated perfused rat liver was characterized. A saturable uptake mechanism [Ka=0.17± 0.07 mM (SD); Vmax=0.84± 0.16\\ μ mol/min × g dry weight] and a nonsaturable mechanism (through which uptake is proportional to choline concentration in the perfusate) were identified. Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin. Free choline also accumulated within the intracellular space, suggesting that choline oxidase activity does not always limit choline's uptake by the liver.

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

    PubMed Central

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

    2016-01-01

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

  14. Diagnostic and clinical benefit of combined coronary calcium and perfusion assessment in patients undergoing PET/CT myocardial perfusion stress imaging.

    PubMed

    Bybee, Kevin A; Lee, John; Markiewicz, Richard; Longmore, Ryan; McGhie, A Iain; O'Keefe, James H; Hsu, Bai-Ling; Kennedy, Kevin; Thompson, Randall C; Bateman, Timothy M

    2010-04-01

    A limitation of stress myocardial perfusion imaging (MPI) is the inability to detect non-obstructive coronary artery disease (CAD). One advantage of MPI with a hybrid CT device is the ability to obtain same-setting measurement of the coronary artery calcium score (CACS). Utilizing our single-center nuclear database, we identified 760 consecutive patients with: (1) no CAD history; (2) a normal clinically indicated Rb-82 PET/CT stress perfusion study; and (3) a same-setting CAC scan. 487 of 760 patients (64.1%) had subclinical CAD based on an abnormal CACS. Of those with CAC, the CACS was > or =100, > or =400, and > or =1000 in 47.0%, 22.4%, and 8.4% of patients, respectively. Less than half of the patients with CAC were receiving aspirin or statin medications prior to PET/CT imaging. Patients with CAC were more likely to be initiated or optimized on proven medical therapy for CAD immediately following PET/CT MPI compared to those without CAC. Subclinical CAD is common in patients without known CAD and normal myocardial perfusion assessed by hybrid PET/CT imaging. Identification of CAC influences subsequent physician prescribing patterns such that those with CAC are more likely to be treated with proven medical therapy for the treatment of CAD.

  15. Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta.

    PubMed

    Malek, A; Leiser, R

    2009-01-01

    Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v. administration of a dose equivalent to that used in the treatment of preeclampsia to nonpregnant volunteers, a 10-fold increase of aspartic acid (Asp) over the physiological level was observed. Animal experiments have demonstrated that highly increased fetal levels of acidic amino acids such as Asp could be associated with neurotoxic damage in the fetal brain. The influence of such an elevation of Asp concentration in the maternal circuit on the fetal level, using the in vitro perfusion model of human placenta, was investigated. After a control phase (2h), a therapeutic dose of Mg combined with Asp (Magnesiocard, Mg-Asp-HCl) was applied to the maternal circuit approaching 10 times the physiological level of Asp. The administration was performed in two different phases simulating either a peak of maximum concentration (bolus application, 2h) or a steady state level (initially added, 4h). In four experiments, during experimental phases (6h) a slow increase in concentration in the fetal circuit was seen for Mg, AIB (alpha-aminoisobutyric acid, artificial amino acid) and creatinine confirming previous observations. In contrast, no net transfer of Asp across the placenta was seen. A continuous decrease in the concentration of Asp on both maternal and fetal side suggests active uptake and metabolization by the placenta. Viability control parameters remained stable indicating the absence of an effect on placental metabolism, permeability and morphology. Elevation of Asp concentration up to 10 times the physiological level by the administration of Mg-Asp-HCl to the maternal circuit under in vitro perfusion conditions of human placenta has no influence on the fetal level of Asp suggesting no transfer of Asp from the maternal to fetal compartment. Therefore, the administration of Mg-Asp-HCl to

  16. [Lung perfusion studies after percutaneous closure of patent ductus arteriosus using the Amplatzer Duct Occluder in children].

    PubMed

    Parra-Bravo, José Rafael; Apolonio-Martínez, Adriana; Estrada-Loza, María de Jesús; Beirana-Palencia, Luisa Gracia; Ramírez-Portillo, César Iván

    2015-01-01

    The closure of patent ductus arteriosus with multiple devices has been associated with a reduction in lung perfusion. We evaluated the pulmonary perfusion after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder device using perfusion lung scan. Thirty patients underwent successful percutaneous patent ductus arteriosus occlusions using the Amplatzer Duct Occluder device were included in this study. Lung perfusion scans were preformed 6 months after the procedure. Peak flow velocities and protrusion of the device were analyzed by Doppler echocardiography. A left lung perfusion<40% was considered abnormal. The device implantation was successful in all patients. Average perfusion of left lung was 44.7±4.9% (37.8-61.4). Five patients (16.6%) showed decreased perfusion of the left lung. Age, low weight, the length of the ductus arteriosus and the minimum and maximum diameter/length of the ductus arteriosus ratio were statistically significant in patients with abnormalities of lung perfusion. It was observed protrusion the device in 6 patients with a higher maximum flow rate in the left pulmonary artery. The left lung perfusion may be compromised after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder. The increased flow velocity in the origin of the left pulmonary artery can be a poor indicator of reduction in pulmonary perfusion and can occur in the absence of protrusion of the device. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

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

    PubMed Central

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

    2012-01-01

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

  18. Propranolol hydrochloride enhancement of tumor perfusion and uptake of gallium-67 in a mouse sarcoma

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

    Bomber, P.; McCready, R.; Hammersley, P.

    1986-02-01

    The effect of propranolol hydrochloride on the blood perfusion of a mouse sarcoma and other tissues has been studied using /sup 86/Rb. The maximum increase in relative tumor perfusion (2x controls) occurred 15 min after an i.v. administration of 10 mg per kg propranolol hydrochloride. To study the effect of this drug on the uptake of /sup 67/Ga, it was injected at a concentration of 10 mg/kg 10 min before administering 3 microCi (110 kBq) (/sup 67/Ga)citrate. Tissue uptakes were measured 4 hr later. The tumor: blood ratio increased from 1.16 +/- 0.17 to 3.41 +/- 2.27 (s.d.) and tumor:more » liver ratio increased from 2.39 +/- 0.30 to 7.13 +/- 3.52 (s.d.). The results showed that propranolol hydrochloride can improve the relative tumor blood flow and radiopharmaceutical concentration in an animal model. It is hoped that this and other agents will yield similar results in the human situation.« less

  19. Stress perfusion magnetic resonance imaging to detect coronary artery lesions in children.

    PubMed

    Vijarnsorn, Chodchanok; Noga, Michelle; Schantz, Daryl; Pepelassis, Dion; Tham, Edythe B

    2017-05-01

    Stress perfusion cardiovascular magnetic resonance (CMR) is used widely in adult ischemic heart disease, but data in children is limited. We sought to evaluate feasibility, accuracy and prognostic value of stress CMR in children with suspected coronary artery disease (CAD). Stress CMR was reviewed from two pediatric centers over 5 years using a standard pharmacologic protocol. Wall motion abnormalities, perfusion deficits and late enhancement were correlated with coronary angiogram (CAG) when available, and clinical status at 1 year follow-up for major adverse cardiovascular events (MACE; coronary revascularization, non-fatal myocardial infarction and death due to CAD) was recorded. Sixty-four stress perfusion CMR studies in 48 children (10.9 ± 4.8 years) using adenosine; 59 (92%) and dipyridamole; 5 (8%), were reviewed. Indications were Kawasaki disease (39%), post arterial switch operation (12.5%), post heart transplantation (12.5%), post anomalous coronary artery repair (11%), chest pain (11%), suspected myocarditis or CAD (3%), post coronary revascularization (3%), and others (8%). Twenty-six studies were performed under sedation. Of all studies performed, 66% showed no evidence of ischemia or infarction, 28% had perfusion deficits and 6% had late gadolinium enhancement (LGE) without perfusion deficit. Compared to CAG, the positive predictive value (PPV) of stress CMR was 80% with negative predictive value (NPV) of 88%. At 1 year clinical follow-up, the PPV and NPV of stress CMR to predict MACE were 78 and 98%. Stress-perfusion CMR, in combination with LGE and wall motion-analysis is a feasible and an accurate method of diagnosing CAD in children. In difficult cases, it also helps guide clinical intervention by complementing conventional CAG with functional information.

  20. The release and vascular action of bradykinin in the isolated perfused bovine udder

    PubMed Central

    Zeitlin, I J; Eshraghi, H R

    2002-01-01

    It has been postulated that the mammary kinin system may play a role in modulating mammary blood flow. Until the present study, the local release of bradykinin (BK) or other kinin system constituents into the mammary vasculature had not been reported and there were also conflicting findings on the action of BK on udder vasculature. Udders were removed from healthy lactating cows at slaughter. Pairs of ipsilateral quarters were perfused with Tyrode solution through the external pudendalis artery and drained via the cranial superficial epigastric vein. Mammary secretion was collected through teat cannulae. The perfusion pressure was linearly related to perfusate flux between 60 and 210 ml min−1 and the flow rate was adjusted (110-150 ml min−1) to give a basal pressure of 85 mmHg. PO2, PCO2 and pH in the venous effluent perfusate stabilised at 157 ± 10 mmHg, 50.1 ± 2.4 mmHg and 7.1 ± 0.03, respectively. The venous effluent contained immunoreactive BK and BK precursor, tissue kallikrein activity, and bradykinin-destroying enzyme. The concentration of BK stabilised at 378 ± 48 pg (ml perfusate)−1, that of trypsin-activated BK precursor was 679 ± 59 pg BK equivalents ml−1 and that of tissue kallikrein, measured as cleavage of d-Val.Leu.Arg-p-nitroanilide (d-Val.Leu.Arg-pNA), was 5.5 ± 1.7 nmol p-NA h−1 ml−1. Arterial infusion of phenylephrine (0.49-490 μM) produced increases in perfusion pressure (vasoconstriction). Acetylcholine (ACh) (0.55-55 μM) and BK (0.1-10 μM) produced only vasodilatation. BK (EC50 = 1.00±0.04 μM) was a more potent vasodilator than ACh (EC50 = 9.57±0.49 μM). The basal BK concentration was 250 times below the threshold for vasoactivity. The udder produced a milk-like secretion, which was dependent on perfusate flow and contained a concentration of BK which remained unchanged from 60 to 180 min of perfusion (231 ± 31 pg ml−1) unlike that in the venous effluent which doubled between 60 and 120 min. Thus, in addition to its

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

    PubMed

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

    2017-05-20

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

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

    PubMed

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

    2015-10-01

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

  3. Correlations between near-infrared spectroscopy, perfusion index, and cardiac outputs in extremely preterm infants in the first 72 h of life.

    PubMed

    Janaillac, Marie; Beausoleil, Thierry P; Barrington, Keith J; Raboisson, Marie-Josée; Karam, Oliver; Dehaes, Mathieu; Lapointe, Anie

    2018-04-01

    Haemodynamic assessment during the transitional period in preterm infants is challenging. We aimed to describe the relationships between cerebral regional tissue oxygen saturation (CrSO 2 ), perfusion index (PI), echocardiographic, and clinical parameters in extremely preterm infants in their first 72 h of life. Twenty newborns born at < 28 weeks of gestation were continuously monitored with CrSO 2 and preductal PI. Cardiac output was measured at H6, H24, H48, and H72. The median gestational age and birth weight were 25.0 weeks (24-26) and 750 g (655-920), respectively. CrSO 2 and preductal PI had r values < 0.35 with blood gases, lactates, haemoglobin, and mean blood pressure. Cardiac output significantly increased over the 72 h of the study period. Fifteen patients had at least one episode of low left and/or right ventricular output (RVO), during which there was a strong correlation between CrSO 2 and superior vena cava (SVC) flow (at H6 (r = 0.74) and H24 (r = 0.86)) and between PI and RVO (at H6 (r = 0.68) and H24 (r = 0.92)). Five patients had low SVC flow (≤ 40 mL/kg/min) at H6, during which PI was strongly correlated with RVO (r = 0.98). CrSO 2 and preductal PI are strongly correlated with cardiac output during low cardiac output states. What is Known: • Perfusion index and near-infrared spectroscopy are non-invasive tools to evaluate haemodynamics in preterm infants. • Pre- and postductal perfusion indexes strongly correlate with left ventricular output in term infants, and near-infrared spectroscopy has been validated to assess cerebral oxygenation in term and preterm infants. What is New: • Cerebral regional tissue oxygen saturation and preductal perfusion index were strongly correlated with cardiac output during low cardiac output states. • The strength of the correlation between cerebral regional tissue oxygen saturation, preductal perfusion index, and cardiac output varied in the first 72 h of life, reflecting

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

    PubMed

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

    2012-12-01

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

  5. Use of gold nanoshells to mediate heating induced perfusion changes in prostate tumors

    NASA Astrophysics Data System (ADS)

    Shetty, Anil; Elliott, Andrew M.; Schwartz, Jon A.; Wang, James; Esparza-Coss, Emilio; Klumpp, Sherry; Taylor, Brian; Hazle, John D.; Stafford, R. Jason

    2008-02-01

    This study investigates the potential of using gold nanoshells to mediate a thermally induced modulation of tumor vasculature in experimental prostate tumors. We demonstrate that after passive extravasation and retention of the circulating nanoshells from the tumor vasculature into the tumor interstitium, the enhanced nanoshells absorption of near-infrared irradiation over normal vasculature, can be used to increase tumor perfusion or shut it down at powers which result in no observable affects on tissue without nanoshells. Temperature rise was monitored in real time using magnetic resonance temperature imaging and registered with perfusion changes as extrapolated from MR dynamic contrast enhanced (DCE) imaging results before and after each treatment. Results indicate that nanoshell mediated heating can be used to improve perfusion and subsequently enhance drug delivery and radiation effects, or be used to shut down perfusion to assist in thermal ablative therapy delivery.

  6. Development of a perfusion reversed-phase high performance liquid chromatography method for the characterisation of maize products using multivariate analysis.

    PubMed

    Rodriguez-Nogales, J M; Garcia, M C; Marina, M L

    2006-02-03

    A perfusion reversed-phase high performance liquid chromatography (RP-HPLC) method has been designed to allow rapid (3.4 min) separations of maize proteins with high resolution. Several factors, such as extraction conditions, temperature, detection wavelength and type and concentration of ion-pairing agent were optimised. A fine optimisation of the gradient elution was also performed by applying experimental design. Commercial maize products for human consumption (flours, precocked flours, fried snacks and extruded snacks) were characterised for the first time by perfusion RP-HPLC and their chromatographic profiles allowed a differentiation among products relating the different technological process used for their preparation. Furthermore, applying discriminant analysis makes it possible to group the samples according with the technological process suffered by maize products, obtaining a good prediction in 92% of the samples.

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

    NASA Astrophysics Data System (ADS)

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

    2017-05-01

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

  8. Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics

    PubMed Central

    Sommer, Wieland H; Bollwein, Christine; Thierfelder, Kolja M; Baumann, Alena; Janssen, Hendrik; Ertl-Wagner, Birgit; Reiser, Maximilian F; Plate, Annika; Straube, Andreas

    2015-01-01

    We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis. PMID:26661242

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

    PubMed

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

    2017-01-01

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

  10. A Simplified Whole-Organ CT Perfusion Technique with Biphasic Acquisition: Preliminary Investigation of Accuracy and Protocol Feasibility in Kidneys.

    PubMed

    Yuan, XiaoDong; Zhang, Jing; Quan, ChangBin; Tian, Yuan; Li, Hong; Ao, GuoKun

    2016-04-01

    To determine the feasibility and accuracy of a protocol for calculating whole-organ renal perfusion (renal blood flow [RBF]) and regional perfusion on the basis of biphasic computed tomography (CT), with concurrent dynamic contrast material-enhanced (DCE) CT perfusion serving as the reference standard. This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Biphasic CT of the kidneys, including precontrast and arterial phase imaging, was integrated with a first-pass dynamic volume CT protocol and performed and analyzed in 23 patients suspected of having renal artery stenosis. The perfusion value derived from biphasic CT was calculated as CT number enhancement divided by the area under the arterial input function and compared with the DCE CT perfusion data by using the paired t test, correlation analysis, and Bland-Altman plots. Correlation analysis was made between the RBF and the extent of renal artery stenosis. All postprocessing was independently performed by two observers and then averaged as the final result. Mean ± standard deviation biphasic and DCE CT perfusion data for RBF were 425.62 mL/min ± 124.74 and 419.81 mL/min ± 121.13, respectively (P = .53), and for regional perfusion they were 271.15 mL/min per 100 mL ± 82.21 and 266.33 mL/min per 100 mL ± 74.40, respectively (P = .31). Good correlation and agreement were shown between biphasic and DCE CT perfusion for RBF (r = 0.93; ±10% variation from mean perfusion data [P < .001]) and for regional perfusion (r = 0.90; ±13% variation from mean perfusion data [P < .001]). The extent of renal artery stenosis was negatively correlated with RBF with biphasic CT perfusion (r = -0.81, P = .012). Biphasic CT perfusion is clinically feasible and provides perfusion data comparable to DCE CT perfusion data at both global and regional levels in the kidney. Online supplemental material is available for this article.

  11. Analyzing the value of monitoring duodenal mucosal perfusion using photoplethysmography.

    PubMed

    Fink, Mitchell P

    2014-10-13

    Photoplethysmography (PPG) is a technique that permits noninvasive measurement of changes in the volume of tissues. A novel device uses PPG to assess changes in duodenal mucosal perfusion. When tested in septic piglets, data obtained using this device correlate with the blood lactate concentration and duodenal serosal microvascular blood flow as measured with a laser Doppler flowmeter. This new PPG-based approach for continuously monitoring gut mucosal perfusion warrants further development, leading to prospective clinical trials in patients.

  12. Optic nerve head blood flow response to reduced ocular perfusion pressure by alteration of either the blood pressure or intraocular pressure.

    PubMed

    Wang, Lin; Cull, Grant A; Fortune, Brad

    2015-04-01

    To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Twelve normal non-human primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n = 6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n = 6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. The optic nerve head blood flow showed significant difference between the two groups (p = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (p < 0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (p = 0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence related to the

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

    PubMed

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

    2018-05-11

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

  14. Using a pulse oximeter to determine clinical depth of anesthesia-investigation of the utility of the perfusion index.

    PubMed

    Krishnamohan, Anirudh; Siriwardana, Viraj; Skowno, Justin J

    2016-11-01

    Peripheral vasodilation is a well-recognized side effect of general anesthesia, and induces changes in the amplitude of the pulse plethysmograph (PPG) waveform. This can be continuously quantitaed using the Perfusion Index (PI), a ratio of the pulsatile to nonpulsatile signal amplitude in the PPG waveform. We hypothesized that the perfusion index would rise with the induction of anesthesia in children, and fall with emergence, and performed a prospective, observational study to test this. Our primary aim was to test whether the different clinical stages of anesthesia were associated with changes in the perfusion index, and the secondary aim was to test the correlation between the normalized perfusion index and the MAC value. Twenty-one patients between the ages of 1 and 18 undergoing minor procedures with no anticipated painful stimuli were recruited. Patients with significant illnesses were excluded. Data collection commenced with a preinduction baseline, and data were collected continuously, with event marking, until completion of the anesthesia and removal of the pulse oximeter. Data collected included perfusion index, heart rate, and anesthetic gas concentration values. A normalized perfusion index was calculated by subtracting the initial baseline perfusion index value from all perfusion index values, allowing changes, from a standardized initial baseline value of zero, to be analyzed. During induction, the mean normalized perfusion index rose from 0.0 to 4.2, and then declined to 0.470 when the patients returned to consciousness. P < 0.001 using repeated measures anova test. The normalized perfusion index was correlated with MAC values (r 2 = 0.33, 95% CI 0.18-0.47, P < 0.01). The perfusion index changed significantly during different stages of anesthesia. There is a significant correlation between the perfusion index, measured by pulse oximetry, and the MAC value, in pediatric patients undergoing minor procedures. © 2016 John Wiley & Sons Ltd.

  15. Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT.

    PubMed

    Gardner, Ann; Åstrand, Disa; Öberg, Johanna; Jacobsson, Hans; Jonsson, Cathrine; Larsson, Stig; Pagani, Marco

    2014-08-30

    Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. 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.

  17. Optimization of OSEM parameters in myocardial perfusion imaging reconstruction as a function of body mass index: a clinical approach*

    PubMed Central

    de Barros, Pietro Paolo; Metello, Luis F.; Camozzato, Tatiane Sabriela Cagol; Vieira, Domingos Manuel da Silva

    2015-01-01

    Objective The present study is aimed at contributing to identify the most appropriate OSEM parameters to generate myocardial perfusion imaging reconstructions with the best diagnostic quality, correlating them with patients’ body mass index. Materials and Methods The present study included 28 adult patients submitted to myocardial perfusion imaging in a public hospital. The OSEM method was utilized in the images reconstruction with six different combinations of iterations and subsets numbers. The images were analyzed by nuclear cardiology specialists taking their diagnostic value into consideration and indicating the most appropriate images in terms of diagnostic quality. Results An overall scoring analysis demonstrated that the combination of four iterations and four subsets has generated the most appropriate images in terms of diagnostic quality for all the classes of body mass index; however, the role played by the combination of six iterations and four subsets is highlighted in relation to the higher body mass index classes. Conclusion The use of optimized parameters seems to play a relevant role in the generation of images with better diagnostic quality, ensuring the diagnosis and consequential appropriate and effective treatment for the patient. PMID:26543282

  18. Short-term fasting alters cytochrome P450-mediated drug metabolism in humans.

    PubMed

    Lammers, Laureen A; Achterbergh, Roos; de Vries, Emmely M; van Nierop, F Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R; Boelen, Anita; Romijn, Johannes A; Mathôt, Ron A A

    2015-06-01

    Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug metabolism. In a randomized crossover study design, nine healthy subjects ingested a cocktail consisting of five P450-specific probe drugs [caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4)] on two occasions (control study after an overnight fast and after 36 h of fasting). Blood samples were drawn for pharmacokinetic analysis using nonlinear mixed effects modeling. In addition, we studied in Wistar rats the effects of short-term fasting on hepatic mRNA expression of P450 isoforms corresponding with the five studied P450 enzymes in humans. In the healthy subjects, short-term fasting increased oral caffeine clearance by 20% (P = 0.03) and decreased oral S-warfarin clearance by 25% (P < 0.001). In rats, short-term fasting increased mRNA expression of the orthologs of human CYP1A2, CYP2C19, CYP2D6, and CYP3A4 (P < 0.05), and decreased the mRNA expression of the ortholog of CYP2C9 (P < 0.001) compared with the postabsorptive state. These results demonstrate that short-term fasting alters cytochrome P450-mediated drug metabolism in a nonuniform pattern. Therefore, short-term fasting is another factor affecting cytochrome P450-mediated drug metabolism in humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Brain Perfusion and Arterial Blood Flow Velocity During Prolonged Body Tilting.

    PubMed

    Montero, David; Rauber, Sven

    2016-08-01

    It remains unknown whether brain perfusion is preserved and mirrored by middle cerebral blood flow velocity (MCA BFV) during prolonged changes in body posture. Herein, we examined the impact of sustained (180 min) 30° head-up (HUT) and head-down (HDT) tilt on brain perfusion, as determined by MCA BFV and blood flow in the extracranial arteries. In 10 healthy male subjects, arterial diameters, BFVs, and blood flows were determined in the left internal carotid (ICA) and vertebral (VA) arteries using duplex Doppler ultrasound in supine rest, and 5, 20, 60, 120, and 180 min following 30° HUT and HDT. MCA BFV was recorded throughout with transcranial Doppler ultrasound. ICA as well as VA diameters and blood flows were unaltered during HUT. Likewise, brain blood flow and MCA BFV were preserved with HUT. In the HDT protocol, ICA and VA diameters were gradually increased, although ICA, VA, and brain blood flows were preserved. MCA BFV was progressively reduced during HDT. In addition, MCA BFV was positively associated with ICA BFV (β = 0.9) and negatively associated with ICA diameter (β = -125.5). MCA BFV was positively associated with brain blood flow during HUT (β = 0.2) but not HDT. Brain perfusion is preserved whereas MCA BFV is progressively decreased and associated with extracranial arterial BFV during sustained 30° HDT. Therefore, MCA BFV may not be a surrogate of brain perfusion in conditions including prolonged HDT. Montero D, Rauber S. Brain perfusion and arterial blood flow velocity during prolonged body tilting. Aerosp Med Hum Perform. 2016; 87(8):682-687.

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

    PubMed

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

    2017-10-24

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